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Sample records for hyaline cartilage regeneration

  1. Surgical correction of joint deformities and hyaline cartilage regeneration

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    Vyacheslav Alexandrovich Vinokurov

    2015-12-01

    Full Text Available Aim. To determine a method of extra-articular osteochondral fragment formation for the improvement of surgical correction results of joint deformities and optimization of regenerative conditions for hyaline cartilage. Materials and Methods. The method of formation of an articular osteochondral fragment without penetration into the joint cavity was devised experimentally. More than 30 patients with joint deformities underwent the surgery. Results. During the experiments, we postulated that there may potentially be a complete recovery of joint defects because of hyaline cartilage regeneration. By destructing the osteochondral fragment and reforming it extra-articularally, joint defects were recovered in all patients. The results were evaluated as excellent and good in majority of the patients. Conclusion. These findings indicate a novel method in which the complete recovery of joint defects due to dysplastic genesis or osteochondral defects as a result of injuries can be obtained. The devised method can be used in future experiments for objectification and regenerative potential of hyaline cartilage (e.g., rate and volume of the reformed joints that regenerate, detection of cartilage elements, and the regeneration process.

  2. Joint immobilization inhibits spontaneous hyaline cartilage regeneration induced by a novel double-network gel implantation.

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    Arakaki, Kazunobu; Kitamura, Nobuto; Kurokawa, Takayuki; Onodera, Shin; Kanaya, Fuminori; Gong, Jian-Ping; Yasuda, Kazunori

    2011-02-01

    We have recently discovered that spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect in the rabbit, when we implant a novel double-network (DN) gel plug at the bottom of the defect. To clarify whether joint immobilization inhibits the spontaneous hyaline cartilage regeneration, we conducted this study with 20 rabbits. At 4 or 12 weeks after surgery, the defect in the mobile knees was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type-2 collagen, while no cartilage tissues were observed in the defect in the immobilized knees. Type-2 collagen, Aggrecan, and SOX9 mRNAs were expressed only in the mobile knees at each period. This study demonstrated that joint immobilization significantly inhibits the spontaneous hyaline cartilage regeneration induced by the DN gel implantation. This fact suggested that the mechanical environment is one of the significant factors to induce this phenomenon.

  3. Magnetic resonance imaging of hyaline cartilage regeneration in neocartilage graft implantation.

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    Tan, C F; Ng, K K; Ng, S H; Cheung, Y C

    2003-12-01

    The purpose of this study was to investigate the regenerative potential of hyaline cartilage in a neocartilage graft implant with the aid of MR cartilage imaging using a rabbit model. Surgical osteochondral defects were created in the femoral condyles of 30 mature New Zealand rabbits. The findings of neocartilage in autologous cartilage grafts packed into osteochondral defects were compared with control group of no implant to the osteochondral defect. The outcome of the implantations was correlated with histologic and MR cartilage imaging findings over a 3-month interval. Neocartilage grafts packed into osteochondral defects showed regeneration of hyaline cartilage at the outer layer of the implant using MR cartilage imaging. Fibrosis of fibrocartilage developed at the outer layer of the autologous cartilage graft together with an inflammatory reaction within the osteochondral defect. This animal study provides evidence of the regenerative ability of hyaline cartilage in neocartilage transplants to repair articular cartilage.

  4. Which cartilage is regenerated, hyaline cartilage or fibrocartilage? Non-invasive ultrasonic evaluation of tissue-engineered cartilage.

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    Hattori, K; Takakura, Y; Ohgushi, H; Habata, T; Uematsu, K; Takenaka, M; Ikeuchi, K

    2004-09-01

    To investigate ultrasonic evaluation methods for detecting whether the repair tissue is hyaline cartilage or fibrocartilage in new cartilage regeneration therapy. We examined four experimental rabbit models: a spontaneous repair model (group S), a large cartilage defect model (group L), a periosteal graft model (group P) and a tissue-engineered cartilage regeneration model (group T). From the resulting ultrasonic evaluation, we used %MM (the maximum magnitude of the measurement area divided by that of the intact cartilage) as a quantitative index of cartilage regeneration. The results of the ultrasonic evaluation were compared with the histological findings and histological score. The %MM values were 61.1 +/- 16.5% in group S, 29.8 +/- 15.1% in group L, 36.3 +/- 18.3% in group P and 76.5 +/- 18.7% in group T. The results showed a strong similarity to the histological scoring. The ultrasonic examination showed that all the hyaline-like cartilage in groups S and T had a high %MM (more than 60%). Therefore, we could define the borderline between the two types of regenerated cartilage by the %MM.

  5. Hyaline Articular Matrix Formed by Dynamic Self-Regenerating Cartilage and Hydrogels.

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    Meppelink, Amanda M; Zhao, Xing; Griffin, Darvin J; Erali, Richard; Gill, Thomas J; Bonassar, Lawrence J; Redmond, Robert W; Randolph, Mark A

    2016-07-01

    Injuries to the articular cartilage surface are challenging to repair because cartilage possesses a limited capacity for self-repair. The outcomes of current clinical procedures aimed to address these injuries are inconsistent and unsatisfactory. We have developed a novel method for generating hyaline articular cartilage to improve the outcome of joint surface repair. A suspension of 10(7) swine chondrocytes was cultured under reciprocating motion for 14 days. The resulting dynamic self-regenerating cartilage (dSRC) was placed in a cartilage ring and capped with fibrin and collagen gel. A control group consisted of chondrocytes encapsulated in fibrin gel. Constructs were implanted subcutaneously in nude mice and harvested after 6 weeks. Gross, histological, immunohistochemical, biochemical, and biomechanical analyses were performed. In swine patellar groove, dSRC was implanted into osteochondral defects capped with collagen gel and compared to defects filled with osteochondral plugs, collagen gel, or left empty after 6 weeks. In mice, the fibrin- and collagen-capped dSRC constructs showed enhanced contiguous cartilage matrix formation over the control of cells encapsulated in fibrin gel. Biochemically, the fibrin and collagen gel dSRC groups were statistically improved in glycosaminoglycan and hydroxyproline content compared to the control. There was no statistical difference in the biomechanical data between the dSRC groups and the control. The swine model also showed contiguous cartilage matrix in the dSRC group but not in the collagen gel and empty defects. These data demonstrate the survivability and successful matrix formation of dSRC under the mechanical forces experienced by normal hyaline cartilage in the knee joint. The results from this study demonstrate that dSRC capped with hydrogels successfully engineers contiguous articular cartilage matrix in both nonload-bearing and load-bearing environments.

  6. Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells.

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    Xiaowei Zhang

    Full Text Available Microfracture, a common procedure for treatment of cartilage injury, induces fibrocartilage repair by recruiting bone marrow derived mesenchymal stem cells (MSC to the site of cartilage injury. However, fibrocartilage is inferior biomechanically to hyaline cartilage. SRY-type high-mobility group box-9 (SOX9 is a master regulator of chondrogenesis by promoting proliferation and differentiation of MSC into chondrocytes. In this study we aimed to test the therapeutic potential of cell penetrating recombinant SOX9 protein in regeneration of hyaline cartilage in situ at the site of cartilage injury. We generated a recombinant SOX9 protein which was fused with super positively charged green fluorescence protein (GFP (scSOX9 to facilitate cell penetration. scSOX9 was able to induce chondrogenesis of bone marrow derived MSC in vitro. In a rabbit cartilage injury model, scSOX9 in combination with microfracture significantly improved quality of repaired cartilage as shown by macroscopic appearance. Histological analysis revealed that the reparative tissue induced by microfracture with scSOX9 had features of hyaline cartilage; and collagen type II to type I ratio was similar to that in normal cartilage. This short term in vivo study demonstrated that when administered at the site of microfracture, scSOX9 was able to induce reparative tissue with features of hyaline cartilage.

  7. Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells.

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    Zhang, Xiaowei; Wu, Shili; Naccarato, Ty; Prakash-Damani, Manan; Chou, Yuan; Chu, Cong-Qiu; Zhu, Yong

    2017-01-01

    Microfracture, a common procedure for treatment of cartilage injury, induces fibrocartilage repair by recruiting bone marrow derived mesenchymal stem cells (MSC) to the site of cartilage injury. However, fibrocartilage is inferior biomechanically to hyaline cartilage. SRY-type high-mobility group box-9 (SOX9) is a master regulator of chondrogenesis by promoting proliferation and differentiation of MSC into chondrocytes. In this study we aimed to test the therapeutic potential of cell penetrating recombinant SOX9 protein in regeneration of hyaline cartilage in situ at the site of cartilage injury. We generated a recombinant SOX9 protein which was fused with super positively charged green fluorescence protein (GFP) (scSOX9) to facilitate cell penetration. scSOX9 was able to induce chondrogenesis of bone marrow derived MSC in vitro. In a rabbit cartilage injury model, scSOX9 in combination with microfracture significantly improved quality of repaired cartilage as shown by macroscopic appearance. Histological analysis revealed that the reparative tissue induced by microfracture with scSOX9 had features of hyaline cartilage; and collagen type II to type I ratio was similar to that in normal cartilage. This short term in vivo study demonstrated that when administered at the site of microfracture, scSOX9 was able to induce reparative tissue with features of hyaline cartilage.

  8. Biostable scaffolds of polyacrylate polymers implanted in the articular cartilage induce hyaline-like cartilage regeneration in rabbits.

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    Sancho-Tello, María; Forriol, Francisco; Martín de Llano, José J; Antolinos-Turpin, Carmen; Gómez-Tejedor, José A; Gómez Ribelles, José L; Carda, Carmen

    2017-07-05

    To study the influence of scaffold properties on the organization of in vivo cartilage regeneration. Our hypothesis was that stress transmission to the cells seeded inside the pores of the scaffold or surrounding it, which is highly dependent on the scaffold properties, determines the differentiation of both mesenchymal cells and dedifferentiated autologous chondrocytes. 4 series of porous scaffolds made of different polyacrylate polymers, previously seeded with cultured rabbit chondrocytes or without cells, were implanted in cartilage defects in rabbits. Subchondral bone was injured during the surgery to allow blood to reach the implantation site and fill the scaffold pores. At 3 months after implantation, excellent tissue regeneration was obtained, with a well-organized layer of hyaline-like cartilage at the condylar surface in most cases of the hydrophobic or slightly hydrophilic series. The most hydrophilic material induced the poorest regeneration. However, no statistically significant difference was observed between preseeded and non-preseeded scaffolds. All of the materials used were biocompatible, biostable polymers, so, in contrast to some other studies, our results were not perturbed by possible effects attributable to material degradation products or to the loss of scaffold mechanical properties over time due to degradation. Cartilage regeneration depends mainly on the properties of the scaffold, such as stiffness and hydrophilicity, whereas little difference was observed between preseeded and non-preseeded scaffolds.

  9. Adipose stem cells can secrete angiogenic factors that inhibit hyaline cartilage regeneration.

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    Lee, Christopher Sd; Burnsed, Olivia A; Raghuram, Vineeth; Kalisvaart, Jonathan; Boyan, Barbara D; Schwartz, Zvi

    2012-08-24

    Adipose stem cells (ASCs) secrete many trophic factors that can stimulate tissue repair, including angiogenic factors, but little is known about how ASCs and their secreted factors influence cartilage regeneration. Therefore, the aim of this study was to determine the effects ASC-secreted factors have in repairing chondral defects. ASCs isolated from male Sprague Dawley rats were cultured in monolayer or alginate microbeads supplemented with growth (GM) or chondrogenic medium (CM). Subsequent co-culture, conditioned media, and in vivo cartilage defect studies were performed. ASC monolayers and microbeads cultured in CM had decreased FGF-2 gene expression and VEGF-A secretion compared to ASCs cultured in GM. Chondrocytes co-cultured with GM-cultured ASCs for 7 days had decreased mRNAs for col2, comp, and runx2. Chondrocytes treated for 12 or 24 hours with conditioned medium from GM-cultured ASCs had reduced sox9, acan, and col2 mRNAs; reduced proliferation and proteoglycan synthesis; and increased apoptosis. ASC-conditioned medium also increased endothelial cell tube lengthening whereas conditioned medium from CM-cultured ASCs had no effect. Treating ASCs with CM reduced or abolished these deleterious effects while adding a neutralizing antibody for VEGF-A eliminated ASC-conditioned medium induced chondrocyte apoptosis and restored proteoglycan synthesis. FGF-2 also mitigated the deleterious effects VEGF-A had on chondrocyte apoptosis and phenotype. When GM-grown ASC pellets were implanted in 1 mm non-critical hyaline cartilage defects in vivo, cartilage regeneration was inhibited as evaluated by radiographic and equilibrium partitioning of an ionic contrast agent via microCT imaging. Histology revealed that defects with GM-cultured ASCs had no tissue ingrowth from the edges of the defect whereas empty defects and defects with CM-grown ASCs had similar amounts of neocartilage formation. ASCs must be treated to reduce the secretion of VEGF-A and other factors that

  10. Hyaline cartilage regeneration by combined therapy of microfracture and long-term bone morphogenetic protein-2 delivery.

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    Yang, Hee Seok; La, Wan-Geun; Bhang, Suk Ho; Kim, Hak-Jun; Im, Gun-Il; Lee, Haeshin; Park, Jung-Ho; Kim, Byung-Soo

    2011-07-01

    Microfracture of cartilage induces migration of bone-marrow-derived mesenchymal stem cells. However, this treatment often results in fibrocartilage regeneration. Growth factors such as bone morphogenetic protein (BMP)-2 induce the differentiation of bone-marrow-derived mesenchymal stem cells into chondrocytes, which can be used for hyaline cartilage regeneration. Here, we tested the hypothesis that long-term delivery of BMP-2 to cartilage defects subjected to microfracture results in regeneration of high-quality hyaline-like cartilage, as opposed to short-term delivery of BMP-2 or no BMP-2 delivery. Heparin-conjugated fibrin (HCF) and normal fibrin were used as carriers for the long- and short-term delivery of BMP-2, respectively. Rabbit articular cartilage defects were treated with microfracture combined with one of the following: no treatment, fibrin, short-term delivery of BMP-2, HCF, or long-term delivery of BMP-2. Eight weeks after treatment, histological analysis revealed that the long-term delivery of BMP-2 group (microfracture + HCF + BMP-2) showed the most staining with alcian blue. A biochemical assay, real-time polymerase chain reaction assay and Western blot analysis all revealed that the long-term delivery of BMP-2 group had the highest glucosaminoglycan content as well as the highest expression level of collagen type II. Taken together, the long-term delivery of BMP-2 to cartilage defects subjected to microfracture resulted in regeneration of hyaline-like cartilage, as opposed to short-term delivery or no BMP-2 delivery. Therefore, this method could be more convenient for hyaline cartilage regeneration than autologous chondrocyte implantation due to its less invasive nature and lack of cell implantation.

  11. Regeneration of hyaline cartilage by cell-mediated gene therapy using transforming growth factor beta 1-producing fibroblasts.

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    Lee, K H; Song, S U; Hwang, T S; Yi, Y; Oh, I S; Lee, J Y; Choi, K B; Choi, M S; Kim, S J

    2001-09-20

    Transforming growth factor beta (TGF-beta) has been considered as a candidate for gene therapy of orthopedic diseases. The possible application of cell-mediated TGF-beta gene therapy as a new treatment regimen for degenerative arthritis was investigated. In this study, fibroblasts expressing active TGF-beta 1 were injected into the knee joints of rabbits with artificially made cartilage defects to evaluate the feasibility of this therapy for orthopedic diseases. Two to 3 weeks after the injection there was evidence of cartilage regeneration, and at 4 to 6 weeks the cartilage defect was completely filled with newly grown hyaline cartilage. Histological analyses of the regenerated cartilage suggested that it was well integrated with the adjacent normal cartilage at the sides of the defect and that the newly formed tissue was indeed hyaline cartilage. Our findings suggest that cell-mediated TGF-beta 1 gene therapy may be a novel treatment for orthopedic diseases in which hyaline cartilage damage has occurred.

  12. Regeneration of hyaline cartilage promoted by xenogeneic mesenchymal stromal cells embedded within elastin-like recombinamer-based bioactive hydrogels.

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    Pescador, David; Ibáñez-Fonseca, Arturo; Sánchez-Guijo, Fermín; Briñón, Jesús G; Arias, Francisco Javier; Muntión, Sandra; Hernández, Cristina; Girotti, Alessandra; Alonso, Matilde; Del Cañizo, María Consuelo; Rodríguez-Cabello, José Carlos; Blanco, Juan Francisco

    2017-08-01

    Over the last decades, novel therapeutic tools for osteochondral regeneration have arisen from the combination of mesenchymal stromal cells (MSCs) and highly specialized smart biomaterials, such as hydrogel-forming elastin-like recombinamers (ELRs), which could serve as cell-carriers. Herein, we evaluate the delivery of xenogeneic human MSCs (hMSCs) within an injectable ELR-based hydrogel carrier for osteochondral regeneration in rabbits. First, a critical-size osteochondral defect was created in the femora of the animals and subsequently filled with the ELR-based hydrogel alone or with embedded hMSCs. Regeneration outcomes were evaluated after three months by gross assessment, magnetic resonance imaging and computed tomography, showing complete filling of the defect and the de novo formation of hyaline-like cartilage and subchondral bone in the hMSC-treated knees. Furthermore, histological sectioning and staining of every sample confirmed regeneration of the full cartilage thickness and early subchondral bone repair, which was more similar to the native cartilage in the case of the cell-loaded ELR-based hydrogel. Overall histological differences between the two groups were assessed semi-quantitatively using the Wakitani scale and found to be statistically significant (p hyaline cartilage in osteochondral lesions.

  13. Mesenchymal Stem Cells in Oriented PLGA/ACECM Composite Scaffolds Enhance Structure-Specific Regeneration of Hyaline Cartilage in a Rabbit Model.

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    Guo, Weimin; Zheng, Xifu; Zhang, Weiguo; Chen, Mingxue; Wang, Zhenyong; Hao, Chunxiang; Huang, Jingxiang; Yuan, Zhiguo; Zhang, Yu; Wang, Mingjie; Peng, Jiang; Wang, Aiyuan; Wang, Yu; Sui, Xiang; Xu, Wenjing; Liu, Shuyun; Lu, Shibi; Guo, Quanyi

    2018-01-01

    Articular cartilage lacks a blood supply and nerves. Hence, articular cartilage regeneration remains a major challenge in orthopedics. Decellularized extracellular matrix- (ECM-) based strategies have recently received particular attention. The structure of native cartilage exhibits complex zonal heterogeneity. Specifically, the development of a tissue-engineered scaffold mimicking the aligned structure of native cartilage would be of great utility in terms of cartilage regeneration. Previously, we fabricated oriented PLGA/ACECM (natural, nanofibrous, articular cartilage ECM) composite scaffolds. In vitro, we found that the scaffolds not only guided seeded cells to proliferate in an aligned manner but also exhibited high biomechanical strength. To detect whether oriented cartilage regeneration was possible in vivo, we used mesenchymal stem cell (MSC)/scaffold constructs to repair cartilage defects. The results showed that cartilage defects could be completely regenerated. Histologically, these became filled with hyaline cartilage and subchondral bone. Moreover, the aligned structure of cartilage was regenerated and was similar to that of native tissue. In conclusion, the MSC/scaffold constructs enhanced the structure-specific regeneration of hyaline cartilage in a rabbit model and may be a promising treatment strategy for the repair of human cartilage defects.

  14. Positive effects of cell-free porous PLGA implants and early loading exercise on hyaline cartilage regeneration in rabbits.

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    Chang, Nai-Jen; Lin, Chih-Chan; Shie, Ming-You; Yeh, Ming-Long; Li, Chien-Feng; Liang, Peir-In; Lee, Kuan-Wei; Shen, Pei-Hsun; Chu, Chih-Jou

    2015-12-01

    The regeneration of hyaline cartilage remains clinically challenging. Here, we evaluated the therapeutic effects of using cell-free porous poly(lactic-co-glycolic acid) (PLGA) graft implants (PGIs) along with early loading exercise to repair a full-thickness osteochondral defect. Rabbits were randomly allocated to a treadmill exercise (TRE) group or a sedentary (SED) group and were prepared as either a PGI model or an empty defect (ED) model. TRE was performed as a short-term loading exercise; SED was physical inactivity in a free cage. The knees were evaluated at 6 and 12 weeks after surgery. At the end of testing, none of the knees developed synovitis, formed osteophytes, or became infected. Macroscopically, the PGI-TRE group regenerated a smooth articular surface, with transparent new hyaline-like tissue soundly integrated with the neighboring cartilage, but the other groups remained distinct at the margins with fibrous or opaque tissues. In a micro-CT analysis, the synthesized bone volume/tissue volume (BV/TV) was significantly higher in the PGI-TRE group, which also had integrating architecture in the regeneration site. The thickness of the trabecular (subchondral) bone was improved in all groups from 6 to 12 weeks. Histologically, remarkable differences in the cartilage regeneration were visible. At week 6, compared with SED groups, the TRE groups manifested modest inflammatory cells with pro-inflammatory cytokines (i.e., TNF-α and IL-6), improved collagen alignment and higher glycosaminoglycan (GAG) content, particularly in the PGI-TRE group. At week 12, the PGI-TRE group had the best regeneration outcomes, showing the formation of hyaline-like cartilage, the development of columnar rounded chondrocytes that expressed enriched levels of collagen type II and GAG, and functionalized trabecular bone with osteocytes. In summary, the combination of implanting cell-free PLGA and performing an early loading exercise can significantly promote the full

  15. Injectable glycosaminoglycan-protein nano-complex in semi-interpenetrating networks: A biphasic hydrogel for hyaline cartilage regeneration.

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    Radhakrishnan, Janani; Subramanian, Anuradha; Sethuraman, Swaminathan

    2017-11-01

    Articular hyaline cartilage regeneration remains challenging due to its less intrinsic reparability. The study develops injectable biphasic semi-interpenetrating polymer networks (SIPN) hydrogel impregnated with chondroitin sulfate (ChS) nanoparticles for functional cartilage restoration. ChS loaded zein nanoparticles (∼150nm) prepared by polyelectrolyte-protein complexation were interspersed into injectable SIPNs developed by blending alginate with poly(vinyl alcohol) and calcium crosslinking. The hydrogel exhibited interconnected porous microstructure (39.9±5.8μm pore diameter, 57.7±5.9% porosity), 92% swellability and >350Pa elastic modulus. Primary chondrocytes compatibility, chondrocyte-matrix interaction with cell-cell clustering and spheroidal morphology was demonstrated in ChS loaded hydrogel and long-term (42days) proliferation was also determined. Higher fold expression of cartilage-specific genes sox9, aggrecan and collagen-II was observed in ChS loaded hydrogel while exhibiting poor expression of collagen-I. Immunoblotting of aggregan and collagen II demonstrate favorable positive influence of ChS on chondrocytes. Thus, the injectable biphasic SIPNs could be promising composition-mimetic substitute for cartilage restoration at irregular defects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Platelet-rich plasma loaded in situ-formed hydrogel enhances hyaline cartilage regeneration by CB1 upregulation.

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    Lee, Hye-Rim; Park, Kyung Min; Joung, Yoon Ki; Park, Ki Dong; Do, Sun Hee

    2012-11-01

    The efficacy of three-dimensional (3D) culture on the proliferation and maturation of chondrocytes seeded into a hydrogel scaffold was assessed. Three types of hydrogel were prepared for the 3D culture of primary isolated chondrocytes. Chondrocyte proliferation was assessed using a live/dead viability/cytotoxicity assay and semiquantitative RT-PCR after 3D culture in hydrogel. Cylindrical defects in the center of rat xyphoids were used for the implantation of platelet-rich plasma (PRP)/hydrogel composites. Rats were killed at day 7 postoperatively and evaluated histochemically and immunohistologically. Xyphoid chondrocytes proliferated well with time in hydrogels. In the PRP-containing hydrogels, xyphoid defects displayed early formation of chondroid matrix with massive peripheral infiltration of spindle cells. These results were consistent with Safranin-O staining for proteoglycans and immunohistochemistry for type II collagen. Gene expression analyses in vitro revealed aggrecan, type II collagen, and ChM-1 and CB1 upregulation by PRP/hydrogel. PRP/hydrogel provided a suitable environment for hyaline cartilaginous regeneration, leading to anti-inflammation by significant increase of CB1 and inhibiting vascular ingrowth via considerable upregulation of ChM-1. The results provide a valuable reference for the clinical application of hydrogel scaffolds for hyaline cartilage regeneration, as well as the use of autologous PRP to improve cellular proliferation and maturation of xyphoid repair. Copyright © 2012 Wiley Periodicals, Inc.

  17. Regeneration of hyaline-like cartilage in situ with SOX9 stimulation of bone marrow-derived mesenchymal stem cells

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    Zhang, Xiaowei; Wu, Shili; Naccarato, Ty; Prakash-Damani, Manan; Chou, Yuan; Chu, Cong-Qiu; Zhu, Yong

    2017-01-01

    Microfracture, a common procedure for treatment of cartilage injury, induces fibrocartilage repair by recruiting bone marrow derived mesenchymal stem cells (MSC) to the site of cartilage injury. However, fibrocartilage is inferior biomechanically to hyaline cartilage. SRY-type high-mobility group box-9 (SOX9) is a master regulator of chondrogenesis by promoting proliferation and differentiation of MSC into chondrocytes. In this study we aimed to test the therapeutic potential of cell penetrat...

  18. Intra-articular administration of hyaluronic acid increases the volume of the hyaline cartilage regenerated in a large osteochondral defect by implantation of a double-network gel.

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    Fukui, Takaaki; Kitamura, Nobuto; Kurokawa, Takayuki; Yokota, Masashi; Kondo, Eiji; Gong, Jian Ping; Yasuda, Kazunori

    2014-04-01

    Implantation of PAMPS/PDMAAm double-network (DN) gel can induce hyaline cartilage regeneration in the osteochondral defect. However, it is a problem that the volume of the regenerated cartilage tissue is gradually reduced at 12 weeks. This study investigated whether intra-articular administration of hyaluronic acid (HA) increases the volume of the cartilage regenerated with the DN gel at 12 weeks. A total of 48 rabbits were used in this study. A cylindrical osteochondral defect created in the bilateral femoral trochlea was treated with DN gel (Group DN) or left without any implantation (Group C). In both Groups, we injected 1.0 mL of HA in the left knee, and 1.0 mL of saline solution in the right knee. Quantitative histological evaluations were performed at 2, 4, and 12 weeks, and PCR analysis was performed at 2 and 4 weeks after surgery. In Group DN, the proteoglycan-rich area was significantly greater in the HA-injected knees than in the saline-injected knees at 12 weeks (P = 0.0247), and expression of type 2 collagen, aggrecan, and Sox9 mRNAs was significantly greater in the HA-injected knees than in the saline-injected knees at 2 weeks (P = 0.0475, P = 0.0257, P = 0.0222, respectively). The intra-articular administration of HA significantly enhanced these gene expression at 2 weeks and significantly increased the volume of the hyaline cartilage regenerated by implantation of a DN gel at 12 weeks. This information is important to develop an additional method to increase the volume of the hyaline cartilage tissue in a potential cartilage regeneration strategy using the DN gel.

  19. Induction of spontaneous hyaline cartilage regeneration using a double-network gel: efficacy of a novel therapeutic strategy for an articular cartilage defect.

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    Kitamura, Nobuto; Yasuda, Kazunori; Ogawa, Munehiro; Arakaki, Kazunobu; Kai, Shuken; Onodera, Shin; Kurokawa, Takayuki; Gong, Jian Ping

    2011-06-01

    A double-network (DN) gel, which was composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) and poly-(N,N'-dimetyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. To establish the efficacy of a therapeutic strategy for an articular cartilage defect using a DN gel. Controlled laboratory study. A 4.3-mm-diameter osteochondral defect was created in rabbit trochlea. A DN gel plug was implanted into the defect of the right knee so that a defect 2 mm in depth remained after surgery. An untreated defect of the left knee provided control data. The osteochondral defects created were examined by histological and immunohistochemical evaluations, surface assessment using confocal laser scanning microscopy, and real-time polymerase chain reaction (PCR) analysis at 4 and 12 weeks. Samples were quantitatively evaluated with 2 scoring systems reported by Wayne et al and O'Driscoll et al. The DN gel-implanted defect was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type 2 collagen. Quantitative evaluation using the grading scales revealed a significantly higher score in the DN gel-implanted defects compared with the untreated control at each period (P cartilage at 12 weeks (P = .0106), while there was no statistical difference between the DN gel-implanted and normal knees. This study using the mature rabbit femoral trochlea osteochondral defect model demonstrated that DN gel implantation is an effective treatment to induce cartilage regeneration in vivo without any cultured cells or mammalian-derived scaffolds. This study has prompted us to develop a potential innovative strategy to repair cartilage lesions in the field of joint surgery.

  20. Spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect created in the femoral condyle using a novel double-network hydrogel.

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    Yokota, Masashi; Yasuda, Kazunori; Kitamura, Nobuto; Arakaki, Kazunobu; Onodera, Shin; Kurokawa, Takayuki; Gong, Jian-Ping

    2011-02-22

    Functional repair of articular osteochondral defects remains a major challenge not only in the field of knee surgery but also in tissue regeneration medicine. The purpose is to clarify whether the spontaneous hyaline cartilage regeneration can be induced in a large osteochondral defect created in the femoral condyle by means of implanting a novel double-network (DN) gel at the bottom of the defect. Twenty-five mature rabbits were used in this study. In the bilateral knees of each animal, we created an osteochondral defect having a diameter of 2.4-mm in the medial condyle. Then, in 21 rabbits, we implanted a DN gel plug into a right knee defect so that a vacant space of 1.5-mm depth (in Group I), 2.5-mm depth (in Group II), or 3.5-mm depth (in Group III) was left. In the left knee, we did not apply any treatment to the defect to obtain the control data. All the rabbits were sacrificed at 4 weeks, and the gross and histological evaluations were performed. The remaining 4 rabbits underwent the same treatment as used in Group II, and real-time PCR analysis was performed at 4 weeks. The defect in Group II was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type-2 collagen. The Wayne's gross appearance and histology scores showed that Group II was significantly greater than Group I, III, and Control (p hyaline cartilage regeneration can be induced in vivo in an osteochondral defect created in the femoral condyle by means of implanting the DN gel plug at the bottom of the defect so that an approximately 2-mm deep vacant space was intentionally left in the defect. This fact has prompted us to propose an innovative strategy without cell culture to repair osteochondral lesions in the femoral condyle.

  1. Microdrilled cartilage defects treated with thrombin-solidified chitosan/blood implant regenerate a more hyaline, stable, and structurally integrated osteochondral unit compared to drilled controls.

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    Marchand, Catherine; Chen, Gaoping; Tran-Khanh, Nicolas; Sun, Jun; Chen, Hongmei; Buschmann, Michael D; Hoemann, Caroline D

    2012-03-01

    This study analyzed the long-term cartilage and subchondral bone repair of microdrilled defects treated with chitosan glycerol-phosphate/blood implant, using thrombin (Factor IIa) to accelerate in situ solidification. We also evaluated the cartilage repair response to six smaller microdrill holes compared with two larger holes. Bilateral knee trochlear cartilage defects were created in n=8 skeletally mature rabbits, drilled with six proximal 0.5 mm and two distal 0.9 mm holes, then covered with in situ-solidified IIa-implants (treated) or with IIa-alone (control). After 6.5 months of repair, cartilage repair tissues were analyzed by histological scoring and histomorphometry for hyaline matrix characteristics and osseous integration. Subchondral repair bone was analyzed by 3D microcomputed tomography and compared to acute defects (n=6) and intact trochlea (n=8). Implant-treated cartilage repair tissues had higher structural integrity through the entire defect (p=0.02), twofold higher percent staining for glycosaminoglycan (p=0.0004), and ~24% more collagen type II staining over the smaller drill holes (p=0.008) compared with controls. Otherwise, hole diameter had no specific effect on cartilage repair. The subchondral bone plate was partially restored in treated and control defects but less dense than intact trochlea, with evidence of incomplete regeneration of the calcified cartilage layer. More residual drill holes (p=0.054) were detected in control versus treated defects, and control defects with more than 40% residual holes presented abnormally thicker trabeculae compared with treated defects. Low osteoclast numbers after 6.5 months repair suggested that bone was no longer remodeling. The subchondral bone plate surrounding the defects exhibited a significant thickening compared with age-matched intact trochlea. These data suggest that debridement and drilling can lead to long-term subchondral bone changes outside the cartilage defect. Compared with drilled

  2. In-situ birth of MSCs multicellular spheroids in poly(L-glutamic acid)/chitosan scaffold for hyaline-like cartilage regeneration.

    Science.gov (United States)

    Zhang, Kunxi; Yan, Shifeng; Li, Guifei; Cui, Lei; Yin, Jingbo

    2015-12-01

    The success of mesenchymal stem cells (MSCs) based articular cartilage tissue engineering is limited by the presence of fibrous tissue in generated cartilage, which is associated with the current scaffold strategy that promotes cellular adhesion and spreading. Here we design a non-fouling scaffold based on amide bonded poly(l-glutamic acid) (PLGA) and chitosan (CS) to drive adipose stem cells (ASCs) to aggregate to form multicellular spheroids with diameter of 80-110 μm in-situ. To illustrate the advantage of the present scaffolds, a cellular adhesive scaffold based on the same amide bonded PLGA and CS was created through a combination of air-drying and freeze-drying to limit the hydration effect while also achieving porous structure. Compared to ASCs spreading along the surface of pores within scaffold, the dense mass of aggregated ASCs in PLGA/CS scaffold exhibited enhanced chondrogenic differentiation capacity, as determined by up-regulated GAGs and COL II expression, and greatly decreased COL I deposition during in vitro chondrogenesis. Furthermore, after 12 weeks of implantation, neo-cartilages generated by ASCs adhered on scaffold significantly presented fibrous matrix which was characterized by high levels of COL I deposition. However, neo-cartilage at 12 weeks post-implantation generated by PLGA/CS scaffold carrying ASC spheroids possessed similar high level of GAGs and COL II and low level of COL I as that in normal cartilage. The in vitro and in vivo results indicated the present strategy could not only promote chondrogenesis of ASCs, but also facilitate hyaline-like cartilage regeneration with reduced fibrous tissue formation which may attenuate cartilage degradation in future long-term follow-up. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Towards Regeneration of Articular Cartilage

    Science.gov (United States)

    Iwamoto, Masahiro; Ohta, Yoichi; Larmour, Colleen; Enomoto-Iwamoto, Motomi

    2014-01-01

    Articular cartilage is classified into permanent hyaline cartilage and has significant differences in structure, extracelluar matrix components, gene expression profile, and mechanical property from transient hyaline cartilage found in growth plate. In the process of synovial joint development, articular cartilage is originated from the interzone, developing at the edge of the cartilaginous anlagen, it establishes zonal structure over time and supports smooth movement of the synovial joint through life. The cascade actions of key regulators such as Wnts, GDF5, Erg, and PTHLH coordinate sequential steps of articular cartilage formation. Articular chondrocytes are restrictedly controlled not to differentiate into a hypertrophic stage by autocrine and paracrine factors and extracerllular matrix microenvironment, but retain potential to undergo hypertrophy. The basal calcified zone of articular cartilage is connected with subchondral bone, but not invaded by blood vessels nor replaced by bone, which is highly contrasted with the growth plate. Articular cartilage has limited regenerative capacity, but likely possesses and potentially uses intrinsic stem cell source in the superficial layer, Ranvier’s groove, the intra-articular tissues such as synovium and fat pad, and marrow below the subchondral bone. Considering the biological views on articular cartilage, several important points are raised for regeneration of articular cartilage. We should evaluate the nature of regenerated cartilage as permanent hyaline cartilage and not just hyaline cartilage. We should study how a hypertrophic phenotype of transplanted cells can be lastingly suppressed in regenerating tissue. Further, we should develop the methods and reagents to activate recruitment of intrinsic stem/progenitor cells into the damaged site. PMID:24078496

  4. Mechano growth factor (MGF) and transforming growth factor (TGF)-β3 functionalized silk scaffolds enhance articular hyaline cartilage regeneration in rabbit model.

    Science.gov (United States)

    Luo, Ziwei; Jiang, Li; Xu, Yan; Li, Haibin; Xu, Wei; Wu, Shuangchi; Wang, Yuanliang; Tang, Zhenyu; Lv, Yonggang; Yang, Li

    2015-06-01

    Damaged cartilage has poor self-healing ability and usually progresses to scar or fibrocartilaginous tissue, and finally degenerates to osteoarthritis (OA). Here we demonstrated that one of alternative isoforms of IGF-1, mechano growth factor (MGF) acted synergistically with transforming growth factor β3 (TGF-β3) embedded in silk fibroin scaffolds to induce chemotactic homing and chondrogenic differentiation of mesenchymal stem cells (MSCs). Combination of MGF and TGF-β3 significantly increased cell recruitment up to 1.8 times and 2 times higher than TGF-β3 did in vitro and in vivo. Moreover, MGF increased Collagen II and aggrecan secretion of TGF-β3 induced hMSCs chondrogenesis, but decreased Collagen I in vitro. Silk fibroin (SF) scaffolds have been widely used for tissue engineering, and we showed that methanol treated pured SF scaffolds were porous, similar to compressive module of native cartilage, slow degradation rate and excellent drug released curves. At 7 days after subcutaneous implantation, TGF-β3 and MGF functionalized silk fibroin scaffolds (STM) recruited more CD29+/CD44+cells (Pcartilage-like extracellular matrix and less fibrillar collagen were detected in STM scaffolds than that in TGF-β3 modified scaffolds (ST) at 2 months after subcutaneous implantation. When implanted into articular joints in a rabbit osteochondral defect model, STM scaffolds showed the best integration into host tissues, similar architecture and collagen organization to native hyaline cartilage, as evidenced by immunostaining of aggrecan, collagen II and collagen I, as well as Safranin O and Masson's trichrome staining, and histological evalution based on the modified O'Driscoll histological scoring system (Pcartilage regeneration. This study demonstrated that TGF-β3 and MGF functionalized silk fibroin scaffolds enhanced endogenous stem cell recruitment and facilitated in situ articular cartilage regeneration, thus providing a novel strategy for cartilage repair

  5. Transplantation of autologous endothelial progenitor cells in porous PLGA scaffolds create a microenvironment for the regeneration of hyaline cartilage in rabbits.

    Science.gov (United States)

    Chang, N-J; Lam, C-F; Lin, C-C; Chen, W-L; Li, C-F; Lin, Y-T; Yeh, M-L

    2013-10-01

    Repairing articular cartilage is clinically challenging. We investigated a simple, effective and clinically feasible cell-based therapeutic approach using a poly(lactide-co-glycolide) (PLGA) scaffold seeded with autologous endothelial progenitor cells (EPC) to repair a full-thickness osteochondral defect in rabbits using a one-step surgery. EPC obtained by purifying a small amount of peripheral blood from rabbits were seeded into a highly porous, biocompatible PLGA scaffold, namely, EPC-PLGA, and implanted into the osteochondral defect in the medial femoral condyle. Twenty two rabbits were randomized into one of three groups: the empty defect group (ED), the PLGA-only group or the EPC-PLGA group. The defect sites were evaluated 4 and 12 weeks after implantation. At the end of testing, only the EPC-PLGA group showed the development of new cartilage tissue with a smooth, transparent and integrated articular surface. Moreover, histological analysis showed obvious differences in cartilage regeneration. At week 4, the EPC-PLGA group showed considerably higher TGF-β2 and TGF-β3 expression, a greater amount of synthesized glycosaminoglycan (GAG) content, and a higher degree of osteochondral angiogenesis in repaired tissues. At week 12, the EPC-PLGA group showed enhanced hyaline cartilage regeneration with a normal columnar chondrocyte arrangement, higher SOX9 expression, and greater GAG and collagen type II (COLII) content. Moreover, the EPC-PLGA group showed organized osteochondral integration, the formation of vessel-rich tubercular bone and significantly higher bone volume per tissue volume and trabecular thickness (Tb.Th). The present EPC-PLGA cell delivery system generates a suitable in situ microenvironment for osteochondral regeneration without the supplement of exogenous growth factors. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  6. Mechanical properties of hyaline and repair cartilage studied by nanoindentation.

    Science.gov (United States)

    Franke, O; Durst, K; Maier, V; Göken, M; Birkholz, T; Schneider, H; Hennig, F; Gelse, K

    2007-11-01

    Articular cartilage is a highly organized tissue that is well adapted to the functional demands in joints but difficult to replicate via tissue engineering or regeneration. Its viscoelastic properties allow cartilage to adapt to both slow and rapid mechanical loading. Several cartilage repair strategies that aim to restore tissue and protect it from further degeneration have been introduced. The key to their success is the quality of the newly formed tissue. In this study, periosteal cells loaded on a scaffold were used to repair large partial-thickness cartilage defects in the knee joint of miniature pigs. The repair cartilage was analyzed 26 weeks after surgery and compared both morphologically and mechanically with healthy hyaline cartilage. Contact stiffness, reduced modulus and hardness as key mechanical properties were examined in vitro by nanoindentation in phosphate-buffered saline at room temperature. In addition, the influence of tissue fixation with paraformaldehyde on the biomechanical properties was investigated. Although the repair process resulted in the formation of a stable fibrocartilaginous tissue, its contact stiffness was lower than that of hyaline cartilage by a factor of 10. Fixation with paraformaldehyde significantly increased the stiffness of cartilaginous tissue by one order of magnitude, and therefore, should not be used when studying biomechanical properties of cartilage. Our study suggests a sensitive method for measuring the contact stiffness of articular cartilage and demonstrates the importance of mechanical analysis for proper evaluation of the success of cartilage repair strategies.

  7. Hyaline cartilage degenerates after autologous osteochondral transplantation.

    Science.gov (United States)

    Tibesku, C O; Szuwart, T; Kleffner, T O; Schlegel, P M; Jahn, U R; Van Aken, H; Fuchs, S

    2004-11-01

    Autologous osteochondral grafting is a well-established clinical procedure to treat focal cartilage defects in patients, although basic research on this topic remains sparse. The aim of the current study was to evaluate (1) histological changes of transplanted hyaline cartilage of osteochondral grafts and (2) the tissue that connects the transplanted cartilage with the adjacent cartilage in a sheep model. Both knee joints of four sheep were opened surgically and osteochondral grafts were harvested and simultaneously transplanted to the contralateral femoral condyle. The animals were sacrificed after three months and the received knee joints were evaluated histologically. Histological evaluation showed a complete ingrowth of the osseous part of the osteochondral grafts. A healing or ingrowth at the level of the cartilage could not be observed. Histological evaluation of the transplanted grafts according to Mankin revealed significantly more and more severe signs of degeneration than the adjacent cartilage, such as cloning of chondrocytes and irregularities of the articular surface. We found no connecting tissue between the transplanted and the adjacent cartilage and histological signs of degeneration of the transplanted hyaline cartilage. In the light of these findings, long-term results of autologous osteochondral grafts in human beings have to be followed critically.

  8. Influence of the gel thickness on in vivo hyaline cartilage regeneration induced by double-network gel implanted at the bottom of a large osteochondral defect: Short-term results

    Directory of Open Access Journals (Sweden)

    Matsuda Hidetoshi

    2013-01-01

    Full Text Available Abstract Background A double-network (DN gel, which is composed of poly(2-acrylamido-2-methylpropanesulfonic acid and poly(N,N’-dimethyl acrylamide, can induce hyaline cartilage regeneration in vivo in a large osteochondral defect. The purpose of this study was to clarify the influence of the thickness of the implanted DN gel on the induction ability of hyaline cartilage regeneration. Methods Thirty-eight mature rabbits were used in this study. We created an osteochondral defect having a diameter of 4.3-mm in the patellofemoral joint. The knees were randomly divided into 4 groups (Group I: 0.5-mm thick gel, Group II: 1.0-mm thick gel, Group III: 5.0-mm thick gel, and Group IV: untreated control. Animals in each group were further divided into 3 sub-groups depending on the gel implant position (2.0-, 3.0-, or 4.0-mm depth from the articular surface in the defect. The regenerated tissues were evaluated with the Wayne’s gross and histological grading scales and real time PCR analysis of the cartilage marker genes at 4 weeks. Results According to the total Wayne’s score, when the depth of the final vacant space was set at 2.0 mm, the scores in Groups I, II, and III were significantly greater than that Group IV (p  Conclusions The 1.0-mm thick DN gel sheet had the same ability to induce hyaline cartilage regeneration as the 5.0-mm thick DN gel plug. However, the induction ability of the 0.5-mm thick sheet was significantly lower when compared with the 1.0-mm thick gel sheet. The 1.0-mm DN gel sheet is a promising device to establish a cell-free cartilage regeneration strategy that minimizes bone loss from the gel implantation.

  9. The junction between hyaline cartilage and engineered cartilage in rabbits.

    Science.gov (United States)

    Komura, Makoto; Komura, Hiroko; Otani, Yushi; Kanamori, Yutaka; Iwanaka, Tadashi; Hoshi, Kazuto; Tsuyoshi, Takato; Tabata, Yasuhiko

    2013-06-01

    Tracheoplasty using costal cartilage grafts to enlarge the tracheal lumen was performed to treat congenital tracheal stenosis. Fibrotic granulomatous tissue was observed at the edge of grafted costal cartilage. We investigated the junction between the native hyaline cartilage and the engineered cartilage plates that were generated by auricular chondrocytes for fabricating the airway. Controlled, prospecive study. In group 1, costal cartilage from New Zealand white rabbits was collected and implanted into a space created in the cervical trachea. In group 2, chondrocytes from auricular cartilages were seeded on absorbable scaffolds. These constructs were implanted in the subcutaneous space. Engineered cartilage plates were then implanted into the trachea after 3 weeks of implantation of the constructs. The grafts in group 1 and 2 were retrieved after 4 weeks. In group 1, histological studies of the junction between the native hyaline cartilage and the implanted costal cartilage demonstrated chondrogenic tissue in four anastomoses sides out of the 10 examined. In group 2, the junction between the native trachea and the engineered cartilage showed neocartilage tissue in nine anastomoses sides out of 10. Engineered cartilage may be beneficial for engineered airways, based on the findings of the junction between the native and engineered grafts. Copyright © 2012 The American Laryngological, Rhinological and Otological Society, Inc.

  10. Quasi-static elastography comparison of hyaline cartilage structures

    Science.gov (United States)

    McCredie, A. J.; Stride, E.; Saffari, N.

    2009-11-01

    Joint cartilage, a load bearing structure in mammals, has only limited ability for regeneration after damage. For tissue engineers to design functional constructs, better understanding of the properties of healthy tissue is required. Joint cartilage is a specialised structure of hyaline cartilage; a poroviscoelastic solid containing fibril matrix reinforcements. Healthy joint cartilage is layered, which is thought to be important for correct tissue function. However, the behaviour of each layer during loading is poorly understood. Ultrasound elastography provides access to depth-dependent information in real-time for a sample during loading. A 15 MHz focussed transducer provided details from scatterers within a small fixed region in each sample. Quasi-static loading was applied to cartilage samples while ultrasonic signals before and during compressions were recorded. Ultrasonic signals were processed to provide time-shift profiles using a sum-squared difference method and cross-correlation. Two structures of hyaline cartilage have been tested ultrasonically and mechanically to determine method suitability for monitoring internal deformation differences under load and the effect of the layers on the global mechanical material behaviour. Results show differences in both the global mechanical properties and the ultrasonically tested strain distributions between the two structures tested. It was concluded that these differences are caused primarily by the fibril orientations.

  11. Influence of the gel thickness on in vivo hyaline cartilage regeneration induced by double-network gel implanted at the bottom of a large osteochondral defect: short-term results.

    Science.gov (United States)

    Matsuda, Hidetoshi; Kitamura, Nobuto; Kurokawa, Takayuki; Arakaki, Kazunobu; Gong, Jian Ping; Kanaya, Fuminori; Yasuda, Kazunori

    2013-01-31

    A double-network (DN) gel, which is composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N'-dimethyl acrylamide), can induce hyaline cartilage regeneration in vivo in a large osteochondral defect. The purpose of this study was to clarify the influence of the thickness of the implanted DN gel on the induction ability of hyaline cartilage regeneration. Thirty-eight mature rabbits were used in this study. We created an osteochondral defect having a diameter of 4.3-mm in the patellofemoral joint. The knees were randomly divided into 4 groups (Group I: 0.5-mm thick gel, Group II: 1.0-mm thick gel, Group III: 5.0-mm thick gel, and Group IV: untreated control). Animals in each group were further divided into 3 sub-groups depending on the gel implant position (2.0-, 3.0-, or 4.0-mm depth from the articular surface) in the defect. The regenerated tissues were evaluated with the Wayne's gross and histological grading scales and real time PCR analysis of the cartilage marker genes at 4 weeks. According to the total Wayne's score, when the depth of the final vacant space was set at 2.0 mm, the scores in Groups I, II, and III were significantly greater than that Group IV (phyaline cartilage regeneration as the 5.0-mm thick DN gel plug. However, the induction ability of the 0.5-mm thick sheet was significantly lower when compared with the 1.0-mm thick gel sheet. The 1.0-mm DN gel sheet is a promising device to establish a cell-free cartilage regeneration strategy that minimizes bone loss from the gel implantation.

  12. Precision of hyaline cartilage thickness measurements

    Energy Technology Data Exchange (ETDEWEB)

    Jonsson, K.; Buckwalter, K.; Helvie, M.; Niklason, L.; Martel, W. (Univ. of Michigan Hospitals, Ann Arbor, MI (United States). Dept. of Radiology)

    1992-05-01

    Measurement of cartilage thickness in vivo is an important indicator of the status of a joint as the various degenerative and inflammatory arthritides directly affect the condition of the cartilage. In order to assess the precision of thickness measurements of hyaline articular cartilage, we undertook a pilot study using MR imaging, plain radiography, and ultrasonography (US). We measured the cartilage of the hip and knee joints in 10 persons (4 healthy volunteers and 6 patients). The joints in each patient were examined on two separate occasions using each modality. In the hips a swell as the knee joints, the most precise measuring method was plain film radiography. For radiographs of the knees obtained in the standing position, the coefficient of variation was 6.5%; in the hips this figure was 6.34%. US of the knees and MR imaging of the hips were the second best modalities in the measurement of cartilage thickness. In addition, MR imaging enabled the most complete visualization of the joint cartilage. (orig.).

  13. Quantification of collagen distributions in rat hyaline and fibro cartilages based on second harmonic generation imaging

    Science.gov (United States)

    Zhu, Xiaoqin; Liao, Chenxi; Wang, Zhenyu; Zhuo, Shuangmu; Liu, Wenge; Chen, Jianxin

    2016-10-01

    Hyaline cartilage is a semitransparent tissue composed of proteoglycan and thicker type II collagen fibers, while fibro cartilage large bundles of type I collagen besides other territorial matrix and chondrocytes. It is reported that the meniscus (fibro cartilage) has a greater capacity to regenerate and close a wound compared to articular cartilage (hyaline cartilage). And fibro cartilage often replaces the type II collagen-rich hyaline following trauma, leading to scar tissue that is composed of rigid type I collagen. The visualization and quantification of the collagen fibrillar meshwork is important for understanding the role of fibril reorganization during the healing process and how different types of cartilage contribute to wound closure. In this study, second harmonic generation (SHG) microscope was applied to image the articular and meniscus cartilage, and textural analysis were developed to quantify the collagen distribution. High-resolution images were achieved based on the SHG signal from collagen within fresh specimens, and detailed observations of tissue morphology and microstructural distribution were obtained without shrinkage or distortion. Textural analysis of SHG images was performed to confirm that collagen in fibrocartilage showed significantly coarser compared to collagen in hyaline cartilage (p < 0.01). Our results show that each type of cartilage has different structural features, which may significantly contribute to pathology when damaged. Our findings demonstrate that SHG microscopy holds potential as a clinically relevant diagnostic tool for imaging degenerative tissues or assessing wound repair following cartilage injury.

  14. Autologous chondrocyte implantation: superior biologic properties of hyaline cartilage repairs.

    Science.gov (United States)

    Henderson, Ian; Lavigne, Patrick; Valenzuela, Herminio; Oakes, Barry

    2007-02-01

    Information regarding the quality of autologous chondrocyte implantation repair is needed to determine whether the current autologous chondrocyte implantation surgical technology and the subsequent biologic repair processes are capable of reliably forming durable hyaline or hyaline-like cartilage in vivo. We report and analyze the properties and qualities of autologous chondrocyte implantation repairs. We evaluated 66 autologous chondrocyte implantation repairs in 57 patients, 55 of whom had histology, indentometry, and International Cartilage Repair Society repair scoring at reoperation for mechanical symptoms or pain. International Knee Documentation Committee scores were used to address clinical outcome. Maximum stiffness, normalized stiffness, and International Cartilage Repair Society repair scoring were higher for hyaline articular cartilage repairs compared with fibrocartilage, with no difference in clinical outcome. Reoperations revealed 32 macroscopically abnormal repairs (Group B) and 23 knees with normal-looking repairs in which symptoms leading to arthroscopy were accounted for by other joint disorders (Group A). In Group A, 65% of repairs were either hyaline or hyaline-like cartilage compared with 28% in Group B. Autologous chondrocyte repairs composed of fibrocartilage showed more morphologic abnormalities and became symptomatic earlier than hyaline or hyaline-like cartilage repairs. The hyaline articular cartilage repairs had biomechanical properties comparable to surrounding cartilage and superior to those associated with fibrocartilage repairs.

  15. Brief report: reconstruction of joint hyaline cartilage by autologous progenitor cells derived from ear elastic cartilage.

    Science.gov (United States)

    Mizuno, Mitsuru; Kobayashi, Shinji; Takebe, Takanori; Kan, Hiroomi; Yabuki, Yuichiro; Matsuzaki, Takahisa; Yoshikawa, Hiroshi Y; Nakabayashi, Seiichiro; Ik, Lee Jeong; Maegawa, Jiro; Taniguchi, Hideki

    2014-03-01

    In healthy joints, hyaline cartilage covering the joint surfaces of bones provides cushioning due to its unique mechanical properties. However, because of its limited regenerative capacity, age- and sports-related injuries to this tissue may lead to degenerative arthropathies, prompting researchers to investigate a variety of cell sources. We recently succeeded in isolating human cartilage progenitor cells from ear elastic cartilage. Human cartilage progenitor cells have high chondrogenic and proliferative potential to form elastic cartilage with long-term tissue maintenance. However, it is unknown whether ear-derived cartilage progenitor cells can be used to reconstruct hyaline cartilage, which has different mechanical and histological properties from elastic cartilage. In our efforts to develop foundational technologies for joint hyaline cartilage repair and reconstruction, we conducted this study to obtain an answer to this question. We created an experimental canine model of knee joint cartilage damage, transplanted ear-derived autologous cartilage progenitor cells. The reconstructed cartilage was rich in proteoglycans and showed unique histological characteristics similar to joint hyaline cartilage. In addition, mechanical properties of the reconstructed tissues were higher than those of ear cartilage and equal to those of joint hyaline cartilage. This study suggested that joint hyaline cartilage was reconstructed from ear-derived cartilage progenitor cells. It also demonstrated that ear-derived cartilage progenitor cells, which can be harvested by a minimally invasive method, would be useful for reconstructing joint hyaline cartilage in patients with degenerative arthropathies. © AlphaMed Press.

  16. Augmented cartilage regeneration by implantation of cellular versus acellular implants after bone marrow stimulation: a systematic review and meta-analysis of animal studies

    NARCIS (Netherlands)

    Pot, M.W.; Kuppevelt, T.H. van; Gonzales, V.K.; Buma, P.; Hout, J. in't; Vries, R.B.M. de; Daamen, W.F.

    2017-01-01

    Bone marrow stimulation may be applied to regenerate focal cartilage defects, but generally results in transient clinical improvement and formation of fibrocartilage rather than hyaline cartilage. Tissue engineering and regenerative medicine strive to develop new solutions to regenerate hyaline

  17. Subchondral chitosan/blood implant-guided bone plate resorption and woven bone repair is coupled to hyaline cartilage regeneration from microdrill holes in aged rabbit knees.

    Science.gov (United States)

    Guzmán-Morales, J; Lafantaisie-Favreau, C-H; Chen, G; Hoemann, C D

    2014-02-01

    Little is known of how to routinely elicit hyaline cartilage repair tissue in middle-aged patients. We tested the hypothesis that in skeletally aged rabbit knees, microdrill holes can be stimulated to remodel the bone plate and induce a more integrated, voluminous and hyaline cartilage repair tissue when treated by subchondral chitosan/blood implants. New Zealand White rabbits (13 or 32 months old, N = 7) received two 1.5 mm diameter, 2 mm depth drill holes in each knee, either left to bleed as surgical controls or press-fit with a 10 kDa (distal hole: 10K) or 40 kDa (proximal hole: 40K) chitosan/blood implant with fluorescent chitosan tracer. Post-operative knee effusion was documented. Repair tissues at day 0 (N = 1) and day 70 post-surgery (N = 6) were analyzed by micro-computed tomography, and by histological scoring and histomorphometry (SafO, Col-2, and Col-1) at day 70. All chitosan implants were completely cleared after 70 days, without increasing transient post-operative knee effusion compared to controls. Proximal control holes had worse osteochondral repair than distal holes. Both implant formulations induced bone remodeling and improved lateral integration of the bone plate at the hole edge. The 40K implant inhibited further bone repair inside 50% of the proximal holes, while the 10K implant specifically induced a "wound bloom" reaction, characterized by decreased bone plate density in a limited zone beyond the initial hole edge, and increased woven bone (WB) plate repair inside the initial hole (P = 0.016), which was accompanied by a more voluminous and hyaline cartilage repair (P holes with a biodegradable subchondral implant that elicits bone plate resorption followed by anabolic WB repair within a 70-day repair period. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  18. Influence of Structure and Composition on Dynamic Viscoelastic Property of Cartilaginous Tissue: Criteria for Classification between Hyaline Cartilage and Fibrocartilage Based on Mechanical Function

    Science.gov (United States)

    Miyata, Shogo; Tateishi, Tetsuya; Furukawa, Katsuko; Ushida, Takashi

    Recently, many types of methodologies have been developed to regenerate articular cartilage. It is important to assess whether the reconstructed cartilaginous tissue has the appropriate mechanical functions to qualify as hyaline (articular) cartilage. In some cases, the reconstructed tissue may become fibrocartilage and not hyaline cartilage. In this study, we determined the dynamic viscoelastic properties of these two types of cartilage by using compression and shear tests, respectively. Hyaline cartilage specimens were harvested from the articular surface of bovine knee joints and fibrocartilage specimens were harvested from the meniscus tissue of the same. The results of this study revealed that the compressive energy dissipation of hyaline cartilage showed a strong dependence on testing frequency at low frequencies, while that of fibrocartilage did not. Therefore, the compressive energy dissipation that is indicated by the loss tangent could become the criterion for the in vitro assessment of the mechanical function of regenerated cartilage.

  19. Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem cells.

    Science.gov (United States)

    Saito, Taku; Yano, Fumiko; Mori, Daisuke; Kawata, Manabu; Hoshi, Kazuto; Takato, Tsuyoshi; Masaki, Hideki; Otsu, Makoto; Eto, Koji; Nakauchi, Hiromitsu; Chung, Ung-il; Tanaka, Sakae

    2015-01-01

    Induced pluripotent stem cells (iPSCs) are a promising cell source for cartilage regenerative medicine. Meanwhile, the risk of tumorigenesis should be considered in the clinical application of human iPSCs (hiPSCs). Here, we report in vitro chondrogenic differentiation of hiPSCs and maturation of the differentiated hiPSCs through transplantation into mouse knee joints. Three hiPSC clones showed efficient chondrogenic differentiation using an established protocol for human embryonic stem cells. The differentiated hiPSCs formed hyaline cartilage tissues at 8 weeks after transplantation into the articular cartilage of NOD/SCID mouse knee joints. Although tumors were not observed during the 8 weeks after transplantation, an immature teratoma had developed in one mouse at 16 weeks. In conclusion, hiPSCs are a potent cell source for regeneration of hyaline articular cartilage. However, the risk of tumorigenesis should be managed for clinical application in the future.

  20. Similar hyaline-like cartilage repair of osteochondral defects in rabbits using isotropic and anisotropic collagen scaffolds.

    Science.gov (United States)

    de Mulder, Eric L W; Hannink, Gerjon; van Kuppevelt, Toin H; Daamen, Willeke F; Buma, Pieter

    2014-02-01

    Lesions in knee joint articular cartilage (AC) have limited repair capacity. Many clinically available treatments induce a fibrous-like cartilage repair instead of hyaline cartilage. To induce hyaline cartilage repair, we hypothesized that type I collagen scaffolds with fibers aligned perpendicular to the AC surface would result in qualitatively better tissue repair due to a guided cellular influx from the subchondral bone. By specific freezing protocols, type I collagen scaffolds with isotropic and anisotropic fiber architectures were produced. Rabbits were operated on bilaterally and two full thickness defects were created in each knee joint. The defects were filled with (1) an isotropic scaffold, (2) an anisotropic scaffold with pores parallel to the cartilage surface, and (3) an anisotropic scaffold with pores perpendicular to the cartilage surface. Empty defects served as controls. After 4 (n=13) and 12 (n=13) weeks, regeneration was scored qualitatively and quantitatively using histological analysis and a modified O'Driscoll score. After 4 weeks, all defects were completely filled with partially differentiated hyaline cartilage tissue. No differences in O'Driscoll scores were measured between empty defects and scaffold types. After 12 weeks, all treatments led to hyaline cartilage repair visualized by increased glycosaminoglycan staining. Total scores were significantly increased for parallel anisotropic and empty defects over time (phyaline-like cartilage repair. Fiber architecture had no effect on cartilage repair.

  1. MR Imaging of Articular Hyaline Cartilage

    OpenAIRE

    Uetani, Masataka

    2005-01-01

    MR imaging is still an evolving technique for the diagnosis of joint cartilage lesions. Early morphologic changes in the degenerative cartilage are not reliably diagnosed even with use of tailored MR imaging techniques. The detection of the biochemical changes of cartilage or high-resolution MRI will serve as an important tool for the early diagnosis of cartilage degeneration in near future. Further prospective studies are needed to establish the role of MR imaging in clinical use.

  2. Hyaline cartilage cells outperform mandibular condylar cartilage cells in a TMJ fibrocartilage tissue engineering application.

    Science.gov (United States)

    Wang, L; Lazebnik, M; Detamore, M S

    2009-03-01

    To compare temporomandibular joint (TMJ) condylar cartilage cells in vitro to hyaline cartilage cells cultured in a three-dimensional (3D) environment for tissue engineering of mandibular condylar cartilage. Mandibular condylar cartilage and hyaline cartilage cells were harvested from pigs and cultured for 6 weeks in polyglycolic acid (PGA) scaffolds. Both types of cells were treated with glucosamine sulfate (0.4 mM), insulin-like growth factor-I (IGF-I) (100 ng/ml) and their combination. At weeks 0 and 6, cell number, glycosaminoglycan (GAG) and collagen content were determined, types I and II collagen were visualized by immunohistochemistry and GAGs were visualized by histology. Hyaline cartilage cells produced from half an order to a full order of magnitude more GAGs and collagen than mandibular condylar cartilage cells in 3D culture. IGF-I was a highly effective signal for biosynthesis with hyaline cartilage cells, while glucosamine sulfate decreased cell proliferation and biosynthesis with both types of cells. In vitro culture of TMJ condylar cartilage cells produced a fibrous tissue with predominantly type I collagen, while hyaline cartilage cells formed a fibrocartilage-like tissue with types I and II collagen. The combination of IGF and glucosamine had a synergistic effect on maintaining the phenotype of TMJ condylar cells to generate both types I and II collagen. Given the superior biosynthetic activity by hyaline cartilage cells and the practical surgical limitations of harvesting cells from the TMJ of a patient requiring TMJ reconstruction, cartilage cells from elsewhere in the body may be a potentially better alternative to cells harvested from the TMJ for TMJ tissue engineering. This finding may also apply to other fibrocartilages such as the intervertebral disc and knee meniscus in applications where a mature cartilage cell source is desired.

  3. Mesenchymal stem cells in cartilage regeneration.

    Science.gov (United States)

    Savkovic, Vuk; Li, Hanluo; Seon, Jong-Keun; Hacker, Michael; Franz, Sandra; Simon, Jan-Christoph

    2014-01-01

    Articular cartilage provides life-long weight-bearing and mechanical lubrication with extraordinary biomechanical performance and simple structure. However, articular cartilage is apparently vulnerable to multifactorial damage and insufficient to self-repair, isolated in articular capsule without nerves or blood vessels. Osteoarthritis (OA) is known as a degenerative articular cartilage deficiency progressively affecting large proportion of the world population, and restoration of hyaline cartilage is clinical challenge to repair articular cartilage lesion and recreate normal functionality over long period. Mesenchymal stem cells (MSC) are highly proliferative and multipotent somatic cells that are able to differentiate mesoderm-derived cells including chondrocytes and osteoblasts. Continuous endeavors in basic research and preclinical trial have achieved promising outcomes in cartilage regeneration using MSCs. This review focuses on rationale and technologies of MSC-based hyaline cartilage repair involving tissue engineering, 3D biomaterials and growth factors. By comparing conventional treatment and current research progress, we describe insights of advantage and challenge in translation and application of MSC-based chondrogenesis for OA treatment.

  4. Microscopic and histochemical manifestations of hyaline cartilage dynamics.

    Science.gov (United States)

    Malinin, G I; Malinin, T I

    1999-01-01

    Structure and function of hyaline cartilages has been the focus of many correlative studies for over a hundred years. Much of what is known regarding dynamics and function of cartilage constituents has been derived or inferred from biochemical and electron microscopic investigations. Here we show that in conjunction with ultrastructural, and high-magnification transmission light and polarization microscopy, the well-developed histochemical methods are indispensable for the analysis of cartilage dynamics. Microscopically demonstrable aspects of cartilage dynamics include, but are not limited to, formation of the intracellular liquid crystals, phase transitions of the extracellular matrix and tubular connections between chondrocytes. The role of the interchondrocytic liquid crystals is considered in terms of the tensegrity hypothesis and non-apoptotic cell death. Phase transitions of the extracellular matrix are discussed in terms of self-alignment of chondrons, matrix guidance pathways and cartilage growth in the absence of mitosis. The possible role of nonenzymatic glycation reactions in cartilage dynamics is also reviewed.

  5. Elastic cartilage reconstruction by transplantation of cultured hyaline cartilage-derived chondrocytes.

    Science.gov (United States)

    Mizuno, M; Takebe, T; Kobayashi, S; Kimura, S; Masutani, M; Lee, S; Jo, Y H; Lee, J I; Taniguchi, H

    2014-05-01

    Current surgical intervention of craniofacial defects caused by injuries or abnormalities uses reconstructive materials, such as autologous cartilage grafts. Transplantation of autologous tissues, however, places a significant invasiveness on patients, and many efforts have been made for establishing an alternative graft. Recently, we and others have shown the potential use of reconstructed elastic cartilage from ear-derived chondrocytes or progenitors with the unique elastic properties. Here, we examined the differentiation potential of canine joint cartilage-derived chondrocytes into elastic cartilage for expanding the cell sources, such as hyaline cartilage. Articular chondrocytes are isolated from canine joint, cultivated, and compared regarding characteristic differences with auricular chondrocytes, including proliferation rates, gene expression, extracellular matrix production, and cartilage reconstruction capability after transplantation. Canine articular chondrocytes proliferated less robustly than auricular chondrocytes, but there was no significant difference in the amount of sulfated glycosaminoglycan produced from redifferentiated chondrocytes. Furthermore, in vitro expanded and redifferentiated articular chondrocytes have been shown to reconstruct elastic cartilage on transplantation that has histologic characteristics distinct from hyaline cartilage. Taken together, cultured hyaline cartilage-derived chondrocytes are a possible cell source for elastic cartilage reconstruction. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  6. Harnessing biomechanics to develop cartilage regeneration strategies.

    Science.gov (United States)

    Athanasiou, Kyriacos A; Responte, Donald J; Brown, Wendy E; Hu, Jerry C

    2015-02-01

    As this review was prepared specifically for the American Society of Mechanical Engineers H.R. Lissner Medal, it primarily discusses work toward cartilage regeneration performed in Dr. Kyriacos A. Athanasiou's laboratory over the past 25 years. The prevalence and severity of degeneration of articular cartilage, a tissue whose main function is largely biomechanical, have motivated the development of cartilage tissue engineering approaches informed by biomechanics. This article provides a review of important steps toward regeneration of articular cartilage with suitable biomechanical properties. As a first step, biomechanical and biochemical characterization studies at the tissue level were used to provide design criteria for engineering neotissues. Extending this work to the single cell and subcellular levels has helped to develop biochemical and mechanical stimuli for tissue engineering studies. This strong mechanobiological foundation guided studies on regenerating hyaline articular cartilage, the knee meniscus, and temporomandibular joint (TMJ) fibrocartilage. Initial tissue engineering efforts centered on developing biodegradable scaffolds for cartilage regeneration. After many years of studying scaffold-based cartilage engineering, scaffoldless approaches were developed to address deficiencies of scaffold-based systems, resulting in the self-assembling process. This process was further improved by employing exogenous stimuli, such as hydrostatic pressure, growth factors, and matrix-modifying and catabolic agents, both singly and in synergistic combination to enhance neocartilage functional properties. Due to the high cell needs for tissue engineering and the limited supply of native articular chondrocytes, costochondral cells are emerging as a suitable cell source. Looking forward, additional cell sources are investigated to render these technologies more translatable. For example, dermis isolated adult stem (DIAS) cells show potential as a source of

  7. Hyaline articular cartilage dissected by papain: light and scanning electron microscopy and micromechanical studies.

    OpenAIRE

    O'Connor, P; Brereton, J D; Gardner, D L

    1984-01-01

    Papain was used to digest the hyaline femoral condylar cartilages of 30 adult Wistar rats. Matrix proteoglycan degradation was assessed by the light microscopy of paraffin sections stained with toluidine blue. The extent of surface structural change was estimated by scanning electron microscopy, and the structural integrity of the hyaline cartilage tested by the controlled impact of a sharp pin. The results demonstrated an early loss of cartilage metachromasia, increasing with time of papain ...

  8. Similar hyaline-like cartilage repair of osteochondral defects in rabbits using isotropic and anisotropic collagen scaffolds

    NARCIS (Netherlands)

    Mulder, E.L.W. de; Hannink, G.J.; Kuppevelt, T.H. van; Daamen, W.F.; Buma, P.

    2014-01-01

    Lesions in knee joint articular cartilage (AC) have limited repair capacity. Many clinically available treatments induce a fibrous-like cartilage repair instead of hyaline cartilage. To induce hyaline cartilage repair, we hypothesized that type I collagen scaffolds with fibers aligned perpendicular

  9. 1. 5 MRT of the hyaline articular cartilage of the knee joint

    Energy Technology Data Exchange (ETDEWEB)

    Adam, G.; Bohndorf, K.; Krasny, R.; Guenther, R.W.; Prescher, A.

    1988-06-01

    MRI is a new method for imaging the knee joint. There is still some uncertainty regarding the extent and the signal from hyaline articular cartilage. MRI images were therefore compared with anatomical and histological preparations of the knee joint and the difference between MRI and the anatomical sections have been determined. It was shown that demonstration of hyaline cartilage was obscured by an artifact. Further investigations are required to determine the cause of this artifact and to achieve accurate imaging of hyaline cartilage by MRI.

  10. Cartilage T2 assessment: differentiation of normal hyaline cartilage and reparative tissue after arthroscopic cartilage repair in equine subjects.

    Science.gov (United States)

    White, Lawrence M; Sussman, Marshall S; Hurtig, Mark; Probyn, Linda; Tomlinson, George; Kandel, Rita

    2006-11-01

    To prospectively assess T2 mapping characteristics of normal articular cartilage and of cartilage at sites of arthroscopic repair, including comparison with histologic results and collagen organization assessed at polarized light microscopy (PLM). Study protocol was compliant with the Canadian Council on Animal Care Guidelines and approved by the institutional animal care committee. Arthroscopic osteochondral autograft transplantation (OAT) and microfracture arthroplasty (MFx) were performed in knees of 10 equine subjects (seven female, three male; age range, 3-5 years). A site of arthroscopically normal cartilage was documented in each joint as a control site. Joints were harvested at 12 (n = 5) and 24 (n = 5) weeks postoperatively and were imaged at 1.5-T magnetic resonance (MR) with a 10-echo sagittal fast spin-echo acquisition. T2 maps of each site (21 OAT harvest, 10 MFx, 12 OAT plug, and 10 control sites) were calculated with linear least-squares curve fitting. Cartilage T2 maps were qualitatively graded as "organized" (normal transition of low-to-high T2 signal from deep to superficial cartilage zones) or "disorganized." Quantitative mean T2 values were calculated for deep, middle, and superficial cartilage at each location. Results were compared with histologic and PLM assessments by using kappa analysis. T2 maps were qualitatively graded as organized at 20 of 53 sites and as disorganized at 33 sites. Perfect agreement was seen between organized T2 and histologic findings of hyaline cartilage and between disorganized T2 and histologic findings of fibrous reparative tissue (kappa = 1.0). Strong agreement was seen between organized T2 and normal PLM findings and between disorganized T2 and abnormal PLM findings (kappa = .92). Quantitative assessment of the deep, middle, and superficial cartilage, respectively, showed mean T2 values of 53.3, 58.6, and 54.9 msec at reparative fibrous tissue sites and 40.7, 53.6, and 61.6 msec at hyaline cartilage sites. A

  11. Treatment of deep hyalin cartilage defects with autologous perichondrial grafts.

    Science.gov (United States)

    Bruns, J; Steinhagen, J

    2003-07-01

    Perichondrial transplantation was performed in 29 patients suffering from a deep chondral lesion with different etiologies. Only those patients with a cartilage lesion in the knee joint were included. Patients were initially and postoperatively examined using the Lysholm- and HSS-Score. In most of the patients (20/29) trauma and the recurrence of osteochondrosis dissecans (6/29) were the cause of the cartilage lesion. Most often the medial femoral condyle (19/29) and, secondly, the lateral femoral condyle (5/29) were involved. In six patients additional therapeutic measures (ACL-plasty, n = 2; high tibial osteotomy because of varus mal-alignment, n = 4) had to be adopted. Follow-up examination was possible in 26/29 patients after a minimum postoperative period of 12 months. All patients exhibited a distinct and significant increase in both the Lysholm and the HSS-score. A follow-up after a minimum of 24 months was possible in 13/29 patients. Even these patients exhibited a distinct and significant improvement. Multiple follow-up examinations in 9/29 patients demonstrated maintenance of the first postoperative results obtained after one postoperative year for a maximum of 49 months in most of the patients. Only in one female patient, implantation of a semi-constrained total knee replacement was necessary because of osteoarthrosis resulting from crystal arthropathy (chondrocalcinosis). It was possible to obtain biopsies from three patients at the time osteosynthetic material was removed. In all cases hyaline-like cartilage was histologically observed. In the treatment of selected patients suffering from a circumscript cartilaginous lesion resulting from trauma or the recurrence of osteochondritis dissecans with a concomitant cartilage lesion but without major signs of osteoarthritis, perichondrial grafting can achieve acceptable clinical results, after a short follow-up period. In order to achieve satisfying results a good selection of patients and additional

  12. Research studies of aging changes of hyaline cartilage surface by using Raman-scattering spectroscopy

    Science.gov (United States)

    Timchenko, E. V.; Timchenko, P. E.; Dolgushkin, D. A.; Volova, L. T.; Lazarev, V. A.; Tyumchenkova, A. S.; Markova, M. D.

    2017-08-01

    The paper presents the results of a comparative analysis by the method of Raman spectroscopy of the joint hyaline cartilage of adults and children. Differences in the spectral characteristics of the surface of articular cartilage are shown. New optical coefficients have been introduced, which make it possible to evaluate the age-related changes in cartilaginous tissue.

  13. Quantitative assessment of hyaline cartilage elasticity during optical clearing using optical coherence elastography

    Science.gov (United States)

    Liu, Chih-Hao; Singh, Manmohan; Li, Jiasong; Han, Zhaolong; Wu, Chen; Wang, Shang; Idugboe, Rita; Raghunathan, Raksha; Zakharov, Valery P.; Sobol, Emil N.; Tuchin, Valery V.; Twa, Michael; Larin, Kirill V.

    2015-03-01

    We report the first study on using optical coherence elastography (OCE) to quantitatively monitor the elasticity change of the hyaline cartilage during the optical clearing administrated by glucose solution. The measurement of the elasticity is verified using uniaxial compression test, demonstrating the feasibility of using OCE to quantify the Young's modulus of the cartilage tissue. As the results, we found that the stiffness of the hyaline cartilage increases during the optical clearing of the tissue. This study might be potentially useful for the early detection of osteoarthritis disease.

  14. The development of hyaline-cell cartilage in the head of the black molly, Poecilia sphenops. Evidence for secondary cartilage in a teleost.

    OpenAIRE

    Benjamin, M

    1989-01-01

    The development of hyaline-cell cartilage attached to membrane (dentary, maxilla, nasal, lacrimal and cleithrum) and cartilage (basioccipital) bones has been studied in the viviparous black molly, Poecilia sphenops. Intramembranous ossification commences before the first appearance of hyaline cells. As hyaline-cell cartilage is densely cellular and as that attached to the dentary, maxilla and cleithrum develops from the periosteum of these membrane bones, it must be regarded as secondary cart...

  15. Effects of growth factors and glucosamine on porcine mandibular condylar cartilage cells and hyaline cartilage cells for tissue engineering applications.

    Science.gov (United States)

    Wang, Limin; Detamore, Michael S

    2009-01-01

    Temporomandibular joint (TMJ) condylar cartilage is a distinct cartilage that has both fibrocartilaginous and hyaline-like character, with a thin proliferative zone that separates the fibrocartilaginous fibrous zone at the surface from the hyaline-like mature and hypertrophic zones below. In this study, we compared the effects of insulin-like growth factor-I (IGF-I), basic fibroblast growth factor (bFGF), transforming growth factor beta1 (TGF-beta1), and glucosamine sulphate on porcine TMJ condylar cartilage and ankle cartilage cells in monolayer culture. In general, TMJ condylar cartilage cells proliferated faster than ankle cartilage cells, while ankle cells produced significantly greater amounts of glycosaminoglycans (GAGs) and collagen than TMJ condylar cartilage cells. IGF-I and bFGF were potent stimulators of TMJ cell proliferation, while no signals statistically outperformed controls for ankle cell proliferation. IGF-I was the most effective signal for GAG production with ankle cells, and the most potent upregulator of collagen synthesis for both cell types. Glucosamine sulphate promoted cell proliferation and biosynthesis at specific concentrations and outperformed growth factors in certain instances. In conclusion, hyaline cartilage cells had lower cell numbers and superior biosynthesis compared to TMJ condylar cartilage cells, and we have found IGF-I at 100 ng/mL and glucosamine sulphate at 100 microg/mL to be the most effective signals for these cells under the prescribed conditions.

  16. Fibrous cartilage of human menisci is less shock-absorbing and energy-dissipating than hyaline cartilage.

    Science.gov (United States)

    Gaugler, Mario; Wirz, Dieter; Ronken, Sarah; Hafner, Mirjam; Göpfert, Beat; Friederich, Niklaus F; Elke, Reinhard

    2015-04-01

    To test meniscal mechanical properties such as the dynamic modulus of elasticity E* and the loss angle δ at two loading frequencies ω at different locations of the menisci and compare it to E* and δ of hyaline cartilage in indentation mode with spherical indenters. On nine pairs of human menisci, the dynamic E*-modulus and loss angle δ (as a measure of the energy dissipation) were determined. The measurements were performed at two different strain rates (slow sinusoidal and fast single impact) to show the strain rate dependence of the material. The measurements were compared to previous similar measurements with the same equipment on human hyaline cartilage. The resultant E* at fast indentation (median 1.16 MPa) was significantly higher, and the loss angle was significantly lower (median 10.2°) compared to slow-loading mode's E* and δ (median 0.18 MPa and 16.9°, respectively). Further, significant differences for different locations are shown. On the medial meniscus, the anterior horn shows the highest resultant dynamic modulus. In dynamic measurements with a spherical indenter, the menisci are much softer and less energy-dissipating than hyaline cartilage. Further, the menisci are stiffer and less energy-dissipating in the middle, intermediate part compared to the meniscal base. In compression, the energy dissipation of meniscus cartilage plays a minor role compared to hyaline cartilage. At high impacts, energy dissipation is less than on low impacts, similar to cartilage.

  17. Chitosan-glycerol phosphate/blood implants elicit hyaline cartilage repair integrated with porous subchondral bone in microdrilled rabbit defects.

    Science.gov (United States)

    Hoemann, C D; Sun, J; McKee, M D; Chevrier, A; Rossomacha, E; Rivard, G-E; Hurtig, M; Buschmann, M D

    2007-01-01

    We have previously shown that microfractured ovine defects are repaired with more hyaline cartilage when the defect is treated with in situ-solidified implants of chitosan-glycerol phosphate (chitosan-GP) mixed with autologous whole blood. The objectives of this study were (1) to characterize chitosan-GP/blood clots in vitro, and (2) to develop a rabbit marrow stimulation model in order to determine the effects of the chitosan-GP/blood implant and of debridement on the formation of incipient cartilage repair tissue. Blood clots were characterized by histology and in vitro clot retraction tests. Bilateral 3.5 x 4 mm trochlear defects debrided into the calcified layer were pierced with four microdrill holes and filled with a chitosan-GP/blood implant or allowed to bleed freely as a control. At 1 day post-surgery, initial defects were characterized by histomorphometry (n=3). After 8 weeks of repair, osteochondral repair tissues between or through the drill holes were evaluated by histology, histomorphometry, collagen type II expression, and stereology (n=16). Chitosan-GP solutions structurally stabilized the blood clots by inhibiting clot retraction. Treatment of drilled defects with chitosan-GP/blood clots led to the formation of a more integrated and hyaline repair tissue above a more porous and vascularized subchondral bone plate compared to drilling alone. Correlation analysis of repair tissue between the drill holes revealed that the absence of calcified cartilage and the presence of a porous subchondral bone plate were predictors of greater repair tissue integration with subchondral bone (Phyaline and integrated repair tissue associated with a porous subchondral bone replete with blood vessels. Concomitant regeneration of a vascularized bone plate during cartilage repair could provide progenitors, anabolic factors and nutrients that aid in the formation of hyaline cartilage.

  18. Biophysical Stimuli: A Review of Electrical and Mechanical Stimulation in Hyaline Cartilage.

    Science.gov (United States)

    Vaca-González, Juan J; Guevara, Johana M; Moncayo, Miguel A; Castro-Abril, Hector; Hata, Yoshie; Garzón-Alvarado, Diego A

    2017-09-01

    Objective Hyaline cartilage degenerative pathologies induce morphologic and biomechanical changes resulting in cartilage tissue damage. In pursuit of therapeutic options, electrical and mechanical stimulation have been proposed for improving tissue engineering approaches for cartilage repair. The purpose of this review was to highlight the effect of electrical stimulation and mechanical stimuli in chondrocyte behavior. Design Different information sources and the MEDLINE database were systematically revised to summarize the different contributions for the past 40 years. Results It has been shown that electric stimulation may increase cell proliferation and stimulate the synthesis of molecules associated with the extracellular matrix of the articular cartilage, such as collagen type II, aggrecan and glycosaminoglycans, while mechanical loads trigger anabolic and catabolic responses in chondrocytes. Conclusion The biophysical stimuli can increase cell proliferation and stimulate molecules associated with hyaline cartilage extracellular matrix maintenance.

  19. Study of MR sequence in detecting hyaline cartilage defects of the knee joint

    International Nuclear Information System (INIS)

    Li Songbai; He Cuiju; Sun Wenge; Li Chunkui; Qi Xixun; Li Yanliang; Xu Ke; Bai Xizhuang; Wu Zhenhua

    2003-01-01

    Objective: To evaluate the value of various MR imaging sequences for detecting hyaline cartilage defects. Methods: Ten animal models of cartilage defect were established in 5 pig knees. 5 knees were examined with nine different MR sequences. The signal noise ratio of cartilage and contrast noise ratio were calculated and compared between cartilage and adjacent tissue. Measurement of the defect depth and width on the imaging was correlated with the actual measurement before imaging. 23 patients with hyaline cartilage defects of the knee were evaluated with MR imaging. All these patients underwent subsequent arthroscopy. MR imaging protocol included the selected sequences in the experimental study. Results: The cartilage SNR was better in FSE PD, FS 3D FSPGR, and FS FSE PD sequences. CNR between cartilage and subcartilaginous bone was best in FS 3D FSPGR and FS FSE PD sequences. CNR between cartilage and joint fluid was best in FS 3D FSPGR and FS FSE T 2 WI sequences. CNR between cartilage and meniscus and ligament was best in FS 3D FSPGR, FS FSE PD, SE T 1 WI, and IR TI700 sequences. CNR between cartilage and fat was best in FS 3D FSPGR and SE T 1 WI sequences. The width and depth correlation was best in IR TI700 sequence, which showed the statistical significance (P 2 WI sequence, 68%, 99%, and 0.74, respectively with IR TI700 sequence. Conclusion: The sensitivity of FS 3D FSPGR sequence in detecting hyaline cartilage defect is the highest. T 1 WI of spin echo sequence and T 2 WI/PDWI of fast spin-echo with fat saturation should be the standard sequence in the examination of knee joint. T 1 WI of IR sequence has potential clinical value for cartilage examination

  20. Uninduced adipose-derived stem cells repair the defect of full-thickness hyaline cartilage.

    Science.gov (United States)

    Zhang, Hai-Ning; Li, Lei; Leng, Ping; Wang, Ying-Zhen; Lv, Cheng-Yu

    2009-04-01

    To testify the effect of the stem cells derived from the widely distributed fat tissue on repairing full-thickness hyaline cartilage defects. Adipose-derived stem cells (ADSCs) were derived from adipose tissue and cultured in vitro. Twenty-seven New Zealand white rabbits were divided into three groups randomly. The cultured ADSCs mixed with calcium alginate gel were used to fill the full-thickness hyaline cartilage defects created at the patellafemoral joint, and the defects repaired with gel or without treatment served as control groups. After 4, 8 and 12 weeks, the reconstructed tissue was evaluated macroscopically and microscopically. Histological analysis and qualitative scoring were also performed to detect the outcome. Full thickness hyaline cartilage defects were repaired completely with ADSCs-derived tissue. The result was better in ADSCs group than the control ones. The microstructure of reconstructed tissue with ADSCs was similar to that of hyaline cartilage and contained more cells and regular matrix fibers, being better than other groups. Plenty of collagen fibers around cells could be seen under transmission electron microscopy. Statistical analysis revealed a significant difference in comparison with other groups at each time point (t equal to 4.360, P less than 0.01). These results indicate that stem cells derived from mature adipose without induction possess the ability to repair cartilage defects.

  1. Development of hybrid scaffolds using ceramic and hydrogel for articular cartilage tissue regeneration.

    Science.gov (United States)

    Seol, Young-Joon; Park, Ju Young; Jeong, Wonju; Kim, Tae-Ho; Kim, Shin-Yoon; Cho, Dong-Woo

    2015-04-01

    The regeneration of articular cartilage consisting of hyaline cartilage and hydrogel scaffolds has been generally used in tissue engineering. However, success in in vivo studies has been rarely reported. The hydrogel scaffolds implanted into articular cartilage defects are mechanically unstable and it is difficult for them to integrate with the surrounding native cartilage tissue. Therefore, it is needed to regenerate cartilage and bone tissue simultaneously. We developed hybrid scaffolds with hydrogel scaffolds for cartilage tissue and with ceramic scaffolds for bone tissue. For in vivo study, hybrid scaffolds were press-fitted into osteochondral tissue defects in a rabbit knee joints and the cartilage tissue regeneration in blank, hydrogel scaffolds, and hybrid scaffolds was compared. In 12th week after implantation, the histological and immunohistochemical analyses were conducted to evaluate the cartilage tissue regeneration. In the blank and hydrogel scaffold groups, the defects were filled with fibrous tissues and the implanted hydrogel scaffolds could not maintain their initial position; in the hybrid scaffold group, newly generated cartilage tissues were morphologically similar to native cartilage tissues and were smoothly connected to the surrounding native tissues. This study demonstrates hybrid scaffolds containing hydrogel and ceramic scaffolds can provide mechanical stability to hydrogel scaffolds and enhance cartilage tissue regeneration at the defect site. © 2014 Wiley Periodicals, Inc.

  2. Can one generate stable hyaline cartilage from adult mesenchymal stem cells? A developmental approach.

    Science.gov (United States)

    Hellingman, Catharine A; Koevoet, Wendy; van Osch, Gerjo J V M

    2012-11-01

    Chondrogenically differentiating bone marrow-derived mesenchymal stem cells (BMSCs) display signs of chondrocyte hypertrophy, such as production of collagen type X, MMP13 and alkaline phosphatase (ALPL). For cartilage reconstructions this is undesirable, as terminally differentiated cartilage produced by BMSCs mineralizes when implanted in vivo. Terminal differentiation is not restricted to BMSCs but is also encountered in chondrogenic differentiation of adipose-derived mesenchymal stem cells (MSCs) as well as embryonic stem cells, which by definition should be able to generate all types of tissues, including stable cartilage. Therefore, we propose that the currently used culture conditions may drive the cells towards terminal differentiation. In this manuscript we aim to review the literature, supplemented by our own data to answer the question, is it possible to generate stable hyaline cartilage from adult MSCs? We demonstrate that recently published methods for inhibiting terminal differentiation (through PTHrP, MMP13 or blocking phosphorylation of Smad1/5/8) result in cartilage formation with reduction of hypertrophic markers, although this does not reach the low level of stable chondrocytes. A set of hypertrophy markers should be included in future studies to characterize the phenotype more precisely. Finally, we used what is currently known in developmental biology about the differential development of hyaline and terminally differentiated cartilage to provide thought and insights to change current culture models for creating hyaline cartilage. Inhibiting terminal differentiation may not result in stable hyaline cartilage if the right balance of signals has not been created from the start of culture onwards. Copyright © 2011 John Wiley & Sons, Ltd.

  3. Synovium-derived stem cells: a tissue-specific stem cell for cartilage engineering and regeneration.

    Science.gov (United States)

    Jones, Brendan A; Pei, Ming

    2012-08-01

    Articular cartilage is difficult to heal once injury or disease occurs. Autologous chondrocyte transplantation is a biological treatment with good prognosis, but donor site morbidity and limited cell source are disadvantages. Currently, mesenchymal stem cells (MSCs) are a promising approach for cartilage regeneration. Despite there being various sources, the best candidate for cartilage regeneration is the one with the greatest chondrogenic potential and the least hypertrophic differentiation. These properties are able to insure that the regenerated tissue is hyaline cartilage of high quality. This review article will summarize relevant literature to justify synovium-derived stem cells (SDSCs) as a tissue-specific stem cell for chondrogenesis by comparing synovium and cartilage with respect to anatomical location and functional structure, comparing the growth characterization and chondrogenic capacity of SDSCs and MSCs, evaluating the application of SDSCs in regenerative medicine and diseases, and discussing potential future directions.

  4. Is the T1ρ MRI profile of hyaline cartilage in the normal hip uniform?

    Science.gov (United States)

    Rakhra, Kawan S; Cárdenas-Blanco, Arturo; Melkus, Gerd; Schweitzer, Mark E; Cameron, Ian G; Beaulé, Paul E

    2015-04-01

    T1ρ MRI is an imaging technique sensitive to proteoglycan (PG) content of hyaline cartilage. However, normative T1ρ values have not been established for the weightbearing cartilage of the hip, and it is not known whether it is uniform or whether there is topographic variation. Knowledge of the T1ρ profile of hyaline cartilage in the normal hip is important for establishing a baseline against which comparisons can be made to experimental and clinical arthritic subjects. In this diagnostic study, we determined (1) the T1ρ MRI values of hyaline cartilage of the normal hip; and (2) whether the T1ρ MRI profile of the normal hip hyaline cartilage is uniform. Fourteen asymptomatic volunteers (11 men, three women; mean age, 35 years) prospectively underwent 1.5-T T1ρ MRI of a single hip. The weightbearing hyaline cartilage bilayer of the acetabulum and femoral head was evaluated on sagittal images and segmented into four zones: (1) anterior; (2) anterosuperior; (3) posterosuperior; and (4) and posterior. For the full region of interest and within each zone and each sagittal slice, we calculated the mean T1ρ relaxation value, a parameter that indirectly quantifies PG content, where T1ρ is inversely related to PG concentration. There was variation in the T1ρ relaxation values depending on zone (anterior to posterior) and slice (medial to lateral). When combining the most anterior quadrants (Zones 1 and 2), the T1ρ relaxation values were lower than those in the combined posterior quadrants (Zones 3 and 4) (30.4 msec versus 32.2 msec, respectively; p = 0.002), reflecting higher PG concentration. There was a difference between the T1ρ relaxation values of the sagittal slices (p = 0.038), most pronounced anteriorly in Zone 1 (26.6 msec, p = 0.001). With a selective combination of zones and slices, there were lower mean T1ρ values in the anterolateral-most region compared with the remainder of the weightbearing portion of the hip (28.6 msec versus 32.2 msec

  5. Assessment of hyaline cartilage matrix composition using near infrared spectroscopy.

    Science.gov (United States)

    Palukuru, Uday P; McGoverin, Cushla M; Pleshko, Nancy

    2014-09-01

    Changes in the composition of the extracellular matrix (ECM) are characteristic of injury or disease in cartilage tissue. Various imaging modalities and biochemical techniques have been used to assess the changes in cartilage tissue but lack adequate sensitivity, or in the case of biochemical techniques, result in destruction of the sample. Fourier transform near infrared (FT-NIR) spectroscopy has shown promise for the study of cartilage composition. In the current study NIR spectroscopy was used to identify the contributions of individual components of cartilage in the NIR spectra by assessment of the major cartilage components, collagen and chondroitin sulfate, in pure component mixtures. The NIR spectra were obtained using homogenous pellets made by dilution with potassium bromide. A partial least squares (PLS) model was calculated to predict composition in bovine cartilage samples. Characteristic absorbance peaks between 4000 and 5000 cm(-1) could be attributed to components of cartilage, i.e. collagen and chondroitin sulfate. Prediction of the amount of collagen and chondroitin sulfate in tissues was possible within 8% (w/dw) of values obtained by gold standard biochemical assessment. These results support the use of NIR spectroscopy for in vitro and in vivo applications to assess matrix composition of cartilage tissues, especially when tissue destruction should be avoided. Copyright © 2014. Published by Elsevier B.V.

  6. Cartilage extracellular matrix as a biomaterial for cartilage regeneration.

    Science.gov (United States)

    Kiyotake, Emi A; Beck, Emily C; Detamore, Michael S

    2016-11-01

    The extracellular matrix (ECM) of various tissues possesses the model characteristics that biomaterials for tissue engineering strive to mimic; however, owing to the intricate hierarchical nature of the ECM, it has yet to be fully characterized and synthetically fabricated. Cartilage repair remains a challenge because the intrinsic properties that enable its durability and long-lasting function also impede regeneration. In the last decade, cartilage ECM has emerged as a promising biomaterial for regenerating cartilage, partly because of its potentially chondroinductive nature. As this research area of cartilage matrix-based biomaterials emerged, investigators facing similar challenges consequently developed convergent solutions in constructing robust and bioactive scaffolds. This review discusses the challenges, emerging trends, and future directions of cartilage ECM scaffolds, including a comparison between two different forms of cartilage matrix: decellularized cartilage (DCC) and devitalized cartilage (DVC). To overcome the low permeability of cartilage matrix, physical fragmentation greatly enhances decellularization, although the process itself may reduce the chondroinductivity of fabricated scaffolds. The less complex processing of a scaffold composed of DVC, which has not been decellularized, appears to have translational advantages and potential chondroinductive and mechanical advantages over DCC, without detrimental immunogenicity, to ultimately enhance cartilage repair in a clinically relevant way. © 2016 New York Academy of Sciences.

  7. In vitro uptake of 153gadolinium and gadolinium complexes by hyaline articular cartilage

    International Nuclear Information System (INIS)

    Engel, A.; Fleischmann, D.; Hamilton, G.; Hajek, P.

    1990-01-01

    This in vitro study evaluated whether Gadolinium (Gd) penetrates into hyaline cartilage and would be incorporated into vital chondrocytes. Hyaline joint cartilage of rabbits was exposed to radioactive 153 GdCl 3 and to a radioactive 153 Gd-DTPA-BSA-complex (DTPA, diethylene-triaminepentaacetic acid; BSA, bovine serum albumine). In addition an exchange experiment with radioactive 153 GdCl 3 versus Gd-DTPA-di-N-methylglucamine (Magnevist) was performed. Incorporation of 153 GdCl 3 into neuroblastoma cells, connective tissue cells and chondrocytes was tested. The results showed that the depth and extent of incorporation of Gd depends on the molecular mass and time of exposure. 153 Gd-DTPA-BSA complexes exhibited an incorporation rate of maximal 11 per cent ± 2.8 per cent up to the middle third of the cartilage within 24 h with almost no incorporation (2 ± 1.9 per cent) for the deep layer. The exchange experiment revealed no uptake of Gd for the deep layer. The maximal incorporation rate of 153 GdCl 3 into vital chondrocytes was 6.3 per cent. These data indicate that under the condition of MR-arthrography, Gd-DTPA-di-N-methylglucamine will not be absorbed into the deep layers of hyaline cartilage and will not be incorporated into vital chondrocytes. (author). 8 refs.; 3 tabs

  8. Delayed Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) of Cadaveric Shoulders: Comparison of Contrast Dynamics in Hyaline and Fibrous Cartilage after Intraarticular Gadolinium Injection

    Energy Technology Data Exchange (ETDEWEB)

    Wiener, E. (Dept. of Radiology, Charite Universitaetsmedizin Berlin (Germany)); Hodler, J.; Pfirrmann, C.W.A. (Dept. of Radiology, Orthopedic Univ. Hospital Balgrist, Zuerich (Switzerland))

    2009-01-15

    Background: Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) is a novel method to investigate cartilaginous and fibrocartilaginous structures. Purpose: To investigate the contrast dynamics in hyaline and fibrous cartilage of the glenohumeral joint after intraarticular injection of gadopentetate dimeglumine. Material and Methods: Transverse T1 maps were acquired on a 1.5T scanner before and after intraarticular injection of 2.0 mmol/l gadopentetate dimeglumine in five cadaveric shoulders using a dual flip angle three-dimensional gradient echo (3D-GRE) sequence. The acquisition time for the T1 maps was 5 min 5 s for the whole shoulder. Measurements were repeated every 15 min over 2.5 hours. Regions of interest (ROIs) covering the glenoid cartilage and the labrum were drawn to assess the temporal evolution of the relaxation parameters. Results: T1 of unenhanced hyaline cartilage of the glenoid was 568+-34 ms. T1 of unenhanced fibrous cartilage of the labrum was 552+-38 ms. Significant differences (P=0.002 and 0.03) in the relaxation parameters were already measurable after 15 min. After 2 to 2.5 hours, hyaline and fibrous cartilage still demonstrated decreasing relaxation parameters, with a larger range of the T1(Gd) values in fibrous cartilage. T1 and ?R1 values of hyaline and fibrous cartilage after 2.5 hours were 351+-16 ms and 1.1+-0.09/s, and 332+-31 ms and 1.2+-0.1/s, respectively. Conclusion: A significant decrease in T1(Gd) was found 15 min after intraarticular contrast injection. Contrast accumulation was faster in hyaline than in fibrous cartilage. After 2.5 hours, contrast accumulation showed a higher rate of decrease in hyaline cartilage, but neither hyaline nor fibrous cartilage had reached equilibrium

  9. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) of cadaveric shoulders: comparison of contrast dynamics in hyaline and fibrous cartilage after intraarticular gadolinium injection.

    Science.gov (United States)

    Wiener, E; Hodler, J; Pfirrmann, C W A

    2009-01-01

    Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) is a novel method to investigate cartilaginous and fibrocartilaginous structures. To investigate the contrast dynamics in hyaline and fibrous cartilage of the glenohumeral joint after intraarticular injection of gadopentetate dimeglumine. Transverse T(1) maps were acquired on a 1.5T scanner before and after intraarticular injection of 2.0 mmol/l gadopentetate dimeglumine in five cadaveric shoulders using a dual flip angle three-dimensional gradient echo (3D-GRE) sequence. The acquisition time for the T(1) maps was 5 min 5 s for the whole shoulder. Measurements were repeated every 15 min over 2.5 hours. Regions of interest (ROIs) covering the glenoid cartilage and the labrum were drawn to assess the temporal evolution of the relaxation parameters. T(1) of unenhanced hyaline cartilage of the glenoid was 568+/-34 ms. T(1) of unenhanced fibrous cartilage of the labrum was 552+/-38 ms. Significant differences (P=0.002 and 0.03) in the relaxation parameters were already measurable after 15 min. After 2 to 2.5 hours, hyaline and fibrous cartilage still demonstrated decreasing relaxation parameters, with a larger range of the T(1)(Gd) values in fibrous cartilage. T(1) and triangle Delta R(1) values of hyaline and fibrous cartilage after 2.5 hours were 351+/-16 ms and 1.1+/-0.09 s(-1), and 332+/-31 ms and 1.2+/-0.1 s(-1), respectively. A significant decrease in T(1)(Gd) was found 15 min after intraarticular contrast injection. Contrast accumulation was faster in hyaline than in fibrous cartilage. After 2.5 hours, contrast accumulation showed a higher rate of decrease in hyaline cartilage, but neither hyaline nor fibrous cartilage had reached equilibrium.

  10. Lineage plasticity and cell biology of fibrocartilage and hyaline cartilage: Its significance in cartilage repair and replacement

    International Nuclear Information System (INIS)

    Freemont, Anthony J.; Hoyland, Judith

    2006-01-01

    Cartilage repair is a major goal of modern tissue engineering. To produce novel engineered implants requires a knowledge of the basic biology of the tissues that are to be replaced or reproduced. Hyaline articular cartilage and meniscal fibrocartilage are two tissues that have excited attention because of the frequency with which they are damaged. A basic strategy is to re-engineer these tissues ex vivo by stimulating stem cells to differentiate into the cells of the mature tissue capable of producing an intact functional matrix. In this brief review, the sources of cells for tissue engineering cartilage and the culture conditions that have promoted differentiation are discussed within the context of natural cartilage repair. In particular, the role of cell density, cytokines, load, matrices and oxygen tension are discussed

  11. Lineage plasticity and cell biology of fibrocartilage and hyaline cartilage: Its significance in cartilage repair and replacement

    Energy Technology Data Exchange (ETDEWEB)

    Freemont, Anthony J. [Regenerative Medicine Research Group, University of Manchester, England (United Kingdom)]. E-mail: Tony.freemont@man.ac.uk; Hoyland, Judith [Regenerative Medicine Research Group, University of Manchester, England (United Kingdom)

    2006-01-15

    Cartilage repair is a major goal of modern tissue engineering. To produce novel engineered implants requires a knowledge of the basic biology of the tissues that are to be replaced or reproduced. Hyaline articular cartilage and meniscal fibrocartilage are two tissues that have excited attention because of the frequency with which they are damaged. A basic strategy is to re-engineer these tissues ex vivo by stimulating stem cells to differentiate into the cells of the mature tissue capable of producing an intact functional matrix. In this brief review, the sources of cells for tissue engineering cartilage and the culture conditions that have promoted differentiation are discussed within the context of natural cartilage repair. In particular, the role of cell density, cytokines, load, matrices and oxygen tension are discussed.

  12. A comparison of different bioinks for 3D bioprinting of fibrocartilage and hyaline cartilage.

    Science.gov (United States)

    Daly, Andrew C; Critchley, Susan E; Rencsok, Emily M; Kelly, Daniel J

    2016-10-07

    Cartilage is a dense connective tissue with limited self-repair capabilities. Mesenchymal stem cell (MSC) laden hydrogels are commonly used for fibrocartilage and articular cartilage tissue engineering, however they typically lack the mechanical integrity for implantation into high load bearing environments. This has led to increased interested in 3D bioprinting of cell laden hydrogel bioinks reinforced with stiffer polymer fibres. The objective of this study was to compare a range of commonly used hydrogel bioinks (agarose, alginate, GelMA and BioINK™) for their printing properties and capacity to support the development of either hyaline cartilage or fibrocartilage in vitro. Each hydrogel was seeded with MSCs, cultured for 28 days in the presence of TGF-β3 and then analysed for markers indicative of differentiation towards either a fibrocartilaginous or hyaline cartilage-like phenotype. Alginate and agarose hydrogels best supported the development of hyaline-like cartilage, as evident by the development of a tissue staining predominantly for type II collagen. In contrast, GelMA and BioINK ™ (a PEGMA based hydrogel) supported the development of a more fibrocartilage-like tissue, as evident by the development of a tissue containing both type I and type II collagen. GelMA demonstrated superior printability, generating structures with greater fidelity, followed by the alginate and agarose bioinks. High levels of MSC viability were observed in all bioinks post-printing (∼80%). Finally we demonstrate that it is possible to engineer mechanically reinforced hydrogels with high cell viability by co-depositing a hydrogel bioink with polycaprolactone filaments, generating composites with bulk compressive moduli comparable to articular cartilage. This study demonstrates the importance of the choice of bioink when bioprinting different cartilaginous tissues for musculoskeletal applications.

  13. Near infrared spectroscopic evaluation of water in hyaline cartilage.

    Science.gov (United States)

    Padalkar, M V; Spencer, R G; Pleshko, N

    2013-11-01

    In diseased conditions of cartilage such as osteoarthritis, there is typically an increase in water content from the average normal of 60-85% to greater than 90%. As cartilage has very little capability for self-repair, methods of early detection of degeneration are required, and assessment of water could prove to be a useful diagnostic method. Current assessment methods are either destructive, time consuming, or have limited sensitivity. Here, we investigated the hypotheses that non-destructive near infrared spectroscopy (NIRS) of articular cartilage can be used to differentiate between free and bound water, and to quantitatively assess water content. The absorbances centered at 5200 and 6890 cm(-1) were attributed to a combination of free and bound water, and to free water only, respectively. The integrated areas of both absorbance bands were found to correlate linearly with the absolute water content (R = 0.87 and 0.86) and with percent water content (R = 0.97 and 0.96) of the tissue. Partial least square models were also successfully developed and were used to predict water content, and percent free water. These data demonstrate that NIRS can be utilized to quantitatively determine water content in articular cartilage, and may aid in early detection of degenerative tissue changes in a laboratory setting, and with additional validations, possibly in a clinical setting.

  14. Hyaline cartilage involvement in patients with gout and calcium pyrophosphate deposition disease. An ultrasound study.

    Science.gov (United States)

    Filippucci, E; Riveros, M Gutierrez; Georgescu, D; Salaffi, F; Grassi, W

    2009-02-01

    The main aim of the present study was to determine the sensitivity, specificity and accuracy of ultrasonography (US) in detecting monosodium urate and calcium pyrophosphate dihydrate crystals deposits at knee cartilage level using clinical definite diagnosis as standard reference. A total of 32 patients with a diagnosis of gout and 48 patients with pyrophosphate arthropathy were included in the study. Fifty-two patients with rheumatoid arthritis (RA), psoriatic arthritis or osteoarthritis (OA) were recruited as disease controls. All diagnoses were made using an international clinical criterion. US examinations were performed by an experienced sonographer, blind to clinical and laboratory data. Hyaline cartilage was assessed to detect two US findings recently indicated as indicative of crystal deposits: hyperechoic enhancement of the superficial margin of the hyaline cartilage and hyperechoic spots within the cartilage layer not generating a posterior acoustic shadow. Hyperechoic enhancement of the chondrosynovial margin was found in at least one knee of 14 out of 32 (43.7%) patients with gout and in a single knee of only one patient affected by pyrophosphate arthropathy (specificity=99%). Intra-cartilaginous hyperechoic spots were detected in at least one knee of 33 out of 48 (68.7%) patients with pyrophosphate arthropathy and in two disease controls one with OA and the second with RA (specificity=97.6%). The results of the present study indicate that US may play a relevant role in distinguishing cartilage involvement in patients with crystal-related arthropathy. The selected US findings were found to be highly specific.

  15. Changes of rabbit meniscus influenced by hyaline cartilage injury of osteoarthritis.

    Science.gov (United States)

    Zhao, Jiajun; Huang, Suizhu; Zheng, Jia; Zhong, Chunan; Tang, Chao; Zheng, Lei; Zhang, Zhen; Xu, Jianzhong

    2014-01-01

    Osteoarthritis (OA) is a common disease in the elderly population. Most of the previous OA-related researches focused on articular cartilage degeneration, osteophyte formation and synovitis etc. However, the role of the meniscus in these pathological changes has not been given enough attention. The goal of our study was to find the pathological changes of the meniscus in OA knee and determine their relationship. 20 months old female Chinese rabbits received either knee damaging operations with articular cartilage scratch method or sham operation randomly on one of their knees. They were sacrificed after 1-6 weeks post-operation. Medial Displacement Index (MDI) for meniscus dislocation, hematoxylin and eosin (HE) for routine histological evaluation, Toluidine blue (TB) stains for evaluating proteoglycans were carried out. Immunohistochemical (IHC) staining was performed with a two-step detection kit. Histological analysis showed chondrocyte clusters around cartilage lesions and moderate loss of proteoglycans in the operation model, as well as MDI increase and all characteristics of OA. High expression of MMP-3 and TIMP-1 also were found in both hyaline cartilage and meniscus. Biomechanical and biochemistry environment around the meniscus is altered when OA occur. If meniscus showed degeneration, subluxation and dysfunction, OA would be more severe. Prompt repair or reconstruction of hyaline cartilage in weight bearing area when it injured could prevent meniscus degeneration and subluxation, then prevent the development of OA.

  16. Chondrocalcinosis of the hyaline cartilage of the knee: MRI manifestations

    International Nuclear Information System (INIS)

    Beltran, J.; Marty-Delfaut, E.; Bencardino, J.; Rosenberg, Z.S.; Steiner, G.; Aparisi, F.; Padron, M.

    1998-01-01

    Purpose. To determine the ability of MRI to detect the presence of crystals of calcium pyrophosphate in the articular cartilage of the knee. Design and patients. The MR studies of 12 knees (11 cases) were reviewed retrospectively and correlated with r[iographs (12 cases) and the findings at arthroscopy (2 cases) and surgery (1 case). A total of 72 articular surfaces were evaluated. R[iographic, surgical or arthroscopic demonstration of chondrocalcinosis was used as the gold standard. [ditionally, two fragments of the knee of a patient who underwent total knee replacement and demonstrated extensive chondrocalcinosis were studied with r[iography and MRI using spin-echo T1-, T2- and proton-density-weighted images as well as two- and three-dimensional fat saturation (2D and 3D Fat Sat) gr[ient recalled echo (GRE) and STIR sequences. Results. MRI revealed multiple hypointense foci within the articular cartilage in 34 articular surfaces, better shown on 2D and 3D GRE sequences. R[iographs showed 12 articular surfaces with chondrocalcinosis. In three cases with arthroscopic or surgical correlation, MRI demonstrated more diffuse involvement of the articular cartilage than did the r[iographs. The 3D Fat Sat GRE sequences were the best for demonstrating articular calcification in vitro. In no case was meniscal calcification identified with MRI. Hyperintense halos around some of the calcifications were seen on the MR images. Conclusion. MRI can depict articular cartilage calcification as hypointense foci using GRE techniques. Differential diagnosis includes loose bodies, post-surgical changes, marginal osteophytes and hemosiderin deposition. (orig.)

  17. Chondrocalcinosis of the hyaline cartilage of the knee: MRI manifestations

    Energy Technology Data Exchange (ETDEWEB)

    Beltran, J.; Marty-Delfaut, E.; Bencardino, J.; Rosenberg, Z.S. [Department of Radiology, Hospital for Joint Diseases, New York, NY (United States); Steiner, G. [Department of Pathology, Hospital for Joint Diseases, New York, NY (United States); Aparisi, F. [Department of Radiology, Residencia Sanitaria ``La Fe``, Valencia (Spain); Padron, M. [Clinica San Camilo, Madrid (Spain)

    1998-07-01

    Purpose. To determine the ability of MRI to detect the presence of crystals of calcium pyrophosphate in the articular cartilage of the knee. Design and patients. The MR studies of 12 knees (11 cases) were reviewed retrospectively and correlated with radiographs (12 cases) and the findings at arthroscopy (2 cases) and surgery (1 case). A total of 72 articular surfaces were evaluated. Radiographic, surgical or arthroscopic demonstration of chondrocalcinosis was used as the gold standard. Additionally, two fragments of the knee of a patient who underwent total knee replacement and demonstrated extensive chondrocalcinosis were studied with radiography and MRI using spin-echo T1-, T2- and proton-density-weighted images as well as two- and three-dimensional fat saturation (2D and 3D Fat Sat) gradient recalled echo (GRE) and STIR sequences. Results. MRI revealed multiple hypointense foci within the articular cartilage in 34 articular surfaces, better shown on 2D and 3D GRE sequences. Radiographs showed 12 articular surfaces with chondrocalcinosis. In three cases with arthroscopic or surgical correlation, MRI demonstrated more diffuse involvement of the articular cartilage than did the radiographs. The 3D Fat Sat GRE sequences were the best for demonstrating articular calcification in vitro. In no case was meniscal calcification identified with MRI. Hyperintense halos around some of the calcifications were seen on the MR images. Conclusion. MRI can depict articular cartilage calcification as hypointense foci using GRE techniques. Differential diagnosis includes loose bodies, post-surgical changes, marginal osteophytes and hemosiderin deposition. (orig.) With 4 figs., 14 refs.

  18. Formation of Hyaline Cartilage Tissue by Passaged Human Osteoarthritic Chondrocytes.

    Science.gov (United States)

    Bianchi, Vanessa J; Weber, Joanna F; Waldman, Stephen D; Backstein, David; Kandel, Rita A

    2017-02-01

    When serially passaged in standard monolayer culture to expand cell number, articular chondrocytes lose their phenotype. This results in the formation of fibrocartilage when they are used clinically, thus limiting their use for cartilage repair therapies. Identifying a way to redifferentiate these cells in vitro is critical if they are to be used successfully. Transforming growth factor beta (TGFβ) family members are known to be crucial for regulating differentiation of fetal limb mesenchymal cells and mesenchymal stromal cells to chondrocytes. As passaged chondrocytes acquire a progenitor-like phenotype, the hypothesis of this study was that TGFβ supplementation will stimulate chondrocyte redifferentiation in vitro in serum-free three-dimensional (3D) culture. Human articular chondrocytes were serially passaged twice (P2) in monolayer culture. P2 cells were then placed in high-density (3D) culture on top of membranes (Millipore) and cultured for up to 6 weeks in chemically defined serum-free redifferentiation media (SFRM) in the presence or absence of TGFβ. The tissues were evaluated histologically, biochemically, by immunohistochemical staining, and biomechanically. Passaged human chondrocytes cultured in SFRM supplemented with 10 ng/mL TGFβ3 consistently formed a continuous layer of articular-like cartilage tissue rich in collagen type 2 and aggrecan and lacking collagen type 1 and X in the absence of a scaffold. The tissue developed a superficial zone characterized by expression of lubricin and clusterin with horizontally aligned collagen fibers. This study suggests that passaged human chondrocytes can be used to bioengineer a continuous layer of articular cartilage-like tissue in vitro scaffold free. Further study is required to evaluate their ability to repair cartilage defects in vivo.

  19. Developments in dynamic MR elastography for in vitro biomechanical assessment of hyaline cartilage under high-frequency cyclical shear.

    Science.gov (United States)

    Lopez, Orlando; Amrami, Kimberly K; Manduca, Armando; Rossman, Phillip J; Ehman, Richard L

    2007-02-01

    The design, construction, and evaluation of a customized dynamic magnetic resonance elastography (MRE) technique for biomechanical assessment of hyaline cartilage in vitro are described. For quantification of the dynamic shear properties of hyaline cartilage by dynamic MRE, mechanical excitation and motion sensitization were performed at frequencies in the kilohertz range. A custom electromechanical actuator and a z-axis gradient coil were used to generate and image shear waves throughout cartilage at 1000-10,000 Hz. A radiofrequency (RF) coil was also constructed for high-resolution imaging. The technique was validated at 4000 and 6000 Hz by quantifying differences in shear stiffness between soft ( approximately 200 kPa) and stiff ( approximately 300 kPa) layers of 5-mm-thick bilayered phantoms. The technique was then used to quantify the dynamic shear properties of bovine and shark hyaline cartilage samples at frequencies up to 9000 Hz. The results demonstrate that one can obtain high-resolution shear stiffness measurements of hyaline cartilage and small, stiff, multilayered phantoms at high frequencies by generating robust mechanical excitations and using large magnetic field gradients. Dynamic MRE can potentially be used to directly quantify the dynamic shear properties of hyaline and articular cartilage, as well as other cartilaginous materials and engineered constructs. (c) 2007 Wiley-Liss, Inc.

  20. Xiphoid Process-Derived Chondrocytes: A Novel Cell Source for Elastic Cartilage Regeneration

    Science.gov (United States)

    Nam, Seungwoo; Cho, Wheemoon; Cho, Hyunji; Lee, Jungsun

    2014-01-01

    Reconstruction of elastic cartilage requires a source of chondrocytes that display a reliable differentiation tendency. Predetermined tissue progenitor cells are ideal candidates for meeting this need; however, it is difficult to obtain donor elastic cartilage tissue because most elastic cartilage serves important functions or forms external structures, making these tissues indispensable. We found vestigial cartilage tissue in xiphoid processes and characterized it as hyaline cartilage in the proximal region and elastic cartilage in the distal region. Xiphoid process-derived chondrocytes (XCs) showed superb in vitro expansion ability based on colony-forming unit fibroblast assays, cell yield, and cumulative cell growth. On induction of differentiation into mesenchymal lineages, XCs showed a strong tendency toward chondrogenic differentiation. An examination of the tissue-specific regeneration capacity of XCs in a subcutaneous-transplantation model and autologous chondrocyte implantation model confirmed reliable regeneration of elastic cartilage regardless of the implantation environment. On the basis of these observations, we conclude that xiphoid process cartilage, the only elastic cartilage tissue source that can be obtained without destroying external shape or function, is a source of elastic chondrocytes that show superb in vitro expansion and reliable differentiation capacity. These findings indicate that XCs could be a valuable cell source for reconstruction of elastic cartilage. PMID:25205841

  1. Hyaline cartilage thickness in radiographically normal cadaveric hips: comparison of spiral CT arthrographic and macroscopic measurements.

    Science.gov (United States)

    Wyler, Annabelle; Bousson, Valérie; Bergot, Catherine; Polivka, Marc; Leveque, Eric; Vicaut, Eric; Laredo, Jean-Denis

    2007-02-01

    To assess spiral multidetector computed tomographic (CT) arthrography for the depiction of cartilage thickness in hips without cartilage loss, with evaluation of anatomic slices as the reference standard. Permission to perform imaging studies in cadaveric specimens of individuals who had willed their bodies to science was obtained from the institutional review board. Two independent observers measured the femoral and acetabular hyaline cartilage thickness of 12 radiographically normal cadaveric hips (from six women and five men; age range at death, 52-98 years; mean, 76.5 years) on spiral multidetector CT arthrographic reformations and on coronal anatomic slices. Regions of cartilage loss at gross or histologic examination were excluded. CT arthrographic and anatomic measurements in the coronal plane were compared by using Bland-Altman representation and a paired t test. Differences between mean cartilage thicknesses at the points of measurement were tested by means of analysis of variance. Interobserver and intraobserver reproducibilities were determined. At CT arthrography, mean cartilage thickness ranged from 0.32 to 2.53 mm on the femoral head and from 0.95 to 3.13 mm on the acetabulum. Observers underestimated cartilage thickness in the coronal plane by 0.30 mm +/- 0.52 (mean +/- standard error) at CT arthrography (P cartilage thicknesses at the different measurement points was significant for coronal spiral multidetector CT arthrography and anatomic measurement of the femoral head and acetabulum and for sagittal and transverse CT arthrography of the femoral head (P cartilage thickness from the periphery to the center of the joint ("gradients") were found by means of spiral multidetector CT arthrography and anatomic measurement. Spiral multidetector CT arthrography depicts cartilage thickness gradients in radiographically normal cadaveric hips. (c) RSNA, 2007.

  2. Effect of exercise on thicknesses of mature hyaline cartilage, calcified cartilage, and subchondral bone of equine tarsi.

    Science.gov (United States)

    Tranquille, Carolyne A; Blunden, Antony S; Dyson, Sue J; Parkin, Tim D H; Goodship, Allen E; Murray, Rachel C

    2009-12-01

    OBJECTIVE-To investigate effects of exercise on hyaline cartilage (HC), calcified cartilage (CC), and subchondral bone (SCB) thickness patterns of equine tarsi. SAMPLE POPULATION-30 tarsi from cadavers of horses with known exercise history. PROCEDURES-Tarsi were assigned to 3 groups according to known exercise history as follows: pasture exercise only (PE tarsi), low-intensity general-purpose riding exercise (LE tarsi), and high-intensity elite competition riding exercise (EE tarsi). Osteochondral tissue from distal tarsal joints underwent histologic preparation. Hyaline cartilage, CC, and SCB thickness were measured at standard sites at medial, midline, and lateral locations across joints with a histomorphometric technique. RESULTS-HC, CC, and SCB thickness were significantly greater at all sites in EE tarsi, compared with PE tarsi; this was also true when LE tarsi were compared with PE tarsi. At specific sites, HC, CC, and SCB were significantly thicker in EE tarsi, compared with LE tarsi. Along the articular surface of the proximal aspect of the third metatarsal bone, SCB was thickest in EE tarsi and thinnest in LE tarsi; increases were greatest at sites previously reported to undergo peak strains and osteochondral damage. CONCLUSIONS AND CLINICAL RELEVANCE-Increased exercise was associated with increased HC, CC, and SCB thickness in mature horses. At sites that undergo high compressive strains, with a reported predisposition to osteoarthritic change, there was increased CC and SCB thickness. These results may provide insight into the interaction between adaptive response to exercise and pathological change.

  3. The development of hyaline-cell cartilage in the head of the black molly, Poecilia sphenops. Evidence for secondary cartilage in a teleost.

    Science.gov (United States)

    Benjamin, M

    1989-01-01

    The development of hyaline-cell cartilage attached to membrane (dentary, maxilla, nasal, lacrimal and cleithrum) and cartilage (basioccipital) bones has been studied in the viviparous black molly, Poecilia sphenops. Intramembranous ossification commences before the first appearance of hyaline cells. As hyaline-cell cartilage is densely cellular and as that attached to the dentary, maxilla and cleithrum develops from the periosteum of these membrane bones, it must be regarded as secondary cartilage according to current concepts. It is also argued that the hyaline-cell cartilage attached to the perichondral bone of the basioccipital (a cartilage bone), could also be viewed as secondary. The status of the cartilage on the nasal and lacrimal bones is less clear, for it develops, at least in part, from mucochondroid (mucous connective) tissue. This is the first definitive report of secondary cartilage in any lower vertebrate. The tissue is therefore not restricted to birds and mammals as hitherto believed, and a multipotential periosteum must have arisen early in vertebrate evolution. Images Fig. 1 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 PMID:2481666

  4. Sprifermin (rhFGF18) enables proliferation of chondrocytes producing a hyaline cartilage matrix.

    Science.gov (United States)

    Gigout, A; Guehring, H; Froemel, D; Meurer, A; Ladel, C; Reker, D; Bay-Jensen, A C; Karsdal, M A; Lindemann, S

    2017-11-01

    Fibroblast growth factor (FGF) 18 has been shown to increase cartilage volume when injected intra-articularly in animal models of osteoarthritis (OA) and in patients with knee OA (during clinical development of the recombinant human FGF18, sprifermin). However, the exact nature of this effect is still unknown. In this study, we aimed to investigate the effects of sprifermin at the cellular level. A combination of different chondrocyte culture systems was used and the effects of sprifermin on proliferation, the phenotype and matrix production were evaluated. The involvement of MAPKs in sprifermin signalling was also studied. In monolayer, we observed that sprifermin promoted a round cell morphology and stimulated both cellular proliferation and Sox9 expression while strongly decreasing type I collagen expression. In 3D culture, sprifermin increased the number of matrix-producing chondrocytes, improved the type II:I collagen ratio and enabled human OA chondrocytes to produce a hyaline extracellular matrix (ECM). Furthermore, we found that sprifermin displayed a 'hit and run' mode of action, with intermittent exposure required for the compound to fully exert its anabolic effect. Finally, sprifermin appeared to signal through activation of ERK. Our results indicate that intermittent exposure to sprifermin leads to expansion of hyaline cartilage-producing chondrocytes. These in vitro findings are consistent with the increased cartilage volume observed in the knees of OA patients after intra-articular injection with sprifermin in clinical studies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Magnetic resonance tomography (MRT) of the knee joint: Meniscus, cruciate ligaments and hyaline cartilage. Magnetresonanztomographie (MRT) des Kniegelenks: Meniskus, Kreuzbaender und hyaliner Gelenkknorpel

    Energy Technology Data Exchange (ETDEWEB)

    Hodler, J. (Radiologie, Universitaetsspital, Zurich (Switzerland) Orthopaedische Universitaetsklinik Balgrist, Zurich (Switzerland). Radiologische Abt.); Buess, E. (Orthopaedische Universitaetsklinik Balgrist, Zurich (Switzerland)); Rodriguez, M. (Orthopaedische Universitaetsklinik Balgrist, Zurich (Switzerland)); Imhoff, A. (Orthopaedische Universitaetsklinik Balgrist, Zurich (Switzerland))

    1993-08-01

    The use of MRT for diagnosing injury to the meniscus, the cruciate ligaments and hyaline cartilage was evaluated retrospectively in 82 knee joints without any knowledge of operative findings. In 49 cases the results were verified by arthroscopy and in 33 cases by arthrotomy. Sensitivity, specificity and diagnostic accuracy of MRT for meniscus lesions was 73.9%, 96.9%, and 94.6%. Corresponding values for lesions of the anterior cruciate ligament were 88.9%, 96.6%, and 94.7%, and for lesions of the hyaline cartilage 62.6%, 96.1%, and 87.9%, respectively. In addition to its high specificity, MRT proved accurate in excluding lesions of the meniscus (97.1%) of the anterior cruciate ligament (96.6%) and of hyaline cartilage (88.8%). A negative finding on MRT therefore makes the presence of a lesion of the meniscus, cruciate ligaments of cartilage unlikely. In such cases one is justified in delaying the use of arthroscopy or arthrotomy. (orig.)

  6. A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study

    OpenAIRE

    Yvonne Peck; Pengfei He; Geetha Soujanya V. N. Chilla; Chueh Loo Poh; Dong-An Wang

    2015-01-01

    In this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load-bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG...

  7. Engineering of hyaline cartilage with a calcified zone using bone marrow stromal cells.

    Science.gov (United States)

    Lee, W D; Hurtig, M B; Pilliar, R M; Stanford, W L; Kandel, R A

    2015-08-01

    In healthy joints, a zone of calcified cartilage (ZCC) provides the mechanical integration between articular cartilage and subchondral bone. Recapitulation of this architectural feature should serve to resist the constant shear force from the movement of the joint and prevent the delamination of tissue-engineered cartilage. Previous approaches to create the ZCC at the cartilage-substrate interface have relied on strategic use of exogenous scaffolds and adhesives, which are susceptible to failure by degradation and wear. In contrast, we report a successful scaffold-free engineering of ZCC to integrate tissue-engineered cartilage and a porous biodegradable bone substitute, using sheep bone marrow stromal cells (BMSCs) as the cell source for both cartilaginous zones. BMSCs were predifferentiated to chondrocytes, harvested and then grown on a porous calcium polyphosphate substrate in the presence of triiodothyronine (T3). T3 was withdrawn, and additional predifferentiated chondrocytes were placed on top of the construct and grown for 21 days. This protocol yielded two distinct zones: hyaline cartilage that accumulated proteoglycans and collagen type II, and calcified cartilage adjacent to the substrate that additionally accumulated mineral and collagen type X. Constructs with the calcified interface had comparable compressive strength to native sheep osteochondral tissue and higher interfacial shear strength compared to control without a calcified zone. This protocol improves on the existing scaffold-free approaches to cartilage tissue engineering by incorporating a calcified zone. Since this protocol employs no xenogeneic material, it will be appropriate for use in preclinical large-animal studies. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  8. Peptide-Based Materials for Cartilage Tissue Regeneration.

    Science.gov (United States)

    Hastar, Nurcan; Arslan, Elif; Guler, Mustafa O; Tekinay, Ayse B

    2017-01-01

    Cartilaginous tissue requires structural and metabolic support after traumatic or chronic injuries because of its limited capacity for regeneration. However, current techniques for cartilage regeneration are either invasive or ineffective for long-term repair. Developing alternative approaches to regenerate cartilage tissue is needed. Therefore, versatile scaffolds formed by biomaterials are promising tools for cartilage regeneration. Bioactive scaffolds further enhance the utility in a broad range of applications including the treatment of major cartilage defects. This chapter provides an overview of cartilage tissue, tissue defects, and the methods used for regeneration, with emphasis on peptide scaffold materials that can be used to supplement or replace current medical treatment options.

  9. First and second order stereology of hyaline cartilage: Application on mice femoral cartilage.

    Science.gov (United States)

    Noorafshan, Ali; Niazi, Behnam; Mohamadpour, Masoomeh; Hoseini, Leila; Hoseini, Najmeh; Owji, Ali Akbar; Rafati, Ali; Sadeghi, Yasaman; Karbalay-Doust, Saied

    2016-11-01

    Stereological techniques could be considered in research on cartilage to obtain quantitative data. The present study aimed to explain application of the first- and second-order stereological methods on articular cartilage of mice and the methods applied on the mice exposed to cadmium (Cd). The distal femoral articular cartilage of BALB/c mice (control and Cd-treated) was removed. Then, volume and surface area of the cartilage and number of chondrocytes were estimated using Cavalieri and optical dissector techniques on isotropic uniform random sections. Pair-correlation function [g(r)] and cross-correlation function were calculated to express the spatial arrangement of chondrocytes-chondrocytes and chondrocytes-matrix (chondrocyte clustering/dispersing), respectively. The mean±standard deviation of the cartilage volume, surface area, and thickness were 1.4±0.1mm 3 , 26.2±5.4mm 2 , and 52.8±6.7μm, respectively. Besides, the mean number of chondrocytes was 680±200 (×10 3 ). The cartilage volume, cartilage surface area, and number of chondrocytes were respectively reduced by 25%, 27%, and 27% in the Cd-treated mice in comparison to the control animals (pcartilage components carried potential advantages for investigating the cartilage in different joint conditions. Chondrocyte clustering/dispersing and cellularity can be evaluated in cartilage assessment in normal or abnormal situations. Copyright © 2016 Elsevier GmbH. All rights reserved.

  10. Induction of mesenchymal stem cell chondrogenic differentiation and functional cartilage microtissue formation for in vivo cartilage regeneration by cartilage extracellular matrix-derived particles.

    Science.gov (United States)

    Yin, Heyong; Wang, Yu; Sun, Zhen; Sun, Xun; Xu, Yichi; Li, Pan; Meng, Haoye; Yu, Xiaoming; Xiao, Bo; Fan, Tian; Wang, Yiguo; Xu, Wenjing; Wang, Aiyuan; Guo, Quanyi; Peng, Jiang; Lu, Shibi

    2016-03-01

    We propose a method of preparing a novel cell carrier derived from natural cartilage extracellular matrix (ECM), designated cartilage ECM-derived particles (CEDPs). Through a series of processes involving pulverization, sieving, and decellularization, fresh cartilage was made into CEDPs with a median diameter of 263 ± 48 μm. Under microgravity culture conditions in a rotary cell culture system (RCCS), bone marrow stromal cells (BMSCs) can proliferate rapidly on the surface of CEDPs with high viability. Histological evaluation and gene expression analysis indicated that BMSCs were differentiated into mature chondrocytes after 21 days of culture without the use of exogenous growth factors. Functional cartilage microtissue aggregates of BMSC-laden CEDPs formed as time in culture increased. Further, the microtissue aggregates were directly implanted into trochlear cartilage defects in a rat model (CEDP+MSC group). Gait analysis and histological results indicated that the CEDP+MSC group obtained better and more rapid joint function recovery and superior cartilage repair compared to the control groups, in which defects were treated with CEDPs alone or only fibrin glue, at both 6 and 12 weeks after surgery. In conclusion, the innovative cell carrier derived from cartilage ECM could promote chondrogenic differentiation of BMSCs, and the direct use of functional cartilage microtissue facilitated cartilage regeneration. This strategy for cell culture, stem cell differentiation and one-step surgery using cartilage microtissue for cartilage repair provides novel prospects for cartilage tissue engineering and may have further broad clinical applications. We proposed a method to prepare a novel cell carrier derived from natural cartilage ECM, termed cartilage ECM-derived particles (CEDPs), which can support proliferation of MSCs and facilitate their chondrogenic differentiation. Further, the direct use of functional cartilage microtissue of MSC-laden CEDP aggregates for

  11. Microstructural and compositional features of the fibrous and hyaline cartilage on the medial tibial plateau imply a unique role for the hopping locomotion of kangaroo.

    Directory of Open Access Journals (Sweden)

    Bo He

    Full Text Available Hopping provides efficient and energy saving locomotion for kangaroos, but it results in great forces in the knee joints. A previous study has suggested that a unique fibrous cartilage in the central region of the tibial cartilage could serve to decrease the peak stresses generated within kangaroo tibiofemoral joints. However, the influences of the microstructure, composition and mechanical properties of the central fibrous and peripheral hyaline cartilage on the function of the knee joints are still to be defined. The present study showed that the fibrous cartilage was thicker and had a lower chondrocyte density than the hyaline cartilage. Despite having a higher PG content in the middle and deep zones, the fibrous cartilage had an inferior compressive strength compared to the peripheral hyaline cartilage. The fibrous cartilage had a complex three dimensional collagen meshwork with collagen bundles parallel to the surface in the superficial zone, and with collagen bundles both parallel and perpendicular to the surface in the middle and deep zones. The collagen in the hyaline cartilage displayed a typical Benninghoff structure, with collagen fibres parallel to the surface in the superficial zone and collagen fibres perpendicular to the surface in the deep zone. Elastin fibres were found throughout the entire tissue depth of the fibrous cartilage and displayed a similar alignment to the adjacent collagen bundles. In comparison, the elastin fibres in the hyaline cartilage were confined within the superficial zone. This study examined for the first time the fibrillary structure, PG content and compressive properties of the central fibrous cartilage pad and peripheral hyaline cartilage within the kangaroo medial tibial plateau. It provided insights into the microstructure and composition of the fibrous and peripheral hyaline cartilage in relation to the unique mechanical properties of the tissues to provide for the normal activities of kangaroos.

  12. Microstructural and compositional features of the fibrous and hyaline cartilage on the medial tibial plateau imply a unique role for the hopping locomotion of kangaroo.

    Science.gov (United States)

    He, Bo; Wu, Jian Ping; Xu, Jiake; Day, Robert E; Kirk, Thomas Brett

    2013-01-01

    Hopping provides efficient and energy saving locomotion for kangaroos, but it results in great forces in the knee joints. A previous study has suggested that a unique fibrous cartilage in the central region of the tibial cartilage could serve to decrease the peak stresses generated within kangaroo tibiofemoral joints. However, the influences of the microstructure, composition and mechanical properties of the central fibrous and peripheral hyaline cartilage on the function of the knee joints are still to be defined. The present study showed that the fibrous cartilage was thicker and had a lower chondrocyte density than the hyaline cartilage. Despite having a higher PG content in the middle and deep zones, the fibrous cartilage had an inferior compressive strength compared to the peripheral hyaline cartilage. The fibrous cartilage had a complex three dimensional collagen meshwork with collagen bundles parallel to the surface in the superficial zone, and with collagen bundles both parallel and perpendicular to the surface in the middle and deep zones. The collagen in the hyaline cartilage displayed a typical Benninghoff structure, with collagen fibres parallel to the surface in the superficial zone and collagen fibres perpendicular to the surface in the deep zone. Elastin fibres were found throughout the entire tissue depth of the fibrous cartilage and displayed a similar alignment to the adjacent collagen bundles. In comparison, the elastin fibres in the hyaline cartilage were confined within the superficial zone. This study examined for the first time the fibrillary structure, PG content and compressive properties of the central fibrous cartilage pad and peripheral hyaline cartilage within the kangaroo medial tibial plateau. It provided insights into the microstructure and composition of the fibrous and peripheral hyaline cartilage in relation to the unique mechanical properties of the tissues to provide for the normal activities of kangaroos.

  13. Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc.

    Science.gov (United States)

    Mwale, F; Roughley, P; Antoniou, J

    2004-12-15

    Tissue engineering of intervertebral discs (IVD) using mesenchymal stem cells (MSCs) induced to differentiate into a disc-cell phenotype has been considered as an alternative treatment for disc degeneration. However, since there is no unique marker characteristic of discs and since hyaline cartilage and immature nucleus pulposus (NP) possess similar macromolecules in their extracellular matrix, it is currently difficult to recognize MSC conversion to a disc cell. This study was performed to compare the proteoglycan to collagen ratio (measured as GAG to hydroxyproline ratio) in the NP of normal disc to that of the hyaline cartilage of the endplate within the same group of individuals and test the hypothesis that this ratio can be used for in vivo studies to distinguish between a normal NP and hyaline cartilage phenotype. Whole human lumbar spine specimens from fresh cadavers, ranging in age from 12 weeks to 79 years, were used to harvest the IVDs and adjacent endplates. The GAG to hydroxyproline ratio within the NP of young adults is approximately 27:1, whereas the ratio within the hyaline cartilage endplate of the same aged individuals is about 2:1. The production of an extracellular matrix with a high proteoglycan to collagen ratio can be used in vivo to distinguish NP cells from chondrocytes, and could help in identifying a NP-like phenotype in vivo as opposed to a chondrocyte when MSCs are induced to differentiate for tissue engineering of a disc.

  14. Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc

    Directory of Open Access Journals (Sweden)

    Mwale F.

    2004-12-01

    Full Text Available Tissue engineering of intervertebral discs (IVD using mesenchymal stem cells (MSCs induced to differentiate into a disc-cell phenotype has been considered as an alternative treatment for disc degeneration. However, since there is no unique marker characteristic of discs and since hyaline cartilage and immature nucleus pulposus (NP possess similar macromolecules in their extracellular matrix, it is currently difficult to recognize MSC conversion to a disc cell. This study was performed to compare the proteoglycan to collagen ratio (measured as GAG to hydroxyproline ratio in the NP of normal disc to that of the hyaline cartilage of the endplate within the same group of individuals and test the hypothesis that this ratio can be used for in vivo studies to distinguish between a normal NP and hyaline cartilage phenotype. Whole human lumbar spine specimens from fresh cadavers, ranging in age from 12 weeks to 79 years, were used to harvest the IVDs and adjacent endplates. The GAG to hydroxyproline ratio within the NP of young adults is approximately 27:1, whereas the ratio within the hyaline cartilage endplate of the same aged individuals is about 2:1. The production of an extracellular matrix with a high proteoglycan to collagen ratio can be used in vivo to distinguish NP cells from chondrocytes, and could help in identifying a NP-like phenotype in vivo as opposed to a chondrocyte when MSCs are induced to differentiate for tissue engineering of a disc.

  15. Mesenchymal Stem/Progenitor Cells Derived from Articular Cartilage, Synovial Membrane and Synovial Fluid for Cartilage Regeneration: Current Status and Future Perspectives.

    Science.gov (United States)

    Huang, Yi-Zhou; Xie, Hui-Qi; Silini, Antonietta; Parolini, Ornella; Zhang, Yi; Deng, Li; Huang, Yong-Can

    2017-10-01

    Large articular cartilage defects remain an immense challenge in the field of regenerative medicine because of their poor intrinsic repair capacity. Currently, the available medical interventions can relieve clinical symptoms to some extent, but fail to repair the cartilaginous injuries with authentic hyaline cartilage. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stem/progenitor cells with or without scaffolds. Mesenchymal stem/progenitor cells are promising graft cells for tissue regeneration, but the most suitable source of cells for cartilage repair remains controversial. The tissue origin of mesenchymal stem/progenitor cells notably influences the biological properties and therapeutic potential. It is well known that mesenchymal stem/progenitor cells derived from synovial joint tissues exhibit superior chondrogenic ability compared with those derived from non-joint tissues; thus, these cell populations are considered ideal sources for cartilage regeneration. In addition to the progress in research and promising preclinical results, many important research questions must be answered before widespread success in cartilage regeneration is achieved. This review outlines the biology of stem/progenitor cells derived from the articular cartilage, the synovial membrane, and the synovial fluid, including their tissue distribution, function and biological characteristics. Furthermore, preclinical and clinical trials focusing on their applications for cartilage regeneration are summarized, and future research perspectives are discussed.

  16. Rotating three-dimensional dynamic culture of adult human bone marrow-derived cells for tissue engineering of hyaline cartilage.

    Science.gov (United States)

    Sakai, Shinsuke; Mishima, Hajime; Ishii, Tomoo; Akaogi, Hiroshi; Yoshioka, Tomokazu; Ohyabu, Yoshimi; Chang, Fei; Ochiai, Naoyuki; Uemura, Toshimasa

    2009-04-01

    The method of constructing cartilage tissue from bone marrow-derived cells in vitro is considered a valuable technique for hyaline cartilage regenerative medicine. Using a rotating wall vessel (RWV) bioreactor developed in a NASA space experiment, we attempted to efficiently construct hyaline cartilage tissue from human bone marrow-derived cells without using a scaffold. Bone marrow aspirates were obtained from the iliac crest of nine patients during orthopedic operation. After their proliferation in monolayer culture, the adherent cells were cultured in the RWV bioreactor with chondrogenic medium for 2 weeks. Cells from the same source were cultured in pellet culture as controls. Histological and immunohistological evaluations (collagen type I and II) and quantification of glycosaminoglycan were performed on formed tissues and compared. The engineered constructs obtained using the RWV bioreactor showed strong features of hyaline cartilage in terms of their morphology as determined by histological and immunohistological evaluations. The glycosaminoglycan contents per microg DNA of the tissues were 10.01 +/- 3.49 microg/microg DNA in the case of the RWV bioreactor and 6.27 +/- 3.41 microg/microg DNA in the case of the pellet culture, and their difference was significant. The RWV bioreactor could provide an excellent environment for three-dimensional cartilage tissue architecture that can promote the chondrogenic differentiation of adult human bone marrow-derived cells.

  17. Ultrasonography shows disappearance of monosodium urate crystal deposition on hyaline cartilage after sustained normouricemia is achieved.

    Science.gov (United States)

    Thiele, Ralf G; Schlesinger, Naomi

    2010-02-01

    This study aimed at determining whether lowering serum urate (SU) to less than 6 mg/dl in patients with gout affects ultrasonographic findings. Seven joints in five patients with monosodium urate (MSU) crystal proven gout and hyperuricemia were examined over time with serial ultrasonography. Four of the five patients were treated with urate lowering drugs (ULDs) (allopurinol, n = 3; probenecid, n = 1). One patient was treated with colchicine alone. Attention was given to changes in a hyperechoic, irregular coating of the hyaline cartilage in the examined joints (double contour sign or "urate icing"). This coating was considered to represent precipitate of MSU crystals. Index joints included metacarpophalangeal (MCP) joints (n = 2), knee joints (n = 3), and first metatarsophalangeal (MTP) joints (n = 2). The interval between baseline and follow-up images ranged from 7 to 18 months. Serial SU levels were obtained during the follow-up period. During the follow-up period, three patients treated with ULD (allopurinol, n = 2; probenecid, n = 1) achieved a SU level of or =7 mg/dl. In one patient treated with allopurinol, SU levels improved from 13 to 7 mg/dl during the follow-up period. Decrease, but not resolution of the hyperechoic coating was seen in this patient. In the patient treated with colchicine alone, SU levels remained >8 mg/dl, and no sonographic change was observed. In our patients, sonographic signs of deposition of MSU crystals on the surface of hyaline cartilage disappeared completely if sustained normouricemia was achieved. This is the first report showing that characteristic sonographic changes are influenced by ULDs once SU levels remain studies are needed to further assess these potentially important findings.

  18. A cell-free scaffold-based cartilage repair provides improved function hyaline-like repair at one year.

    Science.gov (United States)

    Siclari, Alberto; Mascaro, Gennaro; Gentili, Chiara; Cancedda, Ranieri; Boux, Eugenio

    2012-03-01

    Bone marrow stimulation techniques in cartilage repair such as drilling are limited by the formation of fibrous to hyaline-like repair tissue. It has been suggested such techniques can be enhanced by covering the defect with scaffolds. We present an innovative approach using a polyglycolic acid (PGA)-hyaluronan scaffold with platelet-rich-plasma (PRP) in drilling. We asked whether (1) PRP immersed in a cell-free PGA-hyaluronan scaffold improves patient-reported 1-year outcomes for the Knee injury and Osteoarthritis Score (KOOS), and (2) implantation of the scaffold in combination with bone marrow stimulation leads to the formation of hyaline-like cartilage repair tissue. We reviewed 52 patients who had arthroscopic implantation of the PGA-hyaluronan scaffold immersed with PRP in articular cartilage defects of the knee pretreated with Pridie drilling. Patients were assessed by KOOS. At 9 months followup, histologic staining was performed in specimens obtained from five patients to assess the repair tissue quality. The KOOS subscores improved for pain (55 to 91), symptoms (57 to 88), activities of daily living (69 to 86), sports and recreation (36 to 70), and quality of life (38 to 73). The histologic evaluation showed a homogeneous hyaline-like cartilage repair tissue. The cell-free PGA-hyaluronan scaffold combined with PRP leads to cartilage repair and improved patient-reported outcomes (KOOS) during 12 months of followup. Histologic sections showed morphologic features of hyaline-like repair tissue. Long-term followup is needed to determine if the cartilage repair tissue is durable. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

  19. A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study.

    Science.gov (United States)

    Peck, Yvonne; He, Pengfei; Chilla, Geetha Soujanya V N; Poh, Chueh Loo; Wang, Dong-An

    2015-11-09

    In this pilot study, an autologous synthetic scaffold-free construct with hyaline quality, termed living hyaline cartilaginous graft (LhCG), was applied for treating cartilage lesions. Implantation of autologous LhCG was done at load-bearing regions of the knees in skeletally mature mini-pigs for 6 months. Over the course of this study, significant radiographical improvement in LhCG treated sites was observed via magnetic resonance imaging. Furthermore, macroscopic repair was effected by LhCG at endpoint. Microscopic inspection revealed that LhCG engraftment restored cartilage thickness, promoted integration with surrounding native cartilage, produced abundant cartilage-specific matrix molecules, and re-established an intact superficial tangential zone. Importantly, the repair efficacy of LhCG was quantitatively shown to be comparable to native, unaffected cartilage in terms of biochemical composition and biomechanical properties. There were no complications related to the donor site of cartilage biopsy. Collectively, these results imply that LhCG engraftment may be a viable approach for articular cartilage repair.

  20. Gene expression profile of the cartilage tissue spontaneously regenerated in vivo by using a novel double-network gel: Comparisons with the normal articular cartilage

    Directory of Open Access Journals (Sweden)

    Kurokawa Takayuki

    2011-09-01

    Full Text Available Abstract Background We have recently found a phenomenon that spontaneous regeneration of a hyaline cartilage-like tissue can be induced in a large osteochondral defect by implanting a double-network (DN hydrogel plug, which was composed of poly-(2-Acrylamido-2-methylpropanesulfonic acid and poly-(N, N'-Dimetyl acrylamide, at the bottom of the defect. The purpose of this study was to clarify gene expression profile of the regenerated tissue in comparison with that of the normal articular cartilage. Methods We created a cylindrical osteochondral defect in the rabbit femoral grooves. Then, we implanted the DN gel plug at the bottom of the defect. At 2 and 4 weeks after surgery, the regenerated tissue was analyzed using DNA microarray and immunohistochemical examinations. Results The gene expression profiles of the regenerated tissues were macroscopically similar to the normal cartilage, but showed some minor differences. The expression degree of COL2A1, COL1A2, COL10A1, DCN, FMOD, SPARC, FLOD2, CHAD, CTGF, and COMP genes was greater in the regenerated tissue than in the normal cartilage. The top 30 genes that expressed 5 times or more in the regenerated tissue as compared with the normal cartilage included type-2 collagen, type-10 collagen, FN, vimentin, COMP, EF1alpha, TFCP2, and GAPDH genes. Conclusions The tissue regenerated by using the DN gel was genetically similar but not completely identical to articular cartilage. The genetic data shown in this study are useful for future studies to identify specific genes involved in spontaneous cartilage regeneration.

  1. Reconstruction of Hyaline Cartilage Deep Layer Properties in 3-Dimensional Cultures of Human Articular Chondrocytes.

    Science.gov (United States)

    Nanduri, Vibudha; Tattikota, Surendra Mohan; T, Avinash Raj; Sriramagiri, Vijaya Rama Rao; Kantipudi, Suma; Pande, Gopal

    2014-06-01

    Articular cartilage (AC) injuries and malformations are commonly noticed because of trauma or age-related degeneration. Many methods have been adopted for replacing or repairing the damaged tissue. Currently available AC repair methods, in several cases, fail to yield good-quality long-lasting results, perhaps because the reconstructed tissue lacks the cellular and matrix properties seen in hyaline cartilage (HC). To reconstruct HC tissue from 2-dimensional (2D) and 3-dimensional (3D) cultures of AC-derived human chondrocytes that would specifically exhibit the cellular and biochemical properties of the deep layer of HC. Descriptive laboratory study. Two-dimensional cultures of human AC-derived chondrocytes were established in classical medium (CM) and newly defined medium (NDM) and maintained for a period of 6 weeks. These cells were suspended in 2 mm-thick collagen I gels, placed in 24-well culture inserts, and further cultured up to 30 days. Properties of chondrocytes, grown in 2D cultures and the reconstructed 3D cartilage tissue, were studied by optical and scanning electron microscopic techniques, immunohistochemistry, and cartilage-specific gene expression profiling by reverse transcription polymerase chain reaction and were compared with those of the deep layer of native human AC. Two-dimensional chondrocyte cultures grown in NDM, in comparison with those grown in CM, showed more chondrocyte-specific gene activity and matrix properties. The NDM-grown chondrocytes in 3D cultures also showed better reproduction of deep layer properties of HC, as confirmed by microscopic and gene expression analysis. The method used in this study can yield cartilage tissue up to approximately 1.6 cm in diameter and 2 mm in thickness that satisfies the very low cell density and matrix composition properties present in the deep layer of normal HC. This study presents a novel and reproducible method for long-term culture of AC-derived chondrocytes and reconstruction of cartilage

  2. Calcineurin Inhibition at Physiological Osmolarity: Toward improving cartilage regeneration

    NARCIS (Netherlands)

    A.E. van der Windt (Anna)

    2017-01-01

    markdownabstractArticular hyaline cartilage is a white, smooth structure covering the ends of bones in synovial joints, like in the hip and knee. Because of its unique stiff yet flexible properties, it distributes the loads, as a consequence of weight bearing and locomotion, over the surface of the

  3. Enhanced hyaline cartilage matrix synthesis in collagen sponge scaffolds by using siRNA to stabilize chondrocytes phenotype cultured with bone morphogenetic protein-2 under hypoxia.

    Science.gov (United States)

    Legendre, Florence; Ollitrault, David; Hervieu, Magalie; Baugé, Catherine; Maneix, Laure; Goux, Didier; Chajra, Hanane; Mallein-Gerin, Frédéric; Boumediene, Karim; Galera, Philippe; Demoor, Magali

    2013-07-01

    Cartilage healing by tissue engineering is an alternative strategy to reconstitute functional tissue after trauma or age-related degeneration. However, chondrocytes, the major player in cartilage homeostasis, do not self-regenerate efficiently and lose their phenotype during osteoarthritis. This process is called dedifferentiation and also occurs during the first expansion step of autologous chondrocyte implantation (ACI). To ensure successful ACI therapy, chondrocytes must be differentiated and capable of synthesizing hyaline cartilage matrix molecules. We therefore developed a safe procedure for redifferentiating human chondrocytes by combining appropriate physicochemical factors: hypoxic conditions, collagen scaffolds, chondrogenic factors (bone morphogenetic protein-2 [BMP-2], and insulin-like growth factor I [IGF-I]) and RNA interference targeting the COL1A1 gene. Redifferentiation of dedifferentiated chondrocytes was evaluated using gene/protein analyses to identify the chondrocyte phenotypic profile. In our conditions, under BMP-2 treatment, redifferentiated and metabolically active chondrocytes synthesized a hyaline-like cartilage matrix characterized by type IIB collagen and aggrecan molecules without any sign of hypertrophy or osteogenesis. In contrast, IGF-I increased both specific and noncharacteristic markers (collagens I and X) of chondrocytes. The specific increase in COL2A1 gene expression observed in the BMP-2 treatment was shown to involve the specific enhancer region of COL2A1 that binds the trans-activators Sox9/L-Sox5/Sox6 and Sp1, which are associated with a decrease in the trans-inhibitors of COL2A1, c-Krox, and p65 subunit of NF-kappaB. Our procedure in which BMP-2 treatment under hypoxia is associated with a COL1A1 siRNA, significantly increased the differentiation index of chondrocytes, and should offer the opportunity to develop new ACI-based therapies in humans.

  4. Laser-induced activation of regeneration processes in spine disc cartilage

    Science.gov (United States)

    Sobol, Emil N.; Vorobjeva, Natalia N.; Sviridov, Alexander P.; Omelchenko, Alexander I.; Baskov, Andrey V.; Shekhter, Anatoliy B.; Baskov, Vladimir A.; Feldchtein, Felix I.; Kamensky, Vladislav A.; Kuranov, Roman V.

    2000-05-01

    The effect of laser radiation on the regeneration processes in spine disk cartilage has been studied in-vivo. We used rabbits as a model and a Holmium (2.09 micrometer) and an Erbium fiber (1.56 micrometer) lasers for irradiation the discs which were preliminary opened to remove annulus fibrosus and the nucleus pulposus of the intervertebral disc. The irradiated zone has been examined using an optical coherent tomography in one month after the operation and conventional histological technique in two months after the laser operation. It has been shown that laser radiation promotes the growth of the new cartilaginous tissue of fibrous and hyaline types.

  5. Biochemical characterisation of navicular hyaline cartilage, navicular fibrocartilage and the deep digital flexor tendon in horses with navicular disease.

    Science.gov (United States)

    Viitanen, M; Bird, J; Smith, R; Tulamo, R-M; May, S A

    2003-10-01

    The study hypothesis was that navicular disease is a process analogous to degenerative joint disease, which leads to changes in navicular fibrocartilage and in deep digital flexor tendon (DDFT) matrix composition and that the process extends to the adjacent distal interphalangeal joint. The objectives were to compare the biochemical composition of the navicular articular and palmar cartilages from 18 horses with navicular disease with 49 horses with no history of front limb lameness, and to compare navicular fibrocartilage with medial meniscus of the stifle and collateral cartilage of the hoof. Cartilage oligomeric matrix protein (COMP), deoxyribonucleic acid (DNA), total glycosaminoglycan (GAG), metalloproteinases MMP-2 and MMP-9 and water content in tissues were measured. Hyaline cartilage had the highest content of COMP and COMP content in hyaline cartilage and tendon was higher in lame horses than in sound horses (phyaline cartilage was higher in lame horses than in sound horses. The MMP-2 amounts were significantly higher in tendons compared to other tissue types. Overall, 79% of the lame horses with lesions had MMP-9 in their tendons and the amount was higher than in sound horses (phyaline and fibrocartilage as well as the DDFT with potential implications for the pathogenesis and management of the condition.

  6. Augmented cartilage regeneration by implantation of cellular versus acellular implants after bone marrow stimulation: a systematic review and meta-analysis of animal studies

    Directory of Open Access Journals (Sweden)

    Michiel W. Pot

    2017-10-01

    Full Text Available Bone marrow stimulation may be applied to regenerate focal cartilage defects, but generally results in transient clinical improvement and formation of fibrocartilage rather than hyaline cartilage. Tissue engineering and regenerative medicine strive to develop new solutions to regenerate hyaline cartilage tissue. This systematic review and meta-analysis provides a comprehensive overview of current literature and assesses the efficacy of articular cartilage regeneration by implantation of cell-laden versus cell-free biomaterials in the knee and ankle joint in animals after bone marrow stimulation. PubMed and EMBASE (via OvidSP were systematically searched using tissue engineering, cartilage and animals search strategies. Included were primary studies in which cellular and acellular biomaterials were implanted after applying bone marrow stimulation in the knee or ankle joint in healthy animals. Study characteristics were tabulated and outcome data were collected for meta-analysis for studies applying semi-quantitative histology as outcome measure (117 studies. Cartilage regeneration was expressed on an absolute 0–100% scale and random effects meta-analyses were performed. Implantation of cellular biomaterials significantly improved cartilage regeneration by 18.6% compared to acellular biomaterials. No significant differences were found between biomaterials loaded with stem cells and those loaded with somatic cells. Culture conditions of cells did not affect cartilage regeneration. Cartilage formation was reduced with adipose-derived stem cells compared to other cell types, but still improved compared to acellular scaffolds. Assessment of the risk of bias was impaired due to incomplete reporting for most studies. Implantation of cellular biomaterials improves cartilage regeneration compared to acellular biomaterials.

  7. Augmented cartilage regeneration by implantation of cellular versus acellular implants after bone marrow stimulation: a systematic review and meta-analysis of animal studies.

    Science.gov (United States)

    Pot, Michiel W; van Kuppevelt, Toin H; Gonzales, Veronica K; Buma, Pieter; IntHout, Joanna; de Vries, Rob B M; Daamen, Willeke F

    2017-01-01

    Bone marrow stimulation may be applied to regenerate focal cartilage defects, but generally results in transient clinical improvement and formation of fibrocartilage rather than hyaline cartilage. Tissue engineering and regenerative medicine strive to develop new solutions to regenerate hyaline cartilage tissue. This systematic review and meta-analysis provides a comprehensive overview of current literature and assesses the efficacy of articular cartilage regeneration by implantation of cell-laden versus cell-free biomaterials in the knee and ankle joint in animals after bone marrow stimulation. PubMed and EMBASE (via OvidSP) were systematically searched using tissue engineering, cartilage and animals search strategies. Included were primary studies in which cellular and acellular biomaterials were implanted after applying bone marrow stimulation in the knee or ankle joint in healthy animals. Study characteristics were tabulated and outcome data were collected for meta-analysis for studies applying semi-quantitative histology as outcome measure (117 studies). Cartilage regeneration was expressed on an absolute 0-100% scale and random effects meta-analyses were performed. Implantation of cellular biomaterials significantly improved cartilage regeneration by 18.6% compared to acellular biomaterials. No significant differences were found between biomaterials loaded with stem cells and those loaded with somatic cells. Culture conditions of cells did not affect cartilage regeneration. Cartilage formation was reduced with adipose-derived stem cells compared to other cell types, but still improved compared to acellular scaffolds. Assessment of the risk of bias was impaired due to incomplete reporting for most studies. Implantation of cellular biomaterials improves cartilage regeneration compared to acellular biomaterials.

  8. Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc

    OpenAIRE

    Mwale F.; Roughley P.; Antoniou J.

    2004-01-01

    Tissue engineering of intervertebral discs (IVD) using mesenchymal stem cells (MSCs) induced to differentiate into a disc-cell phenotype has been considered as an alternative treatment for disc degeneration. However, since there is no unique marker characteristic of discs and since hyaline cartilage and immature nucleus pulposus (NP) possess similar macromolecules in their extracellular matrix, it is currently difficult to recognize MSC conversion to a disc cell. This study was performed to c...

  9. In Vitro Analysis of Cartilage Regeneration Using a Collagen Type I Hydrogel (CaReS) in the Bovine Cartilage Punch Model.

    Science.gov (United States)

    Horbert, Victoria; Xin, Long; Foehr, Peter; Brinkmann, Olaf; Bungartz, Matthias; Burgkart, Rainer H; Graeve, T; Kinne, Raimund W

    2018-02-01

    Objective Limitations of matrix-assisted autologous chondrocyte implantation to regenerate functional hyaline cartilage demand a better understanding of the underlying cellular/molecular processes. Thus, the regenerative capacity of a clinically approved hydrogel collagen type I implant was tested in a standardized bovine cartilage punch model. Methods Cartilage rings (outer diameter 6 mm; inner defect diameter 2 mm) were prepared from the bovine trochlear groove. Collagen implants (± bovine chondrocytes) were placed inside the cartilage rings and cultured up to 12 weeks. Cartilage-implant constructs were analyzed by histology (hematoxylin/eosin; safranin O), immunohistology (aggrecan, collagens 1 and 2), and for protein content, RNA expression, and implant push-out force. Results Cartilage-implant constructs revealed vital morphology, preserved matrix integrity throughout culture, progressive, but slight proteoglycan loss from the "host" cartilage or its surface and decreasing proteoglycan release into the culture supernatant. In contrast, collagen 2 and 1 content of cartilage and cartilage-implant interface was approximately constant over time. Cell-free and cell-loaded implants showed (1) cell migration onto/into the implant, (2) progressive deposition of aggrecan and constant levels of collagens 1 and 2, (3) progressively increased mRNA levels for aggrecan and collagen 2, and (4) significantly augmented push-out forces over time. Cell-loaded implants displayed a significantly earlier and more long-lasting deposition of aggrecan, as well as tendentially higher push-out forces. Conclusion Preserved tissue integrity and progressively increasing cartilage differentiation and push-out forces for up to 12 weeks of cultivation suggest initial cartilage regeneration and lateral bonding of the implant in this in vitro model for cartilage replacement materials.

  10. MR imaging of hyaline cartilage in chondromalacia patellae and osteochondrosis dissecans: A comparison with CT-arthrography and arthroscopy

    International Nuclear Information System (INIS)

    Lehner, K.; Heuck, A.; Lukas, P.; Rodammer, G.; Allgayer, B.; Pasquay, E.

    1987-01-01

    Superior to spin-echo sequences, the articular hyaline cartilage was imaged with fast-field-echo sequences (FFE, Gyroscan 0.5-T, Philips) with an excitation pulse angle of 40 0 to 60 0 . Chondromalaceous lesions could be demonstrated in 30 patients with chondropathia patellae with the same sensitivity compared with CT arthrography. In a further 50 patients with osteochondrosis dissecans, discontinuities of the cartilage could be predicted using the deeply invading articular fluid as an indicator. The sensitivity of MR imaging, as controlled by arthroscopy, was very high in that respect. Separate from the nonhemorrhagic articular fluid, the cartilaginous defects could be imaged directly by variation of the FFE parameters

  11. Effect of low-dose irradiation on structural and mechanical properties of hyaline cartilage-like fibrocartilage.

    Science.gov (United States)

    Öncan, Tevfik; Demirağ, Burak; Ermutlu, Cenk; Yalçinkaya, Ulviye; Özkan, Lütfü

    2013-01-01

    The aim of this study was to analyze the effect of low-dose irradiation on fibrous cartilage and to obtain a hyaline cartilage-like fibrocartilage (HCLF) with similar structural and mechanical properties to hyaline cartilage. An osteochondral defect was created in 40 knees of 20 rabbits. At the 7th postoperative day, a single knee of each rabbit was irradiated with a total dose of 5.0 Gy in 1.0 Gy fractions for 5 days (radiotherapy group), while the other knee was not irradiated (control group). Rabbits were then divided into four groups of 5 rabbits each. The first three groups were sacrificed at the 4th, 8th and the 12th postoperative weeks and cartilage defects were macroscopically and microscopically evaluated. The remaining group of 5 rabbits was sacrificed at the 12th week and biomechanical compression tests were performed on the cartilage defects. There was no significant biomechanical difference between the radiotherapy and the control group (p=0.686). There was no significant macroscopic and microscopic difference between groups (p=0.300). Chondrocyte clustering was observed in the irradiated group. Low-dose irradiation does not affect the mechanical properties of HCLF in vivo. However, structural changes such as chondrocyte clustering were observed.

  12. Annulus Fibrosus Can Strip Hyaline Cartilage End Plate from Subchondral Bone: A Study of the Intervertebral Disk in Tension.

    Science.gov (United States)

    Balkovec, Christian; Adams, Michael A; Dolan, Patricia; McGill, Stuart M

    2015-10-01

    Study Design Biomechanical study on cadaveric spines. Objective Spinal bending causes the annulus to pull vertically (axially) on the end plate, but failure mechanisms in response to this type of loading are poorly understood. Therefore, the objective of this study was to identify the weak point of the intervertebral disk in tension. Methods Cadaveric motion segments (aged 79 to 88 years) were dissected to create midsagittal blocks of tissue, with ∼10 mm of bone superior and inferior to the disk. From these blocks, 14 bone-disk-bone slices (average 4.8 mm thick) were cut in the frontal plane. Each slice was gripped by its bony ends and stretched to failure at 1 mm/s. Mode of failure was recorded using a digital camera. Results Of the 14 slices, 10 failed by the hyaline cartilage being peeled off the subchondral bone, with the failure starting opposite the lateral annulus and proceeding medially. Two slices failed by rupturing of the trabecular bone, and a further two failed in the annulus. Conclusions The hyaline cartilage-bone junction is the disk's weak link in tension. These findings provide a plausible mechanism for the appearance of bone and cartilage fragments in herniated material. Stripping cartilage from the bony end plate would result in the herniated mass containing relatively stiff cartilage that does not easily resorb.

  13. Release of transgenic progranulin from a living hyaline cartilage graft model: An in vitro evaluation on anti-inflammation.

    Science.gov (United States)

    Lau, Ting Ting; Zhang, Feng; Tang, Wei; Wang, Dong-An

    2016-12-01

    Osteoarthritis (OA) is a prevalent condition that compromises and even jeopardizes the life quality of millions of people. Common symptoms in OA includes joint stiffness and soreness, and they are often associated with inflammations to various extend. Due to the avascular and aneural nature of articular hyaline cartilage, it has limited self-repair capabilities; especially under inflammatory conditions, damages inflicted on cartilage are often irreversible. Hence, treatment approaches focus on anti-inflammation or articular cartilage replacement. In this study, an engineered, dual-functional living hyaline cartilage graft (LhCG), capable of releasing transgenic anti-inflammatory cytokine-progranulin (PGRN) is developed and envisioned to simultaneously fulfil both requirements. The therapeutic functionality of PGRN releasing LhCG is evaluated by co-culturing the constructs with tumor necrosis factor-alpha (TNFα) secreting THP-1 cells to simulate the inflammatory condition in arthritis. Non-transgenic LhCG constructs and non-coculture sample groups were set up as controls. Gene expression and ECM composition changes across samples were assessed to understand the effects of PGRN as well as inflammatory environment on the cartilage graft. Collectively, the results in this study suggest that in situ release of transgenic recombinant PGRN protects LhCG from induced inflammation in vitro; contrastively, in the absence of PGRN, cartilage grafts are at risk of being degraded and mineralized under exposure to TNFα signaling. This shows that cartilage graft itself can be at risk of degradation or calcification when implanted in arthritic microenvironment. Hence, the inflammatory microenvironment has to be considered in cartilage replacement therapy to increase chances of successful joint mobility restoration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2968-2977, 2016. © 2016 Wiley Periodicals, Inc.

  14. Regeneration of spine disc and joint cartilages under temporal and space modulated laser radiation

    Science.gov (United States)

    Sobol, E.; Shekhter, A.; Baskov, A.; Baskov, V.; Baum, O.; Borchshenko, I.; Golubev, V.; Guller, A.; Kolyshev, I.; Omeltchenko, A.; Sviridov, A.; Zakharkina, O.

    2009-02-01

    The effect of laser radiation on the generation of hyaline cartilage in spine disc and joints has been demonstrated. The paper considers physical processes and mechanisms of laser regeneration, presents results of investigations aimed to optimize laser settings and to develop feedback control system for laser reconstruction of spine discs. Possible mechanisms of laser-induced regeneration include: (1) Space and temporary modulated laser beam induces nonhomogeneous and pulse repetitive thermal expansion and stress in the irradiated zone of cartilage. Mechanical effect due to controllable thermal expansion of the tissue and micro and nano gas bubbles formation in the course of the moderate (up to 45-50 oC) heating of the NP activate biological cells (chondrocytes) and promote cartilage regeneration. (2) Nondestructive laser radiation leads to the formation of nano and micro-pores in cartilage matrix. That promotes water permeability and increases the feeding of biological cells. Results provide the scientific and engineering basis for the novel low-invasive laser procedures to be used in orthopedics for the treatment cartilages of spine and joints. The technology and equipment for laser reconstruction of spine discs have been tested first on animals, and then in a clinical trial. Since 2001 the laser reconstruction of intervertebral discs have been performed for 340 patients with chronic symptoms of low back or neck pain who failed to improve with non-operative care. Substantial relief of back pain was obtained in 90% of patients treated who returned to their daily activities. The experiments on reparation of the defects in articular cartilage of the porcine joints under temporal and spase modulated laser radiation have shown promising results.

  15. Bioactive Scaffolds for Regeneration of Cartilage and Subchondral Bone Interface

    Science.gov (United States)

    Deng, Cuijun; Zhu, Huiying; Li, Jiayi; Feng, Chun; Yao, Qingqiang; Wang, Liming; Chang, Jiang; Wu, Chengtie

    2018-01-01

    The cartilage lesion resulting from osteoarthritis (OA) always extends into subchondral bone. It is of great importance for simultaneous regeneration of two tissues of cartilage and subchondral bone. 3D-printed Sr5(PO4)2SiO4 (SPS) bioactive ceramic scaffolds may achieve the aim of regenerating both of cartilage and subchondral bone. We hypothesized that strontium (Sr) and silicon (Si) ions released from SPS scaffolds play a crucial role in osteochondral defect reconstruction. Methods: SPS bioactive ceramic scaffolds were fabricated by a 3D-printing method. The SEM and ICPAES were used to investigate the physicochemical properties of SPS scaffolds. The proliferation and maturation of rabbit chondrocytes stimulated by SPS bioactive ceramics were measured in vitro. The stimulatory effect of SPS scaffolds for cartilage and subchondral bone regeneration was investigated in vivo. Results: SPS scaffolds significantly stimulated chondrocyte proliferation, and SPS extracts distinctly enhanced the maturation of chondrocytes and preserved chondrocytes from OA. SPS scaffolds markedly promoted the regeneration of osteochondral defects. The complex interface microstructure between cartilage and subchondral bone was obviously reconstructed. The underlying mechanism may be related to Sr and Si ions stimulating cartilage regeneration by activating HIF pathway and promoting subchondral bone reconstruction through activating Wnt pathway, as well as preserving chondrocytes from OA via inducing autophagy and inhibiting hedgehog pathway. Conclusion: Our findings suggest that SPS scaffolds can help osteochondral defect reconstruction and well reconstruct the complex interface between cartilage and subchondral bone, which represents a promising strategy for osteochondral defect regeneration. PMID:29556366

  16. Chitosan-glycerol phosphate/blood implants improve hyaline cartilage repair in ovine microfracture defects.

    Science.gov (United States)

    Hoemann, Caroline D; Hurtig, Mark; Rossomacha, Evgeny; Sun, Jun; Chevrier, Anik; Shive, Matthew S; Buschmann, Michael D

    2005-12-01

    one hour postoperatively, chitosan-glycerol phosphate/blood clots showed increased adhesion to the walls of the defects as compared with the blood clots in the untreated microfracture defects. After histological processing, all blood clots in the control microfracture defects had been lost, whereas chitosanglycerol phosphate/blood clot adhered to and was partly retained on the surfaces of the defect. At six months, defects that had been treated with chitosan-glycerol phosphate/blood were filled with significantly more hyaline repair tissue (p cartilage repair compared with microfracture alone by increasing the amount of tissue and improving its biochemical composition and cellular organization.

  17. The effect of high-energy extracorporeal shock waves on hyaline cartilage of adult rats in vivo.

    Science.gov (United States)

    Mayer-Wagner, Susanne; Ernst, Judith; Maier, Markus; Chiquet, Matthias; Joos, Helga; Müller, Peter E; Jansson, Volkmar; Sievers, Birte; Hausdorf, Jörg

    2010-08-01

    The aim of this study was to determine if extracorporeal shock wave therapy (ESWT) in vivo affects the structural integrity of articular cartilage. A single bout of ESWT (1500 shock waves of 0.5 mJ/mm(2)) was applied to femoral heads of 18 adult Sprague-Dawley rats. Two sham-treated animals served as controls. Cartilage of each femoral head was harvested at 1, 4, or 10 weeks after ESWT (n = 6 per treatment group) and scored on safranin-O-stained sections. Expression of tenascin-C and chitinase 3-like protein 1 (Chi3L1) was analyzed by immunohistochemistry. Quantitative real-time polymerase chain reaction (PCR) was used to examine collagen (II)alpha(1) (COL2A1) expression and chondrocyte morphology was investigated by transmission electron microscopy no changes in Mankin scores were observed after ESWT. Positive immunostaining for tenascin-C and Chi3L1 was found up to 10 weeks after ESWT in experimental but not in control cartilage. COL2A1 mRNA was increased in samples 1 and 4 weeks after ESWT. Alterations found on the ultrastructural level showed expansion of the rough-surfaced endoplasmatic reticulum, detachment of the cell membrane and necrotic chondrocytes. Extracorporeal shock waves caused alterations of hyaline cartilage on a molecular and ultrastructural level that were distinctly different from control. Similar changes were described before in the very early phase of osteoarthritis (OA). High-energy ESWT might therefore cause degenerative changes in hyaline cartilage as they are found in initial OA. Copyright 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  18. Production of hyaline-like cartilage by bone marrow mesenchymal stem cells in a self-assembly model.

    Science.gov (United States)

    Elder, Steven H; Cooley, Avery J; Borazjani, Ali; Sowell, Brittany L; To, Harrison; Tran, Scott C

    2009-10-01

    A scaffoldless or self-assembly approach to cartilage tissue engineering has been used to produce hyaline cartilage from bone marrow-derived mesenchymal stem cells (bMSCs), but the mechanical properties of such engineered cartilage and the effects the transforming growth factor (TGF) isoform have not been fully explored. This study employs a cell culture insert model to produce tissue-engineered cartilage using bMSCs. Neonatal pig bMSCs were isolated by plastic adherence and expanded in monolayer before being seeded into porous transwell inserts and cultured for 4 or 8 weeks in defined chondrogenic media containing either TGF-beta1 or TGF-beta3. Following biomechanical evaluation in confined compression, colorimetric dimethyl methylene blue and Sircol dye-binding assays were used to analyze glycosaminoglycan (GAG) and collagen contents, respectively. Histological sections were stained with toluidine blue for proteoglycans and with picrosirius red to reveal collagen orientation, and immunostained for detection of collagen types I and II. Neocartilage increased in thickness, collagen, and GAG content between 4 and 8 weeks. Proteoglycan concentration increased with depth from the top surface. The tissue contained much more collagen type II than type I, and there was a consistent pattern of collagen alignment. TGF-beta1-treated and TGF-beta3-treated constructs were similar at 4 weeks, but 8-week TGF-beta1 constructs had a higher aggregate modulus and GAG content compared to TGF-beta3. These results demonstrate that bMSCs can generate functional hyaline-like cartilage through a self-assembling process.

  19. Reappraisal of mesenchymal chondrosarcoma: novel morphologic observations of the hyaline cartilage and endochondral ossification and beta-catenin, Sox9, and osteocalcin immunostaining of 22 cases.

    Science.gov (United States)

    Fanburg-Smith, Julie C; Auerbach, Aaron; Marwaha, Jayson S; Wang, Zengfeng; Rushing, Elisabeth J

    2010-05-01

    Mesenchymal chondrosarcoma, a rare malignant round cell and hyaline cartilage tumor, is most commonly intraosseous but can occur in extraskeletal sites. We intensively observed the morphology and applied Sox9 (master regulator of chondrogenesis), beta-catenin (involved in bone formation, thought to inhibit chondrogenesis in a Sox9-dependent manner), and osteocalcin (a marker for osteoblastic phenotype) to 22 central nervous system and musculoskeletal mesenchymal chondrosarcoma. Cases of mesenchymal chondrosarcoma were retrieved and reviewed from our files. Immunohistochemistry and follow-up were obtained on mesenchymal chondrosarcoma and tumor controls. Twenty-two mesenchymal chondrosarcomas included 5 central nervous system (all female; mean age, 30.2; mean size, 7.8 cm; in frontal lobe [n = 4] and spinal cord [n = 1]) and 17 musculoskeletal (female-male ratio, 11:6; mean age, 31.1; mean size, 6.2 cm; 3 each of humerus and vertebrae; 2 each of pelvis, rib, tibia, neck soft tissue; one each of femur, unspecified bone, and elbow soft tissue). The hyaline cartilage in most tumors revealed a consistent linear progression of chondrocyte morphology, from resting to proliferating to hypertrophic chondrocytes. Sixty-seven percent of cases demonstrated cell death and acquired osteoblastic phenotype, cells positive for osteocalcin at the site of endochondral ossification. Small round cells of mesenchymal chondrosarcoma were negative for osteocalcin. SOX9 was positive in both components of 21 of 22 cases of mesenchymal chondrosarcoma. beta-Catenin highlighted rare nuclei at the interface between round cells and hyaline cartilage in 35% cases. Control skull and central nervous system cases were compared, including chondrosarcomas and small cell osteosarcoma, the latter positive for osteocalcin in small cells. Mesenchymal chondrosarcoma demonstrates centrally located hyaline cartilage with a linear progression of chondrocytes from resting to proliferative to hypertrophic

  20. Use of Interim Scaffolding and Neotissue Development to Produce a Scaffold-Free Living Hyaline Cartilage Graft.

    Science.gov (United States)

    Lau, Ting Ting; Leong, Wenyan; Peck, Yvonne; Su, Kai; Wang, Dong-An

    2015-01-01

    The fabrication of three-dimensional (3D) constructs relies heavily on the use of biomaterial-based scaffolds. These are required as mechanical supports as well as to translate two-dimensional cultures to 3D cultures for clinical applications. Regardless of the choice of scaffold, timely degradation of scaffolds is difficult to achieve and undegraded scaffold material can lead to interference in further tissue development or morphogenesis. In cartilage tissue engineering, hydrogel is the highly preferred scaffold material as it shares many similar characteristics with native cartilaginous matrix. Hence, we employed gelatin microspheres as porogens to create a microcavitary alginate hydrogel as an interim scaffold to facilitate initial chondrocyte 3D culture and to establish a final scaffold-free living hyaline cartilaginous graft (LhCG) for cartilage tissue engineering.

  1. [Current overview of cartilage regeneration procedures].

    Science.gov (United States)

    Schenker, H; Wild, M; Rath, B; Tingart, M; Driessen, A; Quack, V; Betsch, M

    2017-11-01

    Cartilage is an avascular, alymphatic and non-innervated tissue with limited intrinsic repair potential. The high prevalence of cartilage defects and their tremendous clinical importance are a challenge for all treating physicians. This article provides the reader with an overview about current cartilage treatment options and their clinical outcome. Microfracture is still considered the gold standard in the treatment of small cartilage lesions. Small osteochondral defects can be effectively treated with the autologous osteochondral transplantation system. Larger cartilage defects are successfully treated by autologous membrane-induced chondrogenesis (AMIC) or by membrane-assisted autologous chondrocyte implantation (MACI). Despite limitations of current cartilage repair strategies, such procedures can result in short- and mid-term clinical improvement of the patients. Further developments and clinical studies are necessary to improve the long-term outcome following cartilage repair.

  2. [Water-exchange processes in hyaline cartilage and its basic components in a normal state and in osteoarthritis].

    Science.gov (United States)

    Nikolaeva, S S; Chkhol, K Z; Bykov, V A; Roshchina, A A; Iakovleva, L V; Koroleva, O A; Omel'ianenko, N P; Rebrov, L B

    2000-01-01

    The content of different forms of tissue water was studied in the normal articular cartilage and osteoarthrosis cartilage and its structural components: collagen, potassium hyaluronate, sodium chondroitinsulphate and its complexes. In the components of cartilage matrix a few of fractions of bound water different in the strength of binding are present. At the maximal humidity, all water in collagen binds with the active groups of biopolymers and in the glycosaminoglycans, in addition to bound water, are present, two crystal forms of freezing water (free water) at least. The quantity of free water in the collagen-chondroitin sulphat membrane, is increased with the increase of chondroitin sulphate. In the collagen-hyaluronate complex, fraction of free water is found only at the low concentration of hyaluronate kalium. It was shown that in the hyalin cartilage, in different from the other connective tissue (skin, achilles tendon), the most part of water is free water and its quantity is increased in the osteoarthrosis. It is supposed that the rearrangement of binding and free-water fractions in the osteoarthrosis is the result of deficiency of hyaluronic acid and therefore this may be regarded in the improvement of methods of treatment. This scientific and methodical approach allow to receive information on the forms and binding energy of water in the biological tissues, which is absorbed from fluids and steam phase and determine characters of the pathological changes.

  3. Hyaline articular cartilage: relaxation times, pulse-sequence parameters and MR appearance at 1.5 T

    Energy Technology Data Exchange (ETDEWEB)

    Chalkias, S.M. [Dept. of Radiology, A.H.E.P.A. General Hospital of the Aristotelian Univ., Thessaloniki (Greece); Pozzi-Mucelli, R.S. [Dept. of Radiology, Univ. of Trieste (Italy); Pozzi-Mucelli, M. [Orthopaedic Clinic, Univ. of Trieste (Italy); Frezza, F. [Dept. of Radiology, Univ. of Trieste (Italy); Longo, R. [Dept. of Radiology, Univ. of Trieste (Italy)

    1994-08-01

    In order to optimize the parameters for the best visualization of the internal architecture of the hyaline articular cartilage a study both ex vivo and in vivo was performed. Accurate T1 and T2 relaxation times of articular cartilage were obtained with a particular mixed sequence and then used for the creation of isocontrast intensity graphs. These graphs subsequently allowed in all pulse sequences (spin echo, SE and gradient echo, GRE) the best combination of repetition time (TR), echo time (TE) and flip angle (FA) for optimization of signal differences between MR cartilage zones. For SE sequences maximum contrast between cartilage zones can be obtained by using a long TR (> 1,500 ms) with a short TE (< 30 ms), whereas for GRE sequences maximum contrast is obtained with the shortest TE (< 15 ms) combined with a relatively long TR (> 400 ms) and an FA greater than 40 . A trilaminar appearance was demonstrated with a superficial and deep hypointense zone in all sequences and an intermediate zone that was moderately hyperintense on SE T1-weighted images, slightly more hyperintense on proton density Rho and SE T2-weighted images and even more hyperintense on GRE images. (orig.)

  4. A comparative Study between the Structure of Cartilage Tissue Produced from Murine MSCs Differentiation and Hyaline Costal Cartilage

    OpenAIRE

    M.R. Baghban Eslaminezhad, Ph.D.;  L. Taghiyar, M.Sc; A. Piryaee, M.Sc

    2007-01-01

    Background and purpose: Vitro cartilage differentiation of mesenchymal stem cells (MSCs) has been noticed in several investigations. In this regard, almost always molecular differentiation of the cells has been examined, while structural and morphological differentiation of them has been ignored. Therefore, the present study examines the structure and ultrastructure of the cartilage differentiated from murine MSCs compared with that of costal cartilage.Materials and Methods: 2× 105 MSCs isola...

  5. Mesenchymal Stem Cells for Cartilage Regeneration of TMJ Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Dixin Cui

    2017-01-01

    Full Text Available Temporomandibular joint osteoarthritis (TMJ OA is a degenerative disease, characterized by progressive cartilage degradation, subchondral bone remodeling, synovitis, and chronic pain. Due to the limited self-healing capacity in condylar cartilage, traditional clinical treatments have limited symptom-modifying and structure-modifying effects to restore impaired cartilage as well as other TMJ tissues. In recent years, stem cell-based therapy has raised much attention as an alternative approach towards tissue repair and regeneration. Mesenchymal stem cells (MSCs, derived from the bone marrow, synovium, and even umbilical cord, play a role as seed cells for the cartilage regeneration of TMJ OA. MSCs possess multilineage differentiation potential, including chondrogenic differentiation as well as osteogenic differentiation. In addition, the trophic modulations of MSCs exert anti-inflammatory and immunomodulatory effects under aberrant conditions. Furthermore, MSCs combined with appropriate scaffolds can form cartilaginous or even osseous compartments to repair damaged tissue and impaired function of TMJ. In this review, we will briefly discuss the pathogenesis of cartilage degeneration in TMJ OA and emphasize the potential sources of MSCs and novel approaches for the cartilage regeneration of TMJ OA, particularly focusing on the MSC-based therapy and tissue engineering.

  6. Animal models used for testing hydrogels in cartilage regeneration.

    Science.gov (United States)

    Zhu, Chuntie; Wu, Qiong; Zhang, Xu; Chen, Fubo; Liu, Xiyang; Yang, Qixiang; Zhu, Lei

    2018-05-14

    Focal cartilage or osteochondral lesions can be painful and detrimental. Besides pain and limited function of joints, cartilage defect is considered as one of the leading extrinsic risk factors for osteoarthritis (OA). Thus, clinicians and scientists have paid great attention to regenerative therapeutic methods for the early treatment of cartilaginous defects. Regenerative medicine, showing great hope for regenerating cartilage tissue, rely on the combination of biodegradable scaffolds and specific biological cues, such as growth factors, adhesive factors and genetic materials. Among all biomaterials, hydrogels have emerged as promising cartilage tissue engineering scaffolds for simultaneous cell growth and drug delivery. A wide range of animal models have been applied in testing repair with hydrogels in cartilage defects. This review summarized the current animal models used to test hydrogels technologies for the regeneration of cartilage. Advantages and disadvantages in the establishment of the cartilage defect animal models among different species were emphasized, as well as feasibility of replication of diseases in animals. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Deciphering chondrocyte behaviour in matrix-induced autologous chondrocyte implantation to undergo accurate cartilage repair with hyaline matrix.

    Science.gov (United States)

    Demoor, M; Maneix, L; Ollitrault, D; Legendre, F; Duval, E; Claus, S; Mallein-Gerin, F; Moslemi, S; Boumediene, K; Galera, P

    2012-06-01

    Since the emergence in the 1990s of the autologous chondrocytes transplantation (ACT) in the treatment of cartilage defects, the technique, corresponding initially to implantation of chondrocytes, previously isolated and amplified in vitro, under a periosteal membrane, has greatly evolved. Indeed, the first generations of ACT showed their limits, with in particular the dedifferentiation of chondrocytes during the monolayer culture, inducing the synthesis of fibroblastic collagens, notably type I collagen to the detriment of type II collagen. Beyond the clinical aspect with its encouraging results, new biological substitutes must be tested to obtain a hyaline neocartilage. Therefore, the use of differentiated chondrocytes phenotypically stabilized is essential for the success of ACT at medium and long-term. That is why researchers try now to develop more reliable culture techniques, using among others, new types of biomaterials and molecules known for their chondrogenic activity, giving rise to the 4th generation of ACT. Other sources of cells, being able to follow chondrogenesis program, are also studied. The success of the cartilage regenerative medicine is based on the phenotypic status of the chondrocyte and on one of its essential component of the cartilage, type II collagen, the expression of which should be supported without induction of type I collagen. The knowledge accumulated by the scientific community and the experience of the clinicians will certainly allow to relief this technological challenge, which influence besides, the validation of such biological substitutes by the sanitary authorities. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  8. Programmed Application of Transforming Growth Factor β3 and Rac1 Inhibitor NSC23766 Committed Hyaline Cartilage Differentiation of Adipose-Derived Stem Cells for Osteochondral Defect Repair.

    Science.gov (United States)

    Zhu, Shouan; Chen, Pengfei; Wu, Yan; Xiong, Si; Sun, Heng; Xia, Qingqing; Shi, Libing; Liu, Huanhuan; Ouyang, Hong Wei

    2014-10-01

    Hyaline cartilage differentiation is always the challenge with application of stem cells for joint repair. Transforming growth factors (TGFs) and bone morphogenetic proteins can initiate cartilage differentiation but often lead to hypertrophy and calcification, related to abnormal Rac1 activity. In this study, we developed a strategy of programmed application of TGFβ3 and Rac1 inhibitor NSC23766 to commit the hyaline cartilage differentiation of adipose-derived stem cells (ADSCs) for joint cartilage repair. ADSCs were isolated and cultured in a micromass and pellet culture model to evaluate chondrogenic and hypertrophic differentiation. The function of Rac1 was investigated with constitutively active Rac1 mutant and dominant negative Rac1 mutant. The efficacy of ADSCs with programmed application of TGFβ3 and Rac1 inhibitor for cartilage repair was studied in a rat model of osteochondral defects. The results showed that TGFβ3 promoted ADSCs chondro-lineage differentiation and that NSC23766 prevented ADSC-derived chondrocytes from hypertrophy in vitro. The combination of ADSCs, TGFβ3, and NSC23766 promoted quality osteochondral defect repair in rats with much less chondrocytes hypertrophy and significantly higher International Cartilage Repair Society macroscopic and microscopic scores. The findings have illustrated that programmed application of TGFβ3 and Rac1 inhibitor NSC23766 can commit ADSCs to chondro-lineage differentiation and improve the efficacy of ADSCs for cartilage defect repair. These findings suggest a promising stem cell-based strategy for articular cartilage repair. ©AlphaMed Press.

  9. T(2) relaxation time of hyaline cartilage in presence of different gadolinium-based contrast agents.

    Science.gov (United States)

    Wiener, Edzard; Settles, Marcus; Diederichs, Gerd

    2010-01-01

    The transverse relaxation time, T(2), of native cartilage is used to quantify cartilage degradation. T(2) is frequently measured after contrast administration, assuming that the impact of gadolinium-based contrast agents on cartilage T(2) is negligible. To verify this assumption the depth-dependent variation of T(2) in the presence of gadopentetate dimeglumine, gadobenate dimeglumine and gadoteridol was investigated. Furthermore, the r(2)/r(1) relaxivity ratios were quantified in different cartilage layers to demonstrate differences between T(2) and T(1) relaxation effects. Transverse high-spatial-resolution T(1)- and T(2)-maps were simultaneously acquired on a 1.5 T MR scanner before and after contrast administration in nine bovine patellae using a turbo-mixed sequence. The r(2)/r(1) ratios were calculated for each contrast agent in cartilage. Profiles of T(1), T(2) and r(2)/r(1) across cartilage thickness were generated in the absence and presence of contrast agent. The mean values in different cartilage layers were compared for global variance using the Kruskal-Wallis test and pairwise using the Mann-Whitney U-test. T(2) of unenhanced cartilage was 98 +/- 5 ms at 1 mm and 65 +/- 4 ms at 3 mm depth. Eleven hours after contrast administration significant differences (p cartilage thickness were close to 1.0 (range 0.9-1.3). At 1.5 T, T(2) decreased significantly in the presence of contrast agents, more pronounced in superficial than in deep cartilage. The change in T(2) relaxation rate was similar to the change in T(1). Cartilage T(2) measurements after contrast administration will lead to systematic errors in the quantification of cartilage degradation. 2010 John Wiley & Sons, Ltd.

  10. MRI of the hyaline knee joint cartilage. Animal experimental and clinical studies; MRT des hyalinen Kniegelenkknorpels. Tierexperimentelle und klinische Untersuchungen

    Energy Technology Data Exchange (ETDEWEB)

    Adam, G. [Technische Hochschule Aachen (Germany). Klinik fuer Radiologische Diagnostik; Prescher, A. [Technische Hochschule Aachen (Germany). Inst. fuer Anatomie; Nolte-Ernsting, C. [Technische Hochschule Aachen (Germany). Klinik fuer Radiologische Diagnostik; Buehne, M. [Technische Hochschule Aachen (Germany). Klinik fuer Radiologische Diagnostik; Scherer, K. [Technische Hochschule Aachen (Germany). Inst. fuer Versuchstierkunde; Kuepper, W. [Technische Hochschule Aachen (Germany). Inst. fuer Versuchstierkunde; Guenther, R.W. [Technische Hochschule Aachen (Germany). Klinik fuer Radiologische Diagnostik

    1994-02-01

    The value of MR imaging for the detection of hyaline cartilage lesions using 2-D spin-echo and 3-D gradient-echo imaging was evaluated in an animal experiment in 10 dogs and in a clinical study in 30 patients. MR imaging findings were compared with histopathological and arthroscopy findings, respectively. Using MRI neither grade I nor grade II hyaline cartilage lesions were detectable. In the animal experiments 77% of grade III lesions and all the grade IV lesions were seen. However, in the clinical study only about the half of grade III and IV lesions were detected. 3-D gradient-echo MR imaging was superior to 2-D spin-echo imaging (p<0.001), while 3-D FLASH and 3-D FISP did not differ significantly in the detection rate (p<0.34). 3-D gradient-echo MR imaging seems to be the best method for the delineation of high grade cartilage lesions. However, early stages of cartilage degeneration are invisible even with this imaging modality. (orig.) [Deutsch] Die Wertigkeit der MRT in der Erfassung von Knorpellaesionen mit 2-D-Spin-Echo- und 3-D-Grafienten-Echo-Sequenzen wurde in einer tierexperimentellen Untersuchung an 10 Hunden sowie in einer klinischen Studie an 30 Patienten ueberprueft. Die kernspintomographischen Ergebnisse wurden mit dem pathologisch-anatomischen Befund bzw. der Arthroskopie verglichen. MR-tomographisch konnten weder Grad-I- noch Grad-II-Knorpellaesionen erfasst werden. Die Erkennbarkeitsrate der Grad-III- und -IV-Laesionen lag fuer die tierexperimentellen Untersuchungen bei 77 bzw. 100%, waehrend klinisch nur etwa 50% dieser Veraenderungen erkannt werden konnten. Dabei waren die 3-D-Gradienten-Echo-Sequenzen den 2-D-Spin-Echo-Sequenzen signifikant ueberlegen (p<0,001), waehrend sich die 3-D-Gradienten-Echo-Sequenzen FISP und FLASH nicht voneinander unterschieden (p<0,34). Derzeit muessen die 3-D-Gradienten-Echo-Sequenzen als die beste Methode zur Erfassung hoehergradiger Knorpellaesionen angesehen werden. Fruehe Stadien der Knorpelschaedigung sind

  11. Vascular Canals in Permanent Hyaline Cartilage: Development, Corrosion of Nonmineralized Cartilage Matrix, and Removal of Matrix Degradation Products.

    Science.gov (United States)

    Gabner, Simone; Häusler, Gabriele; Böck, Peter

    2017-06-01

    Core areas in voluminous pieces of permanent cartilage are metabolically supplied via vascular canals (VCs). We studied cartilage corrosion and removal of matrix degradation products during the development of VCs in nose and rib cartilage of piglets. Conventional staining methods were used for glycosaminoglycans, immunohistochemistry was performed to demonstrate collagens types I and II, laminin, Ki-67, von Willebrand factor, VEGF, macrophage marker MAC387, S-100 protein, MMPs -2,-9,-13,-14, and their inhibitors TIMP1 and TIMP2. VCs derived from connective tissue buds that bulged into cartilage matrix ("perichondrial papillae", PPs). Matrix was corroded at the tips of PPs or resulting VCs. Connective tissue stromata in PPs and VCs comprised an axial afferent blood vessel, peripherally located wide capillaries, fibroblasts, newly synthesized matrix, and residues of corroded cartilage matrix (collagen type II, acidic proteoglycans). Multinucleated chondroclasts were absent, and monocytes/macrophages were not seen outside the blood vessels. Vanishing acidity characterized areas of extracellular matrix degradation ("preresorptive layers"), from where the dismantled matrix components diffused out. Leached-out material stained in an identical manner to intact cartilage matrix. It was detected in the stroma and inside capillaries and associated downstream veins. We conclude that the delicate VCs are excavated by endothelial sprouts and fibroblasts, whilst chondroclasts are specialized to remove high volumes of mineralized cartilage. VCs leading into permanent cartilage can be formed by corrosion or inclusion, but most VCs comprise segments that have developed in either of these ways. Anat Rec, 300:1067-1082, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. LASER APPLICATIONS AND OTHER TOPICS IN QUANTUM ELECTRONICS: Change in the optical properties of hyaline cartilage heated by the near-IR laser radiation

    Science.gov (United States)

    Bagratashvili, Viktor N.; Bagratashvili, N. V.; Gapontsev, V. P.; Makhmutova, G. Sh; Minaev, V. P.; Omel'chenko, A. I.; Samartsev, I. E.; Sviridov, A. P.; Sobol', E. N.; Tsypina, S. I.

    2001-06-01

    The in vitro dynamics of the change in optical properties of hyaline cartilage heated by fibre lasers at wavelengths 0.97 and 1.56 μm is studied. The laser-induced bleaching (at 1.56 μm) and darkening (at 0.97 μm) of the cartilage, caused by the heating and transport of water as well as by a change in the cartilage matrix, were observed and studied. These effects should be taken into account while estimating the depth of heating of the tissue. The investigated dynamics of light scattering in the cartilage allows one to choose the optimum radiation dose for laser plastic surgery of cartilage tissues.

  13. Optical methods for diagnostics and feedback control in laser-induced regeneration of spine disc and joint cartilages

    Science.gov (United States)

    Sobol, Emil; Sviridov, Alexander; Omeltchenko, Alexander; Baum, Olga; Baskov, Andrey; Borchshenko, Igor; Golubev, Vladimir; Baskov, Vladimir

    2011-03-01

    In 1999 we have introduced a new approach for treatment of spine diseases based on the mechanical effect of nondestructive laser radiation on the nucleus pulposus of the intervertebral disc. Laser reconstruction of spine discs (LRD) involves puncture of the disc and non-destructive laser irradiation of the nucleus pulposus to activate reparative processes in the disc tissues. In vivo animal study has shown that LRD allows activate the growth of hyaline type cartilage in laser affected zone. The paper considers physical processes and mechanisms of laser regeneration, presents results of investigations aimed to optimize laser settings and to develop feedback control system for laser reparation in cartilages of spine and joints. The results of laser reconstruction of intervertebral discs for 510 patients have shown substantial relief of back pain for 90% of patients. Laser technology has been experimentally tested for reparation of traumatic and degenerative diseases in joint cartilage of 20 minipigs. It is shown that laser regeneration of cartilage allows feeling large (more than 5 mm) defects which usually never repair on one's own. Optical techniques have been used to promote safety and efficacy of the laser procedures.

  14. The properties of bioengineered chondrocyte sheets for cartilage regeneration

    Directory of Open Access Journals (Sweden)

    Ota Naoshi

    2009-03-01

    Full Text Available Abstract Background Although the clinical results of autologous chondrocyte implantation for articular cartilage defects have recently improved as a result of advanced techniques based on tissue engineering procedures, problems with cell handling and scaffold imperfections remain to be solved. A new cell-sheet technique has been developed, and is potentially able to overcome these obstacles. Chondrocyte sheets applicable to cartilage regeneration can be prepared with this cell-sheet technique using temperature-responsive culture dishes. However, for clinical application, it is necessary to evaluate the characteristics of the cells in these sheets and to identify their similarities to naive cartilage. Results The expression of SOX 9, collagen type 2, 27, integrin α10, and fibronectin genes in triple-layered chondrocyte sheets was significantly increased in comparison to those in conventional monolayer culture and in a single chondrocyte sheet, implying a nature similar to ordinary cartilage. In addition, immunohistochemistry demonstrated that collagen type II, fibronectin, and integrin α10 were present in the triple-layered chondrocyte sheets. Conclusion The results of this study indicate that these chondrocyte sheets with a consistent cartilaginous phenotype and adhesive properties may lead to a new strategy for cartilage regeneration.

  15. INJURED ARTICULAR CARTILAGE REPAIR

    Directory of Open Access Journals (Sweden)

    Ariana Barlič

    2008-02-01

    Surveys show that the most frequently used surgical methods are mosaicplasty and bonemarrow stimulation with microfracturing. The efficacy of the autologous chondrocyte implantationmethod should be superior to microfracturing on a long run. Especially when(regeneration of the hyaline cartilage instead of fibrous tissue (fibrocartilage is concerned.However, it has not been scientifically proved yet

  16. Talocalcaneal Joint Middle Facet Coalition Resection With Interposition of a Juvenile Hyaline Cartilage Graft.

    Science.gov (United States)

    Tower, Dyane E; Wood, Ryan W; Vaardahl, Michael D

    2015-01-01

    Talocalcaneal joint middle facet coalition is the most common tarsal coalition, occurring in ≤2% of the population. Fewer than 50% of involved feet obtain lasting relief of symptoms after nonoperative treatment, and surgical intervention is commonly used to relieve symptoms, increase the range of motion, improve function, reconstruct concomitant pes planovalgus, and prevent future arthrosis from occurring at the surrounding joints. Several approaches to surgical intervention are available for patients with middle facet coalitions, ranging from resection to hindfoot arthrodesis. We present a series of 4 cases, in 3 adolescent patients, of talocalcaneal joint middle facet coalition resection with interposition of a particulate juvenile hyaline cartilaginous allograft (DeNovo(®) NT Natural Tissue Graft, Zimmer, Inc., Warsaw, IN). With a mean follow-up period of 42.8 ± 2.9 (range 41 to 47) months, the 3 adolescent patients in the present series were doing well with improved subtalar joint motion and decreased pain, and 1 foot showed no bony regrowth on a follow-up computed tomography scan. The use of a particulate juvenile hyaline cartilaginous allograft as interposition material after talocalcaneal middle facet coalition resection combined with adjunct procedures to address concomitant pes planovalgus resulted in good short-term outcomes in 4 feet in 3 adolescent patients. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  17. In-vivo study and histological examination of laser reshaping of cartilage

    Science.gov (United States)

    Sviridov, Alexander P.; Sobol, Emil N.; Bagratashvili, Victor N.; Omelchenko, Alexander I.; Ovchinnikov, Yuriy M.; Shekhter, Anatoliy B.; Svistushkin, Valeriy M.; Shinaev, Andrei A.; Nikiforova, G.; Jones, Nicholas

    1999-06-01

    The results of recent study of cartilage reshaping in vivo are reported. The ear cartilage of piglets of 8-12 weeks old have been reshaped in vivo using the radiation of a holmium laser. The stability of the shape and possible side effects have been examined during four months. Histological investigation shown that the healing of irradiated are could accompany by the regeneration of ear cartilage. Finally, elastic type cartilage has been transformed into fibrous cartilage or cartilage of hyaline type.

  18. Species-Independent Modeling of High-Frequency Ultrasound Backscatter in Hyaline Cartilage.

    Science.gov (United States)

    Männicke, Nils; Schöne, Martin; Liukkonen, Jukka; Fachet, Dominik; Inkinen, Satu; Malo, Markus K; Oelze, Michael L; Töyräs, Juha; Jurvelin, Jukka S; Raum, Kay

    2016-06-01

    Apparent integrated backscatter (AIB) is a common ultrasound parameter used to assess cartilage matrix degeneration. However, the specific contributions of chondrocytes, proteoglycan and collagen to AIB remain unknown. To reveal these relationships, this work examined biopsies and cross sections of human, ovine and bovine cartilage with 40-MHz ultrasound biomicroscopy. Site-matched estimates of collagen concentration, proteoglycan concentration, collagen orientation and cell number density were employed in quasi-least-squares linear regression analyses to model AIB. A positive correlation (R(2) = 0.51, p 70°) to the sound beam direction. These findings indicate causal relationships between AIB and cartilage structural parameters and could aid in more sophisticated future interpretations of ultrasound backscatter. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  19. Animal experimental research on microstructural behavior on the hyaline arthroidal cartilage after immobilization and remobilization

    Science.gov (United States)

    Refior, H. J.

    1980-01-01

    The degeneration of the articular cartilage after a period of immobilization was investigated. The experiment was carried out by the immobilization of the knee joints of rabbits. Even after remobilization there was an increase in the alterations. These changes did not prove to be reversible.

  20. [Histologic assessment of tissue healing of hyaline cartilage by use of semiquantitative evaluation scale].

    Science.gov (United States)

    Vukasović, Andreja; Ivković, Alan; Jezek, Davor; Cerovecki, Ivan; Vnuk, Drazen; Kreszinger, Mario; Hudetz, Damir; Pećina, Marko

    2011-01-01

    Articular cartilage is an avascular and aneural tissue lacking lymph drainage, hence its inability of spontaneous repair following injury. Thus, it offers an interesting model for scientific research. A number of methods have been suggested to enhance cartilage repair, but none has yet produced significant success. The possible application of the aforementioned methods has brought about the necessity to evaluate their results. The objective of this study was to analyze results of a study of the effects of the use of TGF-beta gene transduced bone marrow clot on articular cartilage defects using ICRS visual histological assessment scale. The research was conducted on 28 skeletally mature sheep that were randomly assigned to four groups and surgically inflicted femoral chondral defects. The articular surfaces were then treated with TGF-beta1 gene transduced bone marrow clot (TGF group), GFP transduced bone marrow clot (GFP group), untransduced bone marrow clot (BM group) or left untreated (NC group). The analysis was performed by visual examination of cartilage samples and results were obtained using ICRS visual histological assessment scale. The results were subsequently subjected to statistical assessment using Kruskal-Wallis and Mann-Whitney tests. Kruskal-Wallis test yielded statistically significant difference with respect to cell distribution. Mann-Whitney test showed statistically significant difference between TGF and NC groups (P = 0.002), as well as between BM and NC groups (P = 0.002 with Bonferroni correction). Twenty-six of the twenty-eight samples were subjected to histologic and subsequent statistical analysis; two were discarded due to faulty histology technique. Our results indicated a level of certainty as to the positive effect of TGF-beta1 gene transduced bone marrow clot in restoration of articular cartilage defects. However, additional research is necessary in the field. One of the significant drawbacks on histologic assessment of cartilage

  1. Assessment of apoptosis and MMP-1, MMP-3 and TIMP-2 expression in tibial hyaline cartilage after viable medial meniscus transplantation in the rabbit.

    Science.gov (United States)

    Zwierzchowski, Tomasz J; Stasikowska-Kanicka, Olga; Danilewicz, Marian; Fabiś, Jarosław

    2012-12-20

    The porpuse of this animal study was to assess chondrocyte apoptosis and MMP-1, MMP-3 and TIMP-2 expression in rabbit tibial cartilage 6 months after viable medial meniscal autografts and allografts. Twenty white male New Zealand rabbits were chosen for the study. The medial meniscus was excised from 14 animals and stored under tissue culture conditions for 2 weeks, following which t of them were implantated as autografts and 7 as allografts. The control group consisted of 6 animals which underwent arthtrotomy. When the animals were eutanized, the tibial cartilage was used for immunohisochemical examination. Apoptosis (TUNEL method) and MMP-1, MMP-3 and TIMP-2 expression were estimated semiquantatively. An increased level of chodrocyte apoptosis in the tibail cartilage was observed after both kinds of transplants (p hyaline cartilage against excessive apoptosis. The results of experimantal studies on humans indicate the need to device a method of apoptosis inhibition in the hyaline cartilage to improve long-term results of meniscal transplantation.

  2. Quantitative Assessment of Hyaline Cartilage Elasticity During Optical Clearing Using Optical Coherence Elastography

    OpenAIRE

    Chih-Hao Liu; Manmohan Singh; Jiasong Li; Zhaolong Han; Chen Wu; Shang Wang; Rita Idugboe; Raksha Raghunathan; Emil N. Sobol; Valery V. Tuchin; Michael Twa; Kirill V. Larin

    2015-01-01

    Tissue optical clearing is an emerging technique for dynamically modifying tissue optical properties to increase imaging depth, which is useful in applications such as imaging and functional diagnostics of many diseases. For example, optical clearing of cartilage allowed imaging of subchondral bone that is used to assess orthopedic diseases. However, the effect of the clearing processes on tissue elastic properties has not been investigated yet. In this study we report the first use of phase-...

  3. Effects of microcurrent stimulation on Hyaline cartilage repair in immature male rats (Rattus norvegicus

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    de Campos Ciccone Carla

    2013-01-01

    Full Text Available Abstract Background In this study, we investigate the effects of microcurrent stimulation on the repair process of xiphoid cartilage in 45-days-old rats. Methods Twenty male rats were divided into a control group and a treated group. A 3-mm defect was then created with a punch in anesthetized animals. In the treated group, animals were submitted to daily applications of a biphasic square pulse microgalvanic continuous electrical current during 5 min. In each application, it was used a frequency of 0.3 Hz and intensity of 20 μA. The animals were sacrificed at 7, 21 and 35 days after injury for structural analysis. Results Basophilia increased gradually in control animals during the experimental period. In treated animals, newly formed cartilage was observed on days 21 and 35. No statistically significant differences in birefringent collagen fibers were seen between groups at any of the time points. Treated animals presented a statistically larger number of chondroblasts. Calcification points were observed in treated animals on day 35. Ultrastructural analysis revealed differences in cell and matrix characteristics between the two groups. Chondrocyte-like cells were seen in control animals only after 35 days, whereas they were present in treated animals as early as by day 21. The number of cuprolinic blue-stained proteoglycans was statistically higher in treated animals on days 21 and 35. Conclusion We conclude that microcurrent stimulation accelerates the cartilage repair in non-articular site from prepuberal animals.

  4. Effects of microcurrent stimulation on hyaline cartilage repair in immature male rats (Rattus norvegicus).

    Science.gov (United States)

    de Campos Ciccone, Carla; Zuzzi, Denise Cristina; Neves, Lia Mara Grosso; Mendonça, Josué Sampaio; Joazeiro, Paulo Pinto; Esquisatto, Marcelo Augusto Marretto

    2013-01-19

    In this study, we investigate the effects of microcurrent stimulation on the repair process of xiphoid cartilage in 45-days-old rats. Twenty male rats were divided into a control group and a treated group. A 3-mm defect was then created with a punch in anesthetized animals. In the treated group, animals were submitted to daily applications of a biphasic square pulse microgalvanic continuous electrical current during 5 min. In each application, it was used a frequency of 0.3 Hz and intensity of 20 μA. The animals were sacrificed at 7, 21 and 35 days after injury for structural analysis. Basophilia increased gradually in control animals during the experimental period. In treated animals, newly formed cartilage was observed on days 21 and 35. No statistically significant differences in birefringent collagen fibers were seen between groups at any of the time points. Treated animals presented a statistically larger number of chondroblasts. Calcification points were observed in treated animals on day 35. Ultrastructural analysis revealed differences in cell and matrix characteristics between the two groups. Chondrocyte-like cells were seen in control animals only after 35 days, whereas they were present in treated animals as early as by day 21. The number of cuprolinic blue-stained proteoglycans was statistically higher in treated animals on days 21 and 35. We conclude that microcurrent stimulation accelerates the cartilage repair in non-articular site from prepuberal animals.

  5. Hyaline cartilage calcification of the first metatarsophalangeal joint is associated with osteoarthritis but independent of age and BMI.

    Science.gov (United States)

    Hubert, Jan; Hawellek, Thelonius; Hischke, Sandra; Bertrand, Jessica; Krause, Matthias; Püschel, Klaus; Rüther, Wolfgang; Niemeier, Andreas

    2016-11-15

    Hyaline cartilage calcification (CC) is associated with osteoarthritis (OA) in hip and knee joints. The first metatarsophalangeal joint (1 st MTPJ) is frequently affected by OA, but it is unclear if CC occurs in the 1 st MTPJ. The aim of the present study was to analyze the prevalence of CC of the 1 st MTPJ in the general population by high-resolution digital contact radiography (DCR) and to determine its association with histological OA severity, age and body mass index (BMI). 168 metatarsal heads of 84 donors (n = 47 male, n = 37 female; mean age 62.73 years, SD ±18.8, range 20-93) were analyzed by DCR for the presence of CC. Histological OA grade (hOA) by OARSI was analyzed in the central load-bearing zone of the first metatarsal head (1 st MH). Structural equation modeling (SEM) was performed to analyze the interrelationship between CC, hOA, age and BMI. The prevalence of CC of 1 st MH was 48.8 % (41/84) (95 %-CI [37.7 %, 60.0 %]), independent of the affected side (p = 0.42), gender (p = 0.41) and BMI (p = 0.51). The mean amount of CC of one MH correlated significantly with that of the contralateral side (r s  = 0.4, 95 %-CI [0.26, 0.52], p cartilage area) of the MH correlated significantly with the severity of hOA (r s  = 0.51, 95 %-CI [0.32, 0.65], p studies.

  6. Osteochondral lesions in distal tarsal joints of Icelandic horses reveal strong associations between hyaline and calcified cartilage abnormalities

    Directory of Open Access Journals (Sweden)

    CJ Ley

    2014-03-01

    Full Text Available Osteochondral lesions in the joints of the distal tarsal region of young Icelandic horses provide a natural model for the early stages of osteoarthritis (OA in low-motion joints. We describe and characterise mineralised and non-mineralised osteochondral lesions in left distal tarsal region joint specimens from twenty-two 30 ±1 month-old Icelandic horses. Combinations of confocal scanning light microscopy, backscattered electron scanning electron microscopy (including, importantly, iodine staining and three-dimensional microcomputed tomography were used on specimens obtained with guidance from clinical imaging. Lesion-types were described and classified into groups according to morphological features. Their locations in the hyaline articular cartilage (HAC, articular calcified cartilage (ACC, subchondral bone (SCB and the joint margin tissues were identified and their frequency in the joints recorded. Associations and correlations between lesion-types were investigated for centrodistal joints only. In centrodistal joints the lesion-types HAC chondrocyte loss, HAC fibrillation, HAC central chondrocyte clusters, ACC arrest and ACC advance had significant associations and strong correlations. These lesion-types had moderate to high frequency in centrodistal joints but low frequencies in tarsometatarsal and talocalcaneal-centroquartal joints. Joint margin lesion-types had no significant associations with other lesion-types in the centrodistal joints but high frequency in both the centrodistal and tarsometatarsal joints. The frequency of SCB lesion-types in all joints was low. Hypermineralised infill phase lesion-types were detected. Our results emphasise close associations between HAC and ACC lesions in equine centrodistal joints and the importance of ACC lesions in the development of OA in low-motion compression-loaded equine joints.

  7. Osteochondral lesions in distal tarsal joints of Icelandic horses reveal strong associations between hyaline and calcified cartilage abnormalities.

    Science.gov (United States)

    Ley, C J; Ekman, S; Hansson, K; Björnsdóttir, S; Boyde, A

    2014-03-25

    Osteochondral lesions in the joints of the distal tarsal region of young Icelandic horses provide a natural model for the early stages of osteoarthritis (OA) in low-motion joints. We describe and characterise mineralised and non-mineralised osteochondral lesions in left distal tarsal region joint specimens from twenty-two 30 ±1 month-old Icelandic horses. Combinations of confocal scanning light microscopy, backscattered electron scanning electron microscopy (including, importantly, iodine staining) and three-dimensional microcomputed tomography were used on specimens obtained with guidance from clinical imaging. Lesion-types were described and classified into groups according to morphological features. Their locations in the hyaline articular cartilage (HAC), articular calcified cartilage (ACC), subchondral bone (SCB) and the joint margin tissues were identified and their frequency in the joints recorded. Associations and correlations between lesion-types were investigated for centrodistal joints only. In centrodistal joints the lesion-types HAC chondrocyte loss, HAC fibrillation, HAC central chondrocyte clusters, ACC arrest and ACC advance had significant associations and strong correlations. These lesion-types had moderate to high frequency in centrodistal joints but low frequencies in tarsometatarsal and talocalcaneal-centroquartal joints. Joint margin lesion-types had no significant associations with other lesion-types in the centrodistal joints but high frequency in both the centrodistal and tarsometatarsal joints. The frequency of SCB lesion-types in all joints was low. Hypermineralised infill phase lesion-types were detected. Our results emphasise close associations between HAC and ACC lesions in equine centrodistal joints and the importance of ACC lesions in the development of OA in low-motion compression-loaded equine joints.

  8. A transduced living hyaline cartilage graft releasing transgenic stromal cell-derived factor-1 inducing endogenous stem cell homing in vivo.

    Science.gov (United States)

    Zhang, Feng; Leong, Wenyan; Su, Kai; Fang, Yu; Wang, Dong-An

    2013-05-01

    Stromal cell-derived factor-1 (SDF-1), also known as a homing factor, is a potent chemokine that activates and directs mobilization, migration, and retention of certain cell species via systemic circulation. The responding homing cells largely consist of activated stem cells, so that, in case of tissue lesions, such SDF-1-induced cell migration may execute recruitment of endogenous stem cells to perform autoreparation and compensatory regeneration in situ. In this study, a recombinant adenoviral vector carrying SDF-1 transgene was constructed and applied to transduce a novel scaffold-free living hyaline cartilage graft (SDF-t-LhCG). As an engineered transgenic living tissue, SDF-t-LhCG is capable of continuously producing and releasing SDF-1 in vitro and in vivo. The in vitro trials were examined with ELISA, while the in vivo trials were subsequently performed via a subcutaneous implantation of SDF-t-LhCG in a nude mouse model, followed by series of biochemical and biological analyses. The results indicate that transgenic SDF-1 enhanced the presence of this chemokine in mouse's circulation system; in consequence, SDF-1-induced activation and recruitment of endogenous stem cells were also augmented in both peripheral blood and SDF-t-LhCG implant per se. These results were obtained via flow cytometry analyses on mouse blood samples and implanted SDF-t-LhCG samples, indicating an upregulation of the CXCR4(+)(SDF-1 receptor) cell population, accompanied by upregulation of the CD34(+), CD44(+), and Sca-1(+) cell populations as well as a downregulation of the CD11b(+) cell population. With the supply of SDF-1-recruited endogenous stem cells, enhanced chondrogenesis was observed in SDF-t-LhCG implants in situ.

  9. A tissue regeneration approach to bone and cartilage repair

    CERN Document Server

    Dunstan, Colin; Rosen, Vicki

    2015-01-01

    Reviewing exhaustively the current state of the art of tissue engineering strategies for regenerating bones and joints through the use of biomaterials, growth factors and stem cells, along with an investigation of the interactions between biomaterials, bone cells, growth factors and added stem cells and how together skeletal tissues can be optimised, this book serves to highlight the importance of biomaterials composition, surface topography, architectural and mechanical properties in providing support for tissue regeneration. Maximizing reader insights into the importance of the interplay of these attributes with bone cells (osteoblasts, osteocytes and osteoclasts) and cartilage cells (chondrocytes), this book also provides a detailed reference as to how key signalling pathways are activated. The contribution of growth factors to drive tissue regeneration and stem cell recruitment is discussed along with a review the potential and challenges of adult or embryonic mesenchymal stem cells to further enhance the...

  10. Cartilage regeneration for treatment of osteoarthritis: a paradigm for nonsurgical intervention

    OpenAIRE

    Tiku, Moti L.; Sabaawy, Hatem E.

    2015-01-01

    Osteoarthritis (OA) is associated with articular cartilage abnormalities and affects people of older age: preventative or therapeutic treatment measures for OA and related articular cartilage disorders remain challenging. In this perspective review, we have integrated multiple biological, morphological, developmental, stem cell and homeostasis concepts of articular cartilage to develop a paradigm for cartilage regeneration. OA is conceptually defined as an injury of cartilage that initiates c...

  11. The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

    OpenAIRE

    Goldberg, A.; Mitchell, K.; Soans, J.; Kim, L.; Zaidi, R.

    2017-01-01

    BACKGROUND: The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue ...

  12. The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

    OpenAIRE

    Goldberg, Andy; Mitchell, Katrina; Soans, Julian; Kim, Louise; Zaidi, Razi

    2017-01-01

    Background The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue e...

  13. Hydrogels for Cartilage Regeneration, from Polysaccharides to Hybrids

    Directory of Open Access Journals (Sweden)

    Daniela Anahí Sánchez-Téllez

    2017-12-01

    Full Text Available The aims of this paper are: (1 to review the current state of the art in the field of cartilage substitution and regeneration; (2 to examine the patented biomaterials being used in preclinical and clinical stages; (3 to explore the potential of polymeric hydrogels for these applications and the reasons that hinder their clinical success. The studies about hydrogels used as potential biomaterials selected for this review are divided into the two major trends in tissue engineering: (1 the use of cell-free biomaterials; and (2 the use of cell seeded biomaterials. Preparation techniques and resulting hydrogel properties are also reviewed. More recent proposals, based on the combination of different polymers and the hybridization process to improve the properties of these materials, are also reviewed. The combination of elements such as scaffolds (cellular solids, matrices (hydrogel-based, growth factors and mechanical stimuli is needed to optimize properties of the required materials in order to facilitate tissue formation, cartilage regeneration and final clinical application. Polymer combinations and hybrids are the most promising materials for this application. Hybrid scaffolds may maximize cell growth and local tissue integration by forming cartilage-like tissue with biomimetic features.

  14. MR imaging of hyaline cartilage at 0.5 T: a quantitative and qualitative in vitro evaluation of three types of sequences

    International Nuclear Information System (INIS)

    Linden, E. van der; Kroon, H.M.; Doornbos, J.; Bloem, J.L.; Hermans, J.

    1998-01-01

    Objective. To identify an optimal pulse sequence for in vitro imaging of hyaline cartilage at 0.5 T. Materials and methods. Twelve holes of varying diameter and depth were drilled in cartilage of two pig knees. These were submerged in saline and scanned with a 0.5-T MR system. Sixteen T1-weighted gradient echo (GE), two T2-weighted GE, and 16 fast spin echo sequences were used, by varying repetition time (TR), echo time (TE), flip angle (FA), echo train length, profile order, and by use of fat saturation. Contrast-to-noise ratios (CNR) of cartilage versus saline solution and cartilage versus subchondral bone were measured. Cartilaginous lesions were evaluated separately by three independent observers. Interobserver variability and correlation between the quantitative and qualitative analyses were calculated. Results. The mean CNRs of two specimens of cartilage versus saline solution ranged from 6.3 (±2.1) to 27.7 (±2.5), and those of cartilage versus subchondral bone from 0.3 (±0.2) to 22.5 (±1.4). The highest CNR was obtained with a T1-weighted spoiled 3D-GE technique (TR 65 ms, TE 11.5 ms, FA 45 ). The number of lesions observed per sequence varied from 35 to 69. Observer agreement was fair to good. The T1-weighted spoiled GE sequences with a TR of 65 ms, TE of 11.5 ms and FA of 30 and 45 were significantly superior to the other 34 sequences in the qualitative analysis. Conclusion. T1-weighted spoiled 3D-GE sequences with a TR of 65 ms, a TE of 11.5 ms, and a FA of 30-45 were found to be optimal for in vitro imaging of cartilage at 0.5 T. (orig.)

  15. MR imaging of hyaline cartilage at 0.5 T: a quantitative and qualitative in vitro evaluation of three types of sequences

    Energy Technology Data Exchange (ETDEWEB)

    Linden, E. van der; Kroon, H.M.; Doornbos, J.; Bloem, J.L. [Department of Radiology C2-S, Albinusdreef 2, Leiden University Medical Center, Postbus 9600, NL-2300 RC Leiden (Netherlands); Hermans, J. [Department of Medical Statistics, Leiden University Medical Center, Leiden (Netherlands)

    1998-06-01

    Objective. To identify an optimal pulse sequence for in vitro imaging of hyaline cartilage at 0.5 T. Materials and methods. Twelve holes of varying diameter and depth were drilled in cartilage of two pig knees. These were submerged in saline and scanned with a 0.5-T MR system. Sixteen T1-weighted gradient echo (GE), two T2-weighted GE, and 16 fast spin echo sequences were used, by varying repetition time (TR), echo time (TE), flip angle (FA), echo train length, profile order, and by use of fat saturation. Contrast-to-noise ratios (CNR) of cartilage versus saline solution and cartilage versus subchondral bone were measured. Cartilaginous lesions were evaluated separately by three independent observers. Interobserver variability and correlation between the quantitative and qualitative analyses were calculated. Results. The mean CNRs of two specimens of cartilage versus saline solution ranged from 6.3 ({+-}2.1) to 27.7 ({+-}2.5), and those of cartilage versus subchondral bone from 0.3 ({+-}0.2) to 22.5 ({+-}1.4). The highest CNR was obtained with a T1-weighted spoiled 3D-GE technique (TR 65 ms, TE 11.5 ms, FA 45 ). The number of lesions observed per sequence varied from 35 to 69. Observer agreement was fair to good. The T1-weighted spoiled GE sequences with a TR of 65 ms, TE of 11.5 ms and FA of 30 and 45 were significantly superior to the other 34 sequences in the qualitative analysis. Conclusion. T1-weighted spoiled 3D-GE sequences with a TR of 65 ms, a TE of 11.5 ms, and a FA of 30-45 were found to be optimal for in vitro imaging of cartilage at 0.5 T. (orig.) With 8 figs., 1 tab., 31 refs.

  16. Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies

    Directory of Open Access Journals (Sweden)

    Michiel W. Pot

    2016-09-01

    Full Text Available Microfracture surgery may be applied to treat cartilage defects. During the procedure the subchondral bone is penetrated, allowing bone marrow-derived mesenchymal stem cells to migrate towards the defect site and form new cartilage tissue. Microfracture surgery generally results in the formation of mechanically inferior fibrocartilage. As a result, this technique offers only temporary clinical improvement. Tissue engineering and regenerative medicine may improve the outcome of microfracture surgery. Filling the subchondral defect with a biomaterial may provide a template for the formation of new hyaline cartilage tissue. In this study, a systematic review and meta-analysis were performed to assess the current evidence for the efficacy of cartilage regeneration in preclinical models using acellular biomaterials implanted after marrow stimulating techniques (microfracturing and subchondral drilling compared to the natural healing response of defects. The review aims to provide new insights into the most effective biomaterials, to provide an overview of currently existing knowledge, and to identify potential lacunae in current studies to direct future research. A comprehensive search was systematically performed in PubMed and EMBASE (via OvidSP using search terms related to tissue engineering, cartilage and animals. Primary studies in which acellular biomaterials were implanted in osteochondral defects in the knee or ankle joint in healthy animals were included and study characteristics tabulated (283 studies out of 6,688 studies found. For studies comparing non-treated empty defects to defects containing implanted biomaterials and using semi-quantitative histology as outcome measure, the risk of bias (135 studies was assessed and outcome data were collected for meta-analysis (151 studies. Random-effects meta-analyses were performed, using cartilage regeneration as outcome measure on an absolute 0–100% scale. Implantation of acellular

  17. Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies.

    Science.gov (United States)

    Pot, Michiel W; Gonzales, Veronica K; Buma, Pieter; IntHout, Joanna; van Kuppevelt, Toin H; de Vries, Rob B M; Daamen, Willeke F

    2016-01-01

    Microfracture surgery may be applied to treat cartilage defects. During the procedure the subchondral bone is penetrated, allowing bone marrow-derived mesenchymal stem cells to migrate towards the defect site and form new cartilage tissue. Microfracture surgery generally results in the formation of mechanically inferior fibrocartilage. As a result, this technique offers only temporary clinical improvement. Tissue engineering and regenerative medicine may improve the outcome of microfracture surgery. Filling the subchondral defect with a biomaterial may provide a template for the formation of new hyaline cartilage tissue. In this study, a systematic review and meta-analysis were performed to assess the current evidence for the efficacy of cartilage regeneration in preclinical models using acellular biomaterials implanted after marrow stimulating techniques (microfracturing and subchondral drilling) compared to the natural healing response of defects. The review aims to provide new insights into the most effective biomaterials, to provide an overview of currently existing knowledge, and to identify potential lacunae in current studies to direct future research. A comprehensive search was systematically performed in PubMed and EMBASE (via OvidSP) using search terms related to tissue engineering, cartilage and animals. Primary studies in which acellular biomaterials were implanted in osteochondral defects in the knee or ankle joint in healthy animals were included and study characteristics tabulated (283 studies out of 6,688 studies found). For studies comparing non-treated empty defects to defects containing implanted biomaterials and using semi-quantitative histology as outcome measure, the risk of bias (135 studies) was assessed and outcome data were collected for meta-analysis (151 studies). Random-effects meta-analyses were performed, using cartilage regeneration as outcome measure on an absolute 0-100% scale. Implantation of acellular biomaterials significantly

  18. Isolation, characterization, and differentiation of stem cells for cartilage regeneration.

    Science.gov (United States)

    Beane, Olivia S; Darling, Eric M

    2012-10-01

    The goal of tissue engineering is to create a functional replacement for tissues damaged by injury or disease. In many cases, impaired tissues cannot provide viable cells, leading to the investigation of stem cells as a possible alternative. Cartilage, in particular, may benefit from the use of stem cells since the tissue has low cellularity and cannot effectively repair itself. To address this need, researchers are investigating the chondrogenic capabilities of several multipotent stem cell sources, including adult and extra-embryonic mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Comparative studies indicate that each cell type has advantages and disadvantages, and while direct comparisons are difficult to make, published data suggest some sources may be more promising for cartilage regeneration than others. In this review, we identify current approaches for isolating and chondrogenically differentiating MSCs from bone marrow, fat, synovium, muscle, and peripheral blood, as well as cells from extra-embryonic tissues, ESCs, and iPSCs. Additionally, we assess chondrogenic induction with growth factors, identifying standard cocktails used for each stem cell type. Cell-only (pellet) and scaffold-based studies are also included, as is a discussion of in vivo results.

  19. Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF.

    Science.gov (United States)

    Cugat, Ramón; Alentorn-Geli, Eduard; Steinbacher, Gilbert; Álvarez-Díaz, Pedro; Cuscó, Xavier; Seijas, Roberto; Barastegui, David; Navarro, Jordi; Laiz, Patricia; García-Balletbó, Montserrat

    2017-01-01

    Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF). Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them). The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients.

  20. Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF

    Directory of Open Access Journals (Sweden)

    Ramón Cugat

    2017-01-01

    Full Text Available Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF. Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them. The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients.

  1. Exploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury

    Science.gov (United States)

    Embree, Mildred C.; Chen, Mo; Pylawka, Serhiy; Kong, Danielle; Iwaoka, George M.; Kalajzic, Ivo; Yao, Hai; Shi, Chancheng; Sun, Dongming; Sheu, Tzong-Jen; Koslovsky, David A.; Koch, Alia; Mao, Jeremy J.

    2016-01-01

    Tissue regeneration using stem cell-based transplantation faces many hurdles. Alternatively, therapeutically exploiting endogenous stem cells to regenerate injured or diseased tissue may circumvent these challenges. Here we show resident fibrocartilage stem cells (FCSCs) can be used to regenerate and repair cartilage. We identify FCSCs residing within the superficial zone niche in the temporomandibular joint (TMJ) condyle. A single FCSC spontaneously generates a cartilage anlage, remodels into bone and organizes a haematopoietic microenvironment. Wnt signals deplete the reservoir of FCSCs and cause cartilage degeneration. We also show that intra-articular treatment with the Wnt inhibitor sclerostin sustains the FCSC pool and regenerates cartilage in a TMJ injury model. We demonstrate the promise of exploiting resident FCSCs as a regenerative therapeutic strategy to substitute cell transplantation that could be beneficial for patients suffering from fibrocartilage injury and disease. These data prompt the examination of utilizing this strategy for other musculoskeletal tissues. PMID:27721375

  2. Non-invasive monitoring of in vivo hydrogel degradation and cartilage regeneration by multiparametric MR imaging

    Science.gov (United States)

    Chen, Zelong; Yan, Chenggong; Yan, Shina; Liu, Qin; Hou, Meirong; Xu, Yikai; Guo, Rui

    2018-01-01

    Numerous biodegradable hydrogels for cartilage regeneration have been widely used in the field of tissue engineering. However, to non-invasively monitor hydrogel degradation and efficiently evaluate cartilage restoration in situ is still challenging. Methods: A ultrasmall superparamagnetic iron oxide (USPIO)-labeled cellulose nanocrystal (CNC)/silk fibroin (SF)-blended hydrogel system was developed to monitor hydrogel degradation during cartilage regeneration. The physicochemical characterization and biocompatibility of the hydrogel were evaluated in vitro. The in vivo hydrogel degradation and cartilage regeneration of different implants were assessed using multiparametric magnetic resonance imaging (MRI) and further confirmed by histological analysis in a rabbit cartilage defect model for 3 months. Results: USPIO-labeled hydrogels showed sufficient MR contrast enhancement and retained stability without loss of the relaxation rate. Neither the mechanical properties of the hydrogels nor the proliferation of bone-marrow mesenchymal stem cells (BMSCs) were affected by USPIO labeling in vitro. CNC/SF hydrogels with BMSCs degraded more quickly than the acellular hydrogels as reflected by the MR relaxation rate trends in vivo. The morphology of neocartilage was noninvasively visualized by the three-dimensional water-selective cartilage MRI scan sequence, and the cartilage repair was further demonstrated by macroscopic and histological observations. Conclusion: This USPIO-labeled CNC/SF hydrogel system provides a new perspective on image-guided tissue engineering for cartilage regeneration. PMID:29464005

  3. The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells.

    Science.gov (United States)

    Levato, Riccardo; Webb, William R; Otto, Iris A; Mensinga, Anneloes; Zhang, Yadan; van Rijen, Mattie; van Weeren, René; Khan, Ilyas M; Malda, Jos

    2017-10-01

    Cell-laden hydrogels are the primary building blocks for bioprinting, and, also termed bioinks, are the foundations for creating structures that can potentially recapitulate the architecture of articular cartilage. To be functional, hydrogel constructs need to unlock the regenerative capacity of encapsulated cells. The recent identification of multipotent articular cartilage-resident chondroprogenitor cells (ACPCs), which share important traits with adult stem cells, represents a new opportunity for cartilage regeneration. However, little is known about the suitability of ACPCs for tissue engineering, especially in combination with biomaterials. This study aimed to investigate the potential of ACPCs in hydrogels for cartilage regeneration and biofabrication, and to evaluate their ability for zone-specific matrix production. Gelatin methacryloyl (gelMA)-based hydrogels were used to culture ACPCs, bone marrow mesenchymal stromal cells (MSCs) and chondrocytes, and as bioinks for printing. Our data shows ACPCs outperformed chondrocytes in terms of neo-cartilage production and unlike MSCs, ACPCs had the lowest gene expression levels of hypertrophy marker collagen type X, and the highest expression of PRG4, a key factor in joint lubrication. Co-cultures of the cell types in multi-compartment hydrogels allowed generating constructs with a layered distribution of collagens and glycosaminoglycans. By combining ACPC- and MSC-laden bioinks, a bioprinted model of articular cartilage was generated, consisting of defined superficial and deep regions, each with distinct cellular and extracellular matrix composition. Taken together, these results provide important information for the use of ACPC-laden hydrogels in regenerative medicine, and pave the way to the biofabrication of 3D constructs with multiple cell types for cartilage regeneration or in vitro tissue models. Despite its limited ability to repair, articular cartilage harbors an endogenous population of progenitor cells

  4. A novel in vitro bovine cartilage punch model for assessing the regeneration of focal cartilage defects with biocompatible bacterial nanocellulose

    Science.gov (United States)

    2013-01-01

    Introduction Current therapies for articular cartilage defects fail to achieve qualitatively sufficient tissue regeneration, possibly because of a mismatch between the speed of cartilage rebuilding and the resorption of degradable implant polymers. The present study focused on the self-healing capacity of resident cartilage cells in conjunction with cell-free and biocompatible (but non-resorbable) bacterial nanocellulose (BNC). This was tested in a novel in vitro bovine cartilage punch model. Methods Standardized bovine cartilage discs with a central defect filled with BNC were cultured for up to eight weeks with/without stimulation with transforming growth factor-β1 (TGF-β1. Cartilage formation and integrity were analyzed by histology, immunohistochemistry and electron microscopy. Content, release and neosynthesis of the matrix molecules proteoglycan/aggrecan, collagen II and collagen I were also quantified. Finally, gene expression of these molecules was profiled in resident chondrocytes and chondrocytes migrated onto the cartilage surface or the implant material. Results Non-stimulated and especially TGF-β1-stimulated cartilage discs displayed a preserved structural and functional integrity of the chondrocytes and surrounding matrix, remained vital in long-term culture (eight weeks) without signs of degeneration and showed substantial synthesis of cartilage-specific molecules at the protein and mRNA level. Whereas mobilization of chondrocytes from the matrix onto the surface of cartilage and implant was pivotal for successful seeding of cell-free BNC, chondrocytes did not immigrate into the central BNC area, possibly due to the relatively small diameter of its pores (2 to 5 μm). Chondrocytes on the BNC surface showed signs of successful redifferentiation over time, including increase of aggrecan/collagen type II mRNA, decrease of collagen type I mRNA and initial deposition of proteoglycan and collagen type II in long-term high-density pellet cultures

  5. Interleukin-6 is elevated in synovial fluid of patients with focal cartilage defects and stimulates cartilage matrix production in an in vitro regeneration model

    NARCIS (Netherlands)

    Tsuchida, Anika I.; Beekhuizen, Michiel; Rutgers, Marijn; van Osch, Gerjo J.V.M.; Bekkers, Joris E.J.; Bot, Arjan G.J.; Geurts, Bernd; Dhert, Wouter J.A.; Saris, Daniël B.F.; Creemers, Laura B.

    2012-01-01

    Introduction This study aimed to determine whether, as in osteoarthritis, increased levels of interleukin-6 (IL-6) are present in the synovial fluid of patients with symptomatic cartilage defects and whether this IL-6 affects cartilage regeneration as well as the cartilage in the degenerated knee.

  6. The concentration, gene expression, and spatial distribution of aggrecan in canine articular cartilage, meniscus, and anterior and posterior cruciate ligaments: a new molecular distinction between hyaline cartilage and fibrocartilage in the knee joint.

    Science.gov (United States)

    Valiyaveettil, Manojkumar; Mort, John S; McDevitt, Cahir A

    2005-01-01

    The concentration, spatial distribution, and gene expression of aggrecan in meniscus, articular cartilage, and the anterior and posterior cruciate ligaments (ACL and PCL) was determined in the knee joints of five mature dogs. An anti-serum against peptide sequences specific to the G1 domain of aggrecan was employed in competitive-inhibition ELISA of guanidine HCl extracts and immunofluorescence microscopy. Gene expression was determined by Taqman real-time PCR. The concentration of aggrecan in articular cartilage (240.1 +/- 32 nMol/g dry weight) was higher than that in meniscus (medial meniscus: 33.4 +/- 4.3 nMol/g) and ligaments (ACL: 6.8 +/- 0.9 nMol/g). Aggrecan was more concentrated in the inner than the outer zone of the meniscus. Aggrecan in meniscus showed an organized, spatial network, in contrast to its diffuse distribution in articular cartilage. Thus, differences in the concentration, gene expression, and spatial distribution of aggrecan constitute another molecular distinction between hyaline cartilage and fibrocartilage of the knee.

  7. BMP-2, hypoxia, and COL1A1/HtrA1 siRNAs favor neo-cartilage hyaline matrix formation in chondrocytes.

    Science.gov (United States)

    Ollitrault, David; Legendre, Florence; Drougard, Carole; Briand, Mélanie; Benateau, Hervé; Goux, Didier; Chajra, Hanane; Poulain, Laurent; Hartmann, Daniel; Vivien, Denis; Shridhar, Vijayalakshmi; Baldi, Alfonso; Mallein-Gerin, Frédéric; Boumediene, Karim; Demoor, Magali; Galera, Philippe

    2015-02-01

    Osteoarthritis (OA) is an irreversible pathology that causes a decrease in articular cartilage thickness, leading finally to the complete degradation of the affected joint. The low spontaneous repair capacity of cartilage prevents any restoration of the joint surface, making OA a major public health issue. Here, we developed an innovative combination of treatment conditions to improve the human chondrocyte phenotype before autologous chondrocyte implantation. First, we seeded human dedifferentiated chondrocytes into a collagen sponge as a scaffold, cultured them in hypoxia in the presence of a bone morphogenetic protein (BMP), BMP-2, and transfected them with small interfering RNAs targeting two markers overexpressed in OA dedifferentiated chondrocytes, that is, type I collagen and/or HtrA1 serine protease. This strategy significantly decreased mRNA and protein expression of type I collagen and HtrA1, and led to an improvement in the chondrocyte phenotype index of differentiation. The effectiveness of our in vitro culture process was also demonstrated in the nude mouse model in vivo after subcutaneous implantation. We, thus, provide here a new protocol able to favor human hyaline chondrocyte phenotype in primarily dedifferentiated cells, both in vitro and in vivo. Our study also offers an innovative strategy for chondrocyte redifferentiation and opens new opportunities for developing therapeutic targets.

  8. Role of Cartilage Forming Cells in Regenerative Medicine for Cartilage Repair

    OpenAIRE

    Sun, Lin; Reagan, Michaela R.; Kaplan, David L.

    2010-01-01

    Lin Sun1, Michaela R Reagan2, David L Kaplan1,21Department of Chemical and Biological Engineering, 2Department of Biomedical Engineering, Tufts University, Medford, MA, USAAbstract: Currently, cartilage repair remains a major challenge for researchers and physicians due to its limited healing capacity. Cartilage regeneration requires suitable cells; these must be easily obtained and expanded, able to produce hyaline matrix with proper mechanical properties, and demonstrate sustained integrati...

  9. Cartilage regeneration for treatment of osteoarthritis: a paradigm for nonsurgical intervention

    Science.gov (United States)

    Sabaawy, Hatem E.

    2015-01-01

    Osteoarthritis (OA) is associated with articular cartilage abnormalities and affects people of older age: preventative or therapeutic treatment measures for OA and related articular cartilage disorders remain challenging. In this perspective review, we have integrated multiple biological, morphological, developmental, stem cell and homeostasis concepts of articular cartilage to develop a paradigm for cartilage regeneration. OA is conceptually defined as an injury of cartilage that initiates chondrocyte activation, expression of proteases and growth factor release from the matrix. This regenerative process results in the local activation of inflammatory response genes in cartilage without migration of inflammatory cells or angiogenesis. The end results are catabolic and anabolic responses, and it is the balance between these two outcomes that controls remodelling of the matrix and regeneration. A tantalizing clinical clue for cartilage regrowth in OA joints has been observed in surgically created joint distraction. We hypothesize that cartilage growth in these distracted joints may have a biological connection with the size of organs and regeneration. Therefore we propose a novel, practical and nonsurgical intervention to validate the role of distraction in cartilage regeneration in OA. The approach permits normal wake-up activity while during sleep; the index knee is subjected to distraction with a pull traction device. Comparison of follow-up magnetic resonance imaging (MRI) at 3 and 6 months of therapy to those taken before therapy will provide much-needed objective evidence for the use of this mode of therapy for OA. We suggest that the paradigm presented here merits investigation for treatment of OA in knee joints. PMID:26029269

  10. Up-regulated expression of cartilage intermediate-layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease.

    Science.gov (United States)

    Hirose, Jun; Ryan, Lawrence M; Masuda, Ikuko

    2002-12-01

    Excess accumulation of extracellular inorganic pyrophosphate (ePPi) in aged human cartilage is crucial in calcium pyrophosphate dihydrate (CPPD) crystal formation in cartilage matrix. Two sources of ePPi are ePPi-generating ectoenzymes (NTPPPH) and extracellular transport of intracellular PPi by ANK. This study was undertaken to evaluate the role of NTPPPH and ANK in ePPi elaboration, by investigating expression of NTPPPH enzymes (cartilage intermediate-layer protein [CILP] and plasma cell membrane glycoprotein 1 [PC-1]) and ANK in human chondrocytes from osteoarthritic (OA) articular cartilage containing CPPD crystals and without crystals. Chondrocytes were harvested from knee cartilage at the time of arthroplasty (OA with CPPD crystals [CPPD], n = 8; OA without crystals [OA], n = 10). Normal adult human chondrocytes (n = 1) were used as a control. Chondrocytes were cultured with transforming growth factor beta1 (TGFbeta1), which stimulates ePPi elaboration, and/or insulin-like growth factor 1 (IGF-1), which inhibits ePPi elaboration. NTPPPH and ePPi were measured in the media at 48 hours. Media CILP, PC-1, and ANK were determined by dot-immunoblot analysis. Chondrocyte messenger RNA (mRNA) was extracted for reverse transcriptase-polymerase chain reaction to study expression of mRNA for CILP, PC-1, and ANK. NTPPPH and ANK mRNA and protein were also studied in fresh frozen cartilage. Basal ePPi elaboration and NTPPPH activity in conditioned media from CPPD chondrocytes were elevated compared with normal chondrocytes, and tended to be higher compared with OA chondrocytes. Basal expression of mRNA for CILP (chondrocytes) and ANK (cartilage) was higher in both CPPD chondrocytes and CPPD cartilage extract than in OA or normal samples. PC-1 mRNA was less abundant in CPPD chondrocytes and cartilage extract than in OA chondrocytes and extract, although the difference was not significant. CILP, PC-1, and ANK protein levels were similar in CPPD, OA, and normal chondrocytes

  11. Cartilage and bone cells do not participate in skeletal regeneration in Ambystoma mexicanum limbs.

    Science.gov (United States)

    McCusker, Catherine D; Diaz-Castillo, Carlos; Sosnik, Julian; Q Phan, Anne; Gardiner, David M

    2016-08-01

    The Mexican Axolotl is one of the few tetrapod species that is capable of regenerating complete skeletal elements in injured adult limbs. Whether the skeleton (bone and cartilage) plays a role in the patterning and contribution to the skeletal regenerate is currently unresolved. We tested the induction of pattern formation, the effect on cell proliferation, and contributions of skeletal tissues (cartilage, bone, and periosteum) to the regenerating axolotl limb. We found that bone tissue grafts from transgenic donors expressing GFP fail to induce pattern formation and do not contribute to the newly regenerated skeleton. Periosteum tissue grafts, on the other hand, have both of these activities. These observations reveal that skeletal tissue does not contribute to the regeneration of skeletal elements; rather, these structures are patterned by and derived from cells of non-skeletal connective tissue origin. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Laser-induced micropore formation and modification of cartilage structure in osteoarthritis healing

    Energy Technology Data Exchange (ETDEWEB)

    Sobol, Emil [Institute of Applied Physics of the Russian Academy of Sciences, Nizhny Novgorod, RussiabFederal Scientific Research Centre “Crystallography and Photonics” of the Russian Academy of Sciences, Institute of Photonic Technologies, Moscow, Russia; Baum, Olga [Federal Scientific Research Centre “Crystallography and Photonics” of the Russian Academy of Sciences, Institute of Photonic Technologies, Moscow, Russia; Shekhter, Anatoly [Sechenov First Medical University of Moscow, Institute of Regenerative Medicine, Moscow, Russia; Wachsmann-Hogiu, Sebastian [University of California, Center for Biophotonics, Department of Pathology and Laboratory Medicine, Sacramento, California, United StateseMcGill University, Department of Bioengineering, Montreal, Canada; Shnirelman, Alexander [Concordia University, Department of Mathematics and Statistics, Montreal, Canada; Alexandrovskaya, Yulia [Institute of Applied Physics of the Russian Academy of Sciences, Nizhny Novgorod, RussiabFederal Scientific Research Centre “Crystallography and Photonics” of the Russian Academy of Sciences, Institute of Photonic Technologies, Moscow, Russia; Sadovskyy, Ivan [Argonne National Laboratory, Materials Science Division, Argonne, Illinois, United States; Vinokur, Valerii [Argonne National Laboratory, Materials Science Division, Argonne, Illinois, United States

    2017-05-31

    Pores are vital for functioning of avascular tissues. Laser-induced pores play an important role in the process of cartilage regeneration. The aim of any treatment for osteoarthritis is to repair hyaline-type cartilage. The aims of this study are to answer two questions: (1) How do laser-assisted pores affect the cartilaginous cells to synthesize hyaline cartilage (HC)? and (2) How can the size distribution of pores arising in the course of laser radiation be controlled? We have shown that in cartilage, the pores arise predominately near chondrocytes, which promote nutrition of cells and signal molecular transfer that activates regeneration of cartilage. In vivo laser treatment of damaged cartilage of miniature pig joints provides cellular transformation and formation of HC. We propose a simple model of pore formation in biopolymers that paves the way for going beyond the trial-anderror approach when choosing an optimal laser treatment regime. Our findings support the approach toward laser healing of osteoarthritis.

  13. Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model.

    Science.gov (United States)

    Ude, Chinedu C; Sulaiman, Shamsul B; Min-Hwei, Ng; Hui-Cheng, Chen; Ahmad, Johan; Yahaya, Norhamdan M; Saim, Aminuddin B; Idrus, Ruszymah B H

    2014-01-01

    In this study, Adipose stem cells (ADSC) and bone marrow stem cells (BMSC), multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model. Osteoarthritis was induced at the right knee of sheep by complete resection of the anterior cruciate ligament and medial meniscus following a 3-weeks exercise regimen. Stem cells from experimental sheep were culture expanded and induced to chondrogenic lineage. Test sheep received a single dose of 2 × 10(7) autologous PKH26-labelled, chondrogenically induced ADSCs or BMSCs as 5 mls injection, while controls received 5 mls culture medium. The proliferation rate of ADSCs 34.4 ± 1.6 hr was significantly higher than that of the BMSCs 48.8 ± 5.3 hr (P = 0.008). Chondrogenic induced BMSCs had significantly higher expressions of chondrogenic specific genes (Collagen II, SOX9 and Aggrecan) compared to chondrogenic ADSCs (P = 0.031, 0.010 and 0.013). Grossly, the treated knee joints showed regenerated de novo cartilages within 6 weeks post-treatment. On the International Cartilage Repair Society grade scores, chondrogenically induced ADSCs and BMSCs groups had significantly lower scores than controls (P = 0.0001 and 0.0001). Fluorescence of the tracking dye (PKH26) in the injected cells showed that they had populated the damaged area of cartilage. Histological staining revealed loosely packed matrixes of de novo cartilages and immunostaining demonstrated the presence of cartilage specific proteins, Collagen II and SOX9. Autologous chondrogenically induced ADSCs and BMSCs could be promising cell sources for cartilage regeneration in osteoarthritis.

  14. Cartilage regeneration by chondrogenic induced adult stem cells in osteoarthritic sheep model.

    Directory of Open Access Journals (Sweden)

    Chinedu C Ude

    Full Text Available OBJECTIVES: In this study, Adipose stem cells (ADSC and bone marrow stem cells (BMSC, multipotent adult cells with the potentials for cartilage regenerations were induced to chondrogenic lineage and used for cartilage regenerations in surgically induced osteoarthritis in sheep model. METHODS: Osteoarthritis was induced at the right knee of sheep by complete resection of the anterior cruciate ligament and medial meniscus following a 3-weeks exercise regimen. Stem cells from experimental sheep were culture expanded and induced to chondrogenic lineage. Test sheep received a single dose of 2 × 10(7 autologous PKH26-labelled, chondrogenically induced ADSCs or BMSCs as 5 mls injection, while controls received 5 mls culture medium. RESULTS: The proliferation rate of ADSCs 34.4 ± 1.6 hr was significantly higher than that of the BMSCs 48.8 ± 5.3 hr (P = 0.008. Chondrogenic induced BMSCs had significantly higher expressions of chondrogenic specific genes (Collagen II, SOX9 and Aggrecan compared to chondrogenic ADSCs (P = 0.031, 0.010 and 0.013. Grossly, the treated knee joints showed regenerated de novo cartilages within 6 weeks post-treatment. On the International Cartilage Repair Society grade scores, chondrogenically induced ADSCs and BMSCs groups had significantly lower scores than controls (P = 0.0001 and 0.0001. Fluorescence of the tracking dye (PKH26 in the injected cells showed that they had populated the damaged area of cartilage. Histological staining revealed loosely packed matrixes of de novo cartilages and immunostaining demonstrated the presence of cartilage specific proteins, Collagen II and SOX9. CONCLUSION: Autologous chondrogenically induced ADSCs and BMSCs could be promising cell sources for cartilage regeneration in osteoarthritis.

  15. [Progress in application of 3D bioprinting in cartilage regeneration and reconstruction for tissue engineering].

    Science.gov (United States)

    Liao, Junlin; Wang, Shaohua; Chen, Jia; Xie, Hongju; Zhou, Jianda

    2017-02-28

    Three-dimensional (3D) bioprinting provides an advanced technology for tissue engineering and regenerative medicine because of its ability to produce the models or organs with higher precision and more suitable for human body. It has been successfully used to produce a variety of cartilage scaffold materials. In addition, 3D bioprinter can directly to print tissue and organs with live chondrocytes. In conclusion, 3D bioprinting may have broad prospect for cartilage regeneration and reconstruction in tissue engineering.

  16. MRI monitoring of autologous hyaline cartilage grafts in the knee joint: a follow-up study over 12 months; MRT-Monitoring autologer Chondrozytentransplantate im Kniegelenk: Eine Verlaufsstudie ueber 12 Monate

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Horvat, C.; Schick, F.; Claussen, C.D.; Groenewaeller, E. [Abt. fuer Radiologische Diagnostik, Eberhard-Karls-Univ. Tuebingen (Germany)

    2004-12-01

    Purpose: To evaluate the suitability of different MR sequences for monitoring the stage of maturation of hyaline cartilage grafts in the knee joint and the early detection of complications like hypertrophy. In addition, it was analyzed whether indirect MR arthrography can indicate debonding of the graft. Materials and Methods: MRI examinations were performed in 19 patients, aged 17-43 years, with autologous transplantation of a hyaline cartilage tissue graft after knee trauma. Examination dates were prior to transplantation to localize the defect, and 6 weeks, 3, 6 and 12 months after transplantation to control morphology and maturation of the autologous graft. Standard T2- and protondensity-weighted turbo spin echo (TSE) sequences and T1-weighted spin echo (SE) sequences were used, as well as gradient echo (GRE) sequences with and without magnetization transfer (MT) prepulses. In some cases, indirect MR arthrography was performed. Results: Cartilage defect and the hyaline cartilage graft could be detected in all 19 patients. Hypertrophy of the graft could be found early in 3 patients and debonding in 1 patient. For depicting the graft a short time after surgery. T2-weighted TSE-sequences showed the best results. Six and 12 months after transplantation, spoiled 3D-GRE-sequences like FLASH3D (fast low angle shot) showed reduced artifacts due to magnetic residues from the surgery. Difference images from GRE-sequences with and without MT pulse provided high contrast between cartilage and surrounding tissue. The quantification of the MT effect showed an assimilation of the graft to the original cartilage within 12 months. Indirect MR arthrography showed subchondral contrast medium even 12 months after transplantation in 3 patients. (orig.)

  17. Assessment of fixed charge density in regenerated cartilage by Gd-DTPA-enhanced MRI

    International Nuclear Information System (INIS)

    Miyata, Shogo; Homma, Kazuhiro; Numano, Tomokazu; Furukawa, Katsuko; Tateishi, Tetsuya; Ushida, Takashi

    2006-01-01

    Applying regenerated cartilage in a clinical setting requires noninvasive evaluation to detect the maturity of cartilage tissue. Magnetic resonance (MR) imaging of articular cartilage is well accepted and has been applied clinically in recent years. We attempt to establish a noninvasive method to evaluate the maturity of regenerated cartilage tissue using gadolinium-enhanced MR imaging. To reconstruct cartilaginous tissue, we embedded articular chondrocytes harvested from bovine humeral head in agarose gel and cultured the cells in vitro up to 4 weeks. The fixed charge density (FCD) of the cartilage was determined using MRI gadolinium exclusion method. The sulfated glycosaminoglycan (sGAG) content was determined by dimethylmethylene blue dye-binding assay. The sGAG content and FCD of the regenerated cartilage increased with duration of culture. In the T 1 Gd maps, the [Gd-DTPA 2- ] in the specimen decreased, and the boundary between the sample disk and the bath solution of phosphate buffered saline (PBS) became clearer as time in culture increased. In the linear regression analysis, FCD and sGAG content correlated significantly. Gadolinium-enhanced MR imaging measurements can be useful predictors of the degree of cartilaginous tissue formation. (author)

  18. The effect of polymer size and charge of molecules on permeation through synovial membrane and accumulation in hyaline articular cartilage.

    Science.gov (United States)

    Sterner, B; Harms, M; Wöll, S; Weigandt, M; Windbergs, M; Lehr, C M

    2016-04-01

    The treatment of joint related diseases often involves direct intra-articular injections. For rational development of novel delivery systems with extended residence time in the joint, detailed understanding of transport and retention phenomena within the joint is mandatory. This work presents a systematic study on the in vitro permeation, penetration and accumulation of model polymers with differing charges and molecular weights in bovine joint tissue. Permeation experiments with bovine synovial membrane were performed with PEG polymers (6-200 kDa) and methylene blue in customized diffusion chambers. For polyethylene glycol, 2-fold (PEG 6 kDa), 3-fold (PEG 10 kDa) and 13-fold (PEG 35 kDa) retention by the synovial membrane in reference to the small molecule methylene blue was demonstrated. No PEG 200 kDa was found in the acceptor in detectable amounts after 48 h. This showed the potential for a distinct extension of joint residence times by increasing molecular weights. In addition, experiments with bovine cartilage tissue were conducted. The ability for positively charged, high molecular weight chitosans and HEMA-Co-TMAP (HCT) polymers (up to 233 kDa) to distribute throughout the entire cartilage matrix was demonstrated. In contrast, a distribution into cartilage was not observed for neutral PEG polymers (6-200 kDa). Furthermore, the positive charge density of different compounds (chitosan, HEMA-Co-TMAP, methylene blue, MSC C1 (neutral NCE) and MSC D1 (positively charged NCE) was found to correlate with their accumulation in bovine cartilage tissue. In summary, the results offer pre-clinical in vitro data, indicating that the modification of molecular size and charge of a substance has the potential to decelerate its clearance through the synovial membrane and to promote accumulation inside the cartilage matrix. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. [Tribological assessment of articular cartilage. A system for the analysis of the friction coefficient of cartilage, regenerates and tissue engineering constructs; initial results].

    Science.gov (United States)

    Schwarz, M L R; Schneider-Wald, B; Krase, A; Richter, W; Reisig, G; Kreinest, M; Heute, S; Pott, P P; Brade, J; Schütte, A

    2012-10-01

    Values for the friction coefficient of articular cartilage are given in ranges of percentage and lower and are calculated as a quotient of the friction force and the perpendicular loading force acting on it. Thus, a sophisticated system has to be provided for analysing the friction coefficient under different conditions in particular when cartilage should be coupled as friction partner. It is possible to deep-freeze articular cartilage before measuring the friction coefficient as the procedure has no influence on the results. The presented tribological system was able to distinguish between altered and native cartilage. Furthermore, tissue engineered constructs for cartilage repair were differentiated from native cartilage probes by their friction coefficient. In conclusion a tribological equipment is presented to analyze the friction coefficient of articular cartilage, in vivo generated cartilage regenerates and in vitro tissue engineered constructs regarding their biomechanical properties for quality assessment.

  20. Evaluation of native hyaline cartilage and repair tissue after two cartilage repair surgery techniques with 23Na MR imaging at 7 T: initial experience.

    Science.gov (United States)

    Zbýň, S; Stelzeneder, D; Welsch, G H; Negrin, L L; Juras, V; Mayerhoefer, M E; Szomolanyi, P; Bogner, W; Domayer, S E; Weber, M; Trattnig, S

    2012-08-01

    To compare the sodium normalized mean signal intensity (NMSI) values between patients after bone marrow stimulation (BMS) and matrix-associated autologous chondrocyte transplantation (MACT) cartilage repair procedures. Nine BMS and nine MACT patients were included. Each BMS patient was matched with one MACT patient according to age [BMS 36.7 ± 10.7 (mean ± standard deviation) years; MACT 36.9 ± 10.0 years], postoperative interval (BMS 33.5 ± 25.3 months; MACT 33.2 ± 25.7 months), and defect location. All magnetic resonance imaging (MRI) measurements were performed on a 7 T system. Proton images served for morphological evaluation of repair tissue using the magnetic resonance observation of cartilage repair tissue (MOCART) scoring system. Sodium NMSI values in the repair area and morphologically normal cartilage were calculated. Clinical outcome was assessed right after MRI. Analysis of covariance, t-tests, and Pearson correlation coefficients were evaluated. Sodium NMSI was significantly lower in BMS (P = 0.004) and MACT (P = 0.006) repair tissue, compared to reference cartilage. Sodium NMSI was not different between the reference cartilage in MACT and BMS patients (P = 0.664), however it was significantly higher in MACT than in BMS repair tissue (P = 0.028). Better clinical outcome was observed in BMS than in MACT patients. There was no difference between MOCART scores for MACT and BMS patients (P = 0.915). We did not observe any significant correlation between MOCART score and sodium repair tissue NMSI (r = -0.001; P = 0.996). Our results suggest higher glycosaminoglycan (GAG) content, and therefore, repair tissue of better quality in MACT than in BMS patients. Sodium imaging might be beneficial in non-invasive evaluation of cartilage repair surgery efficacy. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  1. Articular Cartilage Increases Transition Zone Regeneration in Bone-tendon Junction Healing

    Science.gov (United States)

    Qin, Ling; Lee, Kwong Man; Leung, Kwok Sui

    2008-01-01

    The fibrocartilage transition zone in the direct bone-tendon junction reduces stress concentration and protects the junction from failure. Unfortunately, bone-tendon junctions often heal without fibrocartilage transition zone regeneration. We hypothesized articular cartilage grafts could increase fibrocartilage transition zone regeneration. Using a goat partial patellectomy repair model, autologous articular cartilage was harvested from the excised distal third patella and interposed between the residual proximal two-thirds bone fragment and tendon during repair in 36 knees. We evaluated fibrocartilage transition zone regeneration, bone formation, and mechanical strength after repair at 6, 12, and 24 weeks and compared them with direct repair. Autologous articular cartilage interposition resulted in more fibrocartilage transition zone regeneration (69.10% ± 14.11% [mean ± standard deviation] versus 8.67% ± 7.01% at 24 weeks) than direct repair at all times. There was no difference in the amount of bone formation and mechanical strength achieved. Autologous articular cartilage interposition increases fibrocartilage transition zone regeneration in bone-tendon junction healing, but additional research is required to ascertain the mechanism of stimulation and to establish the clinical applicability. PMID:18987921

  2. Tailored PVA/ECM Scaffolds for Cartilage Regeneration

    Directory of Open Access Journals (Sweden)

    Elena Stocco

    2014-01-01

    Full Text Available Articular cartilage lesions are a particular challenge for regenerative medicine due to cartilage low self-ability repair in case of damage. Hence, a significant goal of musculoskeletal tissue engineering is the development of suitable structures in virtue of their matrix composition and biomechanical properties. The objective of our study was to design in vitro a supporting structure for autologous chondrocyte growth. We realized a biohybrid composite scaffold combining a novel and nonspecific extracellular matrix (ECM, which is decellularized Wharton’s jelly ECM, with the biomechanical properties of the synthetic hydrogel polyvinyl alcohol (PVA. Wharton’s jelly ECM was tested for its ability in promoting scaffold colonization by chondrocytes and compared with polyvinyl alcohol itself and the more specific decellularized cartilage matrix. Our preliminary evidences highlighted the chance of using Wharton’s jelly ECM in combination with PVA hydrogels as an innovative and easily available scaffold for cartilage restoration.

  3. Differentiating normal hyaline cartilage from post-surgical repair tissue using fast gradient echo imaging in delayed gadolinium-enhanced MRI (dGEMRIC) at 3 Tesla

    Energy Technology Data Exchange (ETDEWEB)

    Trattnig, Siegfried; Pinker, Katja; Welsch, Goetz H. [Medical University of Vienna, MR Center-High field MR, Department of Radiology, Vienna (Austria); Mamisch, Tallal C. [Inselspital Bern, Orthopedic Surgery Department, Bern (Switzerland); Domayer, Stephan [Medical University of Vienna, MR Center-High field MR, Department of Radiology, Vienna (Austria); Medical University of Vienna, Department of Orthopaedics, Vienna (Austria); Szomolanyi, Pavol [Medical University of Vienna, MR Center-High field MR, Department of Radiology, Vienna (Austria); Slovak Academy of Sciences, Department of Imaging Methods, Institute of Measurement Science, Bratislava (Slovakia); Marlovits, Stefan; Kutscha-Lissberg, Florian [Medical University of Vienna, Department of Traumatology, Center for Joints and Cartilage, Vienna (Austria)

    2008-06-15

    The purpose was to evaluate the relative glycosaminoglycan (GAG) content of repair tissue in patients after microfracturing (MFX) and matrix-associated autologous chondrocyte transplantation (MACT) of the knee joint with a dGEMRIC technique based on a newly developed short 3D-GRE sequence with two flip angle excitation pulses. Twenty patients treated with MFX or MACT (ten in each group) were enrolled. For comparability, patients from each group were matched by age (MFX: 37.1 {+-} 16.3 years; MACT: 37.4 {+-} 8.2 years) and postoperative interval (MFX: 33.0 {+-} 17.3 months; MACT: 32.0 {+-} 17.2 months). The {delta} relaxation rate ({delta}R1) for repair tissue and normal hyaline cartilage and the relative {delta}R1 were calculated, and mean values were compared between both groups using an analysis of variance. The mean {delta}R1 for MFX was 1.07 {+-} 0.34 versus 0.32 {+-} 0.20 at the intact control site, and for MACT, 1.90 {+-} 0.49 compared to 0.87 {+-} 0.44, which resulted in a relative {delta}R1 of 3.39 for MFX and 2.18 for MACT. The difference between the cartilage repair groups was statistically significant. The new dGEMRIC technique based on dual flip angle excitation pulses showed higher GAG content in patients after MACT compared to MFX at the same postoperative interval and allowed reducing the data acquisition time to 4 min. (orig.)

  4. Quantitative evaluation of hyaline articular cartilage T2 maps of knee and determine the relationship of cartilage T2 values with age, gender, articular changes.

    Science.gov (United States)

    Cağlar, E; Şahin, G; Oğur, T; Aktaş, E

    2014-11-01

    To identify changes in knee joint cartilage transverse relaxation values depending on the patient's age and gender and to investigate the relationship between knee joint pathologies and the transverse relaxation time. Knee MRI images of 107 symptomatic patients with various pathologic knee conditions were analyzed retrospectively. T2 values were measured at patellar cartilage, posteromedial and posterolateral femoral cartilage adjacent to the central horn of posterior meniscus. 963 measurements were done for 107 knees MRI. Relationship of T2 values with seven features including subarticular bone marrow edema, subarticular cysts, marginal osteophytes, anterior-posterior cruciate and collateral ligament tears, posterior medial and posterior lateral meniscal tears, synovial thickening and effusion were analyzed. T2 values in all three compartments were evaluated according to age and gender. A T2 value increase correlated with age was present in all three compartments measured in the subgroup with no knee joint pathology and in all patient groups. According to the ROC curve, an increase showing a statistically significant difference was present in the patient group aged over 40 compared to the patient group aged 40 and below in all patient groups. There is a statistically difference at T2 values with and without subarticular cysts, marginal osteophytes, synovial thickening and effusion. T2 relaxation time showed a statistically significant increase in the patients with a medial meniscus tear compared to those without a tear and no statistically significant difference was found in T2 relaxation times of patients with and without a posterior lateral meniscus tear. T2 cartilage mapping on MRI provides opportunity to exhibit biochemical and structural changes related with cartilage extracellular matrix without using invasive diagnostic methods.

  5. RHEB: a potential regulator of chondrocyte phenotype for cartilage tissue regeneration.

    Science.gov (United States)

    Ashraf, S; Ahn, J; Cha, B-H; Kim, J-S; Han, I; Park, H; Lee, S-H

    2017-09-01

    As articular cartilage has a limited ability to self-repair, successful cartilage regeneration requires clinical-grade chondrocytes with innate characteristics. However, cartilage regeneration via chondrocyte transplantation is challenging, because chondrocytes lose their innate characteristics during in vitro expansion. Here, we investigated the mechanistic underpinning of the gene Ras homologue enriched in brain (RHEB) in the control of senescence and dedifferentiation through the modulation of oxidative stress in chondrocytes, a hallmark of osteoarthritis. Serial expansion of human chondrocytes led to senescence, dedifferentiation and oxidative stress. RHEB maintained the innate characteristics of chondrocytes by regulating senescence, dedifferentiation and oxidative stress, leading to the upregulation of COL2 expression via SOX9 and the downregulation of p27 expression via MCL1. RHEB also decreased the expression of COL10. RHEB knockdown mimics decreased the expression of SOX9, COL2 and MCL1, while abrogating the suppressive function of RHEB on p27 and COL10 in chondrocytes. RHEB-overexpressing chondrocytes successfully formed cartilage tissue in vitro as well as in vivo, with increased expression of GAG matrix and chondrogenic markers. RHEB induces a distinct gene expression signature that maintained the innate chondrogenic properties over a long period. Therefore, RHEB expression represents a potentially useful mechanism in terms of cartilage tissue regeneration from chondrocytes, by which chondrocyte phenotypic and molecular characteristics can be retained through the modulation of senescence, dedifferentiation and oxidative stress. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Stable subcutaneous cartilage regeneration of bone marrow stromal cells directed by chondrocyte sheet.

    Science.gov (United States)

    Li, Dan; Zhu, Lian; Liu, Yu; Yin, Zongqi; Liu, Yi; Liu, Fangjun; He, Aijuan; Feng, Shaoqing; Zhang, Yixin; Zhang, Zhiyong; Zhang, Wenjie; Liu, Wei; Cao, Yilin; Zhou, Guangdong

    2017-05-01

    In vivo niche plays an important role in regulating differentiation fate of stem cells. Due to lack of proper chondrogenic niche, stable cartilage regeneration of bone marrow stromal cells (BMSCs) in subcutaneous environments is always a great challenge. This study explored the feasibility that chondrocyte sheet created chondrogenic niche retained chondrogenic phenotype of BMSC engineered cartilage (BEC) in subcutaneous environments. Porcine BMSCs were seeded into biodegradable scaffolds followed by 4weeks of chondrogenic induction in vitro to form BEC, which were wrapped with chondrocyte sheets (Sheet group), acellular small intestinal submucosa (SIS, SIS group), or nothing (Blank group) respectively and then implanted subcutaneously into nude mice to trace the maintenance of chondrogenic phenotype. The results showed that all the constructs in Sheet group displayed typical cartilaginous features with abundant lacunae and cartilage specific matrices deposition. These samples became more mature with prolonged in vivo implantation, and few signs of ossification were observed at all time points except for one sample that had not been wrapped completely. Cell labeling results in Sheet group further revealed that the implanted BEC directly participated in cartilage formation. Samples in both SIS and Blank groups mainly showed ossified tissue at all time points with partial fibrogenesis in a few samples. These results suggested that chondrocyte sheet could create a chondrogenic niche for retaining chondrogenic phenotype of BEC in subcutaneous environment and thus provide a novel research model for stable ectopic cartilage regeneration based on stem cells. In vivo niche plays an important role in directing differentiation fate of stem cells. Due to lack of proper chondrogenic niche, stable cartilage regeneration of bone marrow stromal cells (BMSCs) in subcutaneous environments is always a great challenge. The current study demonstrated that chondrocyte sheet generated by

  7. Dental mesenchymal stem cells encapsulated in alginate hydrogel co-delivery microencapsulation system for cartilage regeneration

    Science.gov (United States)

    Moshaverinia, Alireza; Xu, Xingtian; Chen, Chider; Akiyama, Kentaro; Snead, Malcolm L; Shi, Songtao

    2013-01-01

    Dental-derived MSCs are promising candidates for cartilage regeneration, with high chondrogenic differentiation capacity. This property contributes to making dental MSCs an advantageous therapeutic option compared to current treatment modalities. The MSC delivery vehicle is the principal determinant for the success of MSC-mediated cartilage regeneration therapies. The objectives of this study were to: (1) develop a novel co-delivery system based on TGF-β1 loaded RGD-coupled alginate microspheres encapsulating Periodontal Ligament Stem Cells (PDLSCs) or Gingival Mesenchymal Stem Cells (GMSCs); and (2) investigate dental MSC viability and chondrogenic differentiation in alginate microspheres. The results revealed the sustained release of TGF-β1 from the alginate microspheres. After 4 weeks of chondrogenic differentiation in vitro, PDLSCs, GMSCs as well as human bone marrow mesenchymal stem cells (hBMMSC) (as positive control) revealed chondrogenic gene expression markers (Col II and Sox-9) via qPCR, as well as matrix positively stained by toluidine blue and safranin-O. In animal studies, ectopic cartilage tissue regeneration was observed inside and around the transplanted microspheres, confirmed by histochemical and immunofluorescent staining. Interestingly, PDLSCs showed more chondrogenesis than GMSCs and hBMMSCs (Palginate microencapsulating dental MSCs make a promising candidate for cartilage regeneration. Our results highlight the vital role played by the microenvironment, as well as value of presenting inductive signals for viability and differentiation of MSCs. PMID:23891740

  8. Polycaprolactone foam functionalized with chitosan microparticles – a suitable scaffold for cartilage regeneration.

    Czech Academy of Sciences Publication Activity Database

    Filová, Eva; Jakubcová, B.; Danilová, I.; Kuželová Košťáková, E.; Jarošíková, T.; Chernyavskiy, Oleksandr; Hejda, J.; Handl, M.; Beznoska, J.; Nečas, A.; Rosina, J.; Amler, Evžen

    2016-01-01

    Roč. 65, č. 1 (2016), s. 121-131 ISSN 0862-8408 Institutional support: RVO:68378041 ; RVO:67985823 Keywords : poly-epsilon-caprolactone * chitosan * cartilage regeneration * foam Subject RIV: FI - Traumatology, Orthopedics Impact factor: 1.461, year: 2016

  9. [Cartilage regeneration surgery on the hip : What is feasible?

    Science.gov (United States)

    Landgraeber, Stefan; Jäger, Marcus; Fickert, Stefan

    2017-11-01

    Localized cartilage defects at the hip are mainly caused by pre-arthritic deformities, particularly by cam-type femoroacetabular impingement (FAI). Timely elimination of symptomatic deformities can prevent further progression such as cartilage defects. As the defects mostly occur in the anterolateral part of the acetabulum, they can be easily treated either by open surgery or by arthroscopy. To date the most effective methods of treatment are bone marrow stimulation, with or without a covering of biomaterials, and autologous chondrocyte transplantation. In selected cases, readaptation of the damaged cartilage can be attempted by biological procedures. In the present article, the findings reported in current studies on these procedures are summarized and discussed in detail. An outlook is given regarding possible future treatment concepts.

  10. Advances in cartilage tissue engineering : in vitro

    NARCIS (Netherlands)

    E.W. Mandl (Erik)

    2004-01-01

    textabstractWithin the body three subtypes of cartilage can be distinguished: hyaline cartilage, elastic cartilage and fibrocartilage. Hyaline cartilage is the predominant subtype and is mainly located in articular joints and in less extent in the nasal septum and cricoid. Elastic cartilage can be

  11. Extracellular matrix scaffolds for cartilage and bone regeneration

    NARCIS (Netherlands)

    Benders, K.E.M.; van Weeren, P.R.; Badylak, S.F.; Saris, Daniël B.F.; Dhert, W.J.A.; Malda, J.

    2013-01-01

    Regenerative medicine approaches based on decellularized extracellular matrix (ECM) scaffolds and tissues are rapidly expanding. The rationale for using ECM as a natural biomaterial is the presence of bioactive molecules that drive tissue homeostasis and regeneration. Moreover, appropriately

  12. Generation of Scaffoldless Hyaline Cartilaginous Tissue from Human iPSCs

    Directory of Open Access Journals (Sweden)

    Akihiro Yamashita

    2015-03-01

    Full Text Available Defects in articular cartilage ultimately result in loss of joint function. Repairing cartilage defects requires cell sources. We developed an approach to generate scaffoldless hyaline cartilage from human induced pluripotent stem cells (hiPSCs. We initially generated an hiPSC line that specifically expressed GFP in cartilage when teratoma was formed. We optimized the culture conditions and found BMP2, transforming growth factor β1 (TGF-β1, and GDF5 critical for GFP expression and thus chondrogenic differentiation of the hiPSCs. The subsequent use of scaffoldless suspension culture contributed to purification, producing homogenous cartilaginous particles. Subcutaneous transplantation of the hiPSC-derived particles generated hyaline cartilage that expressed type II collagen, but not type I collagen, in immunodeficiency mice. Transplantation of the particles into joint surface defects in immunodeficiency rats and immunosuppressed mini-pigs indicated that neocartilage survived and had potential for integration into native cartilage. The immunodeficiency mice and rats suffered from neither tumors nor ectopic tissue formation. The hiPSC-derived cartilaginous particles constitute a viable cell source for regenerating cartilage defects.

  13. Generation of scaffoldless hyaline cartilaginous tissue from human iPSCs.

    Science.gov (United States)

    Yamashita, Akihiro; Morioka, Miho; Yahara, Yasuhito; Okada, Minoru; Kobayashi, Tomohito; Kuriyama, Shinichi; Matsuda, Shuichi; Tsumaki, Noriyuki

    2015-03-10

    Defects in articular cartilage ultimately result in loss of joint function. Repairing cartilage defects requires cell sources. We developed an approach to generate scaffoldless hyaline cartilage from human induced pluripotent stem cells (hiPSCs). We initially generated an hiPSC line that specifically expressed GFP in cartilage when teratoma was formed. We optimized the culture conditions and found BMP2, transforming growth factor β1 (TGF-β1), and GDF5 critical for GFP expression and thus chondrogenic differentiation of the hiPSCs. The subsequent use of scaffoldless suspension culture contributed to purification, producing homogenous cartilaginous particles. Subcutaneous transplantation of the hiPSC-derived particles generated hyaline cartilage that expressed type II collagen, but not type I collagen, in immunodeficiency mice. Transplantation of the particles into joint surface defects in immunodeficiency rats and immunosuppressed mini-pigs indicated that neocartilage survived and had potential for integration into native cartilage. The immunodeficiency mice and rats suffered from neither tumors nor ectopic tissue formation. The hiPSC-derived cartilaginous particles constitute a viable cell source for regenerating cartilage defects. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Isolation, Characterization, and Differentiation of Stem Cells for Cartilage Regeneration

    OpenAIRE

    Beane, Olivia S.; Darling, Eric M.

    2012-01-01

    The goal of tissue engineering is to create a functional replacement for tissues damaged by injury or disease. In many cases, impaired tissues cannot provide viable cells, leading to the investigation of stem cells as a possible alternative. Cartilage, in particular, may benefit from the use of stem cells since the tissue has low cellularity and cannot effectively repair itself. To address this need, researchers are investigating the chondrogenic capabilities of several multipotent stem cell ...

  15. Original and regenerating lizard tail cartilage contain putative resident stem/progenitor cells.

    Science.gov (United States)

    Alibardi, Lorenzo

    2015-11-01

    Regeneration of cartilaginous tissues is limited in mammals but it occurs with variable extension in lizards (reptiles), including in their vertebrae. The ability of lizard vertebrae to regenerate cartilaginous tissue that is later replaced with bone has been analyzed using tritiated thymidine autoradiography and 5BrdU immunocytochemistry after single pulse or prolonged-pulse and chase experiments. The massive cartilage regeneration that can restore broad vertebral regions and gives rise to a long cartilaginous tube in the regenerating tail, depends from the permanence of some chondrogenic cells within adult vertebrae. Few cells that retain tritiated thymidine or 5-bromodeoxy-uridine for over 35 days are mainly localized in the inter-vertebral cartilage and in sparse chondrogenic regions of the neural arch of the vertebrae, suggesting that they are putative resident stem/progenitor cells. The study supports previous hypothesis indicating that the massive regeneration of the cartilaginous tissue in damaged vertebrae and in the regenerating tail of lizards derive from resident stem cells mainly present in the cartilaginous areas of the vertebrae including in the perichondrium that are retained in adult lizards as growing centers for most of their lifetime. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Patient Profiling in Cartilage Regeneration Prognostic Factors Determining Success of Treatment for Cartilage Defects

    NARCIS (Netherlands)

    de Windt, Tommy S.; Bekkers, Joris E. J.; Creemers, Laura B.; Dhert, Wouter J. A.; Saris, Daniel B. F.

    2009-01-01

    Background: Cartilage therapy for focal articular lesions has been implemented for more than a decade, and it is becoming increasingly available. What is still lacking, however, is analysis of patient characteristics to help improve outcome or select patients for specific treatment. Purpose: To

  17. In Vitro Mimetic Models for the Bone-Cartilage Interface Regeneration.

    Science.gov (United States)

    Bicho, Diana; Pina, Sandra; Oliveira, J Miguel; Reis, Rui L

    2018-01-01

    In embryonic development, pure cartilage structures are in the basis of bone-cartilage interfaces. Despite this fact, the mature bone and cartilage structures can vary greatly in composition and function. Nevertheless, they collaborate in the osteochondral region to create a smooth transition zone that supports the movements and forces resulting from the daily activities. In this sense, all the hierarchical organization is involved in the maintenance and reestablishment of the equilibrium in case of damage. Therefore, this interface has attracted a great deal of interest in order to understand the mechanisms of regeneration or disease progression in osteoarthritis. With that purpose, in vitro tissue models (either static or dynamic) have been studied. Static in vitro tissue models include monocultures, co-cultures, 3D cultures, and ex vivo cultures, mostly cultivated in flat surfaces, while dynamic models involve the use of bioreactors and microfluidic systems. The latter have emerged as alternatives to study the cellular interactions in a more authentic manner over some disadvantages of the static models. The current alternatives of in vitro mimetic models for bone-cartilage interface regeneration are overviewed and discussed herein.

  18. Fabrication of custom-shaped grafts for cartilage regeneration.

    Science.gov (United States)

    Koo, Seungbum; Hargreaves, Brian A; Gold, Garry E; Dragoo, Jason L

    2010-10-01

    to create a custom-shaped graft through 3D tissue shape reconstruction and rapid-prototype molding methods using MRI data, and to test the accuracy of the custom-shaped graft against the original anatomical defect. An iatrogenic defect on the distal femur was identified with a 1.5 Tesla MRI and its shape was reconstructed into a three-dimensional (3D) computer model by processing the 3D MRI data. First, the accuracy of the MRI-derived 3D model was tested against a laser-scan based 3D model of the defect. A custom-shaped polyurethane graft was fabricated from the laser-scan based 3D model by creating custom molds through computer aided design and rapid-prototyping methods. The polyurethane tissue was laser-scanned again to calculate the accuracy of this process compared to the original defect. The volumes of the defect models from MRI and laser-scan were 537 mm3 and 405 mm3, respectively, implying that the MRI model was 33% larger than the laser-scan model. The average (±SD) distance deviation of the exterior surface of the MRI model from the laser-scan model was 0.4 ± 0.4 mm. The custom-shaped tissue created from the molds was qualitatively very similar to the original shape of the defect. The volume of the custom-shaped cartilage tissue was 463 mm3 which was 15% larger than the laser-scan model. The average (±SD) distance deviation between the two models was 0.04 ± 0.19 mm. This investigation proves the concept that custom-shaped engineered grafts can be fabricated from standard sequence 3-D MRI data with the use of CAD and rapid-prototyping technology. The accuracy of this technology may help solve the interfacial problem between native cartilage and graft, if the grafts are custom made for the specific defect. The major source of error in fabricating a 3D custom-shaped cartilage graft appears to be the accuracy of a MRI data itself; however, the precision of the model is expected to increase by the utilization of advanced MR sequences with higher magnet

  19. The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.

    Science.gov (United States)

    Goldberg, Andy; Mitchell, Katrina; Soans, Julian; Kim, Louise; Zaidi, Razi

    2017-03-09

    The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre

  20. Efficient Computational Design of a Scaffold for Cartilage Cell Regeneration

    DEFF Research Database (Denmark)

    Tajsoleiman, Tannaz; Jafar Abdekhodaie, Mohammad; Gernaey, Krist V.

    2018-01-01

    Due to the sensitivity of mammalian cell cultures, understanding the influence of operating conditions during a tissue generation procedure is crucial. In this regard, a detailed study of scaffold based cell culture under a perfusion flow is presented with the aid of mathematical modelling...... and computational fluid dynamics (CFD). With respect to the complexity of the case study, this work focuses solely on the effect of nutrient and metabolite concentrations, and the possible influence of fluid-induced shear stress on a targeted cell (cartilage) culture. The simulation set up gives the possibility...... of predicting the cell culture behavior under various operating conditions and scaffold designs. Thereby, the exploitation of the predictive simulation into a newly developed stochastic routine provides the opportunity of exploring improved scaffold geometry designs. This approach was applied on a common type...

  1. Gallium nitrate: effects on cartilage during limb regeneration in the axolotl, Ambystoma mexicanum.

    Science.gov (United States)

    Tassava, Roy A; Mendenhall, Luciara; Apseloff, Glen; Gerber, Nicholas

    2002-09-01

    Gallium nitrate, a drug shown to have efficacy in Paget's disease of bone, hypercalcemia of malignancy, and a variety of experimental autoimmune diseases, also inhibits the growth of some types of cancer. We examined dose and timing of administration of gallium nitrate on limb regeneration in the Mexican axolotl, Ambystoma mexicanum. Administered by intraperitoneal injection, gallium nitrate inhibited limb regeneration in a dose-dependent manner. Gallium nitrate initially suppressed epithelial wound healing and subsequently distorted both anterior-posterior and proximo-distal chondrogenic patterns. Gallium nitrate given at three days after amputation severely inhibited regeneration at high doses (6.25 mg/axolotl) and altered the normal patterning of the regenerates at low doses (3.75 mg/axolotl). Administration of 6.25 mg of gallium nitrate at four or 14 days prior to amputation also inhibited regeneration. In amputated limbs of gallium-treated axolotls, the chondrocytes were lost from inside the radius/ulna. Limbs that regenerated after gallium treatment was terminated showed blastema formation preferentially over the ulna. New cartilage of the regenerate often attached to the sides of the existing radius/ulna proximally into the stump and less so to the distal cut ends. J. Exp. Zool. 293:384-394, 2002. Copyright 2002 Wiley-Liss, Inc.

  2. Microsphere-based gradient implants for osteochondral regeneration: a long-term study in sheep

    Science.gov (United States)

    Mohan, Neethu; Gupta, Vineet; Sridharan, Banu Priya; Mellott, Adam J; Easley, Jeremiah T; Palmer, Ross H; Galbraith, Richard A; Key, Vincent H; Berkland, Cory J; Detamore, Michael S

    2015-01-01

    Background: The microfracture technique for cartilage repair has limited ability to regenerate hyaline cartilage. Aim: The current study made a direct comparison between microfracture and an osteochondral approach with microsphere-based gradient plugs. Materials & methods: The PLGA-based scaffolds had opposing gradients of chondroitin sulfate and β-tricalcium phosphate. A 1-year repair study in sheep was conducted. Results: The repair tissues in the microfracture were mostly fibrous and had scattered fissures with degenerative changes. Cartilage regenerated with the gradient plugs had equal or superior mechanical properties; had lacunated cells and stable matrix as in hyaline cartilage. Conclusion: This first report of gradient scaffolds in a long-term, large animal, osteochondral defect demonstrated potential for equal or better cartilage repair than microfracture. PMID:26418471

  3. A novel nano-structured porous polycaprolactone scaffold improves hyaline cartilage repair in a rabbit model compared to a collagen type I/III scaffold: in vitro and in vivo studies.

    Science.gov (United States)

    Christensen, Bjørn Borsøe; Foldager, Casper Bindzus; Hansen, Ole Møller; Kristiansen, Asger Albæk; Le, Dang Quang Svend; Nielsen, Agnete Desirée; Nygaard, Jens Vinge; Bünger, Cody Erik; Lind, Martin

    2012-06-01

    To develop a nano-structured porous polycaprolactone (NSP-PCL) scaffold and compare the articular cartilage repair potential with that of a commercially available collagen type I/III (Chondro-Gide) scaffold. By combining rapid prototyping and thermally induced phase separation, the NSP-PCL scaffold was produced for matrix-assisted autologous chondrocyte implantation. Lyophilizing a water-dioxane-PCL solution created micro and nano-pores. In vitro: The scaffolds were seeded with rabbit chondrocytes and cultured in hypoxia for 6 days. qRT-PCR was performed using primers for sox9, aggrecan, collagen type 1 and 2. In vivo: 15 New Zealand White Rabbits received bilateral osteochondral defects in the femoral intercondylar grooves. Autologous chondrocytes were harvested 4 weeks prior to surgery. There were 3 treatment groups: (1) NSP-PCL scaffold without cells. (2) The Chondro-Gide scaffold with autologous chondrocytes and (3) NSP-PCL scaffold with autologous chondrocytes. Observation period was 13 weeks. Histological evaluation was made using the O'Driscoll score. In vitro: The expressions of sox9 and aggrecan were higher in the NSP-PCL scaffold, while expression of collagen 1 was lower compared to the Chondro-Gide scaffold. In vivo: Both NSP-PCL scaffolds with and without cells scored significantly higher than the Chondro-Gide scaffold when looking at the structural integrity and the surface regularity of the repair tissue. No differences were found between the NSP-PCL scaffold with and without cells. The NSP-PCL scaffold demonstrated higher in vitro expression of chondrogenic markers and had higher in vivo histological scores compared to the Chondro-Gide scaffold. The improved chondrocytic differentiation can potentially produce more hyaline cartilage during clinical cartilage repair. It appears to be a suitable cell-free implant for hyaline cartilage repair and could provide a less costly and more effective treatment option than the Chondro-Gide scaffold with cells.

  4. Characterization and use of Equine Bone Marrow Mesenchymal Stem Cells in Equine Cartilage Engineering. Study of their Hyaline Cartilage Forming Potential when Cultured under Hypoxia within a Biomaterial in the Presence of BMP-2 and TGF-ß1.

    Science.gov (United States)

    Branly, Thomas; Bertoni, Lélia; Contentin, Romain; Rakic, Rodolphe; Gomez-Leduc, Tangni; Desancé, Mélanie; Hervieu, Magalie; Legendre, Florence; Jacquet, Sandrine; Audigié, Fabrice; Denoix, Jean-Marie; Demoor, Magali; Galéra, Philippe

    2017-10-01

    Articular cartilage presents a poor capacity for self-repair. Its structure-function are frequently disrupted or damaged upon physical trauma or osteoarthritis in humans. Similar musculoskeletal disorders also affect horses and are the leading cause of poor performance or early retirement of sport- and racehorses. To develop a therapeutic solution for horses, we tested the autologous chondrocyte implantation technique developed on human bone marrow (BM) mesenchymal stem cells (MSCs) on horse BM-MSCs. This technique involves BM-MSC chondrogenesis using a combinatory approach based on the association of 3D-culture in collagen sponges, under hypoxia in the presence of chondrogenic factors (BMP-2 + TGF-β 1 ) and siRNA to knockdown collagen I and HtrA1. Horse BM-MSCs were characterized before being cultured in chondrogenic conditions to find the best combination to enhance, stabilize, the chondrocyte phenotype. Our results show a very high proliferation of MSCs and these cells satisfy the criteria defining stem cells (pluripotency-surface markers expression). The combination of BMP-2 + TGF-β 1 strongly induces the chondrogenic differentiation of MSCs and prevents HtrA1 expression. siRNAs targeting Col1a1 and Htra1 were functionally validated. Ultimately, the combined use of specific culture conditions defined here with specific growth factors and a Col1a1 siRNAs (50 nM) association leads to the in vitro synthesis of a hyaline-type neocartilage whose chondrocytes present an optimal phenotypic index similar to that of healthy, differentiated chondrocytes. Our results lead the way to setting up pre-clinical trials in horses to better understand the reaction of neocartilage substitute and to carry out a proof-of-concept of this therapeutic strategy on a large animal model.

  5. Strategies on process engineering of chondrocyte culture for cartilage tissue regeneration.

    Science.gov (United States)

    Mallick, Sarada Prasanna; Rastogi, Amit; Tripathi, Satyavrat; Srivastava, Pradeep

    2017-04-01

    The current work is an attempt to study the strategies for cartilage tissue regeneration using porous scaffold in wavy walled airlift bioreactor (ALBR). Novel chitosan, poly (L-lactide) and hyaluronic acid based composite scaffold were prepared. The scaffolds were cross-linked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, N-hydroxysuccinimide and chondroitin sulfate to obtain interconnected 3D microstructure showing excellent biocompatibility, higher cellular differentiation and increased stability. The surface morphology and porosity of the scaffolds were analyzed using scanning electron microscopy (SEM) and mercury intrusion porosimeter and optimized for chondrocyte regeneration. The study shows that the scaffolds were highly porous with pore size ranging from 48 to 180 µm and the porosities in the range 80-92%. Swelling and in vitro degradation studies were performed for the composite scaffolds; by increasing the chitosan: HA ratio in the composite scaffolds, the swelling property increases and stabilizes after 24 h. There was controlled degradation of composite scaffolds for 4 weeks. The uniform chondrocyte distribution in the scaffold using various growth modes in the shake flask and ALBR was studied by glycosaminoglycans (GAG) quantification, MTT assay and mixing time evaluation. The cell culture studies demonstrated that efficient designing of ALBR increases the cartilage regeneration as compared to using a shake flask. The free chondrocyte microscopy and cell attachment were performed by inverted microscope and SEM, and from the study it was confirmed that the cells uniformly attached to the scaffold. This study focuses on optimizing strategies for the culture of chondrocyte using suitable scaffold for improved cartilage tissue regeneration.

  6. [Injectable hydrogel functionalised with thrombocyte-rich solution and microparticles for accelerated cartilage regeneration].

    Science.gov (United States)

    Rampichová, M; Buzgo, M; Křížková, B; Prosecká, E; Pouzar, M; Štrajtová, L

    2013-01-01

    Articular cartilage defects arise due to injury or osteochondral disease such as osteonecrosis or osteochondritis dissecans. In adult patients cartilage has minimal ability to repair itself and the lesions develop into degenerative arthritis. Overcoming the low regenerative capacity of the cartilage cells and the Hayflick limit poses a challenge for the therapy of osteochondral defects. Composite scaffolds with appropriate biomechanical properties combined with a suitable blend of proliferation and differentiation factors could be a solution. The aim of this in vitro study was to develop a novel functionalised hydrogel with an integrated drug delivery system stimulating articular cartilage regeneration. Injectable collagen/ hyaluronic acid/fibrin composite hydrogel was mixed with nanofibre-based microparticles. These were loaded with ascorbic acid and dexamethasone. In addition, the effect of thrombocyte-rich solution (TRS) was studied. The gels seeded with mesenchymal stem cells (MSCs) were cultivated for 14 days. The viability, proliferation and morphology of the cells were evaluated using molecular and microscopic methods. Scaffold degradation was also assessed. The cultivation study showed that MSCs remained viable in all experimental groups, which indicated good biocompatibility of the gel. However, the number of cells in the groups enriched with microparticles was lower than in the other groups. On the other hand, confocal microscopy showed higher cell viability and rounded morphology of the cells, which can be associated with chodrogenic differentiation. The scaffolds containing microparticles showed significantly higher stability during the 14-day experiment. Our results suggest that the addition of microparticles to the scaffold improved cell differentiation into the chondrogenic lineage, resulting in a lower proliferation rate. Cell viability was better in the groups enriched with microparticles that served as an efficient drug delivery system. In

  7. Cartilage regeneration using a porous scaffold, a collagen sponge incorporating a hydroxyapatite/chondroitinsulfate composite

    International Nuclear Information System (INIS)

    Ohyabu, Yohimi; Adegawa, Takuro; Yoshioka, Tomohiko; Ikoma, Toshiyuki; Uemura, Toshimasa; Tanaka, Junzo

    2010-01-01

    Because cartilage has limited potential for self-repair, tissue engineering is expected to replace the present therapies for damaged cartilage, such as total knee arthroplasty. However, scaffolds suitable for cartilage tissue engineering have not been established. We synthesized a novel porous scaffold, a collagen sponge incorporating a hydroxyapatite/chondroitinsulfate composite (pCol-HAp/ChS), containing materials which resemble extracellular matrices in bone and cartilage tissues, which needs high compressive strength for clinical use. HAp/ChS had smaller crystals and a larger total surface area than HAp. SEM images showed pCol-HAp/ChS to have the roughest surface compared with pCol and pCol-HAp. The mechanical properties suggest that pCol-HAp/ChS and pCol/HAp are similar, and superior to pCol. Seeding experiments showed a uniform distribution of mesenchymal stem cells (MSCs) in pCol-HAp/ChS and pCol/HAp. Safranin O, Toluidine blue and Alcian blue staining after 2 weeks of culture revealed pCol-HAp/ChS to be the most chondrogenic in each case. In addition, MSCs in pCol-HAp/ChS produced more glycosaminoglycans, a cartilage matrix, than those in pCol-HAp. Further, pCol-HAp/ChS regenerated 15 times more cartilaginous tissue than pCol. From these results, pCol-HAp/ChS is expected to be a candidate for a scaffold for cartilage tissue engineering in place of collagen sponge.

  8. Cartilage regeneration using a porous scaffold, a collagen sponge incorporating a hydroxyapatite/chondroitinsulfate composite

    Energy Technology Data Exchange (ETDEWEB)

    Ohyabu, Yohimi, E-mail: ooyabu.yoshimi@aist.go.jp [Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, 2-12-1, S7-5 Ookayama, Meguro, Tokyo 152-8550 (Japan); Nanotechnology Research Institute (NRI), National Institute of Advanced Industrial Science and Technology (AIST), Central-4, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566 (Japan); Adegawa, Takuro; Yoshioka, Tomohiko [Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, 2-12-1, S7-5 Ookayama, Meguro, Tokyo 152-8550 (Japan); Ikoma, Toshiyuki [Biomaterials Center, National Institute for Materials Science, 1-1 Sengen, Tsukuba, Ibaraki, 305-0047 (Japan); Uemura, Toshimasa [Nanotechnology Research Institute (NRI), National Institute of Advanced Industrial Science and Technology (AIST), Central-4, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566 (Japan); Tanaka, Junzo [Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, 2-12-1, S7-5 Ookayama, Meguro, Tokyo 152-8550 (Japan)

    2010-10-15

    Because cartilage has limited potential for self-repair, tissue engineering is expected to replace the present therapies for damaged cartilage, such as total knee arthroplasty. However, scaffolds suitable for cartilage tissue engineering have not been established. We synthesized a novel porous scaffold, a collagen sponge incorporating a hydroxyapatite/chondroitinsulfate composite (pCol-HAp/ChS), containing materials which resemble extracellular matrices in bone and cartilage tissues, which needs high compressive strength for clinical use. HAp/ChS had smaller crystals and a larger total surface area than HAp. SEM images showed pCol-HAp/ChS to have the roughest surface compared with pCol and pCol-HAp. The mechanical properties suggest that pCol-HAp/ChS and pCol/HAp are similar, and superior to pCol. Seeding experiments showed a uniform distribution of mesenchymal stem cells (MSCs) in pCol-HAp/ChS and pCol/HAp. Safranin O, Toluidine blue and Alcian blue staining after 2 weeks of culture revealed pCol-HAp/ChS to be the most chondrogenic in each case. In addition, MSCs in pCol-HAp/ChS produced more glycosaminoglycans, a cartilage matrix, than those in pCol-HAp. Further, pCol-HAp/ChS regenerated 15 times more cartilaginous tissue than pCol. From these results, pCol-HAp/ChS is expected to be a candidate for a scaffold for cartilage tissue engineering in place of collagen sponge.

  9. Effects of osteochondral defect size on cartilage regeneration using a double-network hydrogel.

    Science.gov (United States)

    Higa, Kotaro; Kitamura, Nobuto; Goto, Keiko; Kurokawa, Takayuki; Gong, Jian Ping; Kanaya, Fuminori; Yasuda, Kazunori

    2017-05-22

    There has been increased interest in one-step cell-free procedures to avoid the problems related to cell manipulation and its inherent disadvantages. We have studied the chondrogenic induction ability of a PAMPS/PDMAAm double-network (DN) gel and found it to induce chondrogenesis in animal osteochondral defect models. The purpose of this study was to investigate whether the healing process and the degree of cartilage regeneration induced by the cell-free method using DN gel are influenced by the size of osteochondral defects. A total of 63 mature female Japanese white rabbits were used in this study, randomly divided into 3 groups of 21 rabbits each. A 2.5-mm diameter osteochondral defect was created in the femoral trochlea of the patellofemoral joint of bilateral knees in Group I, a 4.3-mm osteochondral defect in Group II, and a 5.8-mm osteochondral defect in Group III. In the right knee of each animal, a DN gel plug was implanted so that a vacant space of 2-mm depth was left above the plug. In the left knee, we did not conduct any treatment to obtain control data. Animals were sacrificed at 2, 4, and 12 weeks after surgery, and gross and histological evaluations were made. The present study demonstrated that all sizes of the DN gel implanted defects as well as the 2.5mm untreated defects showed cartilage regeneration at 4 and 12 weeks. The 4.3-mm and 5.8-mm untreated defects did not show cartilage regeneration during the 12-week period. The quantitative score reported by O'Driscoll et al. was significantly higher in the 4.3-mm and 5.8-mm DN gel-implanted defects than the untreated defects at 4 and 12 weeks (p regeneration in defects between 2.5 and 5.8 mm, offering a promising device to establish a cell-free cartilage regeneration therapy and applicable to various sizes of osteochondral defects.

  10. Cartilage constructs from human cord blood stem cells seeded in structurally-graded polycaprolactone scaffolds

    DEFF Research Database (Denmark)

    Munir, Samir; Koch, Thomas Gadegaard; Foldager, Casper Bindzus

    Cartilage is an avascular tissue incapable of regeneration. Current treatment modalities for joint cartilage injuries are inefficient in regenerating hyaline cartilage and often leads to the formation of fibrocartilage with undesirable mechanical properties. There is an increasing interest...... in investigating alternative treatments such as tissue engineering, which combines stem cells with scaffolds to produce cartilage in vitro for subsequent transplant. Previous studies have shown that chondrogenesis of induced stem cells is influenced by various growth factors, oxygen tensions and mechanical...... this novel SGS-PCL scaffold supports the chondrogenic differentiation of MLPCs will be interesting to evaluate since this scaffold possesses mechanical properties absent from other “soft” scaffolds currently being investigated for cartilage regeneration and implantation....

  11. Three-Dimensional Bioprinting and Its Potential in the Field of Articular Cartilage Regeneration

    Science.gov (United States)

    Mouser, Vivian H. M.; Levato, Riccardo; Bonassar, Lawrence J.; D’Lima, Darryl D.; Grande, Daniel A.; Klein, Travis J.; Saris, Daniel B. F.; Zenobi-Wong, Marcy; Gawlitta, Debby; Malda, Jos

    2016-01-01

    Three-dimensional (3D) bioprinting techniques can be used for the fabrication of personalized, regenerative constructs for tissue repair. The current article provides insight into the potential and opportunities of 3D bioprinting for the fabrication of cartilage regenerative constructs. Although 3D printing is already used in the orthopedic clinic, the shift toward 3D bioprinting has not yet occurred. We believe that this shift will provide an important step forward in the field of cartilage regeneration. Three-dimensional bioprinting techniques allow incorporation of cells and biological cues during the manufacturing process, to generate biologically active implants. The outer shape of the construct can be personalized based on clinical images of the patient’s defect. Additionally, by printing with multiple bio-inks, osteochondral or zonally organized constructs can be generated. Relevant mechanical properties can be obtained by hybrid printing with thermoplastic polymers and hydrogels, as well as by the incorporation of electrospun meshes in hydrogels. Finally, bioprinting techniques contribute to the automation of the implant production process, reducing the infection risk. To prompt the shift from nonliving implants toward living 3D bioprinted cartilage constructs in the clinic, some challenges need to be addressed. The bio-inks and required cartilage construct architecture need to be further optimized. The bio-ink and printing process need to meet the sterility requirements for implantation. Finally, standards are essential to ensure a reproducible quality of the 3D printed constructs. Once these challenges are addressed, 3D bioprinted living articular cartilage implants may find their way into daily clinical practice. PMID:28934880

  12. Endogenous Cartilage Repair by Recruitment of Stem Cells.

    Science.gov (United States)

    Im, Gun-Il

    2016-04-01

    Articular cartilage has a very limited capacity for repair after injury. The adult body has a pool of stem cells that are mobilized during injury or disease. These cells exist inside niches in bone marrow, muscle, adipose tissue, synovium, and other connective tissues. A method that mobilizes this endogenous pool of stem cells will provide a less costly and less invasive alternative if these cells successfully regenerate defective cartilage. Traditional microfracture procedures employ the concept of bone marrow stimulation to regenerate cartilage. However, the regenerated tissue usually is fibrous cartilage, which has very poor mechanical properties compared to those of normal hyaline cartilage. A method that directs the migration of a large number of autologous mesenchymal stem cells toward injury sites, retains these cells around the defects, and induces chondrogenic differentiation that would enhance success of endogenous cartilage repair. This review briefly summarizes chemokines and growth factors that induce recruitment, proliferation, and differentiation of endogenous progenitor cells, endogenous cell sources for regenerating cartilage, scaffolds for delivery of bioactive factors, and bioadhesive materials that are necessary to bring about endogenous cartilage repair.

  13. A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration

    Science.gov (United States)

    Meng, Qingyang; Man, Zhentao; Dai, Linghui; Huang, Hongjie; Zhang, Xin; Hu, Xiaoqing; Shao, Zhenxing; Zhu, Jingxian; Zhang, Jiying; Fu, Xin; Duan, Xiaoning; Ao, Yingfang

    2015-12-01

    Articular cartilage injury is still a significant challenge because of the poor intrinsic healing potential of cartilage. Stem cell-based tissue engineering is a promising technique for cartilage repair. As cartilage defects are usually irregular in clinical settings, scaffolds with moldability that can fill any shape of cartilage defects and closely integrate with the host cartilage are desirable. In this study, we constructed a composite scaffold combining mesenchymal stem cells (MSCs) E7 affinity peptide-modified demineralized bone matrix (DBM) particles and chitosan (CS) hydrogel for cartilage engineering. This solid-supported composite scaffold exhibited appropriate porosity, which provided a 3D microenvironment that supports cell adhesion and proliferation. Cell proliferation and DNA content analysis indicated that the DBM-E7/CS scaffold promoted better rat bone marrow-derived MSCs (BMMSCs) survival than the CS or DBM/CS groups. Meanwhile, the DBM-E7/CS scaffold increased matrix production and improved chondrogenic differentiation ability of BMMSCs in vitro. Furthermore, after implantation in vivo for four weeks, compared to those in control groups, the regenerated issue in the DBM-E7/CS group exhibited translucent and superior cartilage-like structures, as indicated by gross observation, histological examination, and assessment of matrix staining. Overall, the functional composite scaffold of DBM-E7/CS is a promising option for repairing irregularly shaped cartilage defects.

  14. In Vivo Articular Cartilage Regeneration Using Human Dental Pulp Stem Cells Cultured in an Alginate Scaffold: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Manuel Mata

    2017-01-01

    Full Text Available Osteoarthritis is an inflammatory disease in which all joint-related elements, articular cartilage in particular, are affected. The poor regeneration capacity of this tissue together with the lack of pharmacological treatment has led to the development of regenerative medicine methodologies including microfracture and autologous chondrocyte implantation (ACI. The effectiveness of ACI has been shown in vitro and in vivo, but the use of other cell types, including bone marrow and adipose-derived mesenchymal stem cells, is necessary because of the poor proliferation rate of isolated articular chondrocytes. In this investigation, we assessed the chondrogenic ability of human dental pulp stem cells (hDPSCs to regenerate cartilage in vitro and in vivo. hDPSCs and primary isolated rabbit chondrocytes were cultured in chondrogenic culture medium and found to express collagen II and aggrecan. Both cell types were cultured in 3% alginate hydrogels and implanted in a rabbit model of cartilage damage. Three months after surgery, significant cartilage regeneration was observed, particularly in the animals implanted with hDPSCs. Although the results presented here are preliminary, they suggest that hDPSCs may be useful for regeneration of articular cartilage.

  15. In Vivo Articular Cartilage Regeneration Using Human Dental Pulp Stem Cells Cultured in an Alginate Scaffold: A Preliminary Study.

    Science.gov (United States)

    Mata, Manuel; Milian, Lara; Oliver, Maria; Zurriaga, Javier; Sancho-Tello, Maria; de Llano, Jose Javier Martin; Carda, Carmen

    2017-01-01

    Osteoarthritis is an inflammatory disease in which all joint-related elements, articular cartilage in particular, are affected. The poor regeneration capacity of this tissue together with the lack of pharmacological treatment has led to the development of regenerative medicine methodologies including microfracture and autologous chondrocyte implantation (ACI). The effectiveness of ACI has been shown in vitro and in vivo , but the use of other cell types, including bone marrow and adipose-derived mesenchymal stem cells, is necessary because of the poor proliferation rate of isolated articular chondrocytes. In this investigation, we assessed the chondrogenic ability of human dental pulp stem cells (hDPSCs) to regenerate cartilage in vitro and in vivo . hDPSCs and primary isolated rabbit chondrocytes were cultured in chondrogenic culture medium and found to express collagen II and aggrecan. Both cell types were cultured in 3% alginate hydrogels and implanted in a rabbit model of cartilage damage. Three months after surgery, significant cartilage regeneration was observed, particularly in the animals implanted with hDPSCs. Although the results presented here are preliminary, they suggest that hDPSCs may be useful for regeneration of articular cartilage.

  16. The role of laminins in cartilaginous tissues: from development to regeneration.

    Science.gov (United States)

    Sun, Y; Wang, T L; Toh, W S; Pei, M

    2017-07-21

    As a key molecule of the extracellular matrix, laminin provides a delicate microenvironment for cell functions. Recent findings suggest that laminins expressed by cartilage-forming cells (chondrocytes, progenitor cells and stem cells) could promote chondrogenesis. However, few papers outline the effect of laminins on providing a favorable matrix microenvironment for cartilage regeneration. In this review, we delineated the expression of laminins in hyaline cartilage, fibrocartilage and cartilage-like tissue (nucleus pulposus) throughout several developmental stages. We also examined the effect of laminins on the biological activities of chondrocytes, including adhesion, migration and survival. Furthermore, we scrutinized the potential influence of various laminin isoforms on cartilage-forming cells' proliferation and chondrogenic differentiation. With this information, we hope to facilitate the understanding of the spatial and temporal interactions between cartilage-forming cells and laminin microenvironment to eventually advance cell-based cartilage engineering and regeneration.

  17. The role of laminins in cartilaginous tissues: from development to regeneration

    Directory of Open Access Journals (Sweden)

    Y Sun

    2017-07-01

    Full Text Available As a key molecule of the extracellular matrix, laminin provides a delicate microenvironment for cell functions. Recent findings suggest that laminins expressed by cartilage-forming cells (chondrocytes, progenitor cells and stem cells could promote chondrogenesis. However, few papers outline the effect of laminins on providing a favorable matrix microenvironment for cartilage regeneration. In this review, we delineated the expression of laminins in hyaline cartilage, fibrocartilage and cartilage-like tissue (nucleus pulposus throughout several developmental stages. We also examined the effect of laminins on the biological activities of chondrocytes, including adhesion, migration and survival. Furthermore, we scrutinized the potential influence of various laminin isoforms on cartilage-forming cells’ proliferation and chondrogenic differentiation. With this information, we hope to facilitate the understanding of the spatial and temporal interactions between cartilage-forming cells and laminin microenvironment to eventually advance cell-based cartilage engineering and regeneration.

  18. Solid freeform-fabricated scaffolds designed to carry multicellular mesenchymal stem cell spheroids for cartilage regeneration

    Directory of Open Access Journals (Sweden)

    G-S Huang

    2013-10-01

    Full Text Available Three-dimensional (3D cellular spheroids have recently emerged as a new trend to replace suspended single cells in modern cell-based therapies because of their greater regeneration capacities in vitro. They may lose the 3D structure during a change of microenvironment, which poses challenges to their translation in vivo. Besides, the conventional microporous scaffolds may have difficulty in accommodating these relatively large spheroids. Here we revealed a novel design of microenvironment for delivering and sustaining the 3D spheroids. Biodegradable scaffolds with macroporosity to accommodate mesenchymal stem cell (MSC spheroids were made by solid freeform fabrication (SFF from the solution of poly(D,L-lactide-co-glycolide. Their internal surface was modified with chitosan following air plasma treatment in order to preserve the morphology of the spheroids. It was demonstrated that human MSC spheroids loaded in SFF scaffolds produced a significantly larger amount of cartilage-associated extracellular matrix in vitro and in NOD/SCID mice compared to single cells in the same scaffolds. Implantation of MSC spheroid-loaded scaffolds into the chondral defects of rabbit knees showed superior cartilage regeneration. This study establishes new perspectives in designing the spheroid-sustaining microenvironment within a tissue engineering scaffold for in vivo applications.

  19. One-Step Cartilage Repair Technique as a Next Generation of Cell Therapy for Cartilage Defects: Biological Characteristics, Preclinical Application, Surgical Techniques, and Clinical Developments.

    Science.gov (United States)

    Zhang, Chi; Cai, You-Zhi; Lin, Xiang-Jin

    2016-07-01

    To provide a comprehensive overview of the basic science rationale, surgical technique, and clinical outcomes of 1-step cartilage repair technique used as a treatment strategy for cartilage defects. A systematic review was performed in the main medical databases to evaluate the several studies concerning 1-step procedures for cartilage repair. The characteristics of cell-seed scaffolds, behavior of cells seeded into scaffolds, and surgical techniques were also discussed. Clinical outcomes and quality of repaired tissue were assessed using several standardized outcome assessment tools, magnetic resonance imaging scans, and biopsy histology. One-step cartilage repair could be divided into 2 types: chondrocyte-matrix complex (CMC) and autologous matrix-induced chondrogenesis (AMIC), both of which allow a simplified surgical approach. Studies with Level IV evidence have shown that 1-step cartilage repair techniques could significantly relieve symptoms and improve functional assessment (P studies clearly showed hyaline-like cartilage tissue in biopsy tissues by second-look arthroscopy. The 1-step cartilage repair technique, with its potential for effective, homogeneous distribution of chondrocytes and multipotent stem cells on the surface of the cartilage defect, is able to regenerate hyaline-like cartilage tissue, and it could be applied to cartilage repair by arthroscopy. Level IV, systematic review of Level II and IV studies. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  20. Stem Cells and Gene Therapy for Cartilage Repair

    Directory of Open Access Journals (Sweden)

    Umile Giuseppe Longo

    2012-01-01

    Full Text Available Cartilage defects represent a common problem in orthopaedic practice. Predisposing factors include traumas, inflammatory conditions, and biomechanics alterations. Conservative management of cartilage defects often fails, and patients with this lesions may need surgical intervention. Several treatment strategies have been proposed, although only surgery has been proved to be predictably effective. Usually, in focal cartilage defects without a stable fibrocartilaginous repair tissue formed, surgeons try to promote a natural fibrocartilaginous response by using marrow stimulating techniques, such as microfracture, abrasion arthroplasty, and Pridie drilling, with the aim of reducing swelling and pain and improving joint function of the patients. These procedures have demonstrated to be clinically useful and are usually considered as first-line treatment for focal cartilage defects. However, fibrocartilage presents inferior mechanical and biochemical properties compared to normal hyaline articular cartilage, characterized by poor organization, significant amounts of collagen type I, and an increased susceptibility to injury, which ultimately leads to premature osteoarthritis (OA. Therefore, the aim of future therapeutic strategies for articular cartilage regeneration is to obtain a hyaline-like cartilage repair tissue by transplantation of tissues or cells. Further studies are required to clarify the role of gene therapy and mesenchimal stem cells for management of cartilage lesions.

  1. High Throughput and Mechano-Active Platforms to Promote Cartilage Regeneration and Repair

    Science.gov (United States)

    Mohanraj, Bhavana

    chondrogenesis, demonstrating the potential of MAMCs to actively deliver therapeutics within demanding mechanical environments. Taken together, this work advances our capacity to identify and deliver new compounds of clinical relevance to modulate disease progression following traumatic injury using state-of-the-art micro-engineered screening tools and a novel mechanically-activated delivery system. These platforms advance strategies for cartilage repair and regeneration in PTOA and provide new options for the treatment of this debilitating condition.

  2. Cartilage tissue engineering: Role of mesenchymal stem cells along with growth factors & scaffolds

    Directory of Open Access Journals (Sweden)

    M B Gugjoo

    2016-01-01

    Full Text Available Articular cartilage injury poses a major challenge for both the patient and orthopaedician. Articular cartilage defects once formed do not regenerate spontaneously, rather replaced by fibrocartilage which is weaker in mechanical competence than the normal hyaline cartilage. Mesenchymal stem cells (MSCs along with different growth factors and scaffolds are currently incorporated in tissue engineering to overcome the deficiencies associated with currently available surgical methods and to facilitate cartilage healing. MSCs, being readily available with a potential to differentiate into chondrocytes which are enhanced by the application of different growth factors, are considered for effective repair of articular cartilage after injury. However, therapeutic application of MSCs and growth factors for cartilage repair remains in its infancy, with no comparative clinical study to that of the other surgical techniques. The present review covers the role of MSCs, growth factors and scaffolds for the repair of articular cartilage injury.

  3. Regeneration of articular cartilage by adipose tissue derived mesenchymal stem cells: perspectives from stem cell biology and molecular medicine.

    Science.gov (United States)

    Wu, Ling; Cai, Xiaoxiao; Zhang, Shu; Karperien, Marcel; Lin, Yunfeng

    2013-05-01

    Adipose-derived stem cells (ASCs) have been discovered for more than a decade. Due to the large numbers of cells that can be harvested with relatively little donor morbidity, they are considered to be an attractive alternative to bone marrow derived mesenchymal stem cells. Consequently, isolation and differentiation of ASCs draw great attention in the research of tissue engineering and regenerative medicine. Cartilage defects cause big therapeutic problems because of their low self-repair capacity. Application of ASCs in cartilage regeneration gives hope to treat cartilage defects with autologous stem cells. In recent years, a lot of studies have been performed to test the possibility of using ASCs to re-construct damaged cartilage tissue. In this article, we have reviewed the most up-to-date articles utilizing ASCs for cartilage regeneration in basic and translational research. Our topic covers differentiation of adipose tissue derived mesenchymal stem cells into chondrocytes, increased cartilage formation by co-culture of ASCs with chondrocytes and enhancing chondrogenic differentiation of ASCs by gene manipulation. Copyright © 2012 Wiley Periodicals, Inc.

  4. Dental mesenchymal stem cells encapsulated in an alginate hydrogel co-delivery microencapsulation system for cartilage regeneration.

    Science.gov (United States)

    Moshaverinia, Alireza; Xu, Xingtian; Chen, Chider; Akiyama, Kentaro; Snead, Malcolm L; Shi, Songtao

    2013-12-01

    Dental-derived mesenchymal stem cells (MSCs) are promising candidates for cartilage regeneration, with a high capacity for chondrogenic differentiation. This property helps make dental MSCs an advantageous therapeutic option compared to current treatment modalities. The MSC delivery vehicle is the principal determinant for the success of MSC-mediated cartilage regeneration therapies. The objectives of this study were to: (1) develop a novel co-delivery system based on TGF-β1 loaded RGD-coupled alginate microspheres encapsulating periodontal ligament stem cells (PDLSCs) or gingival mesenchymal stem cells (GMSCs); and (2) investigate dental MSC viability and chondrogenic differentiation in alginate microspheres. The results revealed the sustained release of TGF-β1 from the alginate microspheres. After 4 weeks of chondrogenic differentiation in vitro, PDLSCs and GMSCs as well as human bone marrow mesenchymal stem cells (hBMMSCs) (as positive control) revealed chondrogenic gene expression markers (Col II and Sox-9) via qPCR, as well as matrix positively stained by Toluidine Blue and Safranin-O. In animal studies, ectopic cartilage tissue regeneration was observed inside and around the transplanted microspheres, confirmed by histochemical and immunofluorescent staining. Interestingly, PDLSCs showed more chondrogenesis than GMSCs and hBMMSCs (palginate microencapsulating dental MSCs make a promising candidate for cartilage regeneration. Our results highlight the vital role played by the microenvironment, as well as value of presenting inductive signals for viability and differentiation of MSCs. Copyright © 2013 Acta Materialia Inc. All rights reserved.

  5. Articular cartilage: from formation to tissue engineering.

    Science.gov (United States)

    Camarero-Espinosa, Sandra; Rothen-Rutishauser, Barbara; Foster, E Johan; Weder, Christoph

    2016-05-26

    Hyaline cartilage is the nonlinear, inhomogeneous, anisotropic, poro-viscoelastic connective tissue that serves as friction-reducing and load-bearing cushion in synovial joints and is vital for mammalian skeletal movements. Due to its avascular nature, low cell density, low proliferative activity and the tendency of chondrocytes to de-differentiate, cartilage cannot regenerate after injury, wear and tear, or degeneration through common diseases such as osteoarthritis. Therefore severe damage usually requires surgical intervention. Current clinical strategies to generate new tissue include debridement, microfracture, autologous chondrocyte transplantation, and mosaicplasty. While articular cartilage was predicted to be one of the first tissues to be successfully engineered, it proved to be challenging to reproduce the complex architecture and biomechanical properties of the native tissue. Despite significant research efforts, only a limited number of studies have evolved up to the clinical trial stage. This review article summarizes the current state of cartilage tissue engineering in the context of relevant biological aspects, such as the formation and growth of hyaline cartilage, its composition, structure and biomechanical properties. Special attention is given to materials development, scaffold designs, fabrication methods, and template-cell interactions, which are of great importance to the structure and functionality of the engineered tissue.

  6. From gristle to chondrocyte transplantation: treatment of cartilage injuries.

    Science.gov (United States)

    Lindahl, Anders

    2015-10-19

    This review addresses the progress in cartilage repair technology over the decades with an emphasis on cartilage regeneration with cell therapy. The most abundant cartilage is the hyaline cartilage that covers the surface of our joints and, due to avascularity, this tissue is unable to repair itself. The cartilage degeneration seen in osteoarthritis causes patient suffering and is a huge burden to society. The surgical approach to cartilage repair was non-existing until the 1950s when new surgical techniques emerged. The use of cultured cells for cell therapy started as experimental studies in the 1970s that developed over the years to a clinical application in 1994 with the introduction of the autologous chondrocyte transplantation technique (ACT). The technology is now spread worldwide and has been further refined by combining arthroscopic techniques with cells cultured on matrix (MACI technology). The non-regenerating hypothesis of cartilage has been revisited and we are now able to demonstrate cell divisions and presence of stem-cell niches in the joint. Furthermore, cartilage derived from human embryonic stem cells and induced pluripotent stem cells could be the base for new broader cell treatments for cartilage injuries and the future technology base for prevention and cure of osteoarthritis. © 2015 The Author(s).

  7. From gristle to chondrocyte transplantation: treatment of cartilage injuries

    Science.gov (United States)

    Lindahl, Anders

    2015-01-01

    This review addresses the progress in cartilage repair technology over the decades with an emphasis on cartilage regeneration with cell therapy. The most abundant cartilage is the hyaline cartilage that covers the surface of our joints and, due to avascularity, this tissue is unable to repair itself. The cartilage degeneration seen in osteoarthritis causes patient suffering and is a huge burden to society. The surgical approach to cartilage repair was non-existing until the 1950s when new surgical techniques emerged. The use of cultured cells for cell therapy started as experimental studies in the 1970s that developed over the years to a clinical application in 1994 with the introduction of the autologous chondrocyte transplantation technique (ACT). The technology is now spread worldwide and has been further refined by combining arthroscopic techniques with cells cultured on matrix (MACI technology). The non-regenerating hypothesis of cartilage has been revisited and we are now able to demonstrate cell divisions and presence of stem-cell niches in the joint. Furthermore, cartilage derived from human embryonic stem cells and induced pluripotent stem cells could be the base for new broader cell treatments for cartilage injuries and the future technology base for prevention and cure of osteoarthritis. PMID:26416680

  8. Cartilage.

    Science.gov (United States)

    Caplan, Arnold I.

    1984-01-01

    Cartilage is a fundamental biological material that helps to shape the body and then helps to support it. Its fundamental properties of strength and resilience are explained in terms of the tissue's molecular structure. (JN)

  9. Role of RHEB in Regulating Differentiation Fate of Mesenchymal Stem Cells for Cartilage and Bone Regeneration

    Directory of Open Access Journals (Sweden)

    Sajjad Ashraf

    2017-04-01

    Full Text Available Advances in mesenchymal stem cells (MSCs and cell replacement therapies are promising approaches to treat cartilage and bone defects since substantial differentiation capacities of MSCs match the demands of tissue regeneration. Our understanding of the dynamic process requiring indispensable differentiation of MSCs remains limited. Herein, we describe the role of RHEB (Ras homolog enriched in brain regulating gene signature for differentiation of human adipose derived mesenchymal stem cells (ASCs into chondrogenic, osteogenic, and adipogenic lineages. RHEB-overexpression increases the proliferation of the ASCs. RHEB enhances the chondrogenic differentiation of ASCs in 3D culture via upregulation of SOX9 with concomitant increase in glycosaminoglycans (GAGs, and type II collagen (COL2. RHEB increases the osteogenesis via upregulation of runt related transcription factor 2 (RUNX2 with an increase in the calcium and phosphate contents. RHEB also increases the expression of osteogenic markers, osteonectin and osteopontin. RHEB knockdown ASCs were incapable of expressing sufficient SRY (Sex determining region Y-box 9 (SOX9 and RUNX2, and therefore had decreased chondrogenic and osteogenic differentiation. RHEB-overexpression impaired ASCs differentiation into adipogenic lineage, through downregulation of CCAAT/enhancer binding protein beta (C/EBPβ. Conversely, RHEB knockdown abolished the negative regulation of adipogenesis. We demonstrate that RHEB is a novel regulator, with a critical role in ASCs lineage determination, and RHEB-modulated ASCs may be useful as a cell therapy for cartilage and bone defect treatments.

  10. Adipose-derived mesenchymal stem cells for cartilage tissue engineering: state-of-the-art in in vivo studies.

    Science.gov (United States)

    Veronesi, Francesca; Maglio, Melania; Tschon, Matilde; Aldini, Nicolò Nicoli; Fini, Milena

    2014-07-01

    Several therapeutic approaches have been developed to address hyaline cartilage regeneration, but to date, there is no universal procedure to promote the restoration of mechanical and functional properties of native cartilage, which is one of the most important challenges in orthopedic surgery. For cartilage tissue engineering, adult mesenchymal stem cells (MSCs) are considered as an alternative cell source to chondrocytes. Since little is known about adipose-derived mesenchymal stem cell (ADSC) cartilage regeneration potential, the aim of this review was to give an overview of in vivo studies about the chondrogenic potential and regeneration ability of culture-expanded ADSCs when implanted in heterotopic sites or in osteoarthritic and osteochondral defects. The review compares the different studies in terms of number of implanted cells and animals, cell harvesting sites, in vitro expansion and chondrogenic induction conditions, length of experimental time, defect dimensions, used scaffolds and post-explant analyses of the cartilage regeneration. Despite variability of the in vivo protocols, it seems that good cartilage formation and regeneration were obtained with chondrogenically predifferentiated ADSCs (1 × 10(7) cells for heterotopic cartilage formation and 1 × 10(6) cells/scaffold for cartilage defect regeneration) and polymeric scaffolds, even if many other aspects need to be clarified in future studies. © 2013 Wiley Periodicals, Inc.

  11. THE FUNCTIONAL EFFECTIVENESS OF A CELL-ENGINEERED CONSTRUCT FOR THE REGENERATION OF ARTICULAR CARTILAGE

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    V. I. Sevastianov

    2015-01-01

    Full Text Available The aim of this study is an analysis of the functional effectiveness of a biomedical cell product consisting of a biopolymer microheterogeneous collagen-containing hydrogel (BMCH, human adipose-derived mesenchymal stromal cells (hADMSCs, and chondrogenic induction medium in the regeneration of articular cartilage. Materials and methods. The test model of the adjuvant arthritis was used (female Soviet Chinchilla rabbits with the further development into osteoarthrosis (OA combined with the clinical, biochemical, radiological, and histochemical trials. Results. On Day 92 of the OA model it has been found that the intra-articular introduction of a BMCH with hADMSCs into the left knee joint (n = 3 30 days after the OA modeling, as opposed to the right joint (negative control, n = 3, stimulates the regenerative processes of the cartilaginous tissue structure characterized by the formation of chondrocyte «columns», the emergence of isogenic groups in the intracellular matrix and the regeneration of its structure. Upon the intra-articular introduction of a BMCH (n = 3 such effects are markedly less pronounced. Conclusions. A significant regenerative potential of a cell-engineered construct of human articular tissue (CEC ATh has been proven. It is possible to presume that biostimulating properties of CEC ATh are due to the activating effect of a biomedical cell product on the stem cell migration processes from the surrounding tissue into the injured area with their subsequent differentiation. 

  12. Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration.

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    Qian-Shi Zhang

    Full Text Available Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1, also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5, after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven days after punch, the wound epidermis morphology was markedly different in the KO, showing a thickened stratum corneum with rounded cell morphology and a reduction of both the granular cell layer and decreased expression of filament aggregating protein. In addition, cytokeratin 6 was expressed in the stratum spinosum and granulosum. Topical application of inhibitors of ASK1 (NQDI-1, the upstream ASK1 activator, calcium activated mitogen kinase 2 (KN93, or the downstream target, c-Jun N-terminal kinase (SP600125 also resulted in enhanced regeneration; whereas inhibition of the other downstream target, the p38 α/β isoforms, (SB203580 had no effect. The results of this investigation indicate ASK1 inhibition prolongs keratinocyte and blastemal cell activation leading to ear regeneration.

  13. Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration

    Science.gov (United States)

    Zhang, Qian-Shi; Kurpad, Deepa S.; Mahoney, My G.; Steinbeck, Marla J.

    2017-01-01

    Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO) or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1), also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5), after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven days after punch, the wound epidermis morphology was markedly different in the KO, showing a thickened stratum corneum with rounded cell morphology and a reduction of both the granular cell layer and decreased expression of filament aggregating protein. In addition, cytokeratin 6 was expressed in the stratum spinosum and granulosum. Topical application of inhibitors of ASK1 (NQDI-1), the upstream ASK1 activator, calcium activated mitogen kinase 2 (KN93), or the downstream target, c-Jun N-terminal kinase (SP600125) also resulted in enhanced regeneration; whereas inhibition of the other downstream target, the p38 α/β isoforms, (SB203580) had no effect. The results of this investigation indicate ASK1 inhibition prolongs keratinocyte and blastemal cell activation leading to ear regeneration. PMID:29045420

  14. Genipin-Crosslinked Chitosan Gels and Scaffolds for Tissue Engineering and Regeneration of Cartilage and Bone.

    Science.gov (United States)

    Muzzarelli, Riccardo A A; El Mehtedi, Mohamad; Bottegoni, Carlo; Aquili, Alberto; Gigante, Antonio

    2015-12-11

    The present review article intends to direct attention to the technological advances made since 2009 in the area of genipin-crosslinked chitosan (GEN-chitosan) hydrogels. After a concise introduction on the well recognized characteristics of medical grade chitosan and food grade genipin, the properties of GEN-chitosan obtained with a safe, spontaneous and irreversible chemical reaction, and the quality assessment of the gels are reviewed. The antibacterial activity of GEN-chitosan has been well assessed in the treatment of gastric infections supported by Helicobacter pylori. Therapies based on chitosan alginate crosslinked with genipin include stem cell transplantation, and development of contraction free biomaterials suitable for cartilage engineering. Collagen, gelatin and other proteins have been associated to said hydrogels in view of the regeneration of the cartilage. Viability and proliferation of fibroblasts were impressively enhanced upon addition of poly-l-lysine. The modulation of the osteocytes has been achieved in various ways by applying advanced technologies such as 3D-plotting and electrospinning of biomimetic scaffolds, with optional addition of nano hydroxyapatite to the formulations. A wealth of biotechnological advances and know-how has permitted reaching outstanding results in crucial areas such as cranio-facial surgery, orthopedics and dentistry. It is mandatory to use scaffolds fully characterized in terms of porosity, pore size, swelling, wettability, compressive strength, and degree of acetylation, if the osteogenic differentiation of human mesenchymal stem cells is sought: in fact, the novel characteristics imparted by GEN-chitosan must be simultaneously of physico-chemical and cytological nature. Owing to their high standard, the scientific publications dated 2010-2015 have met the expectations of an interdisciplinary audience.

  15. Genipin-Crosslinked Chitosan Gels and Scaffolds for Tissue Engineering and Regeneration of Cartilage and Bone

    Directory of Open Access Journals (Sweden)

    Riccardo A. A. Muzzarelli

    2015-12-01

    Full Text Available The present review article intends to direct attention to the technological advances made since 2009 in the area of genipin-crosslinked chitosan (GEN-chitosan hydrogels. After a concise introduction on the well recognized characteristics of medical grade chitosan and food grade genipin, the properties of GEN-chitosan obtained with a safe, spontaneous and irreversible chemical reaction, and the quality assessment of the gels are reviewed. The antibacterial activity of GEN-chitosan has been well assessed in the treatment of gastric infections supported by Helicobacter pylori. Therapies based on chitosan alginate crosslinked with genipin include stem cell transplantation, and development of contraction free biomaterials suitable for cartilage engineering. Collagen, gelatin and other proteins have been associated to said hydrogels in view of the regeneration of the cartilage. Viability and proliferation of fibroblasts were impressively enhanced upon addition of poly-l-lysine. The modulation of the osteocytes has been achieved in various ways by applying advanced technologies such as 3D-plotting and electrospinning of biomimetic scaffolds, with optional addition of nano hydroxyapatite to the formulations. A wealth of biotechnological advances and know-how has permitted reaching outstanding results in crucial areas such as cranio-facial surgery, orthopedics and dentistry. It is mandatory to use scaffolds fully characterized in terms of porosity, pore size, swelling, wettability, compressive strength, and degree of acetylation, if the osteogenic differentiation of human mesenchymal stem cells is sought: in fact, the novel characteristics imparted by GEN-chitosan must be simultaneously of physico-chemical and cytological nature. Owing to their high standard, the scientific publications dated 2010–2015 have met the expectations of an interdisciplinary audience.

  16. Genipin-Crosslinked Chitosan Gels and Scaffolds for Tissue Engineering and Regeneration of Cartilage and Bone

    Science.gov (United States)

    Muzzarelli, Riccardo A. A.; El Mehtedi, Mohamad; Bottegoni, Carlo; Aquili, Alberto; Gigante, Antonio

    2015-01-01

    The present review article intends to direct attention to the technological advances made since 2009 in the area of genipin-crosslinked chitosan (GEN-chitosan) hydrogels. After a concise introduction on the well recognized characteristics of medical grade chitosan and food grade genipin, the properties of GEN-chitosan obtained with a safe, spontaneous and irreversible chemical reaction, and the quality assessment of the gels are reviewed. The antibacterial activity of GEN-chitosan has been well assessed in the treatment of gastric infections supported by Helicobacter pylori. Therapies based on chitosan alginate crosslinked with genipin include stem cell transplantation, and development of contraction free biomaterials suitable for cartilage engineering. Collagen, gelatin and other proteins have been associated to said hydrogels in view of the regeneration of the cartilage. Viability and proliferation of fibroblasts were impressively enhanced upon addition of poly-l-lysine. The modulation of the osteocytes has been achieved in various ways by applying advanced technologies such as 3D-plotting and electrospinning of biomimetic scaffolds, with optional addition of nano hydroxyapatite to the formulations. A wealth of biotechnological advances and know-how has permitted reaching outstanding results in crucial areas such as cranio-facial surgery, orthopedics and dentistry. It is mandatory to use scaffolds fully characterized in terms of porosity, pore size, swelling, wettability, compressive strength, and degree of acetylation, if the osteogenic differentiation of human mesenchymal stem cells is sought: in fact, the novel characteristics imparted by GEN-chitosan must be simultaneously of physico-chemical and cytological nature. Owing to their high standard, the scientific publications dated 2010–2015 have met the expectations of an interdisciplinary audience. PMID:26690453

  17. Effect of platelet-rich plasma on fibrocartilage, cartilage, and bone repair in temporomandibular joint.

    Science.gov (United States)

    Kütük, Nükhet; Baş, Burcu; Soylu, Emrah; Gönen, Zeynep Burçin; Yilmaz, Canay; Balcioğlu, Esra; Özdamar, Saim; Alkan, Alper

    2014-02-01

    The purpose of the present study was to explore the potential use of platelet-rich-plasma (PRP) in the treatment of temporomandibular joint osteoarthritis (TMJ-OA). Surgical defects were created bilaterally on the condylar fibrocartilage, hyaline cartilage, and bone to induce an osteoarthritic TMJ in rabbits. PRP was applied to the right joints of the rabbits (PRP group), and the left joints received physiologic saline (control group). After 4 weeks, the rabbits were sacrificed for histologic and scanning electron microscopy (SEM) examinations. The data were analyzed statistically. The new bone regeneration was significantly greater in the PRP group (P fibrocartilage and hyaline cartilage was greater in the PRP group, no statistically significant difference was found between the 2 groups. SEM showed better ultrastructural architecture of the collagen fibrils in the PRP group. PRP might enhance the regeneration of bone in TMJ-OA. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  18. Comparison of Engineered Peptide-Glycosaminoglycan Microfibrous Hybrid Scaffolds for Potential Applications in Cartilage Tissue Regeneration

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    Steven M. Romanelli

    2015-07-01

    Full Text Available Advances in tissue engineering have enabled the ability to design and fabricate biomaterials at the nanoscale that can actively mimic the natural cellular environment of host tissue. Of all tissues, cartilage remains difficult to regenerate due to its avascular nature. Herein we have developed two new hybrid polypeptide-glycosaminoglycan microfibrous scaffold constructs and compared their abilities to stimulate cell adhesion, proliferation, sulfated proteoglycan synthesis and soluble collagen synthesis when seeded with chondrocytes. Both constructs were designed utilizing self-assembled Fmoc-protected valyl cetylamide nanofibrous templates. The peptide components of the constructs were varied. For Construct I a short segment of dentin sialophosphoprotein followed by Type I collagen were attached to the templates using the layer-by-layer approach. For Construct II, a short peptide segment derived from the integrin subunit of Type II collagen binding protein expressed by chondrocytes was attached to the templates followed by Type II collagen. To both constructs, we then attached the natural polymer N-acetyl glucosamine, chitosan. Subsequently, the glycosaminoglycan chondroitin sulfate was then attached as the final layer. The scaffolds were characterized by Fourier transform infrared spectroscopy (FT-IR, differential scanning calorimetry (DSC, atomic force microscopy and scanning electron microscopy. In vitro culture studies were carried out in the presence of chondrocyte cells for both scaffolds and growth morphology was determined through optical microscopy and scanning electron microscopy taken at different magnifications at various days of culture. Cell proliferation studies indicated that while both constructs were biocompatible and supported the growth and adhesion of chondrocytes, Construct II stimulated cell adhesion at higher rates and resulted in the formation of three dimensional cell-scaffold matrices within 24 h. Proteoglycan

  19. Intra-articular injection of synovium-derived mesenchymal stem cells and hyaluronic acid promote regeneration of massive cartilage defects in rabbits

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    Vyacheslav Ogay

    2014-01-01

    Full Text Available Introduction: The purpose of this study was to investigate whether intra-articular injection of synovium-derived mesenchymal stem cells (SD MSCs with low molecular weight hyaluronic acid (HA could promote regeneration of massive cartilage in rabbits. Material and methods: The SD MSCs were harvested from the knees of 10 Flemish giant rabbits, expanded in culture, and characterized. A reproducible 4-mm cylindrical defect was created in the intercondylar groove area using a kit for the mosaic chondroplasty of femoral condyle COR (De Puy, Mitek. The defect was made within the cartilage layer without destruction of subchondral bone. Two weeks after the cartilage defect, SD MSCs (2 × 106 cell/0.15 ml were suspended in 0.5% low molecular weight HA (0.15 ml and injected into the left knee, and HA solution (0.30 ml alone was placed into the right knee. Cartilage regeneration in the experimental and control groups were evaluated by macroscopically and histologically at 10, 30, and 60 days. Results: On day 10, after intra-articular injection of SD MSCs, we observed an early process of cartilage regeneration in the defect area. Histological studies revealed that cartilage defect was covered by a thin layer of spindle-shaped undifferentiated cells and proliferated chodroblasts. In contrast, an injection of HA did not induce reparation of cartilage in the defect area. At 30 days, macroscopic observation showed that the size of cartilage defect after SD MSC injection was significantly smaller than after HA injection. Histological score was also better in the MSC- treated intercondylar defect. At 60 days after MSC treatment, cartilage defect was nearly nonexistent and looked similar to an intact cartilage. Conclusion: Thus, intra-articular injection of SD MSCs can adhere to the defect in the intercondylar area, and promote cartilage regeneration in rabbits.

  20. Effect of gradual weight-bearing on regenerated articular cartilage after joint distraction and motion in a rabbit model.

    Science.gov (United States)

    Nishino, Tomofumi; Ishii, Tomoo; Chang, Fei; Yanai, Takaji; Watanabe, Arata; Ogawa, Takeshi; Mishima, Hajime; Nakai, Kenjiro; Ochiai, Naoyuki

    2010-05-01

    The purpose of this study was to clarify the effect of gradual weight bearing (GWB) on regenerating cartilage. We developed a novel external fixation device (EFD) with a controllable weight-bearing system and continuous passive motion (CPM). A full-thickness defect was created by resection of the entire articular surface of the tibial plateau after the EFD was fixed in the rabbit's left knee. In the GWB group (n=6), GWB was started 6 weeks after surgery. In the CPM group (n=6), CPM with EFD was applied in the same manner without GWB. The control group (n=5) received only joint distraction. All rabbits were sacrificed 9 weeks after surgery. The central one-third of the regenerated tissue was assessed and scored blindly using a grading scale modified from the International Cartilage Repair Society visual histological assessment scale. The areas stained by Safranin-O and type II collagen antibody were measured, and the percentage of each area was calculated. There was no significant difference in the histological assessment scale among the groups. The percentage of the type II collagen-positive area was significantly larger in the GWB group than in the CPM group. The present study suggests that optimal mechanical stress, such as GWB, may affect regeneration of cartilage, in vivo. Copyright (c) 2009 Orthopaedic Research Society.

  1. Effect of Dietary Phytase Supplementation on Bone and Hyaline Cartilage Development of Broilers Fed with Organically Complexed Copper in a Cu-Deficient Diet.

    Science.gov (United States)

    Muszyński, Siemowit; Tomaszewska, Ewa; Kwiecień, Małgorzata; Dobrowolski, Piotr; Tomczyk, Agnieszka

    2018-04-01

    Tibial mechanical, chemical, and histomorphometrical traits were investigated for growing male Ross 308 broiler chickens fed diets that had copper (Cu) from organic source at a lowered level of 25% of the daily requirement (4 mg kg -1 of a premix) with or without phytase. Dietary treatments were control non-copper, non-phytase group (0 Suppl); 4 mg kg -1 Cu non-phytase group (25%Cu); and 4 mg kg -1 Cu + 500 FTU kg -1 phytase group (25%Cu + phyt). The results show that birds fed with the addition of phytase exhibited improved weight gain and final body weight and had increased serum IGF-1 and osteocalcin concentrations. The serum concentration of Cu and P did not differ between groups; however, Ca concentration decreased in the 25%Cu + phyt group when compared to the 25%Cu group. Added Cu increased bone Ca, P, Cu, and ash content in Cu-supplemented groups, but bone weight and length increased only by the addition of phytase. Bone geometry, yield, and ultimate strengths were affected by Cu and phytase addition. A decrease of the elastic stress and ultimate stress of the tibia in Cu-supplemented groups was observed. The histomorphometric analysis showed a positive effect of Cu supplementation on real bone volume and trabecular thickness in the tibia metaphyseal trabeculae; additionally, phytase increased the trabeculea number. The supplementation with Cu significantly increased the total articular cartilage and growth plate cartilage thickness; however, the changes in thickness of particular zones were dependent upon phytase addition. In summary, dietary Cu supplements given to growing broilers with Cu in their diet restricted to 25% of the daily requirement had a positive effect on bone metabolism, and phytase supplementation additionally improved cartilage development.

  2. The bio in the ink : cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells

    NARCIS (Netherlands)

    Levato, Riccardo; Webb, William R; Otto, Iris A; Mensinga, Anneloes; Zhang, Yadan; van Rijen, Mattie; van Weeren, P. René; Khan, Ilyas M.; Malda, Jos

    2017-01-01

    Cell-laden hydrogels are the primary building blocks for bioprinting, and, also termed bioinks, are the foundations for creating structures that can potentially recapitulate the architecture of articular cartilage. To be functional, hydrogel constructs need to unlock the regenerative capacity of

  3. Cartilage Regeneration in Full-Thickness Patellar Chondral Defects Treated with Particulated Juvenile Articular Allograft Cartilage: An MRI Analysis.

    Science.gov (United States)

    Grawe, Brian; Burge, Alissa; Nguyen, Joseph; Strickland, Sabrina; Warren, Russell; Rodeo, Scott; Shubin Stein, Beth

    2017-10-01

    Background Full-thickness cartilage lesions of the patella represent a common source of pain and dysfunction. Previously reported surgical treatment options include marrow stimulation, cell-based treatments, and osteochondral transfer. Minced juvenile allograft cartilage is a novel treatment option that allows for a single stage approach for these lesions. Hypothesis Particulated juvenile allograft cartilage (PJAC) for the treatment of chondral defects of the patella would offer acceptable lesion fill rates, mature over time, and not be associated with any negative biologic effects on the surrounding tissue. Methods A retrospective chart review of prospectively collected data was conducted to identify consecutive patients who were treated with PJAC for a full thickness symptomatic cartilage lesion. Qualitative (fast spin echo) and quantitative (T2 mapping) magnetic resonance imaging (MRI) was undertaken at the 6-, 12-, and 24-month postoperative mark. Numerous patient, lesion, and graft specific factors were assessed against MRI scores and percent defect fill of the graft. Graft maturation over time was also assessed. Results Forty-five patients total were included in the study. Average age at the time of surgery was 26.5 years (range 13-45 years), average lesion size was 208 mm 2 (range 4-500 mm 2 ), and average donor age was 49.5 months (range 3-120 months). Sixty percent of the patients were female, while 93% of all patients underwent a concomitant procedure at the time of the index operation. Six-month MRI findings revealed that no patient-, graft-, or donor-specific factors correlated with MR scores, and 82% of the knees demonstrated good to excellent fill. Twelve-month MRI findings revealed that T2 relaxation times of deep graft demonstrated negative correlation with patient age ( P = 0.049) and donor age ( P = 0.006), the integration zone showed a negative correlation with donor age ( P = 0.026). In all, 85% of patients at 12 months displayed good to

  4. Elastin-like protein-hyaluronic acid (ELP-HA) hydrogels with decoupled mechanical and biochemical cues for cartilage regeneration.

    Science.gov (United States)

    Zhu, Danqing; Wang, Huiyuan; Trinh, Pavin; Heilshorn, Sarah C; Yang, Fan

    2017-05-01

    Hyaluronic acid (HA) is a major component of cartilage extracellular matrix and is an attractive material for use as 3D injectable matrices for cartilage regeneration. While previous studies have shown the promise of HA-based hydrogels to support cell-based cartilage formation, varying HA concentration generally led to simultaneous changes in both biochemical cues and stiffness. How cells respond to the change of biochemical content of HA remains largely unknown. Here we report an adaptable elastin-like protein-hyaluronic acid (ELP-HA) hydrogel platform using dynamic covalent chemistry, which allows variation of HA concentration without affecting matrix stiffness. ELP-HA hydrogels were created through dynamic hydrazone bonds via the reaction between hydrazine-modified ELP (ELP-HYD) and aldehyde-modified HA (HA-ALD). By tuning the stoichiometric ratio of aldehyde groups to hydrazine groups while maintaining ELP-HYD concentration constant, hydrogels with variable HA concentration (1.5%, 3%, or 5%) (w/v) were fabricated with comparable stiffness. To evaluate the effects of HA concentration on cell-based cartilage regeneration, chondrocytes were encapsulated within ELP-HA hydrogels with varying HA concentration. Increasing HA concentration led to a dose-dependent increase in cartilage-marker gene expression and enhanced sGAG deposition while minimizing undesirable fibrocartilage phenotype. The use of adaptable protein hydrogels formed via dynamic covalent chemistry may be broadly applicable as 3D scaffolds with decoupled niche properties to guide other desirable cell fates and tissue repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Laser-induced micropore formation and modification of cartilage structure in osteoarthritis healing.

    Science.gov (United States)

    Sobol, Emil; Baum, Olga; Shekhter, Anatoly; Wachsmann-Hogiu, Sebastian; Shnirelman, Alexander; Alexandrovskaya, Yulia; Sadovskyy, Ivan; Vinokur, Valerii

    2017-09-01

    Pores are vital for functioning of avascular tissues. Laser-induced pores play an important role in the process of cartilage regeneration. The aim of any treatment for osteoarthritis is to repair hyaline-type cartilage. The aims of this study are to answer two questions: (1) How do laser-assisted pores affect the cartilaginous cells to synthesize hyaline cartilage (HC)? and (2) How can the size distribution of pores arising in the course of laser radiation be controlled? We have shown that in cartilage, the pores arise predominately near chondrocytes, which promote nutrition of cells and signal molecular transfer that activates regeneration of cartilage. In vivo laser treatment of damaged cartilage of miniature pig joints provides cellular transformation and formation of HC. We propose a simple model of pore formation in biopolymers that paves the way for going beyond the trial-and-error approach when choosing an optimal laser treatment regime. Our findings support the approach toward laser healing of osteoarthritis.

  6. Laser-induced micropore formation and modification of cartilage structure in osteoarthritis healing

    Science.gov (United States)

    Sobol, Emil; Baum, Olga; Shekhter, Anatoly; Wachsmann-Hogiu, Sebastian; Shnirelman, Alexander; Alexandrovskaya, Yulia; Sadovskyy, Ivan; Vinokur, Valerii

    2017-09-01

    Pores are vital for functioning of avascular tissues. Laser-induced pores play an important role in the process of cartilage regeneration. The aim of any treatment for osteoarthritis is to repair hyaline-type cartilage. The aims of this study are to answer two questions: (1) How do laser-assisted pores affect the cartilaginous cells to synthesize hyaline cartilage (HC)? and (2) How can the size distribution of pores arising in the course of laser radiation be controlled? We have shown that in cartilage, the pores arise predominately near chondrocytes, which promote nutrition of cells and signal molecular transfer that activates regeneration of cartilage. In vivo laser treatment of damaged cartilage of miniature pig joints provides cellular transformation and formation of HC. We propose a simple model of pore formation in biopolymers that paves the way for going beyond the trial-and-error approach when choosing an optimal laser treatment regime. Our findings support the approach toward laser healing of osteoarthritis.

  7. Validity of T2 mapping in characterization of the regeneration tissue by bone marrow derived cell transplantation in osteochondral lesions of the ankle

    Energy Technology Data Exchange (ETDEWEB)

    Battaglia, M., E-mail: milva.battaglia@ior.it [Service of Ecography and Radiology, Rizzoli Orthopaedic Institute, via Pupilli n. 1, 40136 Bologna (Italy); Rimondi, E. [Service of Ecography and Radiology, Rizzoli Orthopaedic Institute, via Pupilli n. 1, 40136 Bologna (Italy); Monti, C. [Service of CT and MRI, Casa di Cura Madre Fortunata Toniolo, Bologna (Italy); Guaraldi, F. [Department of Pathology, The Johns Hopkins University, School of Medicine, Baltimore, MD (United States); Sant' Andrea, A. [Service of CT and MRI, Casa di Cura Madre Fortunata Toniolo, Bologna (Italy); Buda, R.; Cavallo, M.; Giannini, S.; Vannini, F. [Clinical Orthopaedic and Traumatology Unit II, Rizzoli Orthopaedic Institute, Bologna (Italy)

    2011-11-15

    Objective: Bone marrow derived cell transplantation (BMDCT) has been recently suggested as a possible surgical technique to repair osteochondral lesions. To date, no qualitative MRI studies have evaluated its efficacy. The aim of our study is to investigate the validity of MRI T2-mapping sequence in characterizing the reparative tissue obtained and its ability to correlate with clinical results. Methods and materials: 20 patients with an osteochondral lesion of the talus underwent BMDCT and were evaluated at 2 years follow up using MRI T2-mapping sequence. 20 healthy volunteers were recruited as controls. MRI images were acquired using a protocol suggested by the International Cartilage Repair Society, MOCART scoring system and T2 mapping. Results were then correlated with AOFAS clinical score. Results: AOFAS score increased from 66.8 {+-} 14.5 pre-operatively to 91.2 {+-} 8.3 (p < 0.0005) at 2 years follow-up. T2-relaxation time value of 35-45 ms was derived from healthy ankles evaluation and assumed as normal hyaline cartilage value and used as a control. Regenerated tissue with a T2-relaxation time value comparable to hyaline cartilage was found in all the cases treated, covering a mean of 78% of the repaired lesion area. A high clinical score was related directly to isointense signal in DPFSE fat sat (p = 0.05), and percentage of regenerated hyaline cartilage (p = 0.05), inversely to the percentage of regenerated fibrocartilage. Lesion's depth negatively related to the integrity of the repaired tissue's surface (tau = -0.523, p = 0.007), and to the percentage of regenerated hyaline cartilage (rho = -0.546, p = 0.013). Conclusions: Because of its ability to detect cartilage's quality and to correlate to the clinical score, MRI T2-mapping sequence integrated with Mocart score represent a valid, non-invasive technique for qualitative cartilage assessment after regenerative surgical procedures.

  8. Biocompatible nanocomposite of TiO2 incorporated bi-polymer for articular cartilage tissue regeneration: A facile material.

    Science.gov (United States)

    Cao, Lei; Wu, Xiaofeng; Wang, Qiugen; Wang, Jiandong

    2018-01-01

    The development and design of polymeric hydrogels for articular cartilage tissue engineering have been a vital biomedical research for recent days. Organic/inorganic combined hydrogels with improved surface activity have shown potential for the repair and regeneration of hard tissues, but have not been broadly studied for articular cartilage tissue engineering applications. In this work, bi-polymeric hydrogel composite was designed with the incorporation some quantities of stick-like TiO 2 nanostructures for favorable surface behavior and enhancement of osteoblast adhesions. The microscopic investigations clearly exhibited that the stick-like TiO 2 nanostructured materials are highly inserted into the PVA/PVP bi-polymeric matrix, due to the long-chain PVA molecules are promoted to physical crosslinking density in hydrogel network. The results of improved surface topography of hydrogel matrixes show that more flatted cell morphologies and enhanced osteoblast attachment on the synthesized nanocomposites. The crystalline bone and stick-like TiO 2 nanocomposites significantly improved the bioactivity via lamellipodia and filopodia extension of osteoblast cells, due to its excellent intercellular connection and regulated cell responses. Consequently, these hydrogel has been enhanced the antibacterial activity against Staphylococcus aureus and Escherichia coli bacterial pathogens. Hence it is concluded that these hydrogel nanocomposite with improved morphology, osteoblast behavior and bactericidal activity have highly potential candidates for articular cartilage tissue regeneration applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Nanoparticles for diagnostics and laser medical treatment of cartilage in orthopaedics

    Science.gov (United States)

    Baum, O. I.; Soshnikova, Yu. M.; Omelchenko, A. I.; Sobol, Emil

    2013-02-01

    Laser reconstruction of intervertebral disc (LRD) is a new technique which uses local, non-destructive laser irradiation for the controlled activation of regenerative processes in a targeted zone of damaged disc cartilage. Despite pronounced advancements of LRD, existing treatments may be substantially improved if laser radiation is absorbed near diseased and/or damaged regions in cartilage so that required thermomechanical stress and strain at chondrocytes may be generated and non-specific injury reduced or eliminated. The aims of the work are to study possibility to use nanoparticles (NPs) to provide spatial specificity for laser regeneration of cartilage. Two types of porcine joint cartilage have been impregnated with magnetite NPs: 1) fresh cartilage; 2) mechanically damaged cartilage. NPs distribution was studied using transition electron microscopy, dynamic light scattering and analytical ultracentrifugation techniques. Laser radiation and magnetic field have been applied to accelerate NPs impregnation. It was shown that NPs penetrate by diffusion into the mechanically damaged cartilage, but do not infiltrate healthy cartilage. Temperature dynamics in cartilage impregnated with NPs have been theoretically calculated and measurements using an IR thermo vision system have been performed. Laser-induced alterations of cartilage structure and cellular surviving have been studied for cartilage impregnated with NPs using histological and histochemical techniques. Results of our study suggest that magnetite NPs might be used to provide spatial specificity of laser regeneration. When damaged, the regions of cartilage impreganted with NPs have higher absorption of laser radiation than that for healthy areas. Regions containing NPs form target sites that can be used to generate laser-induced thermo mechanical stress leading to regeneration of cartilage of hyaline type.

  10. An ex vivo human cartilage repair model to evaluate the potency of a cartilage cell transplant.

    Science.gov (United States)

    Bartz, Christoph; Meixner, Miriam; Giesemann, Petra; Roël, Giulietta; Bulwin, Grit-Carsta; Smink, Jeske J

    2016-11-15

    Cell-based therapies such as autologous chondrocyte implantation are promising therapeutic approaches to treat cartilage defects to prevent further cartilage degeneration. To assure consistent quality of cell-based therapeutics, it is important to be able to predict the biological activity of such products. This requires the development of a potency assay, which assesses a characteristic of the cell transplant before implantation that can predict its cartilage regeneration capacity after implantation. In this study, an ex vivo human cartilage repair model was developed as quality assessment tool for potency and applied to co.don's chondrosphere product, a matrix-associated autologous chondrocyte implant (chondrocyte spheroids) that is in clinical use in Germany. Chondrocyte spheroids were generated from 14 donors, and implanted into a subchondral cartilage defect that was manually generated in human articular cartilage tissue. Implanted spheroids and cartilage tissue were co-cultured ex vivo for 12 weeks to allow regeneration processes to form new tissue within the cartilage defect. Before implantation, spheroid characteristics like glycosaminoglycan production and gene and protein expression of chondrogenic markers were assessed for each donor sample and compared to determine donor-dependent variation. After the co-cultivation, histological analyses showed the formation of repair tissue within the cartilage defect, which varied in amount for the different donors. In the repair tissue, aggrecan protein was expressed and extra-cellular matrix cartilage fibers were present, both indicative for a cartilage hyaline-like character of the repair tissue. The amount of formed repair tissue was used as a read-out for regeneration capacity and was correlated with the spheroid characteristics determined before implantation. A positive correlation was found between high level of aggrecan protein expression in spheroids before implantation and a higher regeneration potential

  11. An ex vivo human cartilage repair model to evaluate the potency of a cartilage cell transplant

    Directory of Open Access Journals (Sweden)

    Christoph Bartz

    2016-11-01

    Full Text Available Abstract Background Cell-based therapies such as autologous chondrocyte implantation are promising therapeutic approaches to treat cartilage defects to prevent further cartilage degeneration. To assure consistent quality of cell-based therapeutics, it is important to be able to predict the biological activity of such products. This requires the development of a potency assay, which assesses a characteristic of the cell transplant before implantation that can predict its cartilage regeneration capacity after implantation. In this study, an ex vivo human cartilage repair model was developed as quality assessment tool for potency and applied to co.don’s chondrosphere product, a matrix-associated autologous chondrocyte implant (chondrocyte spheroids that is in clinical use in Germany. Methods Chondrocyte spheroids were generated from 14 donors, and implanted into a subchondral cartilage defect that was manually generated in human articular cartilage tissue. Implanted spheroids and cartilage tissue were co-cultured ex vivo for 12 weeks to allow regeneration processes to form new tissue within the cartilage defect. Before implantation, spheroid characteristics like glycosaminoglycan production and gene and protein expression of chondrogenic markers were assessed for each donor sample and compared to determine donor-dependent variation. Results After the co-cultivation, histological analyses showed the formation of repair tissue within the cartilage defect, which varied in amount for the different donors. In the repair tissue, aggrecan protein was expressed and extra-cellular matrix cartilage fibers were present, both indicative for a cartilage hyaline-like character of the repair tissue. The amount of formed repair tissue was used as a read-out for regeneration capacity and was correlated with the spheroid characteristics determined before implantation. A positive correlation was found between high level of aggrecan protein expression in spheroids

  12. The cranial cartilages of teleosts and their classification.

    OpenAIRE

    Benjamin, M

    1990-01-01

    The structure and distribution of cartilages has been studied in 45 species from 24 families. The resulting data have been used as a basis for establishing a new classification. A cartilage is regarded as 'cell-rich' if its cells or their lacunae occupy more than half of the tissue volume. Five classes of cell-rich cartilage are recognised (a) hyaline-cell cartilage (common in the lips of bottom-dwelling cyprinids) and its subtypes fibro/hyaline-cell cartilage, elastic/hyaline-cell cartilage ...

  13. [Regeneration of autologous tissue-engineered cartilage by using basic-fibroblast growth factor in vitro culture].

    Science.gov (United States)

    Ding, Xiao-bang; Cheng, Ning-xin; Chen, Bing; Xia, Wan-yao; Cui, Lei; Liu, Wei; Cao, Yi-lin

    2004-05-01

    To investigate the effect of the basic fibroblast growth factor (b-FGF) to regenerate an autologous tissue-engineered cartilage in vitro. The Cells were harvested from the elastic auricular cartilage of swine,and were plated at the concentration of 1 x 10(4) cells/cm2 , studied in vitro at two different media enviroments: Group I contained Ham's F-12 with supplements and b-FGF, Group II contained Ham's F-12 only with supplements. The passage 2 cells (after 12.75 +/- 1.26 days) were harvested and mixed with 30% pluronic F-127/Ham's F-12 at the concentration of 50 x 10(6) cells/ml. It was injected subcutaneously at 0.5 ml per implant. The implants were harvested 8 weeks after the vivo culture and examined with the histological stains. The chondrocytes displayed morphologically similar to the fibroblasts in the media containing basic-FGF. The number of cell doublings (after 12.75 +/- 1.26 days) in vitro culture was as the following: Group I, 70; Group II, 5.4. Eight 8 weeks after the vivo autologous implantation, the average weight (g) and volume (cm3) in each group was as the following: Group I, 0.371 g/0.370 cm3 Group II, 0.179 g/0.173 cm3 (P < 0.01). With the b-FGF in vitro culture, the cells were expanded by 70 times after 2 weeks. Histologically, all of the engineered cartilage in the two groups were similar to the native elastic cartilage. These results indicate that the basic-FGF could be used positively to enhance the quality and quantity of the seeding cells for the generation of the well-engineered cartilage.

  14. Adipose-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage: A Systematic Review on Preclinical and Clinical Evidence

    Directory of Open Access Journals (Sweden)

    Francesco Perdisa

    2015-01-01

    Full Text Available Among the current therapeutic approaches for the regeneration of damaged articular cartilage, none has yet proven to offer results comparable to those of native hyaline cartilage. Recently, it has been claimed that the use of mesenchymal stem cells (MSCs provides greater regenerative potential than differentiated cells, such as chondrocytes. Among the different kinds of MSCs available, adipose-derived mesenchymal stem cells (ADSCs are emerging due to their abundancy and easiness to harvest. However, their mechanism of action and potential for cartilage regeneration are still under investigation, and many other aspects still need to be clarified. The aim of this systematic review is to give an overview of in vivo studies dealing with ADSCs, by summarizing the main evidence for the treatment of cartilage disease of the knee.

  15. Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair

    Science.gov (United States)

    Fellows, Christopher R.; Matta, Csaba; Zakany, Roza; Khan, Ilyas M.; Mobasheri, Ali

    2016-01-01

    Current cell-based repair strategies have proven unsuccessful for treating cartilage defects and osteoarthritic lesions, consequently advances in innovative therapeutics are required and mesenchymal stem cell-based (MSC) therapies are an expanding area of investigation. MSCs are capable of differentiating into multiple cell lineages and exerting paracrine effects. Due to their easy isolation, expansion, and low immunogenicity, MSCs are an attractive option for regenerative medicine for joint repair. Recent studies have identified several MSC tissue reservoirs including in adipose tissue, bone marrow, cartilage, periosteum, and muscle. MSCs isolated from these discrete tissue niches exhibit distinct biological activities, and have enhanced regenerative potentials for different tissue types. Each MSC type has advantages and disadvantages for cartilage repair and their use in a clinical setting is a balance between expediency and effectiveness. In this review we explore the challenges associated with cartilage repair and regeneration using MSC-based cell therapies and provide an overview of phenotype, biological activities, and functional properties for each MSC population. This paper also specifically explores the therapeutic potential of each type of MSC, particularly focusing on which cells are capable of producing stratified hyaline-like articular cartilage regeneration. Finally we highlight areas for future investigation. Given that patients present with a variety of problems it is unlikely that cartilage regeneration will be a simple “one size fits all,” but more likely an array of solutions that need to be applied systematically to achieve regeneration of a biomechanically competent repair tissue. PMID:28066501

  16. Adipose, Bone Marrow and Synovial Joint-derived Mesenchymal Stem Cells for Cartilage Repair

    Directory of Open Access Journals (Sweden)

    Christopher Fellows

    2016-12-01

    Full Text Available Current cell-based repair strategies have proven unsuccessful for treating cartilage defects and osteoarthritic lesions, consequently advances in innovative therapeutics are required and mesenchymal stem cell-based (MSC therapies are an expanding area of investigation. MSCs are capable of differentiating into multiple cell lineages and exerting paracrine effects. Due to their easy isolation, expansion and low immunogenicity, MSCs are an attractive option for regenerative medicine for joint repair. Recent studies have identified several MSC tissue reservoirs including in adipose tissue, bone marrow, cartilage, periosteum and muscle. MSCs isolated from these discrete tissue niches exhibit distinct biological activities, and have enhanced regenerative potentials for different tissue types. Each MSC type has advantages and disadvantages for cartilage repair and their use in a clinical setting is a balance between expediency and effectiveness. In this review we explore the challenges associated with cartilage repair and regeneration using MSC-based cell therapies and provide an overview of phenotype, biological activities and functional properties for each MSC population. This paper also specifically explores the therapeutic potential of each type of MSC, particularly focusing on which cells are capable of producing stratified hyaline-like articular cartilage regeneration. Finally we highlight areas for future investigation. Given that patients present with a variety of problems it is unlikely that cartilage regeneration will be a simple ‘one size fits all’, but more likely an array of solutions that need to applied systematically to achieve regeneration of a biomechanically competent repair tissue.

  17. Regeneration of Cartilage in Human Knee Osteoarthritis with Autologous Adipose Tissue-Derived Stem Cells and Autologous Extracellular Matrix

    Directory of Open Access Journals (Sweden)

    Jaewoo Pak

    2016-08-01

    Full Text Available This clinical case series demonstrates that percutaneous injections of autologous adipose tissue-derived stem cells (ADSCs and homogenized extracellular matrix (ECM in the form of adipose stromal vascular fraction (SVF, along with hyaluronic acid (HA and platelet-rich plasma (PRP activated by calcium chloride, could regenerate cartilage-like tissue in human knee osteoarthritis (OA patients. Autologous lipoaspirates were obtained from adipose tissue of the abdominal origin. Afterward, the lipoaspirates were minced to homogenize the ECM. These homogenized lipoaspirates were then mixed with collagenase and incubated. The resulting mixture of ADSCs and ECM in the form of SVF was injected, along with HA and PRP activated by calcium chloride, into knees of three Korean patients with OA. The same affected knees were reinjected weekly with additional PRP activated by calcium chloride for 3 weeks. Pretreatment and post-treatment magnetic resonance imaging (MRI data, functional rating index, range of motion (ROM, and pain score data were then analyzed. All patients' MRI data showed cartilage-like tissue regeneration. Along with MRI evidence, the measured physical therapy outcomes in terms of ROM, subjective pain, and functional status were all improved. This study demonstrates that percutaneous injection of ADSCs with ECM contained in autologous adipose SVF, in conjunction with HA and PRP activated by calcium chloride, is a safe and potentially effective minimally invasive therapy for OA of human knees.

  18. Pronounced biomaterial dependency in cartilage regeneration using nonexpanded compared with expanded chondrocytes

    NARCIS (Netherlands)

    Tsuchida, A.I.; Bekkers, J.E.J.; Beekhuizen, M.; Vonk, L.A.; Dhert, W.J.A.; Saris, Daniël B.F.; Creemers, L.B.

    2013-01-01

    We aimed to investigate freshly isolated compared with culture-expanded chondrocytes with respect to early regenerative response, cytokine production and cartilage formation in response to four commonly used biomaterials. Materials & methods: Chondrocytes were both directly and after expansion to

  19. Articular cartilage tissue engineering with plasma-rich in growth factors and stem cells with nano scaffolds

    Science.gov (United States)

    Montaser, Laila M.; Abbassy, Hadeer A.; Fawzy, Sherin M.

    2016-09-01

    The ability to heal soft tissue injuries and regenerate cartilage is the Holy Grail of musculoskeletal medicine. Articular cartilage repair and regeneration is considered to be largely intractable due to the poor regenerative properties of this tissue. Due to their low self-repair ability, cartilage defects that result from joint injury, aging, or osteoarthritis, are the most often irreversible and are a major cause of joint pain and chronic disability. However, current methods do not perfectly restore hyaline cartilage and may lead to the apparition of fibro- or continue hypertrophic cartilage. The lack of efficient modalities of treatment has prompted research into tissue engineering combining stem cells, scaffold materials and environmental factors. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased cartilage functionality, has evoked intense interest and holds great potential for improving cartilage therapy. Plasma-rich in growth factors (PRGF) and/or stem cells may be effective for tissue repair as well as cartilage regenerative processes. There is a great promise to advance current cartilage therapies toward achieving a consistently successful approach for addressing cartilage afflictions. Tissue engineering may be the best way to reach this objective via the use of stem cells, novel biologically inspired scaffolds and, emerging nanotechnology. In this paper, current and emergent approach in the field of cartilage tissue engineering is presented for specific application. In the next years, the development of new strategies using stem cells, in scaffolds, with supplementation of culture medium could improve the quality of new formed cartilage.

  20. Delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) can be effectively applied for longitudinal cohort evaluation of articular cartilage regeneration

    NARCIS (Netherlands)

    Bekkers, J.E.J.; Lambertus, W.B.; Benink, R.J.; Tsuchida, A.I.; Vincken, K.L.; Dhert, W.J.A.; Creemers, L.B.; Saris, Daniël B.F.

    2013-01-01

    Objective Delayed gadolinium enhanced MRI of cartilage (dGEMRIC) facilitates non-invasive evaluation of the glycosaminoglycan content in articular cartilage. The primary aim of this study was to show that the dGEMRIC technique is able to monitor cartilage repair following regenerative cartilage

  1. Laser-induced modification of structure and shape of cartilage in otolaryngology and orthopaedics

    Science.gov (United States)

    Sobol', E. N.; Baum, O. I.; Omel'chenko, A. I.; Soshnikova, Yu. M.; Yuzhakov, A. V.; Kas'yanenko, E. M.; Tokareva, A. V.; Baskov, A. V.; Svistushkin, V. M.; Selezneva, L. V.; Shekhter, A. B.

    2017-11-01

    We present the results of basic research in laser modification of tissues in otolaryngology (correcting the shape of nasal septum and larynx cartilages), cosmetology (correcting ear and nose shape), orthopaedics and spinal surgery (treatment of diseases of spine disc and joints). The physical processes and mechanisms of laser-induced relaxation of stresses and regeneration of tissues are considered. New results of studies in this fast-developing field of laser surgery are presented, in particular, the results of laser correction of costal cartilage shape in the process of making implants for the treatment of larynx stenosis and controlled regeneration of the hyaline articular cartilage. Presented at the Fundamentals of Laser Assisted Micro- and Nanotechnologies (FLAMN-2016) International Symposium (Pushkin, Leningrad oblast, 27 June to 1 July 2016).

  2. Medical ozone therapy as a potential treatment modality for regeneration of damaged articular cartilage in osteoarthritis

    Directory of Open Access Journals (Sweden)

    Sello Lebohang Manoto

    2018-05-01

    Full Text Available Osteoarthritis (OA is the most common degenerative joint disease and a growing health problem affecting more than half of the population over the age of 65. It is characterized by inflammation in the cartilage and synovium, resulting in the loss of joint structure and progressive damage to the cartilage. Many pro-inflammatory mediators are elevated in OA, including reactive oxygen species (ROS such as nitric oxide (NO and hydrogen peroxide (H2O2. Damaged articular cartilage remains a challenge to treat due to the limited self-healing capacity of the tissue and unsuccessful biological interventions. This highlights the need for better therapeutic strategies to heal damaged articular cartilage. Ozone (O3 therapy has been shown to have positive results in the treatment of OA; however the use of O3 therapy as a therapeutic agent is controversial. There is a perception that O3 is always toxic, whereas evidence indicates that when it is applied following a specified method, O3 can be effective in the treatment of degenerative diseases. The mechanism of action of O3 therapy in OA is not fully understood and this review summarizes the use of O3 therapy in the treatment of damaged articular cartilage in OA. Keywords: Osteoarthritis (OA, Articular cartilage, Ozone (O3 therapy, Reactive oxygen species (ROS

  3. MR imaging of articular cartilage

    International Nuclear Information System (INIS)

    Schaefer, F.K.W.; Muhle, C.; Heller, M.; Brossmann, J.

    2001-01-01

    MR imaging has evolved to the best non-invasive method for the evaluation of articular cartilage. MR imaging helps to understand the structure and physiology of cartilage, and to diagnose cartilage lesions. Numerous studies have shown high accuracy and reliability concerning detection of cartilage lesions and early changes in both structure and biochemistry. High contrast-to-noise ratio and high spatial resolution are essential for analysis of articular cartilage. Fat-suppressed 3D-T 1 weighted gradient echo and T 2 -weighted fast spin echo sequences with or without fat suppression are recommended for clinical routine. In this article the anatomy and pathology of hyaline articular cartilage and the complex imaging characteristics of hyaline cartilage will be discussed. (orig.) [de

  4. Cartilage Repair Using Composites of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronic Acid Hydrogel in a Minipig Model.

    Science.gov (United States)

    Ha, Chul-Won; Park, Yong-Beom; Chung, Jun-Young; Park, Yong-Geun

    2015-09-01

    The cartilage regeneration potential of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) with a hyaluronic acid (HA) hydrogel composite has shown remarkable results in rat and rabbit models. The purpose of the present study was to confirm the consistent regenerative potential in a pig model using three different cell lines. A full-thickness chondral injury was intentionally created in the trochlear groove of each knee in 6 minipigs. Three weeks later, an osteochondral defect, 5 mm wide by 10 mm deep, was created, followed by an 8-mm-wide and 5-mm-deep reaming. A mixture (1.5 ml) of hUCB-MSCs (0.5×10(7) cells per milliliter) and 4% HA hydrogel composite was then transplanted into the defect on the right knee. Each cell line was used in two minipigs. The osteochondral defect created in the same manner on the left knee was untreated to act as the control. At 12 weeks postoperatively, the pigs were sacrificed, and the degree of subsequent cartilage regeneration was evaluated by gross and histological analysis. The transplanted knee resulted in superior and more complete hyaline cartilage regeneration compared with the control knee. The cellular characteristics (e.g., cellular proliferation and chondrogenic differentiation capacity) of the hUCB-MSCs influenced the degree of cartilage regeneration potential. This evidence of consistent cartilage regeneration using composites of hUCB-MSCs and HA hydrogel in a large animal model could be a stepping stone to a human clinical trial in the future. To date, several studies have investigated the chondrogenic potential of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs); however, the preclinical studies are still limited in numbers with various results. In parallel, in the past several years, the cartilage regeneration potential of hUCB-MSCs with a hyaluronic acid (HA) hydrogel composite have been investigated and remarkable results in rat and rabbit models have been attained. (These

  5. MRI of the cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Imhof, H.; Noebauer-Huhmann, I.-M.; Krestan, C.; Gahleitner, A.; Marlovits, S.; Trattnig, S. [Department of Osteology, Universitaetklinik fuer Radiodiagnostik, AKH-Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria); Sulzbacher, I. [Universitaetsklinik fuer Pathologie Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)

    2002-11-01

    With the introduction of fat-suppressed gradient-echo and fast spin-echo (FSE) sequences in clinical routine MR visualization of the hyaline articular cartilage is routinely possible in the larger joints. While 3D gradient-echo with fat suppression allows exact depiction of the thickness and surface of cartilage, FSE outlines the normal and abnormal internal structures of the hyaline cartilage; therefore, both sequences seem to be necessary in a standard MRI protocol for cartilage visualization. In diagnostically ambiguous cases, in which important therapeutic decisions are required, direct MR arthrography is the established imaging standard as an add-on procedure. Despite the social impact and prevalence, until recent years there was a paucity of knowledge about the pathogenesis of cartilage damage. With the introduction of high-resolution MRI with powerful surface coils and fat-suppression techniques, visualization of the articular cartilage is now routinely possible in many joints. After a short summary of the anatomy and physiology of the hyaline cartilage, the different MR imaging methods are discussed and recommended standards are suggested. (orig.)

  6. [Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: a guideline by the working group "Tissue Regeneration" of the German Society of Orthopaedic Surgery and Traumatology (DGOU)].

    Science.gov (United States)

    Niemeyer, P; Andereya, S; Angele, P; Ateschrang, A; Aurich, M; Baumann, M; Behrens, P; Bosch, U; Erggelet, C; Fickert, S; Fritz, J; Gebhard, H; Gelse, K; Günther, D; Hoburg, A; Kasten, P; Kolombe, T; Madry, H; Marlovits, S; Meenen, N M; Müller, P E; Nöth, U; Petersen, J P; Pietschmann, M; Richter, W; Rolauffs, B; Rhunau, K; Schewe, B; Steinert, A; Steinwachs, M R; Welsch, G H; Zinser, W; Albrecht, D

    2013-02-01

    Autologous chondrocyte transplantation/implantation (ACT/ACI) is an established and recognised procedure for the treatment of localised full-thickness cartilage defects of the knee. The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Traumatology (DGOU) describes the biology and function of healthy articular cartilage, the present state of knowledge concerning potential consequences of primary cartilage lesions and the suitable indication for ACI. Based on current evidence, an indication for ACI is given for symptomatic cartilage defects starting from defect sizes of more than 3-4 cm2; in the case of young and active sports patients at 2.5 cm2. Advanced degenerative joint disease is the single most important contraindication. The review gives a concise overview on important scientific background, the results of clinical studies and discusses advantages and disadvantages of ACI. Georg Thieme Verlag KG Stuttgart · New York.

  7. Gremlin 1, Frizzled-related protein, and Dkk-1 are key regulators of human articular cartilage homeostasis

    NARCIS (Netherlands)

    Leijten, Jeroen Christianus Hermanus; Emons, J.; Sticht, C.; van Gool, S.; Decker, E.; Uitterlinden, A.; Rappold, G.; Hofman, A.; Rivadeneira, F.; Scherjon, S.; Wit, J.M.; van Meurs, J.; van Blitterswijk, Clemens; Karperien, Hermanus Bernardus Johannes

    2012-01-01

    Objective The development of osteoarthritis (OA) may be caused by activation of hypertrophic differentiation of articular chondrocytes. Healthy articular cartilage is highly resistant to hypertrophic differentiation, in contrast to other hyaline cartilage subtypes, such as growth plate cartilage.

  8. Wound healing gene therapy: cartilage regeneration induced by vascular endothelial growth factor plasmid

    Czech Academy of Sciences Publication Activity Database

    Kološtová, K.; Taltynov, O.; Pintérová, D.; Boubelík, M.; Raška, O.; Hozák, Pavel; Jirkovská, M.; Bobek, V.

    2012-01-01

    Roč. 33, č. 1 (2012), s. 68-74 ISSN 0196-0709 Institutional research plan: CEZ:AV0Z50520514 Keywords : BALB/c mouse strain * significant angiogenesis * cartilage repair * phVEGF(165) injection Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.228, year: 2012

  9. Effect of Human Adipose Tissue Mesenchymal Stem Cells on the Regeneration of Ovine Articular Cartilage.

    Science.gov (United States)

    Zorzi, Alessandro R; Amstalden, Eliane M I; Plepis, Ana Maria G; Martins, Virginia C A; Ferretti, Mario; Antonioli, Eliane; Duarte, Adriana S S; Luzo, Angela C M; Miranda, João B

    2015-11-09

    Cell therapy is a promising approach to improve cartilage healing. Adipose tissue is an abundant and readily accessible cell source. Previous studies have demonstrated good cartilage repair results with adipose tissue mesenchymal stem cells in small animal experiments. This study aimed to examine these cells in a large animal model. Thirty knees of adult sheep were randomly allocated to three treatment groups: CELLS (scaffold seeded with human adipose tissue mesenchymal stem cells), SCAFFOLD (scaffold without cells), or EMPTY (untreated lesions). A partial thickness defect was created in the medial femoral condyle. After six months, the knees were examined according to an adaptation of the International Cartilage Repair Society (ICRS 1) score, in addition to a new Partial Thickness Model scale and the ICRS macroscopic score. All of the animals completed the follow-up period. The CELLS group presented with the highest ICRS 1 score (8.3 ± 3.1), followed by the SCAFFOLD group (5.6 ± 2.2) and the EMPTY group (5.2 ± 2.4) (p = 0.033). Other scores were not significantly different. These results suggest that human adipose tissue mesenchymal stem cells promoted satisfactory cartilage repair in the ovine model.

  10. Three-Dimensional Bioprinting and Its Potential in the Field of Articular Cartilage Regeneration

    NARCIS (Netherlands)

    Mouser, Vivian H M; Levato, Riccardo; Bonassar, Lawrence J; D'Lima, Darryl D; Grande, Daniel A; Klein, Travis J; Saris, Daniel B F; Zenobi-Wong, Marcy; Gawlitta, Debby; Malda, Jos

    2017-01-01

    Three-dimensional (3D) bioprinting techniques can be used for the fabrication of personalized, regenerative constructs for tissue repair. The current article provides insight into the potential and opportunities of 3D bioprinting for the fabrication of cartilage regenerative constructs. Although 3D

  11. IL-1ß and BMPs - Interactive players of cartilage matrix degradation and regeneration

    Directory of Open Access Journals (Sweden)

    T Aigner

    2006-10-01

    Full Text Available Intact human adult articular cartilage is central for the functioning of the articulating joints. This largely depends on the integrity of its extracellular matrix, given the high loading forces during movements in particular in the weight-bearing joints. Unlike the first impression of a more or less static tissue, articular cartilage shows - albeit in the adult organism a slow - tissue turnover. Thus, one of the most important questions in osteoarthritis research is to understand the balance of catabolic and anabolic factors in articular cartilage as this is the key to understand the biology of cartilage maintenance and degeneration. Anabolic and catabolic pathways are very much intermingled in articular cartilage. The balance between anabolism and catabolism is titrated on numerous levels, starting from the mediator-synthesizing cells which express either catabolic or anabolic factors. Also, on the level of the effector cells (i.e. chondrocytes anabolic and catabolic gene expression compete for a balance of matrix homeostasis, namely the synthesis of matrix components and the expression and activation of matrix-degrading proteases. Also, there are multiple layers of intracellular cross-talks in between the anabolic and catabolic signalling pathways. Maybe the most important lesson from this overview is the notion that the anabolic-catabolic balance as such counts and not so much sufficient net anabolism or limited catabolism alone. Thus, it might be neither the aim of osteoarthritis therapy to foster anabolism nor to knock down catabolism, but the balance of anabolic-catabolic activities as a total might need proper titration and balancing.

  12. Comparative Analysis of Cartilage Marker Gene Expression Patterns during Axolotl and Xenopus Limb Regeneration.

    Directory of Open Access Journals (Sweden)

    Kazumasa Mitogawa

    Full Text Available Axolotls (Ambystoma mexicanum can completely regenerate lost limbs, whereas Xenopus laevis frogs cannot. During limb regeneration, a blastema is first formed at the amputation plane. It is thought that this regeneration blastema forms a limb by mechanisms similar to those of a developing embryonic limb bud. Furthermore, Xenopus laevis frogs can form a blastema after amputation; however, the blastema results in a terminal cone-shaped cartilaginous structure called a "spike." The causes of this patterning defect in Xenopus frog limb regeneration were explored. We hypothesized that differences in chondrogenesis may underlie the patterning defect. Thus, we focused on chondrogenesis. Chondrogenesis marker genes, type I and type II collagen, were compared in regenerative and nonregenerative environments. There were marked differences between axolotls and Xenopus in the expression pattern of these chondrogenesis-associated genes. The relative deficit in the chondrogenic capacity of Xenopus blastema cells may account for the absence of total limb regenerative capacity.

  13. [Tissue engineering with mesenchymal stem cells for cartilage and bone regeneration].

    Science.gov (United States)

    Schaefer, D J; Klemt, C; Zhang, X H; Stark, G B

    2000-09-01

    Tissue engineering offers the possibility to fabricate living substitutes for tissues and organs by combining histogenic cells and biocompatible carrier materials. Pluripotent mesenchymal stem cells are isolated and subcultured ex vivo and then their histogenic differentiation is induced by external factors. The fabrication of bone and cartilage constructs, their combinations and gene therapeutic approaches are demonstrated. Advantages and disadvantages of these methods are described by in vitro and in vitro testing. The proof of histotypical function after implantation in vivo is essential. The use of autologous cells and tissue engineering methods offers the possibility to overcome the disadvantages of classical tissue reconstruction--donor site morbidity of autologous grafts, immunogenicity of allogenic grafts and loosening of alloplastic implants. Furthermore, tissue engineering widens the spectrum of surgical indications in bone and cartilage reconstruction.

  14. Rabbit articular cartilage defects treated by allogenic chondrocyte transplantation

    OpenAIRE

    Boopalan, P. R. J. V. C.; Sathishkumar, Solomon; Kumar, Senthil; Chittaranjan, Samuel

    2006-01-01

    Articular cartilage defects have a poor capacity for repair. Most of the current treatment options result in the formation of fibro-cartilage, which is functionally inferior to normal hyaline articular cartilage. We studied the effectiveness of allogenic chondrocyte transplantation for focal articular cartilage defects in rabbits. Chondrocytes were cultured in vitro from cartilage harvested from the knee joints of a New Zealand White rabbit. A 3 mm defect was created in the articular cartilag...

  15. POSSIBILITIES OF CURRENT CELLULAR TECHNOLOGIES FOR ARTICULAR CARTILAGE REPAIR (ANALYTICAL REVIEW

    Directory of Open Access Journals (Sweden)

    M. S. Bozhokin

    2016-01-01

    Full Text Available Despite a wide variety of surgical procedures utilized in clinical practice for treatment of articular cartilage lesions, the search for other options of articular reconstruction remains a relevant and open issue at the current stage of medicine and biotechnologies development. The recent years demonstrated a strong belief in cellular methods of hyaline cartilage repair such as implantation of autologous chondrocytes (ACI or cultures of mesenchymal stem cells (MSC including techniques for genetic modification of cells.The purpose of presented review is to summarize the published scientific data on up to date results of perspective cellular technologies for articular cartilage repair that are being developed. Autologous chondrocyte transplantation originally performed by Swedish researchers in 1987 is considered the first clinically applied technique for restoration of hyaline cartilage using cellular technologies. However, the transplanted cell culture featured low proliferative capacity and inability to form a regenerate resistant to high physical activity. Another generation of methods originated at the turn of the century utilized mesenchymal stem cells instead of autologous chondrocytes. Preparation of MSCs is a less invasive procedure compared to chondrocytes harvesting and the culture is featured by a higher proliferative ability. Researchers use various biodegradable carriers (matrices to secure cell fixation. Despite good clinical mid-term outcomes the transplanted tissue-engineering structures deteriorate with time due to cellular de-differentiation. Next generation of techniques being currently under pre-clinical studies is featured by the preliminary chondrogenic modification of transplanted cell culture. Usage of various growth factors, modified cell product and gene-activated matrices allow to gain a stable regulatory and key proteins synthesis and achieve a focused influence on regenerate's chondrogenic proliferation and in result

  16. Chondroitin sulfate immobilization at the surface of electrospun nanofiber meshes for cartilage tissue regeneration approaches

    Science.gov (United States)

    Piai, Juliana Francis; da Silva, Marta Alves; Martins, Albino; Torres, Ana Bela; Faria, Susana; Reis, Rui L.; Muniz, Edvani Curti; Neves, Nuno M.

    2017-05-01

    Aiming at improving the biocompatibility of biomaterial scaffolds, surface modification presents a way to preserve their mechanical properties and to improve the surface bioactivity. In this work, chondroitin sulfate (CS) was immobilized at the surface of electrospun poly(caprolactone) nanofiber meshes (PCL NFMs), previously functionalized by UV/O3 exposure and aminolysis. Contact angle, SEM, optical profilometry, FTIR, X-ray photoelectron spectroscopy techniques confirmed the success of CS-immobilization in PCL NFMs. Furthermore, CS-immobilized PCL NFMs showed lower roughness and higher hydrophilicity than the samples without CS. Human articular chondrocytes (hACs) were cultured on electrospun PCL NFMs with or without CS immobilization. It was observed that hACs proliferated through the entire time course of the experiment in both types of nanofibrous scaffolds, as well as for the production of glycosaminoglycans. Quantitative-PCR results demonstrated over-expression of cartilage-related genes such as Aggrecan, Collagen type II, COMP and Sox9 on both types of nanofibrous scaffolds. Morphological observations from SEM and LSCM revealed that hACs maintained their characteristic round shape and cellular agglomeration exclusively on PCL NFMs with CS immobilization. In conclusion, CS immobilization at the surface of PCL NFMs was achieved successfully and provides a valid platform enabling further surface functionalization methods in scaffolds to be developed for cartilage tissue engineering.

  17. 3D Bioprinting of Cartilage for Orthopedic Surgeons: Reading between the Lines.

    Science.gov (United States)

    Di Bella, Claudia; Fosang, Amanda; Donati, Davide M; Wallace, Gordon G; Choong, Peter F M

    2015-01-01

    Chondral and osteochondral lesions represent one of the most challenging and frustrating scenarios for the orthopedic surgeon and for the patient. The lack of therapeutic strategies capable to reconstitute the function and structure of hyaline cartilage and to halt the progression toward osteoarthritis has brought clinicians and scientists together, to investigate the potential role of tissue engineering as a viable alternative to current treatment modalities. In particular, the role of bioprinting is emerging as an innovative technology that allows for the creation of organized 3D tissue constructs via a "layer-by-layer" deposition process. This process also has the capability to combine cells and biomaterials in an ordered and predetermined way. Here, we review the recent advances in cartilage bioprinting and we identify the current challenges and the directions for future developments in cartilage regeneration.

  18. 3D-BIOPRINTING OF CARTILAGE FOR ORTHOPAEDIC SURGEONS.READING BETWEEN THE LINES

    Directory of Open Access Journals (Sweden)

    Claudia eDi Bella

    2015-08-01

    Full Text Available Chondral and Osteochondral lesions represent one of the most challenging and frustrating scenarios for the orthopaedic surgeon and for the patient. The lack of therapeutic strategies capable to reconstitute the function and structure of hyaline cartilage and to halt the progression towards osteoarthritis has brought clinicians and scientists together, to investigate the potential role of tissue engineering as a viable alternative to current treatment modalities. In particular, the role of bioprinting is emerging as an innovative technology that allows for the creation of organized 3D tissue constructs via a layer-by-layer deposition process. This process also has the capability to combine cells and biomaterials in an ordered and predetermined way. Here we review the recent advances in cartilage bioprinting and we identify the current challenges and the directions for future developments in cartilage regeneration.

  19. Cartilage Regeneration in the Head and Neck Area: Combination of Ear or Nasal Chondrocytes and Mesenchymal Stem Cells Improves Cartilage Production

    NARCIS (Netherlands)

    Pleumeekers, M.M.; Nimeskern, L.M.; Koevoet, W.L.M.; Karperien, Hermanus Bernardus Johannes; Stok, K.S.; van Osch, G.J.V.M.

    2015-01-01

    Background: Cartilage tissue engineering can offer promising solutions for restoring cartilage defects in the head and neck area and has the potential to overcome limitations of current treatments. However, to generate a construct of reasonable size, large numbers of chondrocytes are required, which

  20. Chondroitin sulfate immobilization at the surface of electrospun nanofiber meshes for cartilage tissue regeneration approaches

    International Nuclear Information System (INIS)

    Piai, Juliana Francis; Alves da Silva, Marta; Martins, Albino; Torres, Ana Bela; Faria, Susana

    2017-01-01

    Highlights: • Chemical immobilization of chondroitin sulfate at the surface of nanofiber meshes. • CS-immobilized NFMs showed lower roughness and higher hydrophilicity. • CS-immobilized NFMs offer a highly effective substrate for hACs phenotypic stability. - Abstract: Aiming at improving the biocompatibility of biomaterial scaffolds, surface modification presents a way to preserve their mechanical properties and to improve the surface bioactivity. In this work, chondroitin sulfate (CS) was immobilized at the surface of electrospun poly(caprolactone) nanofiber meshes (PCL NFMs), previously functionalized by UV/O_3 exposure and aminolysis. Contact angle, SEM, optical profilometry, FTIR, X-ray photoelectron spectroscopy techniques confirmed the success of CS-immobilization in PCL NFMs. Furthermore, CS-immobilized PCL NFMs showed lower roughness and higher hydrophilicity than the samples without CS. Human articular chondrocytes (hACs) were cultured on electrospun PCL NFMs with or without CS immobilization. It was observed that hACs proliferated through the entire time course of the experiment in both types of nanofibrous scaffolds, as well as for the production of glycosaminoglycans. Quantitative-PCR results demonstrated over-expression of cartilage-related genes such as Aggrecan, Collagen type II, COMP and Sox9 on both types of nanofibrous scaffolds. Morphological observations from SEM and LSCM revealed that hACs maintained their characteristic round shape and cellular agglomeration exclusively on PCL NFMs with CS immobilization. In conclusion, CS immobilization at the surface of PCL NFMs was achieved successfully and provides a valid platform enabling further surface functionalization methods in scaffolds to be developed for cartilage tissue engineering.

  1. Chondroitin sulfate immobilization at the surface of electrospun nanofiber meshes for cartilage tissue regeneration approaches

    Energy Technology Data Exchange (ETDEWEB)

    Piai, Juliana Francis [3B’s Research Group − Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães (Portugal); ICVS/3B’s − PT Government Associate Laboratory, Braga/Guimarães (Portugal); Grupo de Materiais Poliméricos e Compósitos, GMPC – Departamento de Química- Universidade Estadual de Maringá, Av. Colombo 5790, 87020-900, Maringá, Paraná (Brazil); Alves da Silva, Marta; Martins, Albino; Torres, Ana Bela [3B’s Research Group − Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4805-017 Barco, Guimarães (Portugal); ICVS/3B’s − PT Government Associate Laboratory, Braga/Guimarães (Portugal); Faria, Susana [Research Center Officinal Mathematical, Department of Mathematics for Science and Technology, University of Minho, Campus de Azurém, 4800-058 Guimarães (Portugal); and others

    2017-05-01

    Highlights: • Chemical immobilization of chondroitin sulfate at the surface of nanofiber meshes. • CS-immobilized NFMs showed lower roughness and higher hydrophilicity. • CS-immobilized NFMs offer a highly effective substrate for hACs phenotypic stability. - Abstract: Aiming at improving the biocompatibility of biomaterial scaffolds, surface modification presents a way to preserve their mechanical properties and to improve the surface bioactivity. In this work, chondroitin sulfate (CS) was immobilized at the surface of electrospun poly(caprolactone) nanofiber meshes (PCL NFMs), previously functionalized by UV/O{sub 3} exposure and aminolysis. Contact angle, SEM, optical profilometry, FTIR, X-ray photoelectron spectroscopy techniques confirmed the success of CS-immobilization in PCL NFMs. Furthermore, CS-immobilized PCL NFMs showed lower roughness and higher hydrophilicity than the samples without CS. Human articular chondrocytes (hACs) were cultured on electrospun PCL NFMs with or without CS immobilization. It was observed that hACs proliferated through the entire time course of the experiment in both types of nanofibrous scaffolds, as well as for the production of glycosaminoglycans. Quantitative-PCR results demonstrated over-expression of cartilage-related genes such as Aggrecan, Collagen type II, COMP and Sox9 on both types of nanofibrous scaffolds. Morphological observations from SEM and LSCM revealed that hACs maintained their characteristic round shape and cellular agglomeration exclusively on PCL NFMs with CS immobilization. In conclusion, CS immobilization at the surface of PCL NFMs was achieved successfully and provides a valid platform enabling further surface functionalization methods in scaffolds to be developed for cartilage tissue engineering.

  2. The composition of engineered cartilage at the time of implantation determines the likelihood of regenerating tissue with a normal collagen architecture.

    Science.gov (United States)

    Nagel, Thomas; Kelly, Daniel J

    2013-04-01

    The biomechanical functionality of articular cartilage is derived from both its biochemical composition and the architecture of the collagen network. Failure to replicate this normal Benninghoff architecture in regenerating articular cartilage may in turn predispose the tissue to failure. In this article, the influence of the maturity (or functionality) of a tissue-engineered construct at the time of implantation into a tibial chondral defect on the likelihood of recapitulating a normal Benninghoff architecture was investigated using a computational model featuring a collagen remodeling algorithm. Such a normal tissue architecture was predicted to form in the intact tibial plateau due to the interplay between the depth-dependent extracellular matrix properties, foremost swelling pressures, and external mechanical loading. In the presence of even small empty defects in the articular surface, the collagen architecture in the surrounding cartilage was predicted to deviate significantly from the native state, indicating a possible predisposition for osteoarthritic changes. These negative alterations were alleviated by the implantation of tissue-engineered cartilage, where a mature implant was predicted to result in the formation of a more native-like collagen architecture than immature implants. The results of this study highlight the importance of cartilage graft functionality to maintain and/or re-establish joint function and suggest that engineering a tissue with a native depth-dependent composition may facilitate the establishment of a normal Benninghoff collagen architecture after implantation into load-bearing defects.

  3. 3D-Printed ABS and PLA Scaffolds for Cartilage and Nucleus Pulposus Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Derek H. Rosenzweig

    2015-07-01

    Full Text Available Painful degeneration of soft tissues accounts for high socioeconomic costs. Tissue engineering aims to provide biomimetics recapitulating native tissues. Biocompatible thermoplastics for 3D printing can generate high-resolution structures resembling tissue extracellular matrix. Large-pore 3D-printed acrylonitrile butadiene styrene (ABS and polylactic acid (PLA scaffolds were compared for cell ingrowth, viability, and tissue generation. Primary articular chondrocytes and nucleus pulposus (NP cells were cultured on ABS and PLA scaffolds for three weeks. Both cell types proliferated well, showed high viability, and produced ample amounts of proteoglycan and collagen type II on both scaffolds. NP generated more matrix than chondrocytes; however, no difference was observed between scaffold types. Mechanical testing revealed sustained scaffold stability. This study demonstrates that chondrocytes and NP cells can proliferate on both ABS and PLA scaffolds printed with a simplistic, inexpensive desktop 3D printer. Moreover, NP cells produced more proteoglycan than chondrocytes, irrespective of thermoplastic type, indicating that cells maintain individual phenotype over the three-week culture period. Future scaffold designs covering larger pore sizes and better mimicking native tissue structure combined with more flexible or resorbable materials may provide implantable constructs with the proper structure, function, and cellularity necessary for potential cartilage and disc tissue repair in vivo.

  4. 3D-Printed ABS and PLA Scaffolds for Cartilage and Nucleus Pulposus Tissue Regeneration.

    Science.gov (United States)

    Rosenzweig, Derek H; Carelli, Eric; Steffen, Thomas; Jarzem, Peter; Haglund, Lisbet

    2015-07-03

    Painful degeneration of soft tissues accounts for high socioeconomic costs. Tissue engineering aims to provide biomimetics recapitulating native tissues. Biocompatible thermoplastics for 3D printing can generate high-resolution structures resembling tissue extracellular matrix. Large-pore 3D-printed acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA) scaffolds were compared for cell ingrowth, viability, and tissue generation. Primary articular chondrocytes and nucleus pulposus (NP) cells were cultured on ABS and PLA scaffolds for three weeks. Both cell types proliferated well, showed high viability, and produced ample amounts of proteoglycan and collagen type II on both scaffolds. NP generated more matrix than chondrocytes; however, no difference was observed between scaffold types. Mechanical testing revealed sustained scaffold stability. This study demonstrates that chondrocytes and NP cells can proliferate on both ABS and PLA scaffolds printed with a simplistic, inexpensive desktop 3D printer. Moreover, NP cells produced more proteoglycan than chondrocytes, irrespective of thermoplastic type, indicating that cells maintain individual phenotype over the three-week culture period. Future scaffold designs covering larger pore sizes and better mimicking native tissue structure combined with more flexible or resorbable materials may provide implantable constructs with the proper structure, function, and cellularity necessary for potential cartilage and disc tissue repair in vivo.

  5. Allogeneic Mesenchymal Stem Cells Stimulate Cartilage Regeneration and Are Safe for Single-Stage Cartilage Repair in Humans upon Mixture with Recycled Autologous Chondrons

    NARCIS (Netherlands)

    de Windt, Tommy S; Vonk, Lucienne A; Slaper-Cortenbach, Ineke C M; van den Broek, Marcel P H; Nizak, Razmara; van Rijen, Mattie H P; de Weger, Roel A; Dhert, Wouter J A|info:eu-repo/dai/nl/10261847X; Saris, Daniel B F

    Traditionally, mesenchymal stem cells (MSCs) isolated from adult bone marrow were described as being capable of differentiating to various lineages including cartilage. Despite increasing interest in these MSCs, concerns regarding their safety, in vivo behavior and clinical effectiveness have

  6. Allogeneic Mesenchymal Stem Cells Stimulate Cartilage Regeneration and Are Safe for Single-Stage Cartilage Repair in Humans upon Mixture with Recycled Autologous Chondrons

    NARCIS (Netherlands)

    de Windt, Tommy S.; Vonk, Lucienne A.; Slaper-Cortenbach, Ineke C.M.; den Broek, Marcel P. H; Nizak, Razmara; van Rijen, Mattie H.P.; de Weger, Roel A.; Dhert, Wouter J.A.; Saris, Daniel B.F.

    2017-01-01

    Traditionally, mesenchymal stem cells (MSCs) isolated from adult bone marrow were described as being capable of differentiating to various lineages including cartilage. Despite increasing interest in these MSCs, concerns regarding their safety, in vivo behavior and clinical effectiveness have

  7. Biodegradable and injectable cure-on-demand polyurethane scaffolds for regeneration of articular cartilage.

    Science.gov (United States)

    Werkmeister, J A; Adhikari, R; White, J F; Tebb, T A; Le, T P T; Taing, H C; Mayadunne, R; Gunatillake, P A; Danon, S J; Ramshaw, J A M

    2010-09-01

    This paper describes the synthesis and characterization of an injectable methacrylate functionalized urethane-based photopolymerizable prepolymer to form biodegradable hydrogels. The tetramethacrylate prepolymer was based on the reaction between two synthesized compounds, diisocyanato poly(ethylene glycol) and monohydroxy dimethacrylate poly(epsilon-caprolactone) triol. The final prepolymer was hydrated with phosphate-buffered saline (pH 7.4) to yield a biocompatible hydrogel containing up to 86% water. The methacrylate functionalized prepolymer was polymerized using blue light (450 nm) with an initiator, camphorquinone and a photosensitizer, N,N-dimethylaminoethyl methacrylate. The polymer was stable in vitro in culture media over the 28 days tested (1.9% mass loss); in the presence of lipase, around 56% mass loss occurred over the 28 days in vitro. Very little degradation occurred in vivo in rats over the same time period. The polymer was well tolerated with very little capsule formation and a moderate host tissue response. Human chondrocytes, seeded onto Cultispher-S beads, were viable in the tetramethacrylate prepolymer and remained viable during and after polymerization. Chondrocyte-bead-polymer constructs were maintained in static and spinner culture for 8 weeks. During this time, cells remained viable, proliferated and migrated from the beads through the polymer towards the edge of the polymer. New extracellular matrix (ECM) was visualized with Masson's trichrome (collagen) and Alcian blue (glycosaminoglycan) staining. Further, the composition of the ECM was typical for articular cartilage with prominent collagen type II and type VI and moderate keratin sulphate, particularly for tissue constructs cultured under dynamic conditions. 2010. Published by Elsevier Ltd. All rights reserved.

  8. Joint homeostasis in tissue engineering for cartilage repair

    NARCIS (Netherlands)

    Saris, D.B.F.

    2002-01-01

    Traumatic joint damage, articular cartilage and the research into methods of restoring the articulation are not new topics of interest. For centuries, clinicians have recognized the importance of cartilage damage and sought ways of learning about the normal form and function of hyaline cartilage as

  9. Concise review: unraveling stem cell cocultures in regenerative medicine: which cell interactions steer cartilage regeneration and how?

    NARCIS (Netherlands)

    de Windt, T.S.; Hendriks, J.A.; Zhao, X.; Vonk, L.A.; Creemers, L.B.; Dhert, W.J.A.; Randolph, M.A.; Saris, D.B.F.

    2014-01-01

    Cartilage damage and osteoarthritis (OA) impose an important burden on society, leaving both young, active patients and older patients disabled and affecting quality of life. In particular, cartilage injury not only imparts acute loss of function but also predisposes to OA. The increase in knowledge

  10. Priming Adipose-Derived Mesenchymal Stem Cells with Hyaluronan Alters Growth Kinetics and Increases Attachment to Articular Cartilage

    Directory of Open Access Journals (Sweden)

    Peter Succar

    2016-01-01

    Full Text Available Background. Biological therapeutics such as adipose-derived mesenchymal stem cell (MSC therapy are gaining acceptance for knee-osteoarthritis (OA treatment. Reports of OA-patients show reductions in cartilage defects and regeneration of hyaline-like-cartilage with MSC-therapy. Suspending MSCs in hyaluronan commonly occurs in animals and humans, usually without supporting data. Objective. To elucidate the effects of different concentrations of hyaluronan on MSC growth kinetics. Methods. Using a range of hyaluronan concentrations, we measured MSC adherence and proliferation on culture plastic surfaces and a novel cartilage-adhesion assay. We employed time-course and dispersion imaging to assess MSC binding to cartilage. Cytokine profiling was also conducted on the MSC-secretome. Results. Hyaluronan had dose-dependent effects on growth kinetics of MSCs at concentrations of entanglement point (1 mg/mL. At higher concentrations, viscosity effects outweighed benefits of additional hyaluronan. The cartilage-adhesion assay highlighted for the first time that hyaluronan-primed MSCs increased cell attachment to cartilage whilst the presence of hyaluronan did not. Our time-course suggested patients undergoing MSC-therapy for OA could benefit from joint-immobilisation for up to 8 hours. Hyaluronan also greatly affected dispersion of MSCs on cartilage. Conclusion. Our results should be considered in future trials with MSC-therapy using hyaluronan as a vehicle, for the treatment of OA.

  11. Fusarium and other opportunistic hyaline fungi

    Science.gov (United States)

    This chapter focuses on those fungi that grow in tissue in the form of hyaline or lightly colored septate hyphae. These fungi include Fusarium and other hyaline fungi. Disease caused by hyaline fungi is referred to as hyalohyphomycosis. Hyaline fungi described in this chapter include the anamorphic,...

  12. Regeneration

    Science.gov (United States)

    George A. Schier; Wayne D. Shepperd; John R. Jones

    1985-01-01

    There are basically two approaches to regenerating aspen stands-sexual reproduction using seed, or vegetative regeneration by root suckering. In the West, root suckering is the most practical method. The advantage of having an existing, well established root system capable of producing numerous root suckers easily outweighs natural or artificial reforestation in the...

  13. Study of differential properties of fibrochondrocytes and hyaline chondrocytes in growing rabbits.

    Science.gov (United States)

    Huang, L; Li, M; Li, H; Yang, C; Cai, X

    2015-02-01

    We aimed to build a culture model of chondrocytes in vitro, and to study the differential properties between fibrochondrocytes and hyaline chondrocytes. Histological sections were stained with haematoxylin and eosin so that we could analyse the histological structure of the fibrocartilage and hyaline cartilage. Condylar fibrochondrocytes and femoral hyaline chondrocytes were cultured from four, 4-week-old, New Zealand white rabbits. The production of COL2A1, COL1OA1, SOX9 and aggrecan was detected by real time-q polymerase chain reaction (RT-qPCR) and immunoblotting and the differences between them were compared statistically. Histological structures obviously differed between fibrocartilage and hyaline cartilage. COL2A1 and SOX9 were highly expressed within cell passage 2 (P2) of both fibrochondrocytes and hyaline chondrocytes, and reduced significantly after cell passage 4 (P4). The mRNA expressions of COL2A1 (p=0.05), COL10A1 (p=0.04), SOX9 (p=0.03), and aggrecan (p=0.04) were significantly higher in hyaline chondrocytes than in fibrochondrocytes, whereas the expression of COL1A1 (p=0.02) was the opposite. Immunoblotting showed similar results. We have built a simple and effective culture model of chondrocytes in vitro, and the P2 of chondrocytes is recommended for further studies. Condylar fibrocartilage and femoral hyaline cartilage have unique biological properties, and the regulatory mechanisms of endochondral ossification for the condyle should be studied independently in the future. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  14. Generation of hyaline cartilaginous tissue from mouse adult dermal fibroblast culture by defined factors

    Science.gov (United States)

    Hiramatsu, Kunihiko; Sasagawa, Satoru; Outani, Hidetatsu; Nakagawa, Kanako; Yoshikawa, Hideki; Tsumaki, Noriyuki

    2011-01-01

    Repair of cartilage injury with hyaline cartilage continues to be a challenging clinical problem. Because of the limited number of chondrocytes in vivo, coupled with in vitro de-differentiation of chondrocytes into fibrochondrocytes, which secrete type I collagen and have an altered matrix architecture and mechanical function, there is a need for a novel cell source that produces hyaline cartilage. The generation of induced pluripotent stem (iPS) cells has provided a tool for reprogramming dermal fibroblasts to an undifferentiated state by ectopic expression of reprogramming factors. Here, we show that retroviral expression of two reprogramming factors (c-Myc and Klf4) and one chondrogenic factor (SOX9) induces polygonal chondrogenic cells directly from adult dermal fibroblast cultures. Induced cells expressed marker genes for chondrocytes but not fibroblasts, i.e., the promoters of type I collagen genes were extensively methylated. Although some induced cell lines formed tumors when subcutaneously injected into nude mice, other induced cell lines generated stable homogenous hyaline cartilage–like tissue. Further, the doxycycline-inducible induction system demonstrated that induced cells are able to respond to chondrogenic medium by expressing endogenous Sox9 and maintain chondrogenic potential after substantial reduction of transgene expression. Thus, this approach could lead to the preparation of hyaline cartilage directly from skin, without generating iPS cells. PMID:21293062

  15. Experimental study on the role of intra-articular injection of MSCs on cartilage regeneration in haemophilia.

    Science.gov (United States)

    Ravanbod, R; Torkaman, G; Mophid, M; Mohammadali, F

    2015-09-01

    Mesenchymal stem cells (MSCs) therapy is a field in progress in cartilage repair strategies. We tried to investigate the functional properties of the joint and cartilage in experimental haemarthrosis (EH) after MSCs intra-articular (IA) injection. One millilitre of fresh autologous blood was injected twice a week for three consecutive weeks in three groups including control haemophilia 10 days (n = 8), control haemophilia 38 days (n = 8) and MSCs (n = 8) group. In later, 10 days after the end of IA blood injections, MSCs IA injection was performed. Eight animals received no treatment as the normal control group. Thirty-eight days after the end of IA blood injections, animals were sacrificed. Joint friction and stress-relaxation tests were done, inflammatory cytokines of synovial membrane and scanning electron microscopy of the cartilage assessed. Joint friction decreased in MSCs in comparison to other groups and was significant with normal control group, (P = 0.011). The mechanical properties of cartilage showed no significant differences between groups. Tumour necrosis factor alpha and interleukin 1 beta decreased and IL-4 very slightly increased in MSCs in comparison to the time-matched control group. Scanning electron microscopy enabled acquisition of good structural properties of the surface and layers of the cartilage after MSCs injection. The hole induced in the medial plateau of the tibia bones, after inducing haemarthrosis, were covered with cartilage-like structure. The results showed that MSCs IA injection has some beneficial effects on cartilage structure and function in haemarthrosis model and is promising in patients with haemophilia. © 2015 John Wiley & Sons Ltd.

  16. Biomaterial and Cell Based Cartilage Repair

    NARCIS (Netherlands)

    Zhao, X

    2015-01-01

    Injuries to human native cartilage tissue are particularly troublesome because cartilage has little ability to heal or regenerate itself. The reconstruction, repair, and regeneration of cartilage tissue continue to be one of the greatest clinical challenges, especially in orthopaedic and plastic

  17. Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering.

    Science.gov (United States)

    Mirahmadi, Fereshteh; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali; Bonakdar, Shahin

    2013-12-01

    Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber-hydrogel composite for GAG content and in two-layer electrospun fiber-hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. © 2013.

  18. One-stage vs two-stage cartilage repair: a current review

    Directory of Open Access Journals (Sweden)

    Daniel Meyerkort

    2010-10-01

    Full Text Available Daniel Meyerkort, David Wood, Ming-Hao ZhengCenter for Orthopaedic Research, School of Surgery and Pathology, University of Western Australia, Perth, AustraliaIntroduction: Articular cartilage has a poor capacity for regeneration if damaged. Various methods have been used to restore the articular surface, improve pain, function, and slow progression to osteoarthritis.Method: A PubMed review was performed on 18 March, 2010. Search terms included “autologous chondrocyte implantation (ACI” and “microfracture” or “mosaicplasty”. The aim of this review was to determine if 1-stage or 2-stage procedures for cartilage repair produced different functional outcomes.Results: The main procedures currently used are ACI and microfracture. Both first-generation ACI and microfracture result in clinical and functional improvement with no significant differences. A significant increase in functional outcome has been observed in second-generation procedures such as Hyalograft C, matrix-induced ACI, and ChondroCelect compared with microfracture. ACI results in a higher percentage of patients with clinical improvement than mosaicplasty; however, these results may take longer to achieve.Conclusion: Clinical and functional improvements have been demonstrated with ACI, microfracture, mosaicplasty, and synthetic cartilage constructs. Heterogeneous products and lack of good-quality randomized-control trials make product comparison difficult. Future developments involve scaffolds, gene therapy, growth factors, and stem cells to create a single-stage procedure that results in hyaline articular cartilage.Keywords: autologous chondrocyte implantation, microfracture, cartilage repair

  19. In vitro and in vivo evaluation of chitosan–gelatin scaffolds for cartilage tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Whu, Shu Wen [Department of Orthopaedic Surgery, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Hung, Kun-Che; Hsieh, Kuo-Huang [Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan (China); Chen, Chih-Hwa [Department of Orthopaedic Surgery, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Tsai, Ching-Lin, E-mail: tsaicl@ntuh.gov.tw [Department of Orthopaedics, National Taiwan University Hospital, Taipei, Taiwan (China); Hsu, Shan-hui, E-mail: shhsu@ntu.edu.tw [Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan (China)

    2013-07-01

    Chitosan–gelatin polyelectrolyte complexes were fabricated and evaluated as tissue engineering scaffolds for cartilage regeneration in vitro and in vivo. The crosslinker for the gelatin component was selected among glutaraldehyde, bisepoxy, and a water-soluble carbodiimide (WSC) based upon the proliferation of chondrocytes on the crosslinked gelatin. WSC was found to be the most suitable crosslinker. Complex scaffolds made from chitosan and gelatin with a component ratio equal to one possessed the proper degradation rate and mechanical stability in vitro. Chondrocytes were able to proliferate well and secrete abundant extracellular matrix in the chitosan–gelatin (1:1) complex scaffolds crosslinked by WSC (C1G1{sub WSC}) compared to the non-crosslinked scaffolds. Implantation of chondrocytes-seeded scaffolds in the defects of rabbit articular cartilage confirmed that C1G1{sub WSC} promoted the cartilage regeneration. The neotissue formed the histological feature of tide line and lacunae in 6.5 months. The amount of glycosaminoglycans in C1G1{sub WSC} constructs (0.187 ± 0.095 μg/mg tissue) harvested from the animals after 6.5 months was 14 wt.% of that in normal cartilage (1.329 ± 0.660 μg/mg tissue). The average compressive modulus of regenerated tissue at 6.5 months was about 0.539 MPa, which approached to that of normal cartilage (0.735 MPa), while that in the blank control (3.881 MPa) was much higher and typical for fibrous tissue. Type II collagen expression in C1G1{sub WSC} constructs was similarly intense as that in the normal hyaline cartilage. According to the above results, the use of C1G1{sub WSC} scaffolds may enhance the cartilage regeneration in vitro and in vivo. - Highlights: • We developed a chitosan–gelatin scaffold crosslinked with carbodiimide. • Neocartilage formation was more evident in crosslinked vs. non-crosslinked scaffolds. • Histological features of tide line and lacunae were observed in vivo at 6.5 months. • Compressive

  20. Single-Stage Cell-Based Cartilage Regeneration Using a Combination of Chondrons and Mesenchymal Stromal Cells: Comparison With Microfracture

    NARCIS (Netherlands)

    Bekkers, J.E.J.; Tsuchida, A.I.; van Rijen, M.H.P.; Vonk, L.A.; Dhert, W.J.A.; Saris, Daniël B.F.

    2013-01-01

    Background: Autologous chondrocyte implantation (ACI) is traditionally a 2-step procedure used to repair focal articular cartilage lesions. With use of a combination of chondrons (chondrocytes in their own territorial matrix) and mesenchymal stromal cells (MSCs), ACI could be innovated and performed

  1. A new solution in cartilage repair surgery of joint lesions

    Directory of Open Access Journals (Sweden)

    Patrascu JM¹,

    2016-12-01

    Full Text Available OBJECTIVES AND BACKGROUND The purpose of this study is to provide a simple, cost-effective, reproducible technology that is able to regenerate durable hyaline cartilage. Traumas and sports along with different diseases such as obesity or gradual degeneration over time of the joint surface determine cartilage defects resulting in pain and dysfunctionality. MATERIALS AND METHODS Since 2011 a number of 183 pacients were treated using Agili-C, out of which 40 pacients were operated in the IInd Clinic of Orthopaedics of the Timișoara Emergency County Hospital. The implant is a biphasic, porous, resorbable tissue regeneration scaffold used in the treatment of osteochondral defects. The surgical procedure is performed through minimal arthrotomy, with a good exposure of the cartilage defect. The implant is inserted so that the articular surface of the implant is parallel with the surrounding healthy cartilage. When in place, it facilitates vascularization thus allowing tissue formation to commence from the periphery towards the center of the defect. RESULTS Until now, results are promising, showing obvious improvements in pain and function in both degenerative and post-traumatic joint lesions in the knee, ankle and first MP joint. CONCLUSIONS Agili-C is a cell free, single stage, off the shelf implant that will hopefully meet market demands and become a reliable procedure in joint repair surgery in the future. Figure 1: Intra-operative aspect after the implant is in place. REFERENCES 1. Mehdi Kazemzadeh-Narbat et al. Biomaterials.2010. p.31. 2. Scaglione et al. Tissue engineering: Part A. 2009;15:1. FOOTNOTE Agili-C is a product of CartiHeal Company

  2. A new injectable biphasic hydrogel based on partially hydrolyzed polyacrylamide and nano hydroxyapatite, crosslinked with chromium acetate, as scaffold for cartilage regeneration

    Science.gov (United States)

    Koushki, N.; Tavassoli, H.; Katbab, A. A.; Katbab, P.; Bonakdar, S.

    2015-05-01

    Polymer scaffolds are applied in the field of tissue engineering as three dimensional structures to organize cells and present stimuli to direct generation of a desired damaged tissue. In situ gelling scaffolds have attracted great attentions, as they are structurally similar to the extra cellular matrix (ECM). In the present work, attempts have been made to design and fabricate a new injectable and crosslinkable biphasic hydrogel based on partially hydrolyzed polyacrylamide (HPAM), chromium acetate as crosslink agent and nanocrystalline hydroxyapatite (nHAp) as reinforcing and bioactive agent for repair and regeneration of damaged cartilage. The distinct characteristic of HPAM is the presence of carboxylate anion groups on its backbone which allows to engineer the structure of the hydrogel for the desired bioactivity with appropriate cells differentiation towards both soft and hard (bone) tissues. The synthesized hydrogel exhibited bifunctional behavior which was derived by its biphasic structure in which one phase was loaded with nano hydroxyapatite to provide integration capability by subchondral bones and fix the hydrogel at cartilage defect without a need for suturing. The other phase differentiates the rabbit adipogenic mesenchymal stem cells (MSCs) towards soft tissue. Rheomechanical spectrometry (RMS) was employed to study the kinetic of the gelation including induction time and rate, as well as to measure the ultimate elastic modulus of the optimum crosslinked hydrogel. Surface tension measurement was also performed to tailor the surface characteristics of the gels. In vitro culturing of the cells inside the crosslinked hydrogel revealed high viability and high differentiation of the encapsulated rabbit stem cells, providing that the chromium acetate level was kept below 0.2 wt%. Based on the obtained results, the designed and fabricated biphasic hydrogel exhibited high potential as carrier for the stem cells for cartilage tissue engineering application

  3. Allogeneic Umbilical Cord-Derived Mesenchymal Stem Cells as a Potential Source for Cartilage and Bone Regeneration: An In Vitro Study

    Directory of Open Access Journals (Sweden)

    A. Marmotti

    2017-01-01

    Full Text Available Umbilical cord (UC may represent an attractive cell source for allogeneic mesenchymal stem cell (MSC therapy. The aim of this in vitro study is to investigate the chondrogenic and osteogenic potential of UC-MSCs grown onto tridimensional scaffolds, to identify a possible clinical relevance for an allogeneic use in cartilage and bone reconstructive surgery. Chondrogenic differentiation on scaffolds was confirmed at 4 weeks by the expression of sox-9 and type II collagen; low oxygen tension improved the expression of these chondrogenic markers. A similar trend was observed in pellet culture in terms of matrix (proteoglycan production. Osteogenic differentiation on bone-graft-substitute was also confirmed after 30 days of culture by the expression of osteocalcin and RunX-2. Cells grown in the hypertrophic medium showed at 5 weeks safranin o-positive stain and an increased CbFa1 expression, confirming the ability of these cells to undergo hypertrophy. These results suggest that the UC-MSCs isolated from minced umbilical cords may represent a valuable allogeneic cell population, which might have a potential for orthopaedic tissue engineering such as the on-demand cell delivery using chondrogenic, osteogenic, and endochondral scaffold. This study may have a clinical relevance as a future hypothetical option for allogeneic single-stage cartilage repair and bone regeneration.

  4. Cartilage repair by mesenchymal stem cells: Clinical trial update and perspectives

    Directory of Open Access Journals (Sweden)

    Wayne Yuk-wai Lee

    2017-04-01

    The translational potential of this article: This review summarises recent MSC-related clinical research that focuses on cartilage repair. We also propose a novel possible translational direction for hyaline cartilage formation and a new paradigm making use of extra-cellular signalling and epigenetic regulation in the application of MSCs for cartilage repair.

  5. Ready-to-Use Tissue Construct for Military Bone and Cartilage Trauma

    Science.gov (United States)

    2012-10-01

    physiologic hyaline cartilage - osseous transition in massive osteochondral defects in large animals. We will conduct functional outcome analysis, X...10-1-0933 TITLE: Ready-to-Use Tissue Construct for Military Bone and Cartilage Trauma PRINCIPAL INVESTIGATOR: Francis Y. Lee... Cartilage Trauma” addresses the current limitations in treating complex, high-energy musculoskeletal wounds incurred in active combat. High-energy

  6. Computer-aided cartilage tissue-engineering : a numerical evaluation of the influence of inhomogeneities, collagen architecture and temporal culture effects

    NARCIS (Netherlands)

    Khoshgoftar, M.

    2012-01-01

    Hyaline articular cartilage has a crucial role in the distribution of joint mechanical loads and smooth movement of bones. Because of its poor healing capacity, cartilage damage is progressive and may lead to osteoarthritis (OA). Replacing damaged cartilage with tissue engineered (TE) cartilage is

  7. How Can Nanotechnology Help to Repair the Body? Advances in Cardiac, Skin, Bone, Cartilage and Nerve Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Juan Antonio Marchal

    2013-03-01

    Full Text Available Nanotechnologists have become involved in regenerative medicine via creation of biomaterials and nanostructures with potential clinical implications. Their aim is to develop systems that can mimic, reinforce or even create in vivo tissue repair strategies. In fact, in the last decade, important advances in the field of tissue engineering, cell therapy and cell delivery have already been achieved. In this review, we will delve into the latest research advances and discuss whether cell and/or tissue repair devices are a possibility. Focusing on the application of nanotechnology in tissue engineering research, this review highlights recent advances in the application of nano-engineered scaffolds designed to replace or restore the followed tissues: (i skin; (ii cartilage; (iii bone; (iv nerve; and (v cardiac.

  8. MR imaging of articular cartilage in the knee. Evaluation of cadaver knee by 3D FLASH sequence with fat saturation

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Katsuhiko; Hachiya, Junichi; Matsumura, Joji [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine

    1999-06-01

    MR imaging of the articular cartilage of the 24 cadever knees was performed using 3D FLASH sequence with fat saturation. Good correlation was noted between MR findings and either macroscopic or microscopic appearances of the hyaline cartilage. Low signal intensity area without significant thinning of the cartilage was considered to represent the degenerative changes due to relatively early process of osteoarthritis. (author)

  9. Juvenile hyaline fibromatosis. Radiological diagnosis

    International Nuclear Information System (INIS)

    Fuentes, R.; Sar, V.; Cabrera, J.J.; Diaz, L.; Hernandez, B.; Valeron, P.; Baez, O.; Rodriguez, M.

    1993-01-01

    Juvenile hyaline fibromatosis (JHF) is a rare disorder of unknown etiology, very few cases of which have been reported in the literature. It presents similarities to other fibromatosys, but has its particular radiological features which differentiate it from them. The clinical findings consist of several, slow growing, subcutaneous nodules, flexion contractures of the joints which can lead to disability, gingival hypertrophy and muscular atrophy. The suspected radiological diagnosis is confirmed by electron microscopy study of the nodules, although light microscopy can also reveal suggestive images. Author (9 refs.)

  10. Biocompatibility Assessment of Novel Collagen-Sericin Scaffolds Improved with Hyaluronic Acid and Chondroitin Sulfate for Cartilage Regeneration

    Directory of Open Access Journals (Sweden)

    Sorina Dinescu

    2013-01-01

    Full Text Available Cartilage tissue engineering (CTE applications are focused towards the use of implantable biohybrids consisting of biodegradable scaffolds combined with in vitro cultured cells. Hyaluronic acid (HA and chondroitin sulfate (CS were identified as the most potent prochondrogenic factors used to design new biomaterials for CTE, while human adipose-derived stem cells (ASCs were proved to display high chondrogenic potential. In this context, our aim was not only to build novel 3D porous scaffolds based on natural compounds but also to evaluate their in vitro biological performances. Therefore, for prospective CTE, collagen-sericin (Coll-SS scaffolds improved with HA (5% or 10% and CS (5% or 10% were used as temporary physical supports for ASCs and were analyzed in terms of structural, thermal, morphological, and swelling properties and cytotoxic potential. To complete biocompatibility data, ASCs viability and proliferation potential were also assessed. Our studies revealed that Coll-SS hydrogels improved with 10% HA and 5% CS displayed the best biological performances in terms of cell viability, proliferation, morphology, and distribution. Thus, further work will address a novel 3D system including both HA 10% and CS 5% glycoproteins, which will probably be exposed to prochondrogenic conditions in order to assess its potential use in CTE applications.

  11. Nanopolymers Delivery of the Bone Morphogenetic Protein-4 Plasmid to Mesenchymal Stem Cells Promotes Articular Cartilage Repair In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Junjun Shi

    2012-01-01

    Full Text Available The clinical application of viral vectors for gene therapy is limited for biosafety consideration. In this study, to promote articular cartilage repair, poly (lactic-co glycolic acid (PLGA nanopolymers were used as non-viral vectors to transfect rabbit mesenchymal stem cells (MSCs with the pDC316-BMP4-EGFP plasmid. The cytotoxicity and transfection efficiency in vitro were acceptable measuring by CCK-8 and flow cytometry. After transfection, Chondrogenic markers (mRNA of Col2a1, Sox9, Bmp4, and Agg of experimental cells (MSCs being transfected with BMP-4 plasmid by PLGA nanopolymers were increased more than those of control cells (MSCs being transfected with naked BMP-4 plasmid alone. In vivo study, twelve rabbits (24 knees with large full thickness articular cartilage defects were randomly divided into the experimental group (MSCs being transfected with BMP-4 plasmid by PLGA nanopolymers and the control group (MSCs being transfected with naked BMP-4 plasmid. The experimental group showed better regeneration than the control group 6 and 12 weeks postoperatively. Hyaline-like cartilage formed at week 12 in the experimental group, indicating the local delivery of BMP-4 plasmid to MSCs by PLGA nanopolymers improved articular cartilage repair significantly. PLGA nanopolymers could be a promising and effective non-viral vector for gene therapy in cartilage repair.

  12. Autologous chondrocyte implantation: Is it likely to become a saviour of large-sized and full-thickness cartilage defect in young adult knee?

    Science.gov (United States)

    Zhang, Chi; Cai, You-Zhi; Lin, Xiang-Jin

    2016-05-01

    A literature review of the first-, second- and third-generation autologous chondrocyte implantation (ACI) technique for the treatment of large-sized (>4 cm(2)) and full-thickness knee cartilage defects in young adults was conducted, examining the current literature on features, clinical scores, complications, magnetic resonance image (MRI) and histological outcomes, rehabilitation and cost-effectiveness. A literature review was carried out in the main medical databases to evaluate the several studies concerning ACI treatment of large-sized and full-thickness knee cartilage defects in young adults. ACI technique has been shown to relieve symptoms and improve functional assessment in large-sized (>4 cm(2)) and full-thickness knee articular cartilage defect of young adults in short- and medium-term follow-up. Besides, low level of evidence demonstrated its efficiency and durability at long-term follow-up after implantation. Furthermore, MRI and histological evaluations provided the evidence that graft can return back to the previous nearly normal cartilage via ACI techniques. Clinical outcomes tend to be similar in different ACI techniques, but with simplified procedure, low complication rate and better graft quality in the third-generation ACI technique. ACI based on the experience of cell-based therapy, with the high potential to regenerate hyaline-like tissue, represents clinical development in treatment of large-sized and full-thickness knee cartilage defects. IV.

  13. Allogeneic MSCs and Recycled Autologous Chondrons Mixed in a One-Stage Cartilage Cell Transplantion: A First-in-Man Trial in 35 Patients.

    Science.gov (United States)

    de Windt, Tommy S; Vonk, Lucienne A; Slaper-Cortenbach, Ineke C M; Nizak, Razmara; van Rijen, Mattie H P; Saris, Daniel B F

    2017-08-01

    MSCs are known as multipotent mesenchymal stem cells that have been found capable of differentiating into various lineages including cartilage. However, recent studies suggest MSCs are pericytes that stimulate tissue repair through trophic signaling. Aimed at articular cartilage repair in a one-stage cell transplantation, this study provides first clinical evidence that MSCs stimulate autologous cartilage repair in the knee without engrafting in the host tissue. A phase I (first-in-man) clinical trial studied the one-stage application of allogeneic MSCs mixed with 10% or 20% recycled defect derived autologous chondrons for the treatment of cartilage defects in 35 patients. No treatment-related serious adverse events were found and statistically significant improvement in clinical outcome shown. Magnetic resonance imaging and second-look arthroscopies showed consistent newly formed cartilage tissue. A biopsy taken from the center of the repair tissue was found to have hyaline-like features with a high concentration of proteoglycans and type II collagen. DNA short tandem repeat analysis delivered unique proof that the regenerated tissue contained patient-DNA only. These findings support the hypothesis that allogeneic MSCs stimulate a regenerative host response. This first-in-man trial supports a paradigm shift in which MSCs are applied as augmentations or "signaling cells" rather than differentiating stem cells and opens doors for other applications. Stem Cells 2017;35:1984-1993. © 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  14. Nd:YAG 1.44 laser ablation of human cartilage

    Science.gov (United States)

    Cummings, Robert S.; Prodoehl, John A.; Rhodes, Anthony L.; Black, Johnathan D.; Sherk, Henry H.

    1993-07-01

    This study determined the effectiveness of a Neodymium:YAG 1.44 micrometers wavelength laser on human cartilage. This wavelength is strongly absorbed by water. Cadaveric meniscal fibrocartilage and articular hyaline cartilage were harvested and placed in normal saline during the study. A 600 micrometers quartz fiber was applied perpendicularly to the tissues with a force of 0.098 N. Quantitative measurements were then made of the ablation rate as a function of fluence. The laser energy was delivered at a constant repetition rate of 5 Hz., 650 microsecond(s) pulsewidth, and energy levels ranging from 0.5 joules to 2.0 joules. Following the ablation of the tissue, the specimens were fixed in formalin for histologic evaluation. The results of the study indicate that the ablation rate is 0.03 mm/mj/mm2 for hyaline cartilage and fibrocartilage. Fibrocartilage was cut at approximately the same rate as hyaline cartilage. There was a threshold fluence projected to be 987 mj/mm2 for hyaline cartilage and fibrocartilage. Our results indicate that the pulsed Nd:YAG laser operating at 1.44 micrometers has a threshold fluence above which it will ablate human cartilage, and that its ablation rate is directly proportional to fluence over the range of parameters tested. Fibrocartilage and hyaline cartilage demonstrated similar threshold fluence and ablation rates which is related to the high water content of these tissues.

  15. Measurements of surface layer of the articular cartilage using microscopic techniques

    International Nuclear Information System (INIS)

    Ryniewicz, A. M; Ryniewicz, W.; Ryniewicz, A.; Gaska, A.

    2010-01-01

    The articular cartilage is the structure that directly cooperates tribologically in biobearing. It belongs to the connective tissues and in the joints it assumes two basic forms: hyaline cartilage that builds joint surfaces and fibrocartilage which may create joint surfaces. From this fibrocartilage are built semilunar cartilage and joint disc are built as well. The research of articular cartilage have been done in macro, micro and nano scale. In all these measurement areas characteristic features occur which can identify biobearing tribology. The aim of the research was the identification of surface layer of articular cartilage by means of scanning electron microscopy (SEM) and atom force microscopy (AFM) and the analysis of topography of these layers. The material used in the research of surface layer was the animal articular cartilage: hyaline cartilage and fibrocartilage.

  16. Measurements of surface layer of the articular cartilage using microscopic techniques

    Science.gov (United States)

    Ryniewicz, A. M.; Ryniewicz, A.; Ryniewicz, W.; Gaska, A.

    2010-07-01

    The articular cartilage is the structure that directly cooperates tribologically in biobearing. It belongs to the connective tissues and in the joints it assumes two basic forms: hyaline cartilage that builds joint surfaces and fibrocartilage which may create joint surfaces. From this fibrocartilage are built semilunar cartilage and joint disc are built as well. The research of articular cartilage have been done in macro, micro and nano scale. In all these measurement areas characteristic features occur which can identify biobearing tribology. The aim of the research was the identification of surface layer of articular cartilage by means of scanning electron microscopy (SEM) and atom force microscopy (AFM) and the analysis of topography of these layers. The material used in the research of surface layer was the animal articular cartilage: hyaline cartilage and fibrocartilage.

  17. Tissue engineering applications: cartilage lesions repair by the use of autologous chondrocytes

    Directory of Open Access Journals (Sweden)

    L. De Franceschi

    2011-09-01

    Full Text Available Promising new therapies based on tissue engineering have been recently developed for cartilage repair. The association of biomaterials with autologous chondrocytes expanded in vitro can represent a useful tool to regenerate this tissue. The scaffolds utilised in such therapeutical applications should provide a pre-formed three-dimensional shape, prevent cells from floating out of the defect, have sufficient mechanical strength, facilitate uniform spread of cells and stimulate the phenotype of transplanted cells. Hyaff®-11 is a hyaluronic-acid based biodegradable polymer, that has been shown to provide successful cell carrier for tissue-engineered repair. From our findings we can state that human chondrocytes seeded on Hyaff®-11 are able to maintain in vitro the characteristic of differentiated cells, expressing and producing collagen type II and aggrecan which are the main markers of cartilage phenotype, down-regulating collagen type I. Moreover, it seems to be a useful scaffold for cartilage repair both in animal models and clinical trials in humans, favouring the formation of a hyaline-like tissue. In the light of these data, we can hypothesise, for the future, the use of autologous chondrocyte transplantation together with gene therapy as a treatment for rheumatic diseases such as osteoarthritis.

  18. Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering

    International Nuclear Information System (INIS)

    Mirahmadi, Fereshteh; Tafazzoli-Shadpour, Mohammad; Shokrgozar, Mohammad Ali; Bonakdar, Shahin

    2013-01-01

    Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber–hydrogel composite for GAG content and in two-layer electrospun fiber–hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. - Highlights: • Chitosan hydrogel composites fabricated by two forms of silk fiber • Silk fibers provide structural support for the hydrogel matrix. • The mechanical properties of hydrogel significantly improved by associating with silk. • Production of GAG and collagen type II was demonstrated within the scaffolds

  19. Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk fibers for cartilage tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Mirahmadi, Fereshteh [Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of); Tafazzoli-Shadpour, Mohammad, E-mail: Tafazoli@aut.ac.ir [Faculty of Biomedical Engineering, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Shokrgozar, Mohammad Ali, E-mail: mashokrgozar@pasteur.ac.ir [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of); Bonakdar, Shahin [National Cell Bank of Iran, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of)

    2013-12-01

    Articular cartilage has limited repair capability following traumatic injuries and current methods of treatment remain inefficient. Reconstructing cartilage provides a new way for cartilage repair and natural polymers are often used as scaffold because of their biocompatibility and biofunctionality. In this study, we added degummed chopped silk fibers and electrospun silk fibers to the thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel constructs which were used as scaffold for hyaline cartilage regeneration. The gelation temperature and gelation time of hydrogel were analyzed by the rheometer and vial tilting method. Mechanical characterization was measured by uniaxial compression, indentation and dynamic mechanical analysis assay. Chondrocytes were then harvested from the knee joint of the New Zealand white rabbits and cultured in constructs. The cell proliferation, viability, production of glycosaminoglycans and collagen type II were assessed. The results showed that mechanical properties of the hydrogel were significantly enhanced when a hybrid with two layers of electrospun silk fibers was made. The results of GAG and collagen type II in cell-seeded scaffolds indicate support of the chondrogenic phenotype for chondrocytes with a significant increase in degummed silk fiber–hydrogel composite for GAG content and in two-layer electrospun fiber–hydrogel composite for Col II. It was concluded that these two modified scaffolds could be employed for cartilage tissue engineering. - Highlights: • Chitosan hydrogel composites fabricated by two forms of silk fiber • Silk fibers provide structural support for the hydrogel matrix. • The mechanical properties of hydrogel significantly improved by associating with silk. • Production of GAG and collagen type II was demonstrated within the scaffolds.

  20. A retrospective analysis of two independent prospective cartilage repair studies : autogenous perichondrial grafting versus subchondral drilling 10 years post-surgery

    NARCIS (Netherlands)

    Bouwmeester, PSJM; Homminga, GN; Bulstra, SK; Geesink, RGT; Kuijer, Roelof

    Background: Experimental data indicate that perichondrial grafting to restore articular cartilage defects will result in repair with hyaline-like cartilage, In contrast, debridement and drilling results in repair with fibro-cartilage. In this retrospective study the long-term clinical results of

  1. Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies

    NARCIS (Netherlands)

    Pot, M.W.; Gonzales, V.K.; Buma, P.; Hout, J. in't; Kuppevelt, T.H. van; Vries, R.B. de; Daamen, W.F.

    2016-01-01

    Microfracture surgery may be applied to treat cartilage defects. During the procedure the subchondral bone is penetrated, allowing bone marrow-derived mesenchymal stem cells to migrate towards the defect site and form new cartilage tissue. Microfracture surgery generally results in the formation of

  2. Effects of collagen matrix and bioreactor cultivation on cartilage regeneration of a full-thickness critical-size knee joint cartilage defects with subchondral bone damage in a rabbit model.

    Directory of Open Access Journals (Sweden)

    Kuo-Hwa Wang

    Full Text Available Cartilage has limited self-repair ability. The purpose of this study was to investigate the effects of different species of collagen-engineered neocartilage for the treatment of critical-size defects in the articular joint in a rabbit model. Type II and I collagen obtained from rabbits and rats was mixed to form a scaffold. The type II/I collagen scaffold was then mixed with rabbit chondrocytes to biofabricate neocartilage constructs using a rotating cell culture system [three-dimensional (3D-bioreactor]. The rabbit chondrocytes were mixed with rabbit collagen scaffold and rat collagen scaffold to form neoRBT (neo-rabbit cartilage and neoRAT (neo-rat cartilage constructs, respectively. The neocartilage matrix constructs were implanted into surgically created defects in rabbit knee chondyles, and histological examinations were performed after 2 and 3 months. Cartilage-like lacunae formation surrounding the chondrocytes was noted in the cell cultures. After 3 months, both the neoRBT and neoRAT groups showed cartilage-like repair tissue covering the 5-mm circular, 4-mm-deep defects that were created in the rabbit condyle and filled with neocartilage plugs. Reparative chondrocytes were aligned as apparent clusters in both the neoRAT and neoRBT groups. Both neoRBT and neoRAT cartilage repair demonstrated integration with healthy adjacent tissue; however, more integration was obtained using the neoRAT cartilage. Our data indicate that different species of type II/I collagen matrix and 3D bioreactor cultivation can facilitate cartilage engineering in vitro for the repair of critical-size defect.

  3. Scaffold-assisted cartilage tissue engineering using infant chondrocytes from human hip cartilage.

    Science.gov (United States)

    Kreuz, P C; Gentili, C; Samans, B; Martinelli, D; Krüger, J P; Mittelmeier, W; Endres, M; Cancedda, R; Kaps, C

    2013-12-01

    Studies about cartilage repair in the hip and infant chondrocytes are rare. The aim of our study was to evaluate the use of infant articular hip chondrocytes for tissue engineering of scaffold-assisted cartilage grafts. Hip cartilage was obtained from five human donors (age 1-10 years). Expanded chondrocytes were cultured in polyglycolic acid (PGA)-fibrin scaffolds. De- and re-differentiation of chondrocytes were assessed by histological staining and gene expression analysis of typical chondrocytic marker genes. In vivo, cartilage matrix formation was assessed by histology after subcutaneous transplantation of chondrocyte-seeded PGA-fibrin scaffolds in immunocompromised mice. The donor tissue was heterogenous showing differentiated articular cartilage and non-differentiated tissue and considerable expression of type I and II collagens. Gene expression analysis showed repression of typical chondrocyte and/or mesenchymal marker genes during cell expansion, while markers were re-induced when expanded cells were cultured in PGA-fibrin scaffolds. Cartilage formation after subcutaneous transplantation of chondrocyte loaded PGA-fibrin scaffolds in nude mice was variable, with grafts showing resorption and host cell infiltration or formation of hyaline cartilage rich in type II collagen. Addition of human platelet rich plasma (PRP) to cartilage grafts resulted robustly in formation of hyaline-like cartilage that showed type II collagen and regions with type X collagen. These results suggest that culture of expanded and/or de-differentiated infant hip cartilage cells in PGA-fibrin scaffolds initiates chondrocyte re-differentiation. The heterogenous donor tissue containing immature chondrocytes bears the risk of cartilage repair failure in vivo, which may be possibly overcome by the addition of PRP. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  4. Peculiarities in Ankle Cartilage.

    Science.gov (United States)

    Kraeutler, Matthew J; Kaenkumchorn, Tanyaporn; Pascual-Garrido, Cecilia; Wimmer, Markus A; Chubinskaya, Susanna

    2017-01-01

    Posttraumatic osteoarthritis (PTOA) is the most common form of osteoarthritis (OA) of the ankle joint. PTOA occurs as a result of several factors, including the poor regenerative capacity of hyaline articular cartilage as well as increased contact stresses following trauma. The purpose of this article is to review the epidemiology, pathogenesis, and potential targets for treatment of PTOA in the ankle joint. Previous reviews primarily addressed clinical approaches to ankle PTOA, while the focus of the current article will be specifically on the newly acquired knowledge of the cellular mechanisms that drive PTOA in the ankle joint and means for potential targeted therapeutics that might halt the progression of cartilage degeneration and/or improve the outcome of surgical interventions. Three experimental treatment strategies are discussed in this review: (1) increasing the anabolic potential of chondrocytes through treatment with growth factors such as bone morphogenetic protein-7; (2) limiting chondrocyte cell death either through the protection of cell membrane with poloxamer 188 or inhibiting activity of intracellular proteases, caspases, which are responsible for cell death by apoptosis; and (3) inhibiting catabolic/inflammatory responses of chondrocytes by treating them with anti-inflammatory agents such as tumor necrosis factor-α antagonists. Future studies should focus on identifying the appropriate timing for treatment and an appropriate combination of anti-inflammatory, chondro- and matrix-protective biologics to limit the progression of trauma-induced cartilage degeneration and prevent the development of PTOA in the ankle joint.

  5. Optical properties of nasal septum cartilage

    Science.gov (United States)

    Bagratashvili, Nodar V.; Sviridov, Alexander P.; Sobol, Emil N.; Kitai, Moishe S.

    1998-05-01

    Optical parameters (scattering coefficient s, absorption coefficient k and scattering anisotropy coefficient g) of hyaline cartilage were studied for the first time. Optical properties of human and pig nasal septum cartilage, and of bovine ear cartilage were examined using a spectrophotometer with an integrating sphere, and an Optical Multi-Channel Analyser. We measured total transmission Tt, total reflection Rt, and on-axis transmission Ta for light propagating through cartilage sample, over the visible spectral range (14000 - 28000 cm-1). It is shown that transmission and reflection spectra of human, pig and bovine cartilage are rather similar. It allows us to conclude that the pig cartilage can be used for in-vivo studies instead of human cartilage. The data obtained were treated by means of the one-dimensional diffusion approximation solution of the optical transport equation. We have found scattering coefficient s, absorption coefficient k and scattering anisotropy coefficient g by the iterative comparison of measured and calculated Tt, Rt and Ta values for human and pig cartilage. We found, in particular, that for 500 nm irradiation s equals 37,6 plus or minus 3.5 cm-1, g equals 0,56 plus or minus 0.05, k approximately equals 0,5 plus or minus 0.3 cm-1. The above data were used in Monte Carlo simulation for spatial intensity profile of light scattered by a cartilage sample. The computed profile was very similar to the profile measured using an Optical Multi-Channel Analyzer (OMA).

  6. Repair of full-thickness articular cartilage defects by cultured mesenchymal stem cells transfected with the transforming growth factor {beta}{sub 1} gene

    Energy Technology Data Exchange (ETDEWEB)

    Guo Xiaodong [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Zheng Qixin [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Yang Shuhua [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Shao Zengwu [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Yuan Quan [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Pan Zhengqi [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Tang Shuo [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Liu Kai [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Quan Daping [Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275 (China)

    2006-12-15

    Articular cartilage repair remains a clinical and scientific challenge with increasing interest focused on the combined techniques of gene transfer and tissue engineering. Transforming growth factor beta 1 (TGF-{beta}{sub 1}) is a multifunctional molecule that plays a central role in promotion of cartilage repair, and inhibition of inflammatory and alloreactive immune response. Cell mediated gene therapy can allow a sustained expression of TGF-{beta}{sub 1} that may circumvent difficulties associated with growth factor delivery. The objective of this study was to investigate whether TGF-{beta}{sub 1} gene modified mesenchymal stem cells (MSCs) could enhance the repair of full-thickness articular cartilage defects in allogeneic rabbits. The pcDNA{sub 3}-TGF-{beta}{sub 1} gene transfected MSCs were seeded onto biodegradable poly-L-lysine coated polylactide (PLA) biomimetic scaffolds in vitro and allografted into full-thickness articular cartilage defects in 18 New Zealand rabbits. The pcDNA{sub 3} gene transfected MSCs/biomimetic scaffold composites and the cell-free scaffolds were taken as control groups I and II, respectively. The follow-up times were 2, 4, 12 and 24 weeks. Macroscopical, histological and ultrastructural studies were performed. In vitro SEM studies found that abundant cartilaginous matrices were generated and completely covered the interconnected pores of the scaffolds two weeks post-seeding in the experimental groups. In vivo, the quality of regenerated tissue improved over time with hyaline cartilage filling the chondral region and a mixture of trabecular and compact bone filling the subchondral region at 24 weeks post-implantation. Joint repair in the experimental groups was better than that of either control group I or II, with respect to: (1) synthesis of hyaline cartilage specific extracellular matrix at the upper portion of the defect; (2) reconstitution of the subchondral bone at the lower portion of the defect and (3) inhibition of

  7. Repair of full-thickness articular cartilage defects by cultured mesenchymal stem cells transfected with the transforming growth factor β1 gene

    International Nuclear Information System (INIS)

    Guo Xiaodong; Zheng Qixin; Yang Shuhua; Shao Zengwu; Yuan Quan; Pan Zhengqi; Tang Shuo; Liu Kai; Quan Daping

    2006-01-01

    Articular cartilage repair remains a clinical and scientific challenge with increasing interest focused on the combined techniques of gene transfer and tissue engineering. Transforming growth factor beta 1 (TGF-β 1 ) is a multifunctional molecule that plays a central role in promotion of cartilage repair, and inhibition of inflammatory and alloreactive immune response. Cell mediated gene therapy can allow a sustained expression of TGF-β 1 that may circumvent difficulties associated with growth factor delivery. The objective of this study was to investigate whether TGF-β 1 gene modified mesenchymal stem cells (MSCs) could enhance the repair of full-thickness articular cartilage defects in allogeneic rabbits. The pcDNA 3 -TGF-β 1 gene transfected MSCs were seeded onto biodegradable poly-L-lysine coated polylactide (PLA) biomimetic scaffolds in vitro and allografted into full-thickness articular cartilage defects in 18 New Zealand rabbits. The pcDNA 3 gene transfected MSCs/biomimetic scaffold composites and the cell-free scaffolds were taken as control groups I and II, respectively. The follow-up times were 2, 4, 12 and 24 weeks. Macroscopical, histological and ultrastructural studies were performed. In vitro SEM studies found that abundant cartilaginous matrices were generated and completely covered the interconnected pores of the scaffolds two weeks post-seeding in the experimental groups. In vivo, the quality of regenerated tissue improved over time with hyaline cartilage filling the chondral region and a mixture of trabecular and compact bone filling the subchondral region at 24 weeks post-implantation. Joint repair in the experimental groups was better than that of either control group I or II, with respect to: (1) synthesis of hyaline cartilage specific extracellular matrix at the upper portion of the defect; (2) reconstitution of the subchondral bone at the lower portion of the defect and (3) inhibition of inflammatory and alloreactive immune responses. The

  8. New Frontiers for Cartilage Repair and Protection.

    Science.gov (United States)

    Zaslav, Kenneth; McAdams, Timothy; Scopp, Jason; Theosadakis, Jason; Mahajan, Vivek; Gobbi, Alberto

    2012-01-01

    Articular cartilage injury is common after athletic injury and remains a difficult treatment conundrum both for the surgeon and athlete. Although recent treatments for damage to articular cartilage have been successful in alleviating symptoms, more durable and complete, long-term articular surface restoration remains the unattained goal. In this article, we look at both new ways to prevent damage to articular surfaces as well as new techniques to recreate biomechanically sound and biochemically true articular surfaces once an athlete injures this surface. This goal should include reproducing hyaline cartilage with a well-integrated and flexible subchondral base and the normal zonal variability in the articular matrix. A number of nonoperative interventions have shown early promise in mitigating cartilage symptoms and in preclinical studies have shown evidence of chondroprotection. These include the use of glucosamine, chondroitin, and other neutraceuticals, viscosupplementation with hyaluronic acid, platelet-rich plasma, and pulsed electromagnetic fields. Newer surgical techniques, some already in clinical study, and others on the horizon offer opportunities to improve the surgical restoration of the hyaline matrix often disrupted in athletic injury. These include new scaffolds, single-stage cell techniques, the use of mesenchymal stem cells, and gene therapy. Although many of these treatments are in the preclinical and early clinical study phase, they offer the promise of better options to mitigate the sequelae of athletically induced cartilage.

  9. Tissue engineering in the treatment of cartilage lesions

    Directory of Open Access Journals (Sweden)

    Jakob Naranđa

    2013-11-01

    Full Text Available Background: Articular cartilage lesions with the inherent limited healing potential are difficult to treat and thus remain a challenging problem for orthopaedic surgeons. Regenerative treatment techniques, such as autologous chondrocyte implantation (ACI, are promising as a treatment option to restore hyaline-like cartilage tissue in damaged articular surfaces, as opposed to the traditional reparative procedures (e.g. bone marrow stimulation – microfracture, which promote a fibrocartilage formation with lower tissue biomechanical properties and poorer clinical results. ACI technique has undergone several advances and is constantly improving. The new concept of cartilage tissue preservation uses tissue-engineering technologies, combining new biomaterials as a scaffold, application of growth factors, use of stem cells, and mechanical stimulation. The recent development of new generations of ACI uses a cartilage-like tissue in a 3-dimensional culture system that is based on the use of biodegradable material which serves as a temporary scaffold for the in vitro growth and subsequent implantation into the cartilage defect. For clinical practice, single stage procedures appear attractive to reduce cost and patient morbidity. Finally, modern concept of tissue engineering facilitates hyaline-like cartilage formation and a permanent treatment of cartilage lesions.Conclusion: The review focuses on innovations in the treatment of cartilage lesions and covers modern concepts of tissue engineering with the use of biomaterials, growth factors, stem cells and bioreactors, and presents options for clinical use.

  10. Spectrocolorimetric evaluation of repaired articular cartilage after a microfracture

    Directory of Open Access Journals (Sweden)

    Dohi Yoshihiro

    2008-09-01

    Full Text Available Abstract Background In clinical practice, surgeons differentiate color changes in repaired cartilage compared with surrounding intact cartilage, but cannot quantify these color changes. Objective assessments are required. A spectrocolorimeter was used to evaluate whether intact and repaired cartilage can be quantified. Findings We investigated the use of a spectrocolorimeter and the application of two color models (L* a* b* colorimetric system and spectral reflectance distribution to describe and quantify articular cartilage. In this study, we measured the colors of intact and repaired cartilage after a microfracture. Histologically, the repaired cartilage was a mixture of fibrocartilage and hyaline cartilage. In the L* a* b* colorimetric system, the L* and a* values recovered to close to the values of intact cartilage, whereas the b* value decreased over time after the operation. Regarding the spectral reflectance distribution at 12 weeks after the operation, the repaired cartilage had a higher spectral reflectance ratio than intact cartilage between wavelengths of 400 to 470 nm. Conclusion This study reports the first results regarding the relationship between spectrocolorimetric evaluation and the histological findings of repair cartilage after a microfracture. Our findings demonstrate the ability of spectrocolorimetric measurement to judge the repair cartilage after treatment on the basis of objective data such as the L*, a* and b* values and the SRP as a coincidence index of the spectral reflectance curve.

  11. Engineering Cartilage

    Science.gov (United States)

    ... Research Matters NIH Research Matters March 3, 2014 Engineering Cartilage Artistic rendering of human stem cells on ... situations has been a major goal in tissue engineering. Cartilage contains water, collagen, proteoglycans, and chondrocytes. Collagens ...

  12. Shark Cartilage

    Science.gov (United States)

    Shark cartilage (tough elastic tissue that provides support, much as bone does) used for medicine comes primarily from sharks ... Several types of extracts are made from shark cartilage including squalamine lactate, AE-941, and U-995. ...

  13. Gradient nano-engineered in situ forming composite hydrogel for osteochondral regeneration.

    Science.gov (United States)

    Radhakrishnan, Janani; Manigandan, Amrutha; Chinnaswamy, Prabu; Subramanian, Anuradha; Sethuraman, Swaminathan

    2018-04-01

    Fabrication of anisotropic osteochondral-mimetic scaffold with mineralized subchondral zone and gradient interface remains challenging. We have developed an injectable semi-interpenetrating network hydrogel construct with chondroitin sulfate nanoparticles (ChS-NPs) and nanohydroxyapatite (nHA) (∼30-90 nm) in chondral and subchondral hydrogel zones respectively. Mineralized subchondral hydrogel exhibited significantly higher osteoblast proliferation and alkaline phosphatase activity (p gradient interface of nHA and ChS-NPs. Microcomputed tomography (μCT) demonstrated nHA gradation while rheology showed predominant elastic modulus (∼930 Pa) at the interface. Co-culture of osteoblasts and chondrocytes in gradient hydrogels showed layer-specific retention of cells and cell-cell interaction at the interface. In vivo osteochondral regeneration by biphasic (nHA or ChS) and gradient (nHA + ChS) hydrogels was compared with control using rabbit osteochondral defect after 3 and 8 weeks. Complete closure of defect was observed in gradient (8 weeks) while defect remained in other groups. Histology demonstrated collagen and glycosaminoglycan deposition in neo-matrix and presence of hyaline cartilage-characteristic matrix, chondrocytes and osteoblasts. μCT showed mineralized neo-tissue formation, which was confined within the defect with higher bone mineral density in gradient (chondral: 0.42 ± 0.07 g/cc, osteal: 0.64 ± 0.08 g/cc) group. Further, biomechanical push-out studies showed significantly higher load for gradient group (378 ± 56 N) compared to others. Thus, the developed nano-engineered gradient hydrogel enhanced hyaline cartilage regeneration with subchondral bone formation and lateral host-tissue integration. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Cartilage Repair With Autologous Bone Marrow Mesenchymal Stem Cell Transplantation: Review of Preclinical and Clinical Studies.

    Science.gov (United States)

    Yamasaki, Shinya; Mera, Hisashi; Itokazu, Maki; Hashimoto, Yusuke; Wakitani, Shigeyuki

    2014-10-01

    Clinical trials of various procedures, including bone marrow stimulation, mosaicplasty, and autologous chondrocyte implantation, have been explored to treat articular cartilage defects. However, all of them have some demerits. We focused on autologous culture-expanded bone marrow mesenchymal stem cells (BMSC), which can proliferate without losing their capacity for differentiation. First, we transplanted BMSC into the defective articular cartilage of rabbit and succeeded in regenerating osteochondral tissue. We then applied this transplantation in humans. Our previous reports showed that treatment with BMSC relieves the clinical symptoms of chondral defects in the knee and elbow joint. We investigated the efficacy of BMSC for osteoarthritic knee treated with high tibial osteotomy, by comparing 12 BMSC-transplanted patients with 12 cell-free patients. At 16-month follow-up, although the difference in clinical improvement between both groups was not significant, the arthroscopic and histological grading score was better in the cell-transplanted group. At the over 10-year follow-up, Hospital for Special Surgery knee scores improved to 76 and 73 in the BMSC-transplanted and cell-free groups, respectively, which were better than preoperative scores. Additionally, neither tumors nor infections were observed in all patients, and in the clinical study, we have never observed hypertrophy of repaired tissue, thereby guaranteeing the clinical safety of this therapy. Although we have never observed calcification above the tidemark in rabbit model and human histologically, the repair cartilage was not completely hyaline cartilage. To elucidate the optimum conditions for cell therapy, other stem cells, culture conditions, growth factors, and gene transfection methods should be explored.

  15. Evaluation of the potential of rhTGF- β3 encapsulated P(LLA-CL)/collagen nanofibers for tracheal cartilage regeneration using mesenchymal stems cells derived from Wharton's jelly of human umbilical cord

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing; Sun, Binbin [State Key Laboratory of Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China); Tian, Lingling [Center for Nanofibers and Nanotechnology, E3-05-14, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); He, Xiaomin [Department of Pediatric Cardiothoracic Surgery, Shanghai Children' s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Gao, Qiang; Wu, Tong [State Key Laboratory of Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China); Ramakrishna, Seeram [Center for Nanofibers and Nanotechnology, E3-05-14, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Guangdong-Hongkong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou 510632 (China); Zheng, Jinghao, E-mail: zhengjh210@163.com [Department of Pediatric Cardiothoracic Surgery, Shanghai Children' s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127 (China); Mo, Xiumei, E-mail: xmm@dhu.edu.cn [State Key Laboratory of Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620 (China); Shandong International Biotechnology Park Development Co., Ltd. (China)

    2017-01-01

    Tracheal injuries are one of major challenging issues in clinical medicine because of the poor intrinsic ability of tracheal cartilage for repair. Tissue engineering provides an alternative method for the treatment of tracheal defects by generating replacement tracheal structures. In this study, core-shell nanofibrous scaffold was fabricated to encapsulate bovine serum albumin & rhTGF-β3 (recombinant human transforming growth factor-β3) into the core of the nanofibers for tracheal cartilage regeneration. Characterization of the core-shell nanofibrous scaffold was carried out by scanning electron microscope (SEM), transmission electron microscope (TEM), laser scanning confocal microscopy (LSCM), and tensile mechanical test. The rhTGF-β3 released from the scaffolds in a sustained and stable manner for about 2 months. The bioactivity of released rhTGF-β3 was evaluated by its effect on the synthesis of type II collagen (COL2) and glycosaminoglycans (GAGs) by chondrocytes. The results suggested that its bioactivity was retained during release process. The proliferation and morphology analyses of mesenchymal stems cells derived from Wharton's jelly of human umbilical cord (WMSCs) indicated the good biocompatibility of the fabricated nanofibrous scaffold. Meanwhile, the chondrogenic differentiation of WMSCs cultured on core-shell nanofibrous scaffold was evaluated by real-time qPCR and histological staining. The results suggested that the core-shell nanofibrous scaffold with rhTGF-β3 could promote the chondrogenic differentiation ability of WMSCs. Therefore, WMSCs could be a promising seed cells in the construction of tissue-engineered tracheal cartilage. Overall, the core-shell nanofibrous scaffold could be an effective delivery system for rhTGF-β3 and served as a promising tissue engineered scaffold for tracheal cartilage regeneration. - Highlights: • rhTGF-β3 could be encapsulated into core-shell nanofibers via electrospinning. • rhTGF-β3 could release

  16. Fine-tuning Cartilage Tissue Engineering by Applying Principles from Embryonic Development

    OpenAIRE

    Hellingman, Catharine

    2012-01-01

    textabstractCartilage has a very poor capacity for regeneration in vivo. In head and neck surgery cartilage defects are usually reconstructed with autologous cartilage from for instance the external ear or the ribs. Cartilage tissue engineering may be a promising alternative to supply tissue for cartilage reconstructions in otorhinolaryngology as well as in plastic surgery and orthopaedics. The aim of this thesis is to find new tools by which cartilage tissue engineering can be better control...

  17. Repair of articular cartilage defects in the knee with autologous iliac crest cartilage in a rabbit model.

    Science.gov (United States)

    Jing, Lizhong; Zhang, Jiying; Leng, Huijie; Guo, Qinwei; Hu, Yuelin

    2015-04-01

    To demonstrate that iliac crest cartilage may be used to repair articular cartilage defects in the knees of rabbits. Full-thickness cartilage defects were created in the medial femoral condyle on both knees of 36 New Zealand white rabbits. The 72 defects were randomly assigned to be repaired with ipsilateral iliac crest cartilage (Group I), osteochondral tissues removed at defect creation (Group II), or no treatment (negative control, Group III). Animals were killed at 6, 12, and 24 weeks post-operatively. The repaired tissues were harvested for magnetic resonance imaging (MRI), histological studies (haematoxylin and eosin and immunohistochemical staining), and mechanical testing. At 6 weeks, the iliac crest cartilage graft was not yet well integrated with the surrounding articular cartilage, but at 12 weeks, the graft deep zone had partial ossification. By 24 weeks, the hyaline cartilage-like tissue was completely integrated with the surrounding articular cartilage. Osteochondral autografts showed more rapid healing than Group I at 6 weeks and complete healing at 12 weeks. Untreated defects were concave or partly filled with fibrous tissue throughout the study. MRI showed that Group I had slower integration with surrounding normal cartilage compared with Group II. The mechanical properties of Group I were significantly lower than those of Group II at 12 weeks, but this difference was not significant at 24 weeks. Iliac crest cartilage autografts were able to repair knee cartilage defects with hyaline cartilage and showed comparable results with osteochondral autografts in the rabbit model.

  18. Cartilage damage involving extrusion of mineralisable matrix from the articular calcified cartilage and subchondral bone

    Directory of Open Access Journals (Sweden)

    A Boyde

    2011-05-01

    Full Text Available Arthropathy of the distal articular surfaces of the third metacarpal (Mc3 and metatarsal (Mt3 bones in the Thoroughbred racehorse (Tb is a natural model of repetitive overload arthrosis. We describe a novel pathology that affects the articular calcified cartilage (ACC and subchondral bone (SCB and which is associated with hyaline articular cartilage degeneration. Parasagittal slices cut from the palmar quadrant of the distal condyles of the left Mc3/Mt3 of 39 trained Tbs euthanased for welfare reasons were imaged by point projection microradiography, and backscattered electron (BSE scanning electron microscopy (SEM, light microscopy, and confocal scanning light microscopy. Mechanical properties were studied by nanoindentation. Data on the horses' training and racing career were also collected. Highly mineralised projections were observed extending from cracks in the ACC mineralising front into the hyaline articular cartilage (HAC up to two-thirds the thickness of the HAC, and were associated with focal HAC surface fibrillation directly overlying their site. Nanoindentation identified this extruded matrix to be stiffer than any other mineralised phase in the specimen by a factor of two. The presence of projections was associated with a higher cartilage Mankin histology score (P < 0.02 and increased amounts of gross cartilage loss pathologically on the condyle (P < 0.02. Presence of projections was not significantly associated with: total number of racing seasons, age of horse, amount of earnings, number of days in training, total distance galloped in career, or presence of wear lines.

  19. Cartilage repair: Generations of autologous chondrocyte transplantation

    International Nuclear Information System (INIS)

    Marlovits, Stefan; Zeller, Philip; Singer, Philipp; Resinger, Christoph; Vecsei, Vilmos

    2006-01-01

    Articular cartilage in adults has a limited capacity for self-repair after a substantial injury. Surgical therapeutic efforts to treat cartilage defects have focused on delivering new cells capable of chondrogenesis into the lesions. Autologous chondrocyte transplantation (ACT) is an advanced cell-based orthobiologic technology used for the treatment of chondral defects of the knee that has been in clinical use since 1987 and has been performed on 12,000 patients internationally. With ACT, good to excellent clinical results are seen in isolated post-traumatic lesions of the knee joint in the younger patient, with the formation of hyaline or hyaline-like repair tissue. In the classic ACT technique, chondrocytes are isolated from small slices of cartilage harvested arthroscopically from a minor weight-bearing area of the injured knee. The extracellular matrix is removed by enzymatic digestion, and the cells are then expanded in monolayer culture. Once a sufficient number of cells has been obtained, the chondrocytes are implanted into the cartilage defect, using a periosteal patch over the defect as a method of cell containment. The major complications are periosteal hypertrophy, delamination of the transplant, arthrofibrosis and transplant failure. Further improvements in tissue engineering have contributed to the next generation of ACT techniques, where cells are combined with resorbable biomaterials, as in matrix-associated autologous chondrocyte transplantation (MACT). These biomaterials secure the cells in the defect area and enhance their proliferation and differentiation

  20. Cartilage repair: Generations of autologous chondrocyte transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Marlovits, Stefan [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)]. E-mail: stefan.marlovits@meduniwien.ac.at; Zeller, Philip [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Singer, Philipp [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Resinger, Christoph [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Vecsei, Vilmos [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)

    2006-01-15

    Articular cartilage in adults has a limited capacity for self-repair after a substantial injury. Surgical therapeutic efforts to treat cartilage defects have focused on delivering new cells capable of chondrogenesis into the lesions. Autologous chondrocyte transplantation (ACT) is an advanced cell-based orthobiologic technology used for the treatment of chondral defects of the knee that has been in clinical use since 1987 and has been performed on 12,000 patients internationally. With ACT, good to excellent clinical results are seen in isolated post-traumatic lesions of the knee joint in the younger patient, with the formation of hyaline or hyaline-like repair tissue. In the classic ACT technique, chondrocytes are isolated from small slices of cartilage harvested arthroscopically from a minor weight-bearing area of the injured knee. The extracellular matrix is removed by enzymatic digestion, and the cells are then expanded in monolayer culture. Once a sufficient number of cells has been obtained, the chondrocytes are implanted into the cartilage defect, using a periosteal patch over the defect as a method of cell containment. The major complications are periosteal hypertrophy, delamination of the transplant, arthrofibrosis and transplant failure. Further improvements in tissue engineering have contributed to the next generation of ACT techniques, where cells are combined with resorbable biomaterials, as in matrix-associated autologous chondrocyte transplantation (MACT). These biomaterials secure the cells in the defect area and enhance their proliferation and differentiation.

  1. Fine-tuning Cartilage Tissue Engineering by Applying Principles from Embryonic Development

    NARCIS (Netherlands)

    C.A. Hellingman (Catharine)

    2012-01-01

    textabstractCartilage has a very poor capacity for regeneration in vivo. In head and neck surgery cartilage defects are usually reconstructed with autologous cartilage from for instance the external ear or the ribs. Cartilage tissue engineering may be a promising alternative to supply tissue for

  2. Cellular and Acellular Approaches for Cartilage Repair

    Science.gov (United States)

    2015-01-01

    There are several choices of cells to use for cartilage repair. Cells are used as internal or external sources and sometimes in combination. In this article, an analysis of the different cell choices and their use and potential is provided. Embryonic cartilage formation is of importance when finding more about how to be able to perfect cartilage repair. Some suggestions for near future research based on up-to-date knowledge on chondrogenic cells are given to hopefully stimulate more studies on the final goal of cartilage regeneration. PMID:27340516

  3. Time-dependent regulation of morphological changes and cartilage differentiation markers in the mouse pubic symphysis during pregnancy and postpartum recovery.

    Science.gov (United States)

    Castelucci, Bianca Gazieri; Consonni, Sílvio Roberto; Rosa, Viviane Souza; Sensiate, Lucimara Aparecida; Delatti, Paula Cristina Rugno; Alvares, Lúcia Elvira; Joazeiro, Paulo Pinto

    2018-01-01

    Animal models commonly serve as a bridge between in vitro experiments and clinical applications; however, few physiological processes in adult animals are sufficient to serve as proof-of-concept models for cartilage regeneration. Intriguingly, some rodents, such as young adult mice, undergo physiological connective tissue modifications to birth canal elements such as the pubic symphysis during pregnancy; therefore, we investigated whether the differential expression of cartilage differentiation markers is associated with cartilaginous tissue morphological modifications during these changes. Our results showed that osteochondral progenitor cells expressing Runx2, Sox9, Col2a1 and Dcx at the non-pregnant pubic symphysis proliferated and differentiated throughout pregnancy, giving rise to a complex osteoligamentous junction that attached the interpubic ligament to the pubic bones until labour occurred. After delivery, the recovery of pubic symphysis cartilaginous tissues was improved by the time-dependent expression of these chondrocytic lineage markers at the osteoligamentous junction. This process potentially recapitulates embryologic chondrocytic differentiation to successfully recover hyaline cartilaginous pads at 10 days postpartum. Therefore, we propose that this physiological phenomenon represents a proof-of-concept model for investigating the mechanisms involved in cartilage restoration in adult animals.

  4. Polymer Formulations for Cartilage Repair

    Energy Technology Data Exchange (ETDEWEB)

    Gutowska, Anna; Jasionowski, Marek; Morris, J. E.; Chrisler, William B.; An, Yuehuei H.; Mironov, V.

    2001-05-15

    Regeneration of destroyed articular cartilage can be induced by transplantation of cartilage cells into a defect. The best results are obtained with the use of autologus cells. However, obtaining large amounts of autologus cartilage cells causes a problem of creating a large cartilage defect in a donor site. Techniques are currently being developed to harvest a small number of cells and propagate them in vitro. It is a challenging task, however, due to the fact that ordinarily, in a cell culture on flat surfaces, chondrocytes do not maintain their in vivo phenotype and irreversibly diminish or cease the synthesis of aggregating proteoglycans. Therefore, the research is continuing to develop culture conditions for chondrocytes with the preserved phenotype.

  5. Microstructural changes in cartilage and bone related to repetitive overloading in an equine athlete model.

    Science.gov (United States)

    Turley, Sean M; Thambyah, Ashvin; Riggs, Christopher M; Firth, Elwyn C; Broom, Neil D

    2014-06-01

    The palmar aspect of the third metacarpal (MC3) condyle of equine athletes is known to be subjected to repetitive overloading that can lead to the accumulation of joint tissue damage, degeneration, and stress fractures, some of which result in catastrophic failure. However, there is still a need to understand at a detailed microstructural level how this damage progresses in the context of the wider joint tissue complex, i.e. the articular surface, the hyaline and calcified cartilage, and the subchondral bone. MC3 bones from non-fractured joints were obtained from the right forelimbs of 16 Thoroughbred racehorses varying in age between 3 and 8 years, with documented histories of active race training. Detailed microstructural analysis of two clinically important sites, the parasagittal grooves and the mid-condylar regions, identified extensive levels of microdamage in the calcified cartilage and subchondral bone concealed beneath outwardly intact hyaline cartilage. The study shows a progression in microdamage severity, commencing with mild hard-tissue microcracking in younger animals and escalating to severe subchondral bone collapse and lesion formation in the hyaline cartilage with increasing age and thus athletic activity. The presence of a clearly distinguishable fibrous tissue layer at the articular surface immediately above sites of severe subchondral collapse suggested a limited reparative response in the hyaline cartilage. © 2014 Anatomical Society.

  6. Microstructural changes in cartilage and bone related to repetitive overloading in an equine athlete model

    Science.gov (United States)

    Turley, Sean M; Thambyah, Ashvin; Riggs, Christopher M; Firth, Elwyn C; Broom, Neil D

    2014-01-01

    The palmar aspect of the third metacarpal (MC3) condyle of equine athletes is known to be subjected to repetitive overloading that can lead to the accumulation of joint tissue damage, degeneration, and stress fractures, some of which result in catastrophic failure. However, there is still a need to understand at a detailed microstructural level how this damage progresses in the context of the wider joint tissue complex, i.e. the articular surface, the hyaline and calcified cartilage, and the subchondral bone. MC3 bones from non-fractured joints were obtained from the right forelimbs of 16 Thoroughbred racehorses varying in age between 3 and 8 years, with documented histories of active race training. Detailed microstructural analysis of two clinically important sites, the parasagittal grooves and the mid-condylar regions, identified extensive levels of microdamage in the calcified cartilage and subchondral bone concealed beneath outwardly intact hyaline cartilage. The study shows a progression in microdamage severity, commencing with mild hard-tissue microcracking in younger animals and escalating to severe subchondral bone collapse and lesion formation in the hyaline cartilage with increasing age and thus athletic activity. The presence of a clearly distinguishable fibrous tissue layer at the articular surface immediately above sites of severe subchondral collapse suggested a limited reparative response in the hyaline cartilage. PMID:24689513

  7. Supporting Biomaterials for Articular Cartilage Repair

    Science.gov (United States)

    Duarte Campos, Daniela Filipa; Drescher, Wolf; Rath, Björn; Tingart, Markus

    2012-01-01

    Orthopedic surgeons and researchers worldwide are continuously faced with the challenge of regenerating articular cartilage defects. However, until now, it has not been possible to completely mimic the biological and biochemical properties of articular cartilage using current research and development approaches. In this review, biomaterials previously used for articular cartilage repair research are addressed. Furthermore, a brief discussion of the state of the art of current cell printing procedures mimicking native cartilage is offered in light of their use as future alternatives for cartilage tissue engineering. Inkjet cell printing, controlled deposition cell printing tools, and laser cell printing are cutting-edge techniques in this context. The development of mimetic hydrogels with specific biological properties relevant to articular cartilage native tissue will support the development of improved, functional, and novel engineered tissue for clinical application. PMID:26069634

  8. Cartilage Integration: Evaluation of the reasons for failure of integration during cartilage repair. A review

    Directory of Open Access Journals (Sweden)

    IM Khan

    2008-09-01

    Full Text Available Articular cartilage is a challenging tissue to reconstruct or replace principally because of its avascular nature; large chondral lesions in the tissue do not spontaneously heal. Where lesions do penetrate the bony subchondral plate, formation of hematomas and the migration of mesenchymal stem cells provide an inferior and transient fibrocartilagenous replacement for hyaline cartilage. To circumvent the poor intrinsic reparative response of articular cartilage several surgical techniques based on tissue transplantation have emerged. One characteristic shared by intrinsic reparative processes and the new surgical therapies is an apparent lack of lateral integration of repair or graft tissue with the host cartilage that can lead to poor prognosis. Many factors have been cited as impeding cartilage:cartilage integration including; chondrocyte cell death, chondrocyte dedifferentiation, the nature of the collagenous and proteoglycan networks that constitute the extracellular matrix, the type of biomaterial scaffold employed in repair and the origin of the cells used to repopulate the defect or lesion. This review addresses the principal intrinsic and extrinsic factors that impede integration and describe how manipulation of these factors using a host of strategies can positively influence cartilage integration.

  9. Three-year clinical outcome after chondrocyte transplantation using a hyaluronan matrix for cartilage repair

    Energy Technology Data Exchange (ETDEWEB)

    Nehrer, S. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)]. E-mail: stefan.nehrer@meduniwien.ac.at; Domayer, S. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Dorotka, R. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Schatz, K. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Bindreiter, U. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Kotz, R. [Department of Orthopedics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)

    2006-01-15

    Repair of articular cartilage represents a significant clinical problem and although various new techniques - including the use of autologous chondrocytes - have been developed within the last century the clinical efficacy of these procedures is still discussed controversially. Although autologous chondrocyte transplantation (ACT) has been widely used with success, it has several inherent limitations, including its invasive nature and problems related to the use of the periosteal flap. To overcome these problems autologous chondrocytes transplantation combined with the use of biodegradable scaffolds has received wide attention. Among these, a hyaluronan-based scaffold has been found useful for inducing hyaline cartilage regeneration. In the present study, we have investigated the mid-term efficacy and safety of Hyalograft[reg] C grafts in a group of 36 patients undergoing surgery for chronic cartilage lesions of the knee. Clinical Outcome was assessed prospectively before and at 12, 24, and 36 months after surgery. No major adverse events have been reported during the 3-year follow-up. Significant improvements of the evaluated scores were observed (P < 0.02) at 1 year and a continued increase of clinical performance was evident at 2 and 3 years follow-up. Patients under 30 years of age with single lesions showed statistically significant improvements at all follow-up visits compared to those over 30 with multiple defects (P < 0.01). Hyalograft[reg] C compares favorably with classic ACT and is particularly indicated in younger patients with single lesions. The graft can be implanted through a miniarthrotomy and needs no additional fixation with sutures except optional fibrin gluing at the defect borders. These results suggest that Hyalograft[reg] C is a valid alternative to ACT.

  10. Correlation between histological outcome and surgical cartilage repair technique in the knee: A meta-analysis.

    Science.gov (United States)

    DiBartola, Alex C; Everhart, Joshua S; Magnussen, Robert A; Carey, James L; Brophy, Robert H; Schmitt, Laura C; Flanigan, David C

    2016-06-01

    Compare histological outcomes after microfracture (MF), autologous chondrocyte implantation (ACI), and osteochondral autograft transfer (OATS). Literature review using PubMed MEDLINE, SCOPUS, Cumulative Index for Nursing and Allied Health Literature (CINAHL), and Cochrane Collaboration Library. Inclusion criteria limited to English language studies International Cartilage Repair Society (ICRS) grading criteria for cartilage analysis after ACI (autologous chondrocyte implantation), MF (microfracture), or OATS (osteochondral autografting) repair techniques. Thirty-three studies investigating 1511 patients were identified. Thirty evaluated ACI or one of its subtypes, six evaluated MF, and seven evaluated OATS. There was no evidence of publication bias (Begg's p=0.48). No statistically significant correlation was found between percent change in clinical outcome and percent biopsies showing ICRS Excellent scores (R(2)=0.05, p=0.38). Percent change in clinical outcome and percent of biopsies showing only hyaline cartilage were significantly associated (R(2)=0.24, p=0.024). Mean lesion size and histological outcome were not correlated based either on percent ICRS Excellent (R(2)=0.03, p=0.50) or percent hyaline cartilage only (R(2)=0.01, p=0.67). Most common lesion location and histological outcome were not correlated based either on percent ICRS Excellent (R(2)=0.03, p=0.50) or percent hyaline cartilage only (R(2)=0.01, p=0.67). Microfracture has poorer histologic outcomes than other cartilage repair techniques. OATS repairs primarily are comprised of hyaline cartilage, followed closely by cell-based techniques, but no significant difference was found cartilage quality using ICRS grading criteria among OATS, ACI-C, MACI, and ACI-P. IV, meta-analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Recapitulation of physiological spatiotemporal signals promotes in vitro formation of phenotypically stable human articular cartilage

    Science.gov (United States)

    Wei, Yiyong; Zhou, Bin; Bernhard, Jonathan; Robinson, Samuel; Burapachaisri, Aonnicha; Guo, X. Edward

    2017-01-01

    Standard isotropic culture fails to recapitulate the spatiotemporal gradients present during native development. Cartilage grown from human mesenchymal stem cells (hMSCs) is poorly organized and unstable in vivo. We report that human cartilage with physiologic organization and in vivo stability can be grown in vitro from self-assembling hMSCs by implementing spatiotemporal regulation during induction. Self-assembling hMSCs formed cartilage discs in Transwell inserts following isotropic chondrogenic induction with transforming growth factor β to set up a dual-compartment culture. Following a switch in the basal compartment to a hypertrophic regimen with thyroxine, the cartilage discs underwent progressive deep-zone hypertrophy and mineralization. Concurrent chondrogenic induction in the apical compartment enabled the maintenance of functional and hyaline cartilage. Cartilage homeostasis, chondrocyte maturation, and terminal differentiation markers were all up-regulated versus isotropic control groups. We assessed the in vivo stability of the cartilage formed under different induction regimens. Cartilage formed under spatiotemporal regulation in vitro resisted endochondral ossification, retained the expression of cartilage markers, and remained organized following s.c. implantation in immunocompromised mice. In contrast, the isotropic control groups underwent endochondral ossification. Cartilage formed from hMSCs remained stable and organized in vivo. Spatiotemporal regulation during induction in vitro recapitulated some aspects of native cartilage development, and potentiated the maturation of self-assembling hMSCs into stable and organized cartilage resembling the native articular cartilage. PMID:28228529

  12. Biomimetic fiber assembled gradient hydrogel to engineer glycosaminoglycan enriched and mineralized cartilage: An in vitro study.

    Science.gov (United States)

    Mohan, Neethu; Wilson, Jijo; Joseph, Dexy; Vaikkath, Dhanesh; Nair, Prabha D

    2015-12-01

    The study investigated the potential of electrospun fiber assembled hydrogel, with physical gradients of chondroitin sulfate (CS) and sol-gel-derived bioactive glass (BG), to engineer hyaline and mineralized cartilage in a single 3D system. Electrospun poly(caprolactone) (PCL) fibers incorporated with 0.1% w/w of CS (CSL) and 0.5% w/w of CS (CSH), 2.4% w/w of BG (BGL) and 12.5% w/w of BG (BGH) were fabricated. The CS showed a sustained release up to 3 days from CSL and 14 days from CSH fibers. Chondrocytes secreted hyaline like matrix with higher sulfated glycosaminoglycans (sGAG), collagen type II and aggrecan on CSL and CSH fibers. Mineralization was observed on BGL and BGH fibers when incubated in simulated body fluid for 14 days. Chondrocytes cultured on these fibers secreted a mineralized matrix that consisted of sGAG, hypertrophic proteins, collagen type X, and osteocalcin. The CS and BG incorporated PCL fiber mats were assembled in an agarose-gelatin hydrogel to generate a 3D hybrid scaffold. The signals in the fibers diffused and generated continuous opposing gradients of CS (chondrogenic signal) and BG (mineralization) in the hydrogel. The chondrocytes were encapsulated in hybrid scaffolds; live dead assay at 48 h showed viable cells. Cells maintained their phenotype and secreted specific extracellular matrix (ECM) in response to signals within the hydrogel. Continuous opposing gradients of sGAG enriched and mineralized ECM were observed surrounding each cell clusters on gradient hydrogel after 14 days of culture in response to the physical gradients of raw materials CS and BG. A construct with gradient mineralization might accelerate integration to subchondral bone during in vivo regeneration. © 2015 Wiley Periodicals, Inc.

  13. Value of different MR techniques in diagnosis of degenerative disorders of the hyaline cartilage - in vitro study on 50 joint specimens of the knee with 1.5 T; Vergleich von verschiedenen MRT-Techniken in der Diagnose von degenerativen Knorpelerkrankungen - in-vitro-Studie an 50 Gelenkpraeparaten des Knies bei 1,5 T

    Energy Technology Data Exchange (ETDEWEB)

    Bachmann, G. [Klinikum der Univ. Giessen (Germany). Abt. Diagnostische Radiologie; Heinrichs, C. [Klinikum der Univ. Giessen (Germany). Inst. fuer Pathologie; Juergensen, I. [Klinikum der Univ. Giessen (Germany). Orthopaedische Klinik; Rominger, M. [Klinikum der Univ. Giessen (Germany). Abt. Diagnostische Radiologie; Scheiter, A. [Klinikum der Univ. Giessen (Germany). Abt. Diagnostische Radiologie; Rau, W.S. [Klinikum der Univ. Giessen (Germany). Abt. Diagnostische Radiologie

    1997-05-01

    Purpose: An experimental study was performed on joint specimens of the knee to assess the advantages and disadvantages of 14 generally available sequences in cartilage imaging. Methods: Each of the 50 surgically exposed cadaveric joints of the knee was examined by the following sequences: T{sub 1}, proton- and T{sub 2} weighted spin echo(SE) sequences, proton- and T{sub 2} weighted Turbo-SE, T{sub 1} weighted SE with fat suppression, MTC combined with T{sub 1}-weighted SE and T{sub 2} weighted FLASH-2 D, STIR, FISP-3 D, FLASH-3 D (with fat suppression), and MR arthrography. We assessed the image quality by a scale, signal to noise-ratio of cartilage and joint fluid, and the accuracy in detection of cartilage lesions. Pathology and arthroscopy were reference methods to MRI, and demonstrated grade 1-4 lesions on 186 of 300 joint facettes. Results: Advanced stages of cartilage lesions (65 grade 3 and 4 lesions) were detected by standard SE sequences in 67-94%. Application of volume techniques (FISP-3 D, FLASH-3 D), high definition matrix (512 pixel), MTC with FLASH-2 D and MR-arthrography improved the sensitivity up to 82-100%. Superficial lesions (65 grade 2 lesions) were demonstrated in 3-38%, and on MR arthrography in 45%. Structural changes (56 Grade 1 lesions) were recorded on MRI in only 10%. Conclusions: With regard to standard SE sequences, the detectability of cartilage lesions can be improved by techniques that use 512 matrices, selective cartilage imaging, and volume acquisition. (orig.) [Deutsch] Ziel: In einer experimentellen Studie an Gelenkpraeparaten des Knies wurden die Vor- und Nachteile von 14 allgemein verfuegbaren MRT-Sequenzen in der Knorpeldiagnostik dargestellt. Methode: 50 chirurgisch exstirpierte Kniegelenkpraeparate wurden nacheinander mit folgenden Techniken untersucht: Klassische Spin-Echo(SE)-Sequenz in T{sub 1}-, Protonen- und T{sub 2}-Wichtung, Turbo-SE in Protonen- und T{sub 2}-Wichtung, Fettsuppression mit T{sub 1}-gew. SE, MTC in

  14. Cartilage proteoglycans inhibit fibronectin-mediated adhesion

    Science.gov (United States)

    Rich, A. M.; Pearlstein, E.; Weissmann, G.; Hoffstein, S. T.

    1981-09-01

    Normal tissues and organs show, on histological examination, a pattern of cellular and acellular zones that is characteristic and unique for each organ or tissue. This pattern is maintained in health but is sometimes destroyed by disease. For example, in mobile joints, the articular surfaces consist of relatively acellular hyaline cartilage, and the joint space is enclosed by a capsule of loose connective tissue with a lining of fibroblasts and macrophages. In the normal joint these cells are confined to the synovial lining and the articular surface remains acellular. In in vitro culture, macrophages and their precursor monocytes are very adhesive, and fibroblasts can migrate and overgrow surfaces such as collagen or plastic used for tissue culture. The fibroblasts adhere to collagen by means of fibronectin, which they synthesize and secrete1. Because the collagen of cartilage is capable of binding serum fibronectin2 and fibronectin is present in cartilage during its development3, these cells should, in theory, slowly migrate from the synovial lining to the articular surface. It is their absence from the articular cartilage in normal circumstances, and then presence in such pathological states as rheumatoid arthritis, that is striking. We therefore set out to determine whether a component of cartilage could prevent fibroblast adherence in a defined adhesion assay. As normal cartilage is composed of 50% proteoglycans and 50% collagen by dry weight4, we tested the possibility that the proteoglycans in cartilage inhibit fibroblast adhesion to collagen. We present here evidence that fibroblast spreading and adhesion to collagenous substrates is inhibited by cartilage proteoglycans.

  15. The role of calcified cartilage and subchondral bone in the initiation and progression of ochronotic arthropathy in alkaptonuria.

    Science.gov (United States)

    Taylor, A M; Boyde, A; Wilson, P J M; Jarvis, J C; Davidson, J S; Hunt, J A; Ranganath, L R; Gallagher, J A

    2011-12-01

    Alkaptonuria is a genetic disorder of tyrosine metabolism, resulting in elevated circulating concentrations of homogentisic acid. Homogentisic acid is deposited as a polymer, termed ochronotic pigment, in collagenous tissues, especially cartilages of weight-bearing joints, leading to a severe osteoarthropathy. We undertook this study to investigate the initiation and progression of ochronosis from the earliest detection of pigment through complete joint failure. Nine joint samples with varying severities of ochronosis were obtained from alkaptonuria patients undergoing surgery and compared to joint samples obtained from osteoarthritis (OA) patients. Samples were analyzed by light and fluorescence microscopy, 3-dimensional scanning electron microscopy (SEM), and the quantitative backscattered electron mode of SEM. Cartilage samples were mechanically tested by compression to determine Young's modulus of pigmented, nonpigmented, and OA cartilage samples. In alkaptonuria samples with the least advanced ochronosis, pigment was observed intracellularly and in the territorial matrix of individual chondrocytes at the boundary of the subchondral bone and calcified cartilage. In more advanced ochronosis, pigmentation was widespread throughout the hyaline cartilage in either granular composition or as blanket pigmentation in which there is complete and homogenous pigmentation of cartilage matrix. Once hyaline cartilage was extensively pigmented, there was aggressive osteoclastic resorption of the subchondral plate. Pigmented cartilage became impacted on less highly mineralized trabeculae and embedded in the marrow space. Pigmented cartilage samples were much stiffer than nonpigmented or OA cartilage as revealed by a significant difference in Young's modulus. Using alkaptonuria cartilage specimens with a wide spectrum of pigmentation, we have characterized the progression of ochronosis. Intact cartilage appears to be resistant to pigmentation but becomes susceptible following

  16. 308-nm excimer laser ablation of human cartilage

    Science.gov (United States)

    Prodoehl, John A.; Rhodes, Anthony L.; Meller, Menachem M.; Sherk, Henry H.

    1993-07-01

    The XeCl excimer laser was investigated as an ablating tool for human fibrocartilage and hyaline cartilage. Quantitative measurements were made of tissue ablation rates as a function of fluence in meniscal fibrocartilage and articular hyaline cartilage. A force of 1.47 Newtons was applied to an 800 micrometers fiber with the laser delivering a range of fluences (40 to 190 mj/mm2) firing at a frequency of 5 Hz. To assess the effect of repetition rate on ablation rate, a set of measurements was made at a constant fluence of 60 mj/mm2, with the repetition rate varying from 10 to 40 Hz. Histologic and morphometric analysis was performed using light microscopy. The results of these studies revealed that the ablation rate was directly proportional to fluence over the range tested. Fibrocartilage was ablated at a rate 2.56 times faster than hyaline cartilage at the maximum fluence tested. Repetition rate had no effect on the penetration per pulse. Adjacent tissue damage was noted to be minimal (10 - 70 micrometers ).

  17. TGF-β3 encapsulated PLCL scaffold by a supercritical CO2-HFIP co-solvent system for cartilage tissue engineering.

    Science.gov (United States)

    Kim, Su Hee; Kim, Soo Hyun; Jung, Youngmee

    2015-05-28

    Mimicking the native tissue microenvironment is critical for effective tissue regeneration. Mechanical cues and sustained biological cues are important factors, particularly in load-bearing tissues such as articular cartilage or bone. Carriers including hydrogels and nanoparticles have been investigated to achieve sustained release of protein drugs. However, it is difficult to apply such carriers alone as scaffolds for cartilage regeneration because of their weak mechanical properties, and they must be combined with other biomaterials that have adequate mechanical strength. In this study, we developed the multifunctional scaffold which has similar mechanical properties to those of native cartilage and encapsulates TGF-β3 for chondrogenesis. In our previous work, we confirmed that poly(lactide-co-caprolacton) (PLCL) did not foam when exposed to supercritical CO2 below 45°C. Here, we used a supercritical carbon dioxide (scCO2)-1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) co-solvent system to facilitate processing under mild conditions because high temperature causes protein denaturation and decreases bioactivity of the protein. This processing made it possible to fabricate a TGF-β3 encapsulated elastic porous PLCL scaffold at 37°C. We investigated the tissue regeneration efficiency of the TGF-β3 encapsulated PLCL scaffold using human adipose-derived stem cells (ADSCs) in vitro and in vivo (Groups; i. PLCL scaffold+Fibrin gel+TGF-β3, ii. TGF-β3 encapsulated PLCL scaffold+Fibrin gel, iii. TGF-β3 encapsulated PLCL scaffold). We evaluated the chondrogenic abilities of the scaffolds at 4, 8, and 12weeks after subcutaneous implantation of the constructs in immune-deficient mice. Based on TGF-β3 release studies, we confirmed that TGF-β3 molecules were released by 8weeks and remained in the PLCL matrix. Explants of TGF-β3 encapsulated scaffolds by a co-solvent system exhibited distinct improvement in the compressive E-modulus and deposition of extracellular matrix

  18. Biological aspects of tissue-engineered cartilage.

    Science.gov (United States)

    Hoshi, Kazuto; Fujihara, Yuko; Yamawaki, Takanori; Harai, Motohiro; Asawa, Yukiyo; Hikita, Atsuhiko

    2018-04-01

    Cartilage regenerative medicine has been progressed well, and it reaches the stage of clinical application. Among various techniques, tissue engineering, which incorporates elements of materials science, is investigated earnestly, driven by high clinical needs. The cartilage tissue engineering using a poly lactide scaffold has been exploratorily used in the treatment of cleft lip-nose patients, disclosing good clinical results during 3-year observation. However, to increase the reliability of this treatment, not only accumulation of clinical evidence on safety and usefulness of the tissue-engineered products, but also establishment of scientific background on biological mechanisms, are regarded essential. In this paper, we reviewed recent trends of cartilage tissue engineering in clinical practice, summarized experimental findings on cellular and matrix changes during the cartilage regeneration, and discussed the importance of further studies on biological aspects of tissue-engineered cartilage, especially by the histological and the morphological methods.

  19. Effect of histone deacetylase inhibitor, trichostatin A, on cartilage ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research June 2017; 16 (6): 1253-1257 ... Conclusion: Treatment with trichostatin A, an HDAC inhibitor, enhances cartilage regeneration in rabbit ..... deacetylase activity in rheumatoid arthritis and asthma.

  20. A Human Amnion-Derived Extracellular Matrix-Coated Cell-Free Scaffold for Cartilage Repair: In Vitro and In Vivo Studies.

    Science.gov (United States)

    Nogami, Makiko; Kimura, Tomoatsu; Seki, Shoji; Matsui, Yoshito; Yoshida, Toshiko; Koike-Soko, Chika; Okabe, Motonori; Motomura, Hiraku; Gejo, Ryuichi; Nikaido, Toshio

    2016-04-01

    Extracellular matrix (ECM) derived from human amniotic mesenchymal cells (HAMs) has various biological activities. In this study, we developed a novel HAM-derived ECM-coated polylactic-co-glycolic acid (ECM-PLGA) scaffold, examined its property on mesenchymal cells, and investigated its potential as a cell-free scaffold for cartilage repair. ECM-PLGA scaffolds were developed by inoculating HAM on a PLGA. After decellularization by irradiation, accumulated ECM was examined. Exogenous cell growth and differentiation of rat mesenchymal stem cells (MSCs) on the ECM-PLGA were analyzed in vitro by cell attachment/proliferation assay and reverse transcription-polymerase chain reaction. The cell-free ECM-PLGA scaffolds were implanted into osteochondral defects in the trochlear groove of rat knees. After 4, 12, or 24 weeks, the animals were sacrificed and the harvested tissues were examined histologically. The ECM-PLGA contained ECM that mimicked natural amniotic stroma that contains type I collagen, fibronectin, hyaluronic acid, and chondroitin sulfates. The ECM-PLGA showed excellent properties of cell attachment and proliferation. MSCs inoculated on the ECM-PLGA scaffold showed accelerated type II collagen mRNA expression after 3 weeks in culture. The ECM-PLGA implanted into an osteochondral defect in rat knees induced gradual tissue regeneration and resulted in hyaline cartilage repair, which was better than that in the empty control group. These in vitro and in vivo experiments show that the cell-free scaffold composed of HAM-derived ECM and PLGA provides a favorable growth environment for MSCs and facilitates the cartilage repair process. The ECM-PLGA may become a "ready-made" biomaterial for cartilage repair therapy.

  1. Cartilage of the Intervertebral Disc Eng-Plate, A Histological, Histochemical, Fine Structure Study.

    Science.gov (United States)

    1982-08-01

    degeneration (Nachemson et al., 1970). These and related studies consider the end-plates to be composed of hyaline cartilage and thus homologues of articular...results of this study in rhesus indicate, that while present, the cartilage of the end-plate is quite different in structure and presumably...HZSTOLO6ZCAL,-ETCfU) I AUG 82 N 5 NUSSBAUM IUNCLASSIFDATRL8R-1222NL.rnximommmB~iIEND2 AFAMRL-TR-81 - 122 " CARTILAGE OF THE INTERVERTEBRAL DISC END-PLATE A

  2. Pulmonary hyalinizing granuloma presenting with dysphagia: a rare presentation.

    Science.gov (United States)

    Khan, Fazal; Hamid, Arsalan; Fatima, Benish; Hashmi, Shiraz; Fatimi, Saulat

    2017-01-01

    A 25-year-old man presented with a 2-month history of dysphagia and past history of pulmonary and intestinal tuberculosis. A barium swallow showed a point of constriction 42 mm above the gastroesophageal junction. Computed tomography revealed large opacities in bilateral lung fields, encroaching more on the esophagus. The lesion progressively compressed the esophagus as it moved inferiorly. A right posterolateral thoracotomy was performed for sub-anatomical resection of the mass. A biopsy revealed homogenous whirling hyalinized collagen fibers, highly suggestive of pulmonary hyalinizing granuloma, with no evidence of malignancy. Pulmonary hyalinizing granuloma should be considered in the differential diagnosis of longstanding dysphagia.

  3. Combined nanoindentation testing and scanning electron microscopy of bone and articular calcified cartilage in an equine fracture predilection site

    OpenAIRE

    M Doube; EC Firth; A Boyde; AJ Bushby

    2010-01-01

    Condylar fracture of the third metacarpal bone (Mc3) is the commonest cause of racetrack fatality in Thoroughbred horses. Linear defects involving hyaline articular cartilage, articular calcified cartilage (ACC) and subchondral bone (SCB) have been associated with the fracture initiation site, which lies in the sagittal grooves of the Mc3 condyle. We discovered areas of thickened and abnormally-mineralised ACC in the sagittal grooves of several normal 18-month-old horses, at the same site tha...

  4. Advanced Strategies for Articular Cartilage Defect Repair

    Directory of Open Access Journals (Sweden)

    Fergal J. O'Brien

    2013-02-01

    Full Text Available Articular cartilage is a unique tissue owing to its ability to withstand repetitive compressive stress throughout an individual’s lifetime. However, its major limitation is the inability to heal even the most minor injuries. There still remains an inherent lack of strategies that stimulate hyaline-like articular cartilage growth with appropriate functional properties. Recent scientific advances in tissue engineering have made significant steps towards development of constructs for articular cartilage repair. In particular, research has shown the potential of biomaterial physico-chemical properties significantly influencing the proliferation, differentiation and matrix deposition by progenitor cells. Accordingly, this highlights the potential of using such properties to direct the lineage towards which such cells follow. Moreover, the use of soluble growth factors to enhance the bioactivity and regenerative capacity of biomaterials has recently been adopted by researchers in the field of tissue engineering. In addition, gene therapy is a growing area that has found noteworthy use in tissue engineering partly due to the potential to overcome some drawbacks associated with current growth factor delivery systems. In this context, such advanced strategies in biomaterial science, cell-based and growth factor-based therapies that have been employed in the restoration and repair of damaged articular cartilage will be the focus of this review article.

  5. MR imaging of articular cartilage; Gelenkknorpel in der MR-Tomographie

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, F.K.W.; Muhle, C.; Heller, M.; Brossmann, J. [Kiel Univ. (Germany). Klinik fuer Diagnostische Radiologie

    2001-04-01

    MR imaging has evolved to the best non-invasive method for the evaluation of articular cartilage. MR imaging helps to understand the structure and physiology of cartilage, and to diagnose cartilage lesions. Numerous studies have shown high accuracy and reliability concerning detection of cartilage lesions and early changes in both structure and biochemistry. High contrast-to-noise ratio and high spatial resolution are essential for analysis of articular cartilage. Fat-suppressed 3D-T{sub 1} weighted gradient echo and T{sub 2}-weighted fast spin echo sequences with or without fat suppression are recommended for clinical routine. In this article the anatomy and pathology of hyaline articular cartilage and the complex imaging characteristics of hyaline cartilage will be discussed. (orig.) [German] Die MR-Tomographie hat sich zur besten nichtinvasiven bildgebenden Methode fuer die Untersuchung von Gelenkknorpel entwickelt. Die MR-Tomographie liefert einen Beitrag zum Verstaendnis der Knorpelstruktur und der Physiologie sowie zur Diagnostik von Knorpelschaeden. Zahlreiche MR-Studien konnten eine hohe Genauigkeit und Zuverlaessigkeit bei der Detektion chondraler Laesionen sowie frueher Veraenderungen struktureller und biochemischer Natur zeigen. Neben einem hohen Kontrast/Rausch-Verhaeltnis ist fuer die Gelenkknorpelanalyse eine hohe raeumliche Aufloesung erforderlich. Im klinischen Routinebetrieb empfehlen sich fuer die Erkennung von Knorpellaesionen besonders fettunterdrueckte 3D-T{sub 1}-gewichtete Gradientenecho- und T{sub 2}-gewichtete Fastspinecho-Sequenzen mit oder ohne Fettunterdrueckung. Die vorliegende Arbeit geht auf die Anatomie und Pathologie des hyalinen Gelenkknorpels ein und diskutiert das komplexe MR-Signalverhalten. (orig.)

  6. [Effects of in vitro continuous passaging on the phenotype of mouse hyaline chondrocytes and the balance of the extra- cellular matrix].

    Science.gov (United States)

    Linyi, Cai; Xiangli, Kong; Jing, Xie

    2016-06-01

    This study aimed to investigate the effects of in vitro continuous passaging on the morphological phenotype and differentiation characteristics of mouse hyaline chondrocytes, as well as on the balance of the extracellular matrix (ECM). Enzymatic digestion was conducted to isolate mouse hyaline chondrocytes, which expanded over five passages in vitro. Hematoxylin-eosin stain was used to show the changes in chondrocyte morphology. Semi-quantitative polymerase chain reaction was performed to analyze the mRNA changes in the marker genes, routine genes, matrix metalloproteinases (MMPs), and tissue inhibitors of MMPs (TIMPs) in chondrocytes. Zymography was carried out to elucidate changes in gelatinase activities. After continuous expansion in vitro, the morphology of round or polygonal chondrocytes changed to elongated and spindled shape. The expression of marker genes significantly decreased (P 0.05). Meanwhile, the ratio of MMPs/TIMPs was altered. At the protein level, the activities of gelatinases decreased after passaging, especially for P4 and P5 chondrocytes (P cartilage ECM became uncontrollable and led to the imbalance of ECM homeostasis. When hyaline chondrocytes are applied in research on relevant diseases or cartilage tissue engineering, P0-P2 chondrocytes should be used.

  7. Articular Cartilage Repair Using Marrow Stimulation Augmented with a Viable Chondral Allograft: 9-Month Postoperative Histological Evaluation

    Directory of Open Access Journals (Sweden)

    James K. Hoffman

    2015-01-01

    Full Text Available Marrow stimulation is frequently employed to treat focal chondral defects of the knee. However, marrow stimulation typically results in fibrocartilage repair tissue rather than healthy hyaline cartilage, which, over time, predisposes the repair to failure. Recently, a cryopreserved viable chondral allograft was developed to augment marrow stimulation. The chondral allograft is comprised of native viable chondrocytes, chondrogenic growth factors, and extracellular matrix proteins within the superficial, transitional, and radial zones of hyaline cartilage. Therefore, host mesenchymal stem cells that infiltrate the graft from the underlying bone marrow following marrow stimulation are provided with the optimal microenvironment to undergo chondrogenesis. The present report describes treatment of a trochlear defect with marrow stimulation augmented with this novel chondral allograft, along with nine month postoperative histological results. At nine months, the patient demonstrated complete resolution of pain and improvement in function, and the repair tissue consisted of 85% hyaline cartilage. For comparison, a biopsy obtained from a patient 8.2 months after treatment with marrow stimulation alone contained only 5% hyaline cartilage. These outcomes suggest that augmenting marrow stimulation with the viable chondral allograft can eliminate pain and improve outcomes, compared with marrow stimulation alone.

  8. Histological evaluation of calcaneal tuberosity cartilage--A proposed donor site for osteochondral autologous transplant for talar dome osteochondral lesions.

    Science.gov (United States)

    Calder, James D F; Ballal, Moez S; Deol, Rupinderbir S; Pearce, Christopher J; Hamilton, Paul; Lutz, Michael

    2015-09-01

    Osteochondral Autologous Transplant (OATs) as a treatment option for Osteochondral lesions (OCLs) of the talar dome frequently uses the distal femur as the donor site which is associated with donor site morbidity in up to 50%. Some studies have described the presence of hyaline cartilage in the posterior superior calcaneal tuberosity. The aim of this study was to evaluate the posterior superior calcaneal tuberosity to determine if it can be a suitable donor site for OATs of the talus In this cadaveric study, we histologically evaluated 12 osteochondral plugs taken from the posterior superior calcaneal tuberosity and compared them to 12 osteochondral plugs taken from the talar dome. In the talar dome group, all samples had evidence of hyaline cartilage with varying degrees of GAG staining. The average hyaline cartilage thickness in the samples was 1.33 mm. There was no evidence of fibrocartilage, fibrous tissue or fatty tissue in this group. In contrast, the Calcaneal tuberosity samples had no evidence of hyaline cartilage. Fibrocartilage was noted in 3 samples only. We believe that the structural differences between the talus and calcanium grafts render the posterior superior clancaneal tuberosity an unsuitable donor site for OATs in the treatment of OCL of the talus. Copyright © 2014 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  9. Cartilage immunoprivilege depends on donor source and lesion location.

    Science.gov (United States)

    Arzi, B; DuRaine, G D; Lee, C A; Huey, D J; Borjesson, D L; Murphy, B G; Hu, J C Y; Baumgarth, N; Athanasiou, K A

    2015-09-01

    The ability to repair damaged cartilage is a major goal of musculoskeletal tissue engineering. Allogeneic (same species, different individual) or xenogeneic (different species) sources can provide an attractive source of chondrocytes for cartilage tissue engineering, since autologous (same individual) cells are scarce. Immune rejection of non-autologous hyaline articular cartilage has seldom been considered due to the popular notion of "cartilage immunoprivilege". The objective of this study was to determine the suitability of allogeneic and xenogeneic engineered neocartilage tissue for cartilage repair. To address this, scaffold-free tissue engineered articular cartilage of syngeneic (same genetic background), allogeneic, and xenogeneic origin were implanted into two different locations of the rabbit knee (n=3 per group/location). Xenogeneic engineered cartilage and control xenogeneic chondral explants provoked profound innate inflammatory and adaptive cellular responses, regardless of transplant location. Cytological quantification of immune cells showed that, while allogeneic neocartilage elicited an immune response in the patella, negligible responses were observed when implanted into the trochlea; instead the responses were comparable to microfracture-treated empty defect controls. Allogeneic neocartilage survived within the trochlea implant site and demonstrated graft integration into the underlying bone. In conclusion, the knee joint cartilage does not represent an immune privileged site, strongly rejecting xenogeneic but not allogeneic chondrocytes in a location-dependent fashion. This difference in location-dependent survival of allogeneic tissue may be associated with proximity to the synovium. Through a series of in vivo studies this research demonstrates that articular cartilage is not fully immunoprivileged. In addition, we now show that anatomical location of the defect, even within the same joint compartment, strongly influences the degree of the

  10. Effects of Er:YAG laser irradiation on human cartilage

    Science.gov (United States)

    Glinkowski, Wojciech; Brzozowska, Malgorzata; Ciszek, Bogdan; Rowinski, Jan; Strek, Wieslaw

    1996-03-01

    Irradiation of the hyaline or fibrous cartilage excised from the body of a human cadaver with Er:YAG laser beam, single pulse with a dose of 1 J, produces a crater with a depth of approximately 500 micrometers and a diameter varying from 5 to 300 micrometers. Histological examination has revealed that the laser-made craters were surrounded by a thin rim (2-10 micrometer) of charred and coagulated tissue. No damage was observed in the cartilage surrounding the rim. The presence of sharp demarcation between the tissue areas ablated by laser energy and the undamaged areas argues for the potential usefulness of the Er:YAG laser in surgery of cartilages.

  11. 2-photon laser scanning microscopy on native human cartilage

    Science.gov (United States)

    Martini, Joerg; Toensing, Katja; Dickob, Michael; Anselmetti, Dario

    2005-08-01

    Native hyaline cartilage from a human knee joint was directly investigated with laser scanning microscopy via 2-photon autofluorescence excitation with no additional staining or labelling protocols in a nondestructive and sterile manner. Using a femtosecond, near-infrared (NIR) Ti:Sa laser for 2-photon excitation and a dedicated NIR long distance objective, autofluorescence imaging and measurements of the extracellular matrix (ECM) tissue with incorporated chondrocytes were possible with a penetration depth of up to 460 μm inside the sample. Via spectral autofluorescence separation these experiments allowed the discrimination of chondrocytes from the ECM and therefore an estimate of chondrocytic cell density within the cartilage tissue to approximately 0.2-2•107cm3. Furthermore, a comparison of the relative autofluorescence signals between nonarthritic and arthritic cartilage tissue exhibited distinct differences in tissue morphology. As these morphological findings are in keeping with the macroscopic diagnosis, our measurement has the potential of being used in future diagnostic applications.

  12. Pleomorphic Hyalinizing Angiectatic Tumor of Soft Parts

    Directory of Open Access Journals (Sweden)

    Hui-Chin Peng

    2010-08-01

    Full Text Available Pleomorphic hyalinizing angiectatic tumor (PHAT of soft parts is a rare, nonmetastasizing tumor of uncertain lineage which was first reported in 1996. Here, we report a case of PHAT and review the literature. A 49-year-old man presented with a soft and progressively enlarging mass over the right buttock for several years. On suspicion that the mass was a right gluteal lipoma, he underwent surgical excision. The excised lesion measured 14 × 6 × 3.5 cm. It had a variegated appearance with a white-tan to yellowish color on the cut surface. Some punctate hemorrhage and vessel thrombosis were seen. Microscopically, the tumor was a PHAT characterized by clusters of ectatic, fibrin-lined, thin-walled vessels, which were surrounded by a mitotically inert, spindled, pleomorphic, neoplastic stroma that contained a variable inflammatory component. Immunohistochemical study showed that the tumor cells were positive for CD34, and negative for S-100, HMB45 and actin. The patient experienced local recurrence 6 months later. The recurrent tumor was widely excised. No evidence of metastasis was found during the 18 months after the second operation. The recurrent lesion had a microscopic appearance that was similar to the initial lesion.

  13. Similar properties of chondrocytes from osteoarthritis joints and mesenchymal stem cells from healthy donors for tissue engineering of articular cartilage.

    Directory of Open Access Journals (Sweden)

    Amilton M Fernandes

    Full Text Available Lesions of hyaline cartilage do not heal spontaneously, and represent a therapeutic challenge. In vitro engineering of articular cartilage using cells and biomaterials may prove to be the best solution. Patients with osteoarthritis (OA may require tissue engineered cartilage therapy. Chondrocytes obtained from OA joints are thought to be involved in the disease process, and thus to be of insufficient quality to be used for repair strategies. Bone marrow (BM derived mesenchymal stem cells (MSCs from healthy donors may represent an alternative cell source. We have isolated chondrocytes from OA joints, performed cell culture expansion and tissue engineering of cartilage using a disc-shaped alginate scaffold and chondrogenic differentiation medium. We performed real-time reverse transcriptase quantitative PCR and fluorescence immunohistochemistry to evaluate mRNA and protein expression for a range of molecules involved in chondrogenesis and OA pathogenesis. Results were compared with those obtained by using BM-MSCs in an identical tissue engineering strategy. Finally the two populations were compared using genome-wide mRNA arrays. At three weeks of chondrogenic differentiation we found high and similar levels of hyaline cartilage-specific type II collagen and fibrocartilage-specific type I collagen mRNA and protein in discs containing OA and BM-MSC derived chondrocytes. Aggrecan, the dominant proteoglycan in hyaline cartilage, was more abundantly distributed in the OA chondrocyte extracellular matrix. OA chondrocytes expressed higher mRNA levels also of other hyaline extracellular matrix components. Surprisingly BM-MSC derived chondrocytes expressed higher mRNA levels of OA markers such as COL10A1, SSP1 (osteopontin, ALPL, BMP2, VEGFA, PTGES, IHH, and WNT genes, but lower levels of MMP3 and S100A4. Based on the results presented here, OA chondrocytes may be suitable for tissue engineering of articular cartilage.

  14. Allogenic lyophilized cartilage grafts for craniomaxillofacial reconstruction

    International Nuclear Information System (INIS)

    Pill Hoon Choung

    1999-01-01

    Allogenic lyophilized cartilages were made in our clinic after Sailer methods and some modification. In our clinic, we have used allogenic cartilage grafts on 102 defects of craniomaxillofacial area; 1) for defects from cyst or ameloblastoma, 2) for lack of continuity of the mandible, 3) for rhinoplasty, 4) for paranasal augmentation, 5) for augmentation genioplasty, 6) for reconstruction of orbital floor, 7) for oroantral fistula, 8) for temporal augmentation, 9) for TMJ surgery 10) for condyle defect as a costochondral graft, 11) for filling of tooth socket and alveolus augmentation,12) for correction or orbital height and 13) for guided bone regeneration in peripheral implant. The types of lyophilized cartilage used were chip, sheet and block types developed by freeze-dried methods. Some grafts showed change of ossification, in which case we could perform implant on it. We have good results on reconstruction of craniomaxillofacial defects. Allogenic cartilage have advantages such as 1) it has no immune reaction clinically, 2) it is more tolerable to infection than that of autogenous cartilage, 3) it has character of less resorption which require no over correction, 4) it is easy to manipulate contouring, and 5) it has possibility of undergoing ossification. Allogenic cartilage has been considered as good substitutes for bone. The author would like to report the results on 102 allogenic cartilage have

  15. A Stereological Method for the Quantitative Evaluation of Cartilage Repair Tissue

    Science.gov (United States)

    Nyengaard, Jens Randel; Lind, Martin; Spector, Myron

    2015-01-01

    Objective To implement stereological principles to develop an easy applicable algorithm for unbiased and quantitative evaluation of cartilage repair. Design Design-unbiased sampling was performed by systematically sectioning the defect perpendicular to the joint surface in parallel planes providing 7 to 10 hematoxylin–eosin stained histological sections. Counting windows were systematically selected and converted into image files (40-50 per defect). The quantification was performed by two-step point counting: (1) calculation of defect volume and (2) quantitative analysis of tissue composition. Step 2 was performed by assigning each point to one of the following categories based on validated and easy distinguishable morphological characteristics: (1) hyaline cartilage (rounded cells in lacunae in hyaline matrix), (2) fibrocartilage (rounded cells in lacunae in fibrous matrix), (3) fibrous tissue (elongated cells in fibrous tissue), (4) bone, (5) scaffold material, and (6) others. The ability to discriminate between the tissue types was determined using conventional or polarized light microscopy, and the interobserver variability was evaluated. Results We describe the application of the stereological method. In the example, we assessed the defect repair tissue volume to be 4.4 mm3 (CE = 0.01). The tissue fractions were subsequently evaluated. Polarized light illumination of the slides improved discrimination between hyaline cartilage and fibrocartilage and increased the interobserver agreement compared with conventional transmitted light. Conclusion We have applied a design-unbiased method for quantitative evaluation of cartilage repair, and we propose this algorithm as a natural supplement to existing descriptive semiquantitative scoring systems. We also propose that polarized light is effective for discrimination between hyaline cartilage and fibrocartilage. PMID:26069715

  16. Particulated articular cartilage: CAIS and DeNovo NT.

    Science.gov (United States)

    Farr, Jack; Cole, Brian J; Sherman, Seth; Karas, Vasili

    2012-03-01

    Cartilage Autograft Implantation System (CAIS; DePuy/Mitek, Raynham, MA) and DeNovo Natural Tissue (NT; ISTO, St. Louis, MO) are novel treatment options for focal articular cartilage defects in the knee. These methods involve the implantation of particulated articular cartilage from either autograft or juvenile allograft donor, respectively. In the laboratory and in animal models, both CAIS and DeNovo NT have demonstrated the ability of the transplanted cartilage cells to "escape" from the extracellular matrix, migrate, multiply, and form a new hyaline-like cartilage tissue matrix that integrates with the surrounding host tissue. In clinical practice, the technique for both CAIS and DeNovo NT is straightforward, requiring only a single surgery to affect cartilage repair. Clinical experience is limited, with short-term studies demonstrating both procedures to be safe, feasible, and effective, with improvements in subjective patient scores, and with magnetic resonance imaging evidence of good defect fill. While these treatment options appear promising, prospective randomized controlled studies are necessary to refine the indications and contraindications for both CAIS and DeNovo NT.

  17. Orientation-dependent changes in MR signal intensity of articular cartilage: a manifestation of the ``magic angle`` effect

    Energy Technology Data Exchange (ETDEWEB)

    Wacker, F.K.; Bolze, X.; Felsenberg, D.; Wolf, K.J. [Department of Radiology, Benjamin Franklin University Hospital, Free University Berlin, D-12200 Berlin (Germany)

    1998-06-01

    Objective: To study magnetic resonance (MR) imaging pattern of normal hyaline articular cartilage in the knee joint with regard to the contribution of the ``magic angle`` effect to the MR signal. Design. Thirty-two healthy volunteers were imaged in a standard supine position in a 1.5-T unit using spin echo and gradient echo sequences. Nine volunteers were reimaged with the knee flexed. The signal behavior of the hyaline cartilage of the femoral condyles was evaluated qualitatively and quantitatively. The extended and flexed positions of the nine volunteers were compared. Results. A superficial and a deep hyperintense layer and a hypointense middle cartilage layer were observed. Segments of increased signal intensity were visible along the condyles; a magic angle effect on signal intensity was evident in the hypointense middle layer with both gradient echo and spin echo images. Conclusion. The MR signal behavior of hyaline cartilage is influenced by the alignment of the collagen fibers within the cartilage in relation to the magnetic field. Failure to recognize this effect may lead to inaccurate diagnosis. (orig.) With 4 figs., 17 refs.

  18. Tissue-engineered cartilage: the crossroads of biomaterials, cells and stimulating factors.

    Science.gov (United States)

    Bhardwaj, Nandana; Devi, Dipali; Mandal, Biman B

    2015-02-01

    Damage to cartilage represents one of the most challenging tasks of musculoskeletal therapeutics due to its limited propensity for healing and regenerative capabilities. Lack of current treatments to restore cartilage tissue function has prompted research in this rapidly emerging field of tissue regeneration of functional cartilage tissue substitutes. The development of cartilaginous tissue largely depends on the combination of appropriate biomaterials, cell source, and stimulating factors. Over the years, various biomaterials have been utilized for cartilage repair, but outcomes are far from achieving native cartilage architecture and function. This highlights the need for exploration of suitable biomaterials and stimulating factors for cartilage regeneration. With these perspectives, we aim to present an overview of cartilage tissue engineering with recent progress, development, and major steps taken toward the generation of functional cartilage tissue. In this review, we have discussed the advances and problems in tissue engineering of cartilage with strong emphasis on the utilization of natural polymeric biomaterials, various cell sources, and stimulating factors such as biophysical stimuli, mechanical stimuli, dynamic culture, and growth factors used so far in cartilage regeneration. Finally, we have focused on clinical trials, recent innovations, and future prospects related to cartilage engineering. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Reviewing subchondral cartilage surgery: considerations for standardised and outcome predictable cartilage remodelling: a technical note.

    Science.gov (United States)

    Benthien, Jan P; Behrens, Peter

    2013-11-01

    The potential of subchondral mesenchymal stem cell stimulation (MSS) for cartilage repair has led to the widespread use of microfracture as a first line treatment for full thickness articular cartilage defects. Recent focus on the effects of subchondral bone during cartilage injury and repair has expanded the understanding of the strengths and limitations in MSS and opened new pathways for potential improvement. Comparative studies have shown that bone marrow access has positive implications for pluripotential cell recruitment, repair quality and quantity, i.e. deeper channels elicited better cartilage fill, more hyaline cartilage character with higher type II collagen content and lower type I collagen content compared to shallow marrow access. A subchondral needling procedure using standardised and thin subchondral perforations deep into the subarticular bone marrow making the MSS more consistent with the latest developments in subchondral cartilage remodelling is proposed. As this is a novel method clinical studies have been initiated to evaluate the procedure especially compared to microfracturing. However, the first case studies and follow-ups indicate that specific drills facilitate reaching the subchondral bone marrow while the needle size makes perforation of the subchondral bone easier and more predictable. Clinical results of the first group of patients seem to compare well to microfracturing. The authors suggest a new method for a standardised procedure using a new perforating device. Advances in MSS by subchondral bone marrow perforation are discussed. It remains to be determined by clinical studies how this method compares to microfracturing. The subchondral needling offers the surgeon and the investigator a method that facilitates comparison studies because of its defined depth of subchondral penetration and needle size.

  20. Autologous Cartilage Chip Transplantation Improves Repair Tissue Composition Compared With Marrow Stimulation.

    Science.gov (United States)

    Christensen, Bjørn Borsøe; Olesen, Morten Lykke; Lind, Martin; Foldager, Casper Bindzus

    2017-06-01

    Repair of chondral injuries by use of cartilage chips has recently demonstrated clinical feasibility. To investigate in vivo cartilage repair outcome of autologous cartilage chips compared with marrow stimulation in full-thickness cartilage defects in a minipig model. Controlled laboratory study. Six Göttingen minipigs received two 6-mm chondral defects in the medial and lateral trochlea of each knee. The two treatment groups were (1) autologous cartilage chips embedded in fibrin glue (ACC) (n = 12) and (2) marrow stimulation (MST) (n = 12). The animals were euthanized after 6 months, and the composition of repair tissue was quantitatively determined using histomorphometry. Semiquantitative evaluation was performed by means of the International Cartilage Repair Society (ICRS) II score. Collagen type II staining was used to further evaluate the repair tissue composition. Significantly more hyaline cartilage was found in the ACC (17.1%) compared with MST (2.9%) group ( P cartilage repair tissue compared with MST at 6 months postoperatively. Further studies are needed to investigate ACC as a possible alternative first-line treatment for focal cartilage injuries in the knee.

  1. Is the repair of articular cartilage lesion by costal chondrocyte transplantation donor age-dependent? An experimental study in rabbits.

    Directory of Open Access Journals (Sweden)

    Janusz Popko

    2006-09-01

    Full Text Available The repair of chondral injuries is a very important problem and a subject of many experimental and clinical studies. Different techniques to induce articular cartilage repair are under investigation. In the present study, we have investigated whether the repair of articular cartilage folowing costal chondrocyte transplantation is donor age-dependent. Transplantation of costal chondrocytes from 4- and 24-week old donors, with artificially induced femoral cartilage lesion, was performed on fourteen 20-week-old New Zealand White male rabbits. In the control group, the lesion was left without chondrocyte transplantation. The evaluation of the cartilage repair was performed after 12 weeks of transplantation. We analyzed the macroscopic and histological appearance of the newly formed tissue. Immunohistochemistry was also performed using monoclonal antibodies against rabbit collagen type II. The newly formed tissue had a hyaline-like appearance in most of the lesions after chondrocyte transplantation. Positive immunohistochemical reaction for collagen II was also observed in both groups with transplanted chondrocytes. Cartilage from adult donors required longer isolation time and induced slightly poorer repair. However, hyaline-like cartilage was observed in most specimens from this group, in contrast to the control group, where fibrous connective tissue filled the lesions. Rabbit costal chondrocytes seem to be a potentially useful material for inducing articular cartilage repair and, even more important, they can also be derived from adult, sexually mature animals.

  2. Hyaline fibromatosis of Hoffa's fat pad in a patient with a mild type of hyaline fibromatosis syndrome

    International Nuclear Information System (INIS)

    Raak, Sjoerd M. van; Meuffels, Duncan E.; Leenders, Geert J.L.H. van; Oei, Edwin H.G.

    2014-01-01

    Hyaline fibromatosis syndrome (HFS) is a rare, homozygous, autosomal recessive disease, characterized by deposition of hyaline material in skin and other organs, resulting in esthetic problems, disability, and potential life-threatening complications. Most patients become clinically apparent in the first few years of life, and the disorder typically progresses with the appearance of new lesions. We describe a rare case of a 20-year-old patient with juvenile-onset mild HFS who presented with a history of progressive anterior knee pain. Detailed magnetic resonance (MR) imaging findings with histopathological correlation are presented of hyaline fibromatosis of Hoffa's fat pad, including differential diagnosis. The diagnosis of HFS is generally made on basis of clinical and histopathological findings. Imaging findings, however, may contribute to the correct diagnosis in patients who present with a less typical clinical course of HFS. (orig.)

  3. Hyaline fibromatosis syndrome (juvenile hyaline fibromatosis). Whole-body MR findings in two siblings with different subcutaneous nodules distribution

    International Nuclear Information System (INIS)

    Castiglione, Davide; Terranova, Maria Chiara; Picone, Dario; Lo Re, Giuseppe; Salerno, Sergio

    2018-01-01

    Hyaline fibromatosis syndrome (juvenile hyaline fibromatosis) is a rare, progressive, autosomal recessive disorder whose main hallmark is the deposition of amorphous hyaline material in soft tissues, with an evolutionary course and health impairment. It may present involvement of subcutaneous or periskeletal soft tissue, or may develop as a visceral infiltration entity with poor prognosis. Very few radiological data about this inherited condition have been reported, due to the extreme rarity of disease. We herein present a case of two siblings, affected by different severity of the disease, with different clinical features. They were examined by whole-body MR (WBMR) in order to assess different lesions localization, to rule out any visceral involvement and any other associated anomalies and to define patients' management. (orig.)

  4. Hyaline fibromatosis of Hoffa's fat pad in a patient with a mild type of hyaline fibromatosis syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Raak, Sjoerd M. van [Albert Schweitzer Hospital, Department of Radiology, Dordrecht (Netherlands); Meuffels, Duncan E. [Erasmus MC - University Medical Center, Department of Orthopaedic Surgery, Rotterdam (Netherlands); Leenders, Geert J.L.H. van [Erasmus MC - University Medical Center, Department of Pathology, Rotterdam (Netherlands); Oei, Edwin H.G. [Erasmus MC - University Medical Center, Department of Radiology, Rotterdam (Netherlands)

    2014-04-15

    Hyaline fibromatosis syndrome (HFS) is a rare, homozygous, autosomal recessive disease, characterized by deposition of hyaline material in skin and other organs, resulting in esthetic problems, disability, and potential life-threatening complications. Most patients become clinically apparent in the first few years of life, and the disorder typically progresses with the appearance of new lesions. We describe a rare case of a 20-year-old patient with juvenile-onset mild HFS who presented with a history of progressive anterior knee pain. Detailed magnetic resonance (MR) imaging findings with histopathological correlation are presented of hyaline fibromatosis of Hoffa's fat pad, including differential diagnosis. The diagnosis of HFS is generally made on basis of clinical and histopathological findings. Imaging findings, however, may contribute to the correct diagnosis in patients who present with a less typical clinical course of HFS. (orig.)

  5. Hyaline fibromatosis syndrome (juvenile hyaline fibromatosis). Whole-body MR findings in two siblings with different subcutaneous nodules distribution

    Energy Technology Data Exchange (ETDEWEB)

    Castiglione, Davide; Terranova, Maria Chiara; Picone, Dario; Lo Re, Giuseppe; Salerno, Sergio [Policlinico, Universita degli Studi di Palermo, Dipartimento di Biopatologia e Biotecnologie Mediche, Palermo (Italy)

    2018-03-15

    Hyaline fibromatosis syndrome (juvenile hyaline fibromatosis) is a rare, progressive, autosomal recessive disorder whose main hallmark is the deposition of amorphous hyaline material in soft tissues, with an evolutionary course and health impairment. It may present involvement of subcutaneous or periskeletal soft tissue, or may develop as a visceral infiltration entity with poor prognosis. Very few radiological data about this inherited condition have been reported, due to the extreme rarity of disease. We herein present a case of two siblings, affected by different severity of the disease, with different clinical features. They were examined by whole-body MR (WBMR) in order to assess different lesions localization, to rule out any visceral involvement and any other associated anomalies and to define patients' management. (orig.)

  6. MR imaging and histopathology of cartilage tumors

    Energy Technology Data Exchange (ETDEWEB)

    Mizutani, Hirokazu; Ohba, Satoru; Ohtsuka, Takanobu; Matui, Norio; Nakamura, Takaaki (Nagoya City Univ. (Japan). Faculty of Medicine)

    1994-05-01

    The MR imaging-pathologic correlation of cartilaginous bone tumors and the value of intravenously administered Gd-DTPA enhanced MR imaging was studied. The MR studies were retrospectively reviewed. Thirty-seven cases were examined with 0.5 T and 1.0 T scanner and all cases were pathologically proved. We discussed the following MR findings: signal intensities of tumors, Gd-DTPA features, morphological findings, and associated findings. Hyaline cartilage tumors showed low signal intensity on T[sub 1]-weighted images and very high signal intensity on T[sub 2]-weighted images. Lobulated marginal enhancements were recognized in chondrosarcomas. This may be an important finding to suspect chondrosarcoma. (author).

  7. Biochemical and biomechanical characterisation of equine cervical facet joint cartilage.

    Science.gov (United States)

    O'Leary, S A; White, J L; Hu, J C; Athanasiou, K A

    2018-04-15

    The equine cervical facet joint is a site of significant pathology. Located bilaterally on the dorsal spine, these diarthrodial joints work in conjunction with the intervertebral disc to facilitate appropriate spinal motion. Despite the high prevalence of pathology in this joint, the facet joint is understudied and thus lacking in viable treatment options. The goal of this study was to characterise equine facet joint cartilage and provide a comprehensive database describing the morphological, histological, biochemical and biomechanical properties of this tissue. Descriptive cadaver studies. A total of 132 facet joint surfaces were harvested from the cervical spines of six skeletally mature horses (11 surfaces per animal) for compiling biomechanical and biochemical properties of hyaline cartilage of the equine cervical facet joints. Gross morphometric measurements and histological staining were performed on facet joint cartilage. Creep indentation and uniaxial strain-to-failure testing were used to determine the biomechanical compressive and tensile properties. Biochemical assays included quantification of total collagen, sulfated glycosaminoglycan and DNA content. The facet joint surfaces were ovoid in shape with a flat articular surface. Histological analyses highlighted structures akin to articular cartilage of other synovial joints. In general, biomechanical and biochemical properties did not differ significantly between the inferior and superior joint surfaces as well as among spinal levels. Interestingly, compressive and tensile properties of cervical facet articular cartilage were lower than those of articular cartilage from other previously characterised equine joints. Removal of the superficial zone reduced the tissue's tensile strength, suggesting that this zone is important for the tensile integrity of the tissue. Facet surfaces were sampled at a single, central location and do not capture the potential topographic variation in cartilage properties. This

  8. Imaging of articular cartilage

    Directory of Open Access Journals (Sweden)

    Bhawan K Paunipagar

    2014-01-01

    Full Text Available We tried to review the role of magnetic resonance imaging (MRI in understanding microscopic and morphologic structure of the articular cartilage. The optimal protocols and available spin-echo sequences in present day practice are reviewed in context of common pathologies of articular cartilage. The future trends of articular cartilage imaging have been discussed with their appropriateness. In diarthrodial joints of the body, articular cartilage is functionally very important. It is frequently exposed to trauma, degeneration, and repetitive wear and tear. MRI has played a vital role in evaluation of articular cartilage. With the availability of advanced repair surgeries for cartilage lesions, there has been an increased demand for improved cartilage imaging techniques. Recent advances in imaging strategies for native and postoperative articular cartilage open up an entirely new approach in management of cartilage-related pathologies.

  9. Computed tomography findings in patients with pulmonary hyalinizing granulomas: a case report

    International Nuclear Information System (INIS)

    Marchiori, Edson; Valiante, Paulo Marcos; Correia, Ana Helena Pereira; Carneiro, Leonardo Hoehl; Caldas, Carolina Rodrigues; Souza Junior, Arthur Soares

    2003-01-01

    Hyalinizing granulomas are benign fibrotic lesions that generally present multiple nodules seen on radiological examinations, which are frequently cavitary and/or calcified lesions. We report a case of a 28 year-old-woman with hyalinizing granulomas probably secondary to a previous tuberculosis infection. Hyalinizing granulomas should be included in the differential diagnosis of patients with multiple pulmonary nodules. (author)

  10. MRI of the cartilages of the knee, 3-D imaging with a rapid computer system

    Energy Technology Data Exchange (ETDEWEB)

    Adam, G.; Bohndorf, K.; Prescher, A.; Drobnitzky, M.; Guenther, R.W.

    1989-01-01

    2-D spin-echo sequences were compared with 3-D gradient-echo sequences using normal and cadaver knee joints. The important advantages of 3-D-imaging are: sections of less than 1 mm, reconstruction in any required plane, which can be related to the complex anatomy of the knee joint, and very good distinction between intra-articular fluid, fibrocartilage and hyaline cartilage. (orig./GDG).

  11. Elasticity measurement of nasal cartilage as a function of temperature using optical coherence elastography

    Science.gov (United States)

    Liu, Chih Hao; Skryabina, M. N.; Singh, Manmohan; Li, Jiasong; Wu, Chen; Sobol, E.; Larin, Kirill V.

    2015-03-01

    Current clinical methods of reconstruction surgery involve laser reshaping of nasal cartilage. The process of stress relaxation caused by laser heating is the primary method to achieve nasal cartilage reshaping. Based on this, a rapid, non-destructive and accurate elasticity measurement would allow for a more robust reshaping procedure. In this work, we have utilized a phase-stabilized swept source optical coherence elastography (PhSSSOCE) to quantify the Young's modulus of porcine nasal septal cartilage during the relaxation process induced by heating. The results show that PhS-SSOCE was able to monitor changes in elasticity of hyaline cartilage, and this method could potentially be applied in vivo during laser reshaping therapies.

  12. Co-culture systems-based strategies for articular cartilage tissue engineering.

    Science.gov (United States)

    Zhang, Yu; Guo, Weimin; Wang, Mingjie; Hao, Chunxiang; Lu, Liang; Gao, Shuang; Zhang, Xueliang; Li, Xu; Chen, Mingxue; Li, Penghao; Jiang, Peng; Lu, Shibi; Liu, Shuyun; Guo, Quanyi

    2018-03-01

    Cartilage engineering facilitates repair and regeneration of damaged cartilage using engineered tissue that restores the functional properties of the impaired joint. The seed cells used most frequently in tissue engineering, are chondrocytes and mesenchymal stem cells. Seed cells activity plays a key role in the regeneration of functional cartilage tissue. However, seed cells undergo undesirable changes after in vitro processing procedures, such as degeneration of cartilage cells and induced hypertrophy of mesenchymal stem cells, which hinder cartilage tissue engineering. Compared to monoculture, which does not mimic the in vivo cellular environment, co-culture technology provides a more realistic microenvironment in terms of various physical, chemical, and biological factors. Co-culture technology is used in cartilage tissue engineering to overcome obstacles related to the degeneration of seed cells, and shows promise for cartilage regeneration and repair. In this review, we focus first on existing co-culture systems for cartilage tissue engineering and related fields, and discuss the conditions and mechanisms thereof. This is followed by methods for optimizing seed cell co-culture conditions to generate functional neo-cartilage tissue, which will lead to a new era in cartilage tissue engineering. © 2017 Wiley Periodicals, Inc.

  13. Medullary carcinoma of the thyroid - an unusual case of hyalinizing ...

    African Journals Online (AJOL)

    Medullary thyroid carcinoma is a neoplasm occurring in sporadic and familial patterns. A rare variant of medullary thyroid carcinoma shows microscopic features similar to hyalinizing trabecular adenoma of thyroid. Detection of this variant requires a high index of suspicion and immunohistochemical confirmation by ...

  14. Morphometric evaluation of condylar cartilage of growing rats in response to mandibular retractive forces

    Directory of Open Access Journals (Sweden)

    Milena Peixoto Nogueira de Sá

    2013-08-01

    Full Text Available INTRODUCTION: The mandibular condylar surface is made up of four layers, i.e., an external layer composed of dense connective tissue, followed by a layer of undifferentiated cells, hyaline cartilage and bone. Few studies have demonstrated the behavior of the condylar cartilage when the mandible is positioned posteriorly, as in treatments for correcting functional Class III malocclusion. OBJECTIVE: The aim of this study was to assess the morphologic and histological aspects of rat condyles in response to posterior positioning of the mandible. METHODS: Thirty five-week-old male Wistar rats were selected and randomly divided into two groups: A control group (C and an experimental group (E which received devices for inducing mandibular retrusion. The animals were euthanized at time intervals of 7, 21 and 30 days after the experiment had began. For histological analysis, total condylar thickness was measured, including the proliferative, hyaline and hypertrophic layers, as well as each layer separately, totaling 30 measurements for each parameter of each animal. RESULTS: The greatest difference in cartilage thickness was observed in 21 days, although different levels were observed in the other periods. Group E showed an increase of 39.46% in the total layer, reflected by increases in the thickness of the hypertrophic (42.24%, hyaline (46.92% and proliferative (17.70% layers. CONCLUSIONS: Posteriorly repositioning the mandible produced a series of histological and morphological responses in the condyle, suggesting condylar and mandibular adaptation in rats.

  15. Morphometric evaluation of condylar cartilage of growing rats in response to mandibular retractive forces.

    Science.gov (United States)

    de Sá, Milena Peixoto Nogueira; Zanoni, Jacqueline Nelisis; de Salles, Carlos Luiz Fernandes; de Souza, Fabrício Dias; Suga, Uhana Seifert Guimarães; Terada, Raquel Sano Suga

    2013-01-01

    The mandibular condylar surface is made up of four layers, i.e., an external layer composed of dense connective tissue, followed by a layer of undifferentiated cells, hyaline cartilage and bone. Few studies have demonstrated the behavior of the condylar cartilage when the mandible is positioned posteriorly, as in treatments for correcting functional Class III malocclusion. The aim of this study was to assess the morphologic and histological aspects of rat condyles in response to posterior positioning of the mandible. Thirty five-week-old male Wistar rats were selected and randomly divided into two groups: A control group (C) and an experimental group (E) which received devices for inducing mandibular retrusion. The animals were euthanized at time intervals of 7, 21 and 30 days after the experiment had began. For histological analysis, total condylar thickness was measured, including the proliferative, hyaline and hypertrophic layers, as well as each layer separately, totaling 30 measurements for each parameter of each animal. The greatest difference in cartilage thickness was observed in 21 days, although different levels were observed in the other periods. Group E showed an increase of 39.46% in the total layer, reflected by increases in the thickness of the hypertrophic (42.24%), hyaline (46.92%) and proliferative (17.70%) layers. Posteriorly repositioning the mandible produced a series of histological and morphological responses in the condyle, suggesting condylar and mandibular adaptation in rats.

  16. Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues.

    Science.gov (United States)

    Foldager, Casper Bindzus; Toh, Wei Seong; Gomoll, Andreas H; Olsen, Bjørn Reino; Spector, Myron

    2014-04-01

    The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti-collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins

  17. Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues

    Science.gov (United States)

    Toh, Wei Seong; Gomoll, Andreas H.; Olsen, Bjørn Reino; Spector, Myron

    2014-01-01

    Objective: The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Design: Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti–collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. Results: When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. Conclusions: We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional

  18. Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage.

    Directory of Open Access Journals (Sweden)

    Rebecca Williams

    Full Text Available BACKGROUND: Articular cartilage displays a poor repair capacity. The aim of cell-based therapies for cartilage defects is to repair damaged joint surfaces with a functional replacement tissue. Currently, chondrocytes removed from a healthy region of the cartilage are used but they are unable to retain their phenotype in expanded culture. The resulting repair tissue is fibrocartilaginous rather than hyaline, potentially compromising long-term repair. Mesenchymal stem cells, particularly bone marrow stromal cells (BMSC, are of interest for cartilage repair due to their inherent replicative potential. However, chondrocyte differentiated BMSCs display an endochondral phenotype, that is, can terminally differentiate and form a calcified matrix, leading to failure in long-term defect repair. Here, we investigate the isolation and characterisation of a human cartilage progenitor population that is resident within permanent adult articular cartilage. METHODS AND FINDINGS: Human articular cartilage samples were digested and clonal populations isolated using a differential adhesion assay to fibronectin. Clonal cell lines were expanded in growth media to high population doublings and karyotype analysis performed. We present data to show that this cell population demonstrates a restricted differential potential during chondrogenic induction in a 3D pellet culture system. Furthermore, evidence of high telomerase activity and maintenance of telomere length, characteristic of a mesenchymal stem cell population, were observed in this clonal cell population. Lastly, as proof of principle, we carried out a pilot repair study in a goat in vivo model demonstrating the ability of goat cartilage progenitors to form a cartilage-like repair tissue in a chondral defect. CONCLUSIONS: In conclusion, we propose that we have identified and characterised a novel cartilage progenitor population resident in human articular cartilage which will greatly benefit future cell

  19. Effects of Hydrostatic Loading on a Self-Aggregating, Suspension Culture–Derived Cartilage Tissue Analog

    Science.gov (United States)

    Kraft, Jeffrey J.; Jeong, Changhoon; Novotny, John E.; Seacrist, Thomas; Chan, Gilbert; Domzalski, Marcin; Turka, Christina M.; Richardson, Dean W.; Dodge, George R.

    2011-01-01

    Objective: Many approaches are being taken to generate cartilage replacement materials. The goal of this study was to use a self-aggregating suspension culture model of chondrocytes with mechanical preconditioning. Design: Our model differs from others in that it is based on a scaffold-less, self-aggregating culture model that produces a cartilage tissue analog that has been shown to share many similarities with the natural cartilage phenotype. Owing to the known loaded environment under which chondrocytes function in vivo, we hypothesized that applying force to the suspension culture–derived chondrocyte biomass would improve its cartilage-like characteristics and provide a new model for engineering cartilage tissue analogs. Results: In this study, we used a specialized hydrostatic pressure bioreactor system to apply mechanical forces during the growth phase to improve biochemical and biophysical properties of the biomaterial formed. We demonstrated that using this high-density suspension culture, a biomaterial more consistent with the hyaline cartilage phenotype was produced without any foreign material added. Unpassaged chondrocytes responded to a physiologically relevant hydrostatic load by significantly increasing gene expression of critical cartilage molecule collagen and aggrecan along with other cartilage relevant genes, CD44, perlecan, decorin, COMP, and iNOS. Conclusions: This study describes a self-aggregating bioreactor model without foreign material or scaffold in which chondrocytes form a cartilage tissue analog with many features similar to native cartilage. This study represents a promising scaffold-less, methodological advancement in cartilage tissue engineering with potential translational applications to cartilage repair. PMID:26069584

  20. Some Comparative Anatomical and Histological Studies on the Laryngeal Cartilages of Buffaloes, Camels and Donkeys

    Directory of Open Access Journals (Sweden)

    Eman A. Eshra

    2016-01-01

    Full Text Available Comparative studies concerned the upper air ways of domestic animals are few. So this study was carried out to compare between the larynx of buffaloes, camels and donkeys. The present investigation was carried out on 39 larynxes, 13 larynxes (7 males, 6 females of each species. Ten heads from each species were used for gross anatomical study; the remained three heads were used for the histological study. Results revealed that, the laryngeal cartilages of the three species were consisted of three single cartilages; the thyroid, the cricoid and the epiglottis, and two paired cartilages; the arytenoid and the corniculate. The cuneiform cartilages were paired cartilages present only in the larynx of the donkey. Thyroid, arytenoid and cricoid cartilages were of hyaline type, while the epiglottis, cuniform and corniculate cartilages and the vocal process of the arytenoid cartilage were of elastic type. The laryngeal epithelium of aditus laryngis, greater part of epiglottis and vocal folds was lined by non-keratinized stratified squamous epithelium. The remained parts of laryngeal epithelium from base of epiglottis and entire parts caudal to vocal folds were lined by pseudostratified columnar ciliated epithelium with goblet cells. The laryngeal glands of lamina propria were of mixed types in buffaloes and donkeys but in camels it was pure mucous glands. This study will fill a gap in the field of comparative anatomy and help other clinical investigation applied on these animals.

  1. Wavelength-dependent penetration depth of near infrared radiation into cartilage.

    Science.gov (United States)

    Padalkar, M V; Pleshko, N

    2015-04-07

    Articular cartilage is a hyaline cartilage that lines the subchondral bone in the diarthrodial joints. Near infrared (NIR) spectroscopy is emerging as a nondestructive modality for the evaluation of cartilage pathology; however, studies regarding the depth of penetration of NIR radiation into cartilage are lacking. The average thickness of human cartilage is about 1-3 mm, and it becomes even thinner as OA progresses. To ensure that spectral data collected is restricted to the tissue of interest, i.e. cartilage in this case, and not from the underlying subchondral bone, it is necessary to determine the depth of penetration of NIR radiation in different wavelength (frequency) regions. In the current study, we establish how the depth of penetration varies throughout the NIR frequency range (4000-10 000 cm(-1)). NIR spectra were collected from cartilage samples of different thicknesses (0.5 mm to 5 mm) with and without polystyrene placed underneath. A separate NIR spectrum of polystyrene was collected as a reference. It was found that the depth of penetration varied from ∼1 mm to 2 mm in the 4000-5100 cm(-1) range, ∼3 mm in the 5100-7000 cm(-1) range, and ∼5 mm in the 7000-9000 cm(-1) frequency range. These findings suggest that the best NIR region to evaluate cartilage with no subchondral bone contribution is in the range of 4000-7000 cm(-1).

  2. Use of Adult Stem Cells for Cartilage Tissue Engineering: Current Status and Future Developments

    Directory of Open Access Journals (Sweden)

    Catherine Baugé

    2015-01-01

    Full Text Available Due to their low self-repair ability, cartilage defects that result from joint injury, aging, or osteoarthritis, are the most often irreversible and are a major cause of joint pain and chronic disability. So, in recent years, researchers and surgeons have been working hard to elaborate cartilage repair interventions for patients who suffer from cartilage damage. However, current methods do not perfectly restore hyaline cartilage and may lead to the apparition of fibro- or hypertrophic cartilage. In the next years, the development of new strategies using adult stem cells, in scaffolds, with supplementation of culture medium and/or culture in low oxygen tension should improve the quality of neoformed cartilage. Through these solutions, some of the latest technologies start to bring very promising results in repairing cartilage from traumatic injury or chondropathies. This review discusses the current knowledge about the use of adult stem cells in the context of cartilage tissue engineering and presents clinical trials in progress, as well as in the future, especially in the field of bioprinting stem cells.

  3. Biliary atresia with hyaline cartilage at the porta hepatis: a novel ...

    African Journals Online (AJOL)

    Biliary atresia is an important cause of liver disease and morbidity in infants with ... hypoglycemia, nocturnal feed, constipation, or previous hospitalization was present. ... A clinical diagnosis of neonatal cholestasis (BA) was considered.

  4. Aging histological changes in the cartilages of the cricoarytenoid joint

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    Dedivitis Rogério Aparecido

    2004-01-01

    Full Text Available PURPOSE: Analysis of ossification, bone marrow formation, perichondrium thickness, muscle fibers, collagen fibers and elastic fibers quantities of cricoid and arytenoid cartilages. Design: Correlation morphologic study. METHODS: Twenty-four cricoarytenoid joints were obtained from Caucasian male fresh cadavers divided into three groups with eight specimens in each: group I - adolescents, from 15 to 20; group II - adults, from 25 to 35; and group III - elderly, from 60 to 75. The specimens were stained with H-E; trichrome; Picrosirius; and elastic stain. Histometry was performed for quantitative analysis. Bonferroni Test, Fisher Test and the Variance Analysis were used. RESULTS: At the microscopic analysis, the group I specimens presented typical hyaline cartilage, thin perichondrium, bulky muscle fibers and were surrounded by collagen fibers. In group II, there were ossification in small well defined central areas of four specimens, with lamellar bone tissue. In two of these cases there were central bone cavity full of fat tissue. The other parameters were similar to group I. In group III, most part of hyaline cartilage was replaced by typical lamellar bone tissue with poorly outlined haversian systems. Hematopoietic tissue was noted in six cases and fat tissue in the other two. Perichondrium was thicker. Small muscle fibers were smaller and surrounded by collagen in great quantity. Elastic fibers were present in small quantity in the outer portion of perichondrium in all the groups. CONCLUSIONS: In spite of its lack in adolescence, ossification occurs in cricoid and arytenoid cartilages during adulthood and intensifies with age; bone marrow is formed in ossification tissue with hematopoietic tissue in group III; perichondrium becomes thicker in group III; muscle tissue atrophies in group III and is replaced by collagen fibers; these fibers thicken with age; and elastic fibers is always present in the perichondrium in low quantity.

  5. Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures

    OpenAIRE

    Lo Monaco, Melissa; Merckx, Greet; Ratajczak, Jessica; Gervois, Pascal; Hilkens, Petra; Clegg, Peter; Bronckaers, Annelies; Vandeweerd, Jean-Michel; Lambrichts, Ivo

    2018-01-01

    Due to the restricted intrinsic capacity of resident chondrocytes to regenerate the lost cartilage postinjury, stem cell-based therapies have been proposed as a novel therapeutic approach for cartilage repair. Moreover, stem cell-based therapies using mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been used successfully in preclinical and clinical settings. Despite these promising reports, the exact mechanisms underlying stem cell-mediated cartilage repair remain...

  6. Effects of Platelet-Rich Plasma & Platelet-Rich Fibrin with and without Stromal Cell-Derived Factor-1 on Repairing Full-Thickness Cartilage Defects in Knees of Rabbits

    Directory of Open Access Journals (Sweden)

    Soghra Bahmanpour

    2016-11-01

    Full Text Available Background: The purpose of this study was to create biomaterial scaffolds like platelet-rich plasma (PRP and platelet-rich fibrin (PRF containing stromal cell-derived factor-1 (SDF1 as a chemokine to induce hyaline cartilage regeneration of rabbit knee in a full thickness defect. Methods: We created a full thickness defect in the trochlear groove of thirty-six bilateral knees of eighteen mature male rabbits. The knees were randomly divided into six groups (group I: untreated control, group II: PRP, group III: PRF, group IV: Gelatin+SDF1, group V: PRP+SDF1, and group VI: PRF+SDF1. After four weeks, the tissue specimens were evaluated by macroscopic examination and histological grading, immunofluorescent staining for collagen type II, and analyzed for cartilage marker genes by real-time PCR. The data were compared using statistical methods (SPSS 20, Kruskal-Wallis test, Bonferroni post hoc test and P<0.05. Results: Macroscopic evaluations revealed that international cartilage repair society (ICRS scores of the PRF+SDF1 group were higher than other groups. Microscopic analysis showed that the ICRS score of the PRP group was significantly lower than other groups. Immunofluorescent staining for collagen II demonstrated a remarkable distribution of type II collagen in the Gel+SDF1, PRP+SDF1 and PRF+SDF1 groups compared with other groups. Real-time PCR analysis revealed that mRNA expression of SOX9 and aggrecan were significantly greater in the PRF+SDF1, PRP+SDF1, Gel+SDF1 and PRF groups than the control group (P<0.05. Conclusion: Our results indicate that implantation of PRF scaffold containing SDF1 led to the greatest evaluation scores of full-thickness lesions in rabbits.

  7. β1 Integrins Mediate Attachment of Mesenchymal Stem Cells to Cartilage Lesions

    NARCIS (Netherlands)

    D. Zwolanek (Daniela); M. Flicker (Magdalena); E. Kirstätter (Elisabeth); F. Zaucke (Frank); G.J.V.M. van Osch (Gerjo); R.G. Erben (Reinhold)

    2015-01-01

    textabstractMesenchymal stem cells (MSC) may have great potential for cell-based therapies of osteoarthritis. However, after injection in the joint, only few cells adhere to defective articular cartilage and contribute to cartilage regeneration. Little is known about the molecular mechanisms of MSC

  8. Radiological, computertomographic, pathoanatomical and histological examination of the rib cartilage of the dog

    International Nuclear Information System (INIS)

    Lorber, B.

    2000-06-01

    This study was concerned with the representation and description of the rib cartilage of the dog and the abnormalities of such by means of radiological, computer tomographic, pathoanatomical and histological examinations and the comparison of the results of the various examination methods. The study material consisted of 100 ventral thorax walls of dogs of different ages and breeds. In 39 of the subjects, no abnormalities of rib cartilage other than unremarkable calcification were observed. Among the subjects, there were 11 puppies (0-3 months), whose rib cartilage appeared soft tissue dense due to the absence of calcification, 14 juvenile animals (4-18 months), the rib cartilage of which showed a typical finely granulated structure, and 14 adult dogs (over 18 months), whose rib cartilage exhibited a homogeneous to net-like calcified appearance. In the calcified rib cartilage, the histological section showed a centrally located spongiosa rod surrounded by a hyaline cartilage shell. The calcification tendency of the first pair of rib cartilage was remarkable: in 70 dogs, the first pair of rib cartilage remained uncalcified despite calcification of the other rib cartilage. Sixty-one dogs exhibited rib cartilage abnormalities. According to the radiological appearance of the abnormalities, they were divided into groups and their incidence was calculated. Abnormalities seen included interruption in the continuity of the calcified rib cartilage with and without callus formation, enlargement of rib cartilage, cuff formation, and abnormalities on the Articulationes sternocostales (projections in or around articulations, calcified and fractured joint surfaces). In addition, remarkable calcification patterns were observed. By means of CT examination the densities of the tissue forming the various abnormalities was determined. In the course of the pathoanatomical examination, it was shown that the interruptions in continuity with callus and the various enlarged areas of the

  9. [Multicentric hyaline vascular Castleman's disease. A POEMS type variant].

    Science.gov (United States)

    Gracia-Ramos, Abraham Edgar; Cruz-Domínguez, María del Pilar; Vera-Lastra, Olga Lidia

    2013-01-01

    Castleman's disease is an atypical lymphoproliferative disorder which may be compatible with paraneoplastic manifestations of POEMS syndrome. a 53 year old man with a history of type 2 diabetes, hypothyroidism and Addison's disease presented with numbness and weakness in limbs, dyspnea, skin hardening, Raynaud's phenomenon, weight loss and fatigue. A physical exam showed tachypnea, generalized cutaneous hyperpigmentation and skin hardening of extremities, muscle weakness, hypoesthesia and hyporeflexia. Laboratory showed hyperprolactinemia, low testosterone, hypothyroidism and Addison's disease. Electrophoresis of proteins showed polyclonal hypergammaglobulinemia. Somatosensory evoked potentials reported peripheral neuropathy and severe axonal polyneuropathy by electromyography. Chest X-rays showed bilateral reticular infiltrates and mediastinal widening. An echocardiogram displayed moderate pulmonary hypertension. Skin biopsy had no evidence of scleroderma. CT reported axillar, mediastinal and retroperitoneal nodes. The mediastinal lesion biopsy reported hyaline vascular Castleman's disease, multicentric variety. He was treated with rituximab. the case meet criteria for multicentric hyaline vascular Castleman's disease, POEMS variant, treated with rituximab.

  10. A Hyalinized Trichilemmoma of the Eyelid in a Teenager.

    Science.gov (United States)

    Jakobiec, Frederick A; Stagner, Anna M; Sassoon, Jodi; Goldstein, Scott; Mihm, Martin C

    2016-01-01

    A 16-year-old African American male, the youngest patient to date, presented with a well-circumscribed upper eyelid lesion. On excision, the dermal nodule was contiguous with the epidermis, displayed trichohyalin-like bodies in an expanded outer root sheath, and was composed chiefly of small cellular clusters separated by a prominent network of periodic acid Schiff -positive hyaline bands of basement membrane material. The tumor cells were positive for high molecular weight cytokeratins (CK) 5/6, CK14, and CK34βE12 and were negative for CK7, carcinoembryonic antigen and epithelial membrane antigen. Negative S100, glial fibrillary acidic protein, and smooth muscle actin immunoreactions ruled out a myoepithelial lesion. The Ki-67 proliferation index was <10%. The diagnosis was a hyalinized trichilemmoma, contrasting with the more common lobular type. As an isolated lesion, trichilemmoma does not portend Cowden syndrome.

  11. Pulmonary hyalinizing granuloma and retroperitoneal fibrosis in an adolescent

    International Nuclear Information System (INIS)

    Young, Adam S.; Binkovitz, Larry A.; Adler, Brent H.; Nicol, Kathleen K.; Rennebohm, Robert M.

    2007-01-01

    We describe a 15-year-old boy who developed pulmonary hyalinizing granuloma (PHG) and retroperitoneal fibrosis (RPF). His PHG and RPF were not associated with histoplasmosis or tuberculosis and appeared to represent idiopathic autoimmune phenomena. This is the first reported case of PHG in a pediatric patient and the fourth reported co-occurrence of PHG and RPF. The use of F-18 fluorodeoxyglucose positron emission tomography in the diagnostic and follow-up evaluation of PHG is reported. (orig.)

  12. Pulmonary hyalinizing granuloma and retroperitoneal fibrosis in an adolescent

    Energy Technology Data Exchange (ETDEWEB)

    Young, Adam S.; Binkovitz, Larry A.; Adler, Brent H. [Columbus Children' s Hospital, Children' s Radiological Institute, Columbus, OH (United States); Nicol, Kathleen K. [Columbus Children' s Hospital, Department of Pathology, Columbus, OH (United States); Rennebohm, Robert M. [Columbus Children' s Hospital, Department of Rheumatology, Columbus, OH (United States)

    2007-01-15

    We describe a 15-year-old boy who developed pulmonary hyalinizing granuloma (PHG) and retroperitoneal fibrosis (RPF). His PHG and RPF were not associated with histoplasmosis or tuberculosis and appeared to represent idiopathic autoimmune phenomena. This is the first reported case of PHG in a pediatric patient and the fourth reported co-occurrence of PHG and RPF. The use of F-18 fluorodeoxyglucose positron emission tomography in the diagnostic and follow-up evaluation of PHG is reported. (orig.)

  13. Hyalinizing Granuloma: An Unusual Case of a Pulmonary Mass

    Directory of Open Access Journals (Sweden)

    Viviane Brandão

    2010-01-01

    Full Text Available We describe the case of pulmonary hyalinizing granuloma in a 34-year-old asymptomatic man who presented with a pulmonary nodule apparent by chest radiography and computed tomography (CT. He had a history of previous treatment for tuberculosis. His laboratory data were normal. Bronchoscopy and CT-guided percutaneous transthoracic fine needle aspiration cytology were inconclusive. The diagnosis was revealed after the histopathological examination of an open lung biopsy.

  14. Pulmonary Hyalinizing Granuloma Associated with Idiopathic Thrombocytopenic Purpura

    Directory of Open Access Journals (Sweden)

    Christopher Coleman

    2014-01-01

    Full Text Available Pulmonary hyalinizing granuloma (PHG is a rare, benign lung disease of unknown etiology. It manifests as discrete, rounded nodules within the lung parenchyma. A 39-year-old woman presented for investigation after pulmonary nodules were found incidentally. Chest computed tomography showed multiple, discrete, non-enhancing pulmonary nodules bilaterally. Positron emission tomography (PET was negative. Biopsy demonstrated a non-specific lymphoplasmacytic infiltrate. Open resection yielded two nodules consistent with hyalinizing granulomas. The differential for multiple pulmonary nodules is broad. PET scan can help rule out metastatic disease, although some cancers are not hypermetabolic on PET. Furthermore, some non-malignant conditions, including hyalinizing granuloma, can show increased activity on PET. PHG should be included in the differential of multiple pulmonary nodules, especially if nodule stability can be demonstrated and/or needle biopsies are non-diagnostic. Associated immune-mediated conditions, such as idiopathic thrombocytopenic purpura (ITP in our patient, may also favor HG. In this case report we find an association between PHG and ITP.

  15. Three new species of Trichoderma with hyaline ascospores from China.

    Science.gov (United States)

    Zhu, Z X; Zhuang, W Y

    2015-01-01

    Collections of Trichoderma having hyaline ascospores from different areas of China were examined. Using combined analyses of morphological data, culture characters and phylogenetic information based on rDNA sequences of partial nuc translation elongation factor 1-α encoding gene (TEF1-α) and the gene encoding the second largest nuc RNA polymerase subunit (RPB2), three new species, Trichoderma applanatum, T. oligosporum and T. sinoluteum, were discovered and are described. Trichoderma applanatum produces continuous flat to pulvinate, white to cream stromata with dense orange or pale brown ostioles, and simple acremonium-like to verticillium-like conidiophores, belongs to the Hypocreanum clade and is closely related to T. decipiens. Trichoderma oligosporum forms reddish brown stromata with a downy surface, hyaline conidia and gliocladium-like conidiophores, and is closely related to but distinct from T. crystalligenum in the Psychrophila clade. Trichoderma sinoluteum, as a member of the Polysporum clade, is characterized by pale yellow stromata, white pustulate conidiomata, pachybasium-like conidiophores, and hyaline conidia. Differences between the new species and their close relatives are discussed. © 2015 by The Mycological Society of America.

  16. Mechanical testing of hydrogels in cartilage tissue engineering: beyond the compressive modulus.

    Science.gov (United States)

    Xiao, Yinghua; Friis, Elizabeth A; Gehrke, Stevin H; Detamore, Michael S

    2013-10-01

    Injuries to articular cartilage result in significant pain to patients and high medical costs. Unfortunately, cartilage repair strategies have been notoriously unreliable and/or complex. Biomaterial-based tissue-engineering strategies offer great promise, including the use of hydrogels to regenerate articular cartilage. Mechanical integrity is arguably the most important functional outcome of engineered cartilage, although mechanical testing of hydrogel-based constructs to date has focused primarily on deformation rather than failure properties. In addition to deformation testing, as the field of cartilage tissue engineering matures, this community will benefit from the addition of mechanical failure testing to outcome analyses, given the crucial clinical importance of the success of engineered constructs. However, there is a tremendous disparity in the methods used to evaluate mechanical failure of hydrogels and articular cartilage. In an effort to bridge the gap in mechanical testing methods of articular cartilage and hydrogels in cartilage regeneration, this review classifies the different toughness measurements for each. The urgency for identifying the common ground between these two disparate fields is high, as mechanical failure is ready to stand alongside stiffness as a functional design requirement. In comparing toughness measurement methods between hydrogels and cartilage, we recommend that the best option for evaluating mechanical failure of hydrogel-based constructs for cartilage tissue engineering may be tensile testing based on the single edge notch test, in part because specimen preparation is more straightforward and a related American Society for Testing and Materials (ASTM) standard can be adopted in a fracture mechanics context.

  17. Multinuclear nuclear magnetic resonance spectroscopic study of cartilage proteoglycans

    Energy Technology Data Exchange (ETDEWEB)

    Lerner, L.

    1985-01-01

    Hyaline cartilage is a composite material whose major function is to withstand compression while retaining flexibility. Its mechanical properties are affected by tissue hydration and ionic composition. Models of the mechanical behavior of cartilage have incorporated certain assumptions about the interactions of the major components of cartilage: collagen, proteoglycans, water, and cations. To determine the validity of these assumption, the authors have used nuclear magnetic resonance spectroscopy (NMR). Two approaches have been used: (a) natural abundance carbon-13 NMR; and (b) NMR of sodium-23, potassium-39, magnesium-25, and calcium-43. Evidence from studies in intact tissues are reinforced by extensive measurements on solutions of proteoglycans and other relevant macromolecules. Based on the measurements of NMR relaxation rates and lineshapes reported here, it is concluded that neither sodium nor potassium interact strongly with bovine nasal proteoglycan aggregates or their substituent glycosaminoglycan chains in solution. Proteoglycans do bind magnesium and calcium. Therefore there is a qualitative difference between monovalent and divalent cations, which is not taken into account by polyelectrolyte models or models for the ionic dependence of mechanical properties. Cation binding to heparin, which has a higher charge density than cartilage proteoglycans, was also studied. The results presented here establish that heparin binds sodium, magnesium, and calcium.

  18. Photoshop-based image analysis of canine articular cartilage after subchondral damage.

    Science.gov (United States)

    Lahm, A; Uhl, M; Lehr, H A; Ihling, C; Kreuz, P C; Haberstroh, J

    2004-09-01

    The validity of histopathological grading is a major problem in the assessment of articular cartilage. Calculating the cumulative strength of signal intensity of different stains gives information regarding the amount of proteoglycan, glycoproteins, etc. Using this system, we examined the medium-term effect of subchondral lesions on initially healthy articular cartilage. After cadaver studies, an animal model was created to produce pure subchondral damage without affecting the articular cartilage in 12 beagle dogs under MRI control. Quantification of the different stains was provided using a Photoshop-based image analysis (pixel analysis) with the histogram command 6 months after subchondral trauma. FLASH 3D sequences revealed intact cartilage after impact in all cases. The best detection of subchondral fractures was achieved with fat-suppressed TIRM sequences. Semiquantitative image analysis showed changes in proteoglycan and glycoprotein quantities in 9 of 12 samples that had not shown any evidence of damage during the initial examination. Correlation analysis showed a loss of the physiological distribution of proteoglycans and glycoproteins in the different zones of articular cartilage. Currently available software programs can be applied for comparative analysis of histologic stains of hyaline cartilage. After subchondral fractures, significant changes in the cartilage itself occur after 6 months.

  19. Supramolecular Organization of Collagen Fibrils in Healthy and Osteoarthritic Human Knee and Hip Joint Cartilage.

    Directory of Open Access Journals (Sweden)

    Riccardo Gottardi

    Full Text Available Cartilage matrix is a composite of discrete, but interacting suprastructures, i.e. cartilage fibers with microfibrillar or network-like aggregates and penetrating extrafibrillar proteoglycan matrix. The biomechanical function of the proteoglycan matrix and the collagen fibers are to absorb compressive and tensional loads, respectively. Here, we are focusing on the suprastructural organization of collagen fibrils and the degradation process of their hierarchical organized fiber architecture studied at high resolution at the authentic location within cartilage. We present electron micrographs of the collagenous cores of such fibers obtained by an improved protocol for scanning electron microscopy (SEM. Articular cartilages are permeated by small prototypic fibrils with a homogeneous diameter of 18 ± 5 nm that can align in their D-periodic pattern and merge into larger fibers by lateral association. Interestingly, these fibers have tissue-specific organizations in cartilage. They are twisted ropes in superficial regions of knee joints or assemble into parallel aligned cable-like structures in deeper regions of knee joint- or throughout hip joints articular cartilage. These novel observations contribute to an improved understanding of collagen fiber biogenesis, function, and homeostasis in hyaline cartilage.

  20. Degeneration of osteoarthritis cartilage

    DEFF Research Database (Denmark)

    Jørgensen, Dan Richter

    of sensitive biomarkers for monitoring disease progression. This thesis investigates how subregional measures of cartilage thickness can be used to improve upon current imaging biomarkers. The first part of this investigation aims to discover discriminative areas in the cartilage using machine......-learning techniques specifically developed to take advantage of the spatial nature of the problem. The methods were evaluated on data from a longitudinal study where detailed cartilage thickness maps were quantified from magnetic resonance images. The results showed that focal differences in cartilage thickness may...... be relevant for both OA diagnosis and for prediction of future cartilage loss. The second part of the thesis investigates spatial patterns of longitudinal cartilage thickness changes in healthy and OA knees. Based on our findings, we propose a new, conceptually simple biomarker that embraces the heterogeneous...

  1. MR microscopy of articular cartilage at 1.5 T: orientation and site dependence of laminar structures

    Energy Technology Data Exchange (ETDEWEB)

    Yoshioka, Hiroshi; Anno, Izumi; Echigo, Junko; Itai, Yuji [Department of Radiology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575 (Japan); Haishi, Tomoyuki; Uematsu, Takaaki; Matsuda, Yoshimasa; Kose, Katsumi [Institute of Applied Physics, University of Tsukuba, Tsukuba (Japan); Lang, Philipp [Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States)

    2002-09-01

    Abstract Objective. To evaluate MR microscopic images of normal-appearing porcine hyaline cartilage (n=15) in vitro obtained with an MR microscope using an independent console system (MRMICS) at 1.5 T.Design and results. The MRMICS is a portable imaging system consisting of a radiofrequency system, gradient power supplies and a personal computer. The images from the MRMICS showed a laminar structure of porcine cartilage similar to the structure demonstrated with other MR imaging techniques. The laminar structures of the articular cartilage, were, however heterogeneous in respect of signal intensity and thickness, which varied according to the site resected. The MR laminar appearance was most comparable to the staining with Masson's trichrome for collagen.Conclusion. MRMICS is a useful add-on system for obtaining microscopic MR images of articular cartilage in vitro. (orig.)

  2. MR microscopy of articular cartilage at 1.5 T: orientation and site dependence of laminar structures

    International Nuclear Information System (INIS)

    Yoshioka, Hiroshi; Anno, Izumi; Echigo, Junko; Itai, Yuji; Haishi, Tomoyuki; Uematsu, Takaaki; Matsuda, Yoshimasa; Kose, Katsumi; Lang, Philipp

    2002-01-01

    Abstract Objective. To evaluate MR microscopic images of normal-appearing porcine hyaline cartilage (n=15) in vitro obtained with an MR microscope using an independent console system (MRMICS) at 1.5 T.Design and results. The MRMICS is a portable imaging system consisting of a radiofrequency system, gradient power supplies and a personal computer. The images from the MRMICS showed a laminar structure of porcine cartilage similar to the structure demonstrated with other MR imaging techniques. The laminar structures of the articular cartilage, were, however heterogeneous in respect of signal intensity and thickness, which varied according to the site resected. The MR laminar appearance was most comparable to the staining with Masson's trichrome for collagen.Conclusion. MRMICS is a useful add-on system for obtaining microscopic MR images of articular cartilage in vitro. (orig.)

  3. Thermosensitive hydrogels for 3D bioprinting of cartilage constructs

    NARCIS (Netherlands)

    Abbadessa, A.

    2017-01-01

    Tissue engineering (TE) aims to regenerate damaged tissues by the combined use of biomaterials and cells, often in presence of bioactive molecules, such as growth factors. Particularly for tissues with poor regenerative capacity, such as articular cartilage, TE approaches may lead to promising

  4. Effect of histone deacetylase inhibitor, trichostatin A, on cartilage ...

    African Journals Online (AJOL)

    Purpose: To evaluate the effect of histone deacetylase (HDAC) inhibitor, trichostatin A (TCA), on cartilage regeneration in a rabbit perichondrial graft model. Methods: Perichondrial grafts (20 × 20 mm2) were derived from the ears of New Zealand rabbits and transplanted onto the paravertebral muscle of the face of each ...

  5. Hyperinnervation improves Xenopus laevis limb regeneration.

    Science.gov (United States)

    Mitogawa, Kazumasa; Makanae, Aki; Satoh, Akira

    2018-01-15

    Xenopus laevis (an anuran amphibian) shows limb regeneration ability between that of urodele amphibians and that of amniotes. Xenopus frogs can initiate limb regeneration but fail to form patterned limbs. Regenerated limbs mainly consist of cone-shaped cartilage without any joints or branches. These pattern defects are thought to be caused by loss of proper expressions of patterning-related genes. This study shows that hyperinnervation surgery resulted in the induction of a branching regenerate. The hyperinnervated blastema allows the identification and functional analysis of the molecules controlling this patterning of limb regeneration. This paper focuses on the nerve affects to improve Xenopus limb patterning ability during regeneration. The nerve molecules, which regulate limb patterning, were also investigated. Blastemas grown in a hyperinnervated forelimb upregulate limb patterning-related genes (shh, lmx1b, and hoxa13). Nerves projecting their axons to limbs express some growth factors (bmp7, fgf2, fgf8, and shh). Inputs of these factors to a blastema upregulated some limb patterning-related genes and resulted in changes in the cartilage patterns in the regenerates. These results indicate that additional nerve factors enhance Xenopus limb patterning-related gene expressions and limb regeneration ability, and that bmp, fgf, and shh are candidate nerve substitute factors. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. In Vitro Expression of the Extracellular Matrix Components Aggrecan, Collagen Types I and II by Articular Cartilage-Derived Chondrocytes.

    Science.gov (United States)

    Schneevoigt, J; Fabian, C; Leovsky, C; Seeger, J; Bahramsoltani, M

    2017-02-01

    The extracellular matrix (ECM) of hyaline cartilage is perfectly suited to transmit articular pressure load to the subchondral bone. Pressure is transferred by a high amount of aggrecan-based proteoglycans and collagen type II fibres in particular. After any injury, the hyaline cartilage is replaced by fibrocartilage, which is low in proteoglycans and contains collagen type I predominantly. Until now, long-term results of therapeutic procedures including cell-based therapies like autologous chondrocyte transplantation (ACT) lead to a replacement tissue meeting the composition of fibrocartilage. Therefore, it is of particular interest to discover how and to what extent isolation and in vitro cultivation of chondrocytes affect the cells and their expression of ECM components. Hyaline cartilage-derived chondrocytes were cultivated in vitro and observed microscopically over a time period of 35 days. The expression of collagen type I, collagen type II and aggrecan was analysed using RT-qPCR and Western blot at several days of cultivation. Chondrocytes presented a longitudinal shape for the entire cultivation period. While expression of collagen type I prevailed within the first days, only prolonged cultivation led to an increase in collagen type II and aggrecan expression. The results indicate that chondrocyte isolation and in vitro cultivation lead to a dedifferentiation at least to the stage of chondroprogenitor cells. © 2016 Blackwell Verlag GmbH.

  7. Advances in Application of Mechanical Stimuli in Bioreactors for Cartilage Tissue Engineering.

    Science.gov (United States)

    Li, Ke; Zhang, Chunqiu; Qiu, Lulu; Gao, Lilan; Zhang, Xizheng

    2017-08-01

    Articular cartilage (AC) is the weight-bearing tissue in diarthroses. It lacks the capacity for self-healing once there are injuries or diseases due to its avascularity. With the development of tissue engineering, repairing cartilage defects through transplantation of engineered cartilage that closely matches properties of native cartilage has become a new option for curing cartilage diseases. The main hurdle for clinical application of engineered cartilage is how to develop functional cartilage constructs for mass production in a credible way. Recently, impressive hyaline cartilage that may have the potential to provide capabilities for treating large cartilage lesions in the future has been produced in laboratories. The key to functional cartilage construction in vitro is to identify appropriate mechanical stimuli. First, they should ensure the function of metabolism because mechanical stimuli play the role of blood vessels in the metabolism of AC, for example, acquiring nutrition and removing wastes. Second, they should mimic the movement of synovial joints and produce phenotypically correct tissues to achieve the adaptive development between the micro- and macrostructure and function. In this article, we divide mechanical stimuli into three types according to forces transmitted by different media in bioreactors, namely forces transmitted through the liquid medium, solid medium, or other media, then we review and summarize the research status of bioreactors for cartilage tissue engineering (CTE), mainly focusing on the effects of diverse mechanical stimuli on engineered cartilage. Based on current researches, there are several motion patterns in knee joints; but compression, tension, shear, fluid shear, or hydrostatic pressure each only partially reflects the mechanical condition in vivo. In this study, we propose that rolling-sliding-compression load consists of various stimuli that will represent better mechanical environment in CTE. In addition, engineers

  8. Priority of surgical treatment techniques of full cartilage defects of knee joint

    Directory of Open Access Journals (Sweden)

    Андрій Вікторович Літовченко

    2015-10-01

    Full Text Available Aim. Surgical treatment of chondromalacia of knee joint cartilage is an actual problem of the modern orthopedics because the means of conservative therapy can be realized at an initial stage only and almost exhausted at the further ones. Imperfections of palliative surgical techniques are the short-term clinical effect and pathogenetic baselessness because surgical procedure is not directed on reparation of cartilaginous tissue. For today there are a lot of transplantation techniques that are used for biological renewal of articular surface with formation of hyaline or at least hyaline-like cartilage. The deep forage of cartilage defect bottom to the medullary canal is a perspective and priority technique.Methods. The results of treatment of 61 patients with chondromalacia of knee joint of 3-4 degree according to R. Outerbridge are the base of the work. 20 patients of every group underwent microfracturization of cartilage defect bottom and subchondral forage of defect zone. 21 patients underwent the deep forage of defect zone of knee joint according to an offered technique.Result. The results of treatment with microfracturization, subchondral forage and deep forage of defect zone indicate the more strong clinical effect especially in the last clinical group where good and satisfactory results ratios in the term of observation 18 and 24 month remain stable.Conclusions. Deep forage of cartilage defects zone is the most adequate reparative technique of the surgical treatment of local knee joint cartilage defects. Owing to this procedure the number of cells of reparative chondrogenesis predecessors is realized

  9. Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.

    Science.gov (United States)

    Mumme, Marcus; Barbero, Andrea; Miot, Sylvie; Wixmerten, Anke; Feliciano, Sandra; Wolf, Francine; Asnaghi, Adelaide M; Baumhoer, Daniel; Bieri, Oliver; Kretzschmar, Martin; Pagenstert, Geert; Haug, Martin; Schaefer, Dirk J; Martin, Ivan; Jakob, Marcel

    2016-10-22

    Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm 2 ) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of

  10. Repair of full-thickness articular cartilage defect using stem cell-encapsulated thermogel.

    Science.gov (United States)

    Zhang, Yanbo; Zhang, Jin; Chang, Fei; Xu, Weiguo; Ding, Jianxun

    2018-07-01

    Cartilage defect repair by hydrogel-based tissue engineering is becoming one of the most potential treatment strategies. In this work, a thermogel of triblock copolymer poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) was prepared as scaffold of bone marrow mesenchymal stem cells (BMMSCs) for repair of full-thickness articular cartilage defect. At first, the copolymer solution showed a reversible sol-gel transition at physiological temperature range, and the mechanical properties of such thermogel were high enough to support the repair of cartilage. Additionally, excellent biodegradability and biocompatibility of the thermogel were demonstrated. By implanting the BMMSC-encapsulated thermogel into the full-thickness articular cartilage defect (5.0 mm in diameter and 4.0 mm in depth) in the rabbit, it was found that the regenerated cartilage integrated well with the surrounding normal cartilage and subchondral bone at 12 weeks post-surgery. The upregulated expression of glycosaminoglycan and type II collagen in the repaired cartilage, and the comparable biomechanical properties with normal cartilage suggested that the cell-encapsulated PLGA-PEG-PLGA thermogel had great potential in serving as the promising scaffold for cartilage regeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Cryogenic regenerators

    International Nuclear Information System (INIS)

    Kush, P.; Joshi, S.C.; Thirumaleshwar, M.

    1986-01-01

    Importance of regenerators in cryogenic refrigerators is highlighted. Design aspects of regenerator are reviewed and the factors involved in the selection of regenerator material are enumerated. Various methods used to calculate the heat transfer coefficient and regenerator effectiveness are mentioned. Variation of effectiveness with various parameters is calculated by a computer programme using the ideal, Ackermann and Tipler formulae. Results are presented in graphical form. Listing of the computer programme is given in the Appendix. (author)

  12. Analysis of human knee osteoarthritic cartilage using polarization sensitive second harmonic generation microscopy

    Science.gov (United States)

    Kumar, Rajesh; Grønhaug, Kirsten M.; Romijn, Elisabeth I.; Drogset, Jon O.; Lilledahl, Magnus B.

    2014-05-01

    Osteoarthritis is one of the most prevalent joint diseases in the world. Although the cause of osteoarthritis is not exactly clear, the disease results in a degradation of the quality of the articular cartilage including collagen and other extracellular matrix components. We have investigated alterations in the structure of collagen fibers in the cartilage tissue of the human knee using mulitphoton microscopy. Due to inherent high nonlinear susceptibility, ordered collagen fibers present in the cartilage tissue matrix produces strong second harmonic generation (SHG) signals. Significant morphological differences are found in different Osteoarthritic grades of cartilage by SHG microscopy. Based on the polarization analysis of the SHG signal, we find that a few locations of hyaline cartilage (mainly type II collagen) is being replaced by fibrocartilage (mainly type I cartilage), in agreement with earlier literature. To locate the different types and quantify the alteration in the structure of collagen fiber, we employ polarization-SHG microscopic analysis, also referred to as _-tensor imaging. The image analysis of p-SHG image obtained by excitation polarization measurements would represent different tissue constituents with different numerical values at pixel level resolution.

  13. Biomechanical signals guiding stem cell cartilage engineering: from molecular adaption to tissue functionality

    Directory of Open Access Journals (Sweden)

    Y Zhang

    2016-01-01

    Full Text Available In vivo cartilage is in a state of constant mechanical stimulation. It is therefore reasonable to deduce that mechanical forces play an important role in cartilage formation. Mechanical forces, such as compression, tension, and shear force, have been widely applied for cartilage engineering; however, relatively few review papers have summarized the influence of biomechanical signals on stem cell-based neo-cartilage formation and cartilage engineering in both molecular adaption and tissue functionality. In this review, we will discuss recent progress related to the influences of substrate elasticity on stem cell chondrogenic differentiation and elucidate the potential underlying mechanisms. Aside from active sensing and responding to the extracellular environment, stem cells also could respond to various external mechanical forces, which also influence their chondrogenic capacity; this topic will be updated along with associated signaling pathways. We expect that these different regimens of biomechanical signals can be utilized to boost stem cell-based cartilage engineering and regeneration.

  14. Human articular cartilage: in vitro correlation of MRI and histologic findings

    International Nuclear Information System (INIS)

    Uhl, M.; Allmann, K.H.; Laubenberger, J.; Langer, M.; Ihling, C.; Tauer, U.; Adler, C.P.

    1998-01-01

    zone correlated weakly to the accumulation of proteoglycans in the radial zone. The trilaminar MRI appearance of the cartilage was only visible when the cartilage was thicker than 2 mm. In cartilage degeneration, we found either a diffuse thinning of all layers or circumscribed lesions (''cartilage ulcer'') of these cartilage layers in the MR images. Early cartilage degeneration was indicated by a signal loss in the superficial zone, correlating to the histologically proven damage of proteoglycans in the transitional and radial zone along with destruction of the superficial zone. We found a strong effect of cartilage rotation in the main magnetic field, too. A rotation of the cartilage structures caused considerable variation in the signal intensity of the second lamina. Cartilage segments in a 55 angle to the magnetic main field had a homogeneous appearance, not a trilaminar appearance. The signal behavior of hyaline articular cartilage does not reflect the laminar histologic structure. Osteoarthrosis and cartilage degeneration are visible on MR images as intracartilaginous signal changes, superficial erosions, diffuse cartilage thinning, and cartilage ulceration. (orig.)

  15. Human articular cartilage: in vitro correlation of MRI and histologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Uhl, M.; Allmann, K.H.; Laubenberger, J.; Langer, M. [Department of Diagnostic Radiology, University Hospital of Freiburg (Germany); Ihling, C.; Tauer, U.; Adler, C.P. [Department of Pathology, University Hospital of Freiburg (Germany)

    1998-09-01

    zone correlated weakly to the accumulation of proteoglycans in the radial zone. The trilaminar MRI appearance of the cartilage was only visible when the cartilage was thicker than 2 mm. In cartilage degeneration, we found either a diffuse thinning of all layers or circumscribed lesions (``cartilage ulcer``) of these cartilage layers in the MR images. Early cartilage degeneration was indicated by a signal loss in the superficial zone, correlating to the histologically proven damage of proteoglycans in the transitional and radial zone along with destruction of the superficial zone. We found a strong effect of cartilage rotation in the main magnetic field, too. A rotation of the cartilage structures caused considerable variation in the signal intensity of the second lamina. Cartilage segments in a 55 angle to the magnetic main field had a homogeneous appearance, not a trilaminar appearance. The signal behavior of hyaline articular cartilage does not reflect the laminar histologic structure. Osteoarthrosis and cartilage degeneration are visible on MR images as intracartilaginous signal changes, superficial erosions, diffuse cartilage thinning, and cartilage ulceration. (orig.) With 6 figs., 19 refs.

  16. A cytochemical study of histones in the muscular cells of Triturus cristatus limbs in normal regeneration of limbs irradiated by X-rays, of irradiated limbs in which the regenerative power is restored by cartilage implants

    International Nuclear Information System (INIS)

    Desselle, J.-C.

    1976-01-01

    The muscular cells of regenerating limbs and of limbs in which regenerative power is restored, show an important decrease in the amount of cytophotometrically detected histones. This decrease is owing to the arginine rich fraction and to the lysine rich fraction. The muscular cells of irradiated limbs show a decrease in the amount of histones. This decrease is owing only to the arginine rich fraction and continues after the thirtieth day of irradiation and amputation [fr

  17. Cartilage Derived from Bone Marrow Mesenchymal Stem Cells Expresses Lubricin In Vitro and In Vivo

    Science.gov (United States)

    Nakagawa, Yusuke; Muneta, Takeshi; Otabe, Koji; Ozeki, Nobutake; Mizuno, Mitsuru; Udo, Mio; Saito, Ryusuke; Yanagisawa, Katsuaki; Ichinose, Shizuko; Koga, Hideyuki; Tsuji, Kunikazu; Sekiya, Ichiro

    2016-01-01

    Objective Lubricin expression in the superficial cartilage will be a crucial factor in the success of cartilage regeneration. Mesenchymal stem cells (MSCs) are an attractive cell source and the use of aggregates of MSCs has some advantages in terms of chondrogenic potential and efficiency of cell adhesion. Lubricin expression in transplanted MSCs has not been fully elucidated so far. Our goals were to determine (1) whether cartilage pellets of human MSCs expressed lubricin in vitro chondrogenesis, (2) whether aggregates of human MSCs promoted lubricin expression, and (3) whether aggregates of MSCs expressed lubricin in the superficial cartilage after transplantation into osteochondral defects in rats. Methods For in vitro analysis, human bone marrow (BM) MSCs were differentiated into cartilage by pellet culture, and also aggregated using the hanging drop technique. For an animal study, aggregates of BM MSCs derived from GFP transgenic rats were transplanted to the osteochondral defect in the trochlear groove of wild type rat knee joints. Lubricin expression was mainly evaluated in differentiated and regenerated cartilages. Results In in vitro analysis, lubricin was detected in the superficial zone of the pellets and conditioned medium. mRNA expression of Proteoglycan4 (Prg4), which encodes lubricin, in pellets was significantly higher than that of undifferentiated MSCs. Aggregates showed different morphological features between the superficial and deep zone, and the Prg4 mRNA expression increased after aggregate formation. Lubricin was also found in the aggregate. In a rat study, articular cartilage regeneration was significantly better in the MSC group than in the control group as shown by macroscopical and histological analysis. The transmission electron microscope showed that morphology of the superficial cartilage in the MSC group was closer to that of the intact cartilage than in the control group. GFP positive cells remained in the repaired tissue and

  18. Cartilage Morphological and Histological Findings After Reconstruction of the Glenoid With an Iliac Crest Bone Graft.

    Science.gov (United States)

    Auffarth, Alexander; Resch, Herbert; Matis, Nicholas; Hudelmaier, Martin; Wirth, Wolfgang; Forstner, Rosemarie; Neureiter, Daniel; Traweger, Andreas; Moroder, Philipp

    2018-04-01

    The J-bone graft is presumably representative of iliac crest bone grafts in general and allows anatomic glenoid reconstruction in cases of bone defects due to recurrent traumatic anterior shoulder dislocations. As a side effect, these grafts have been observed to be covered by some soft, cartilage-like tissue when arthroscopy has been indicated after such procedures. To evaluate the soft tissue covering of J-bone grafts by use of magnetic resonance imaging (MRI) and histological analysis. Case series; Level of evidence, 4. Patients underwent MRI at 1 year after the J-bone graft procedures. Radiological data were digitally processed and evaluated by segmentation of axial images. Independent from the MRI analysis, 2 biopsy specimens of J-bone grafts were harvested for descriptive histological analysis. Segmentation of the images revealed that all grafts were covered by soft tissue. This layer had an average thickness of 0.87 mm compared with 1.96 mm at the adjacent native glenoid. Of the 2 biopsy specimens, one exhibited evident hyaline-like cartilage and the other presented patches of chondrocytes embedded in a glycosaminoglycan-rich extracellular matrix. J-bone grafts are covered by soft tissue that can differentiate into fibrous and potentially hyaline cartilage. This feature may prove beneficial for delaying the onset of dislocation arthropathy of the shoulder.

  19. MR imaging of articular cartilage in the ankle: comparison of available imaging sequences and methods of measurement in cadavers

    Energy Technology Data Exchange (ETDEWEB)

    Tan, T.C.F. [Department of Radiology, Veterans Administrative Medical Center, San Diego, CA (United States)]|[University of California Medical Center, San Diego, CA (United States)]|[Department of Radiology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan (Taiwan, Province of China); Wilcox, D.M. [Department of Radiology, Veterans Administrative Medical Center, San Diego, CA (United States)]|[University of California Medical Center, San Diego, CA (United States); Frank, L. [Department of Radiology, Veterans Administrative Medical Center, San Diego, CA (United States)]|[University of California Medical Center, San Diego, CA (United States); Shih, C. [Department of Radiology, Veterans Administrative Medical Center, San Diego, CA (United States)]|[University of California Medical Center, San Diego, CA (United States)]|[Department of Radiology, Veterans General Hospital-Taipei (Taiwan, Province of China); Trudell, D.J. [Department of Radiology, Veterans Administrative Medical Center, San Diego, CA (United States)]|[University of California Medical Center, San Diego, CA (United States); Sartoris, D.J. [Department of Radiology, Veterans Administrative Medical Center, San Diego, CA (United States)]|[University of California Medical Center, San Diego, CA (United States); Resnick, D. [Department of Radiology, Veterans Administrative Medical Center, San Diego, CA (United States)]|[University of California Medical Center, San Diego, CA (United States)

    1996-11-01

    Objective. To assess hyaline cartilage of cadaveric ankles using different magnetic resonance (MR) imaging techniques and various methods of measurement. Design and patients. Cartilage thicknesses of the talus and tibia were measured in ten cadaveric ankles by naked eye and by digitized image analysis from MR images of fat-suppressed T1-weighted gradient recalled (FS-SPGR), sequences and pulsed transfer saturation sequences with (FS-STS) and without fat-suppression (STS); these measurements were compared with those derived from direct inspection of cadaveric sections. The accuracy and precision errors were evaluated statistically for each imaging technique as well as measuring method. Contrast-to-noise ratios of cartilage versus joint fluid and marrow were compared for each of the imaging sequences. Results. Statistically, measurements from FS-SPGR images were associated with the smallest estimation error. Precision error of measurements derived from digitized image analysis was found to be smaller than that derived from naked eye measurements. Cartilage thickness measurements in images from STS and FS-STS sequences revealed larger errors in both accuracy and precision. Interobserver variance was larger in naked eye assessment of the cartilage. Contrast-to-noise ratio of cartilage versus joint fluid and marrow was higher with FS-SPGR than with FS-STS or STS sequences. Conclusion. Of the sequences and measurement techniques studied, the FS-SPGR sequence combined with the use of digitized image analysis provides the most accurate method for the assessment of ankle hyaline cartilage. (orig.). With 3 figs., 2 tabs.

  20. MR imaging of articular cartilage in the ankle: comparison of available imaging sequences and methods of measurement in cadavers

    International Nuclear Information System (INIS)

    Tan, T.C.F.; Wilcox, D.M.; Frank, L.; Shih, C.; Trudell, D.J.; Sartoris, D.J.; Resnick, D.

    1996-01-01

    Objective. To assess hyaline cartilage of cadaveric ankles using different magnetic resonance (MR) imaging techniques and various methods of measurement. Design and patients. Cartilage thicknesses of the talus and tibia were measured in ten cadaveric ankles by naked eye and by digitized image analysis from MR images of fat-suppressed T1-weighted gradient recalled (FS-SPGR), sequences and pulsed transfer saturation sequences with (FS-STS) and without fat-suppression (STS); these measurements were compared with those derived from direct inspection of cadaveric sections. The accuracy and precision errors were evaluated statistically for each imaging technique as well as measuring method. Contrast-to-noise ratios of cartilage versus joint fluid and marrow were compared for each of the imaging sequences. Results. Statistically, measurements from FS-SPGR images were associated with the smallest estimation error. Precision error of measurements derived from digitized image analysis was found to be smaller than that derived from naked eye measurements. Cartilage thickness measurements in images from STS and FS-STS sequences revealed larger errors in both accuracy and precision. Interobserver variance was larger in naked eye assessment of the cartilage. Contrast-to-noise ratio of cartilage versus joint fluid and marrow was higher with FS-SPGR than with FS-STS or STS sequences. Conclusion. Of the sequences and measurement techniques studied, the FS-SPGR sequence combined with the use of digitized image analysis provides the most accurate method for the assessment of ankle hyaline cartilage. (orig.). With 3 figs., 2 tabs