Gene therapy with growth factors for periodontal tissue engineering–A review

Science.gov (United States)

Gupta, Shipra; Mahendra, Aneet

2012-01-01

The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. A challenge faced by periodontal therapy is the predictable regeneration of periodontal tissues lost as a consequence of disease. Growth factors are critical to the development, maturation, maintenance and repair of oral tissues as they establish an extra-cellular environment that is conducive to cell and tissue growth. Tissue engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. The aim of this paper is to review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Various such materials have been formulated into devices that can be used as vehicles for delivery of cells, growth factors and DNA. Different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral and tooth supporting structure. Key words: Periodontal disease, gene therapy, regeneration, tissue repair, growth factors, tissue engineering. PMID:22143705

Influence of surgical decompression on the expression of inflammatory and tissue repair biomarkers in periapical cysts.

Science.gov (United States)

Rodrigues, Janderson Teixeira; Dos Santos Antunes, Henrique; Armada, Luciana; Pires, Fábio Ramôa

2017-12-01

The biologic effects of surgical decompression on the epithelium and connective tissues of periapical cysts are not fully understood. The aim of this study was to evaluate the expression of tissue repair and inflammatory biomarkers in periapical cysts before and after surgical decompression. Nine specimens of periapical cysts treated with decompression before undergoing complete enucleation were immunohistochemically analyzed to investigate the expression of interleukin-1β, tumor necrosis factor-α, transforming growth factor-β1, matrix metalloproteinase-9, Ki-67, and epidermal growth factor receptor. Expression of the biomarkers was classified as positive, focal, or negative. Ki-67 immunoexpression was calculated as a cell proliferation index. The expression of the biomarkers was compared in the specimens from decompression and from the final surgical procedure. Computed tomography demonstrated that volume was reduced in all cysts after decompression. There were no differences in the immunoexpression of the proinflammatory and tissue repair biomarkers when comparing the specimens obtained before and after the decompression. Surgical decompression was efficient in reducing the volume of periapical cysts before complete enucleation. When comparing the specimens obtained from surgical decompression and from complete surgical removal, the immunohistochemical analysis did not show a decrease in proinflammatory biomarkers; neither did it show an increase in tissue repair biomarkers. Copyright © 2017 Elsevier Inc. All rights reserved.

The 23rd Annual Meeting of the European Tissue Repair Society (ETRS) in Reims, France

DEFF Research Database (Denmark)

Von den Hoff, Johannes W; Ågren, Sven Per Magnus; Coulomb, Bernard

2014-01-01

The 23rd Annual Meeting of the European Tissue Repair Society, Reims, France, October 23 to 25, 2013 focused on tissue repair and regenerative medicine covering topics such as stem cells, biomaterials, tissue engineering, and burns.......The 23rd Annual Meeting of the European Tissue Repair Society, Reims, France, October 23 to 25, 2013 focused on tissue repair and regenerative medicine covering topics such as stem cells, biomaterials, tissue engineering, and burns....

Mussel-inspired tough hydrogels with self-repairing and tissue adhesion

Science.gov (United States)

Gao, Zijian; Duan, Lijie; Yang, Yongqi; Hu, Wei; Gao, Guanghui

2018-01-01

The mussel-inspired polymeric hydrogels have been attractively explored owing to their self-repairing or adhesive property when the catechol groups of dopamine could chelate metal ions. However, it was a challenge for self-repairing hydrogels owning high mechanical properties. Herein, a synergistic strategy was proposed by combining catechol-Fe3+ complexes and hydrophobic association. The resulting hydrogels exhibited seamless self-repairing behavior, tissue adhesion and high mechanical property. Moreover, the pH-dependent stoichiometry of catechol-Fe3+ and temperature-sensitive hydrophobic association endue hydrogels with pH/thermo responsive characteristics. Subsequently, the self-repairing rate and mechanical property of hydrogels were investigated at different pH and temperature. This bio-inspired strategy would build an avenue for designing and constructing a new generation of self-repairing, tissue-adhesive and tough hydrogel.

Meniscal repair by fibrocartilage in the dog : Characterization of the repair tissue and the role of vascularity

NARCIS (Netherlands)

Veth, RPH; Jansen, HWB; Nielsen, HKL; deGroot, JH; Pennings, AJ; Kuijer, R

Lesions in the avascular part of 20 canine menisci were repaired by implantation of a porous polyurethane. Seven menisci were not repaired and served as controls. The repair tissue was characterized by biochemical and immunological analysis. The role of vascularity in healing was studied by

The influence of platelet- derived products on angiogenesis and tissue repair: a concise update

Directory of Open Access Journals (Sweden)

Constanza E Martínez

2015-10-01

Full Text Available Platelet degranulation allows the release of a large amount of soluble mediators, is an essential step for wound healing initiation, and stimulates clotting and angiogenesis. The latter process is one of the most critical biological events observed during tissue repair,increasing the growth of blood vessels in the maturing wound. Angiogenesis requires the action of a variety of growth factors that act in an appropriate physiological ratio to assure functional blood vessel restoration. Platelets release main regulators of angiogenesis: Vascular Endothelial Growth Factors (VEGFs, basic fibroblast growth factor (FGF-2, and Platelet derived growth factors (PDGFs, among others. In order to stimulate tissue repair, platelet derived fractions have been used as an autologous source of growth factors and biomolecules, namely Platelet Rich Plasma (PRP, Platelet Poor Plasma (PPP and Platelet Rich Fibrin(PRF. The continuous release of these growth factors has been proposed to promote angiogenesis both in vitro and in vivo. Considering the existence of clinical trials currently evaluating the efficacy of autologous PRP, the present review analyses fundamental questions regarding the putative role of platelet derived fractions as regulators of angiogenesis and evaluates the possible clinical implications of these formulations.

The necessity of a theory of biology for tissue engineering: metabolism-repair systems.

Science.gov (United States)

Ganguli, Suman; Hunt, C Anthony

2004-01-01

Since there is no widely accepted global theory of biology, tissue engineering and bioengineering lack a theoretical understanding of the systems being engineered. By default, tissue engineering operates with a "reductionist" theoretical approach, inherited from traditional engineering of non-living materials. Long term, that approach is inadequate, since it ignores essential aspects of biology. Metabolism-repair systems are a theoretical framework which explicitly represents two "functional" aspects of living organisms: self-repair and self-replication. Since repair and replication are central to tissue engineering, we advance metabolism-repair systems as a potential theoretical framework for tissue engineering. We present an overview of the framework, and indicate directions to pursue for extending it to the context of tissue engineering. We focus on biological networks, both metabolic and cellular, as one such direction. The construction of these networks, in turn, depends on biological protocols. Together these concepts may help point the way to a global theory of biology appropriate for tissue engineering.

The effect of platelet rich fibrin on growth factor levels in urethral repair.

Science.gov (United States)

Soyer, Tutku; Ayva, Şebnem; Boybeyi, Özlem; Aslan, Mustafa Kemal; Çakmak, Murat

2013-12-01

Platelet rich fibrin (PRF) is an autologous source of growth factors and promotes wound healing. An experimental study was performed to evaluate the effect of PRF on growth factor levels in urethral repair. Eighteen Wistar albino rats were included in the study. Rats were allocated in three groups (n:6): control (CG), sham (SG), and PRF (PRFG). In SG, a 5 mm vertical incision was performed in the penile urethra and repaired with 10/0 Vicryl® under a microscope. In PRFG, during the urethral repair as described in SG, 1 cc of blood was sampled from each rat and centrifuged for 10 minutes at 2400 rpm. PRF obtained from the centrifugation was placed on the repair site during closure. Penile urethras were sampled 24 hours after PRF application in PRFG and after urethral repair in SG. Transforming growth factor beta receptor (TGF-β-R-CD105), vascular endothelial growth factor (VEGF) and its receptor (VEGF-R), as well as endothelial growth factor receptor (EGFR), were evaluated in subepithelia of the penile skin and urethra. Groups were compared for growth factor levels and growth factor receptor expression with the Kruskal Wallis test. TGF-β-R levels were significantly decreased in SG when compared to CG (p0.05). Use of PRF after urethral repair increases TGF-β-R and VEGF expressions in urethral tissue. PRF can be considered as an alternative measure to improve the success of urethral repair. © 2013.

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.

The tissue injury and repair in cancer radiotherapy

International Nuclear Information System (INIS)

Matsuzawa, Taiju

1975-01-01

One of the difficulties in cancer radiotherapy arises from the fact that the tissue tolerance dose is much smaller than the tumor lethal dose. In our opinion the former depends upon the tolerance of the endothelial cell of the blood vessel in the normal tissue. In this introduction, a new concept regarding the estimation of tissue radiosensitivity was described, and the possible significance of the mode of radiation injury and the repair capability of normal tissue in the cancer radiotheraphy was discussed. (author)

Tissue-Derived Extracellular Matrix Bioscaffolds: Emerging Applications in Cartilage and Meniscus Repair.

Science.gov (United States)

Monibi, Farrah A; Cook, James L

2017-08-01

Musculoskeletal injuries are a common problem in orthopedic practice. Given the long-term consequences of unaddressed cartilage and meniscal pathology, a number of treatments have been attempted to stimulate repair or to replace the injured tissue. Despite advances in orthopedic surgery, effective treatments for cartilage and meniscus injuries remain a significant clinical challenge. Tissue engineering is a developing field that aims to regenerate injured tissues with a combination of cells, scaffolds, and signals. Many natural and synthetic scaffold materials have been developed and tested for the repair and restoration of a number of musculoskeletal tissues. Among these, biological scaffolds derived from cell and tissue-derived extracellular matrix (ECM) have shown great promise in tissue engineering given the critical role of the ECM for maintaining the biological and biomechanical properties, structure, and function of native tissues. This review article presents emerging applications for tissue-derived ECM scaffolds in cartilage and meniscus repair. We examine normal ECM composition and the current and future methods for potential treatment of articular cartilage and meniscal defects with decellularized scaffolds.

Repair in normal tissues and the possible relevance to radiotherapy

International Nuclear Information System (INIS)

Field, S.B.; Hornsey, S.

1977-01-01

Between each fraction in radiotherapy, there is repair and recovery of both normal and neoplastic tissues. Several different types of repair have been identified. Some relate specifically to the effect of changing the number of fractions and others to the overall treatment time. Each will be discussed and particular attention will be paid to slow repair phenomena which have recently been the subject of much interest. (orig.) [de

The 23rd Annual Meeting of the European Tissue Repair Society (ETRS) in Reims, France

NARCIS (Netherlands)

Hoff, J.W. Von den; Agren, M.S.; Coulomb, B.; Eming, S.A.; Lataillade, J.J.

2014-01-01

The 23rd Annual Meeting of the European Tissue Repair Society, Reims, France, October 23 to 25, 2013 focused on tissue repair and regenerative medicine covering topics such as stem cells, biomaterials, tissue engineering, and burns.

Improved repair of bone defects with prevascularized tissue-engineered bones constructed in a perfusion bioreactor.

Science.gov (United States)

Li, De-Qiang; Li, Ming; Liu, Pei-Lai; Zhang, Yuan-Kai; Lu, Jian-Xi; Li, Jian-Min

2014-10-01

Vascularization of tissue-engineered bones is critical to achieving satisfactory repair of bone defects. The authors investigated the use of prevascularized tissue-engineered bone for repairing bone defects. The new bone was greater in the prevascularized group than in the non-vascularized group, indicating that prevascularized tissue-engineered bone improves the repair of bone defects. [Orthopedics. 2014; 37(10):685-690.]. Copyright 2014, SLACK Incorporated.

Mesenchymal Stem Cells in Tissue Repair

Directory of Open Access Journals (Sweden)

Amy M DiMarino

2013-09-01

Full Text Available The advent of mesenchymal stem cell (MSC based therapies for clinical therapeutics has been an exciting and new innovation for the treatment of a variety of diseases associated with inflammation, tissue damage and subsequent regeneration and repair. Application-based ability to measure MSC potency and fate of the cells post-MSC therapy are the variables that confound the use of MSCs therapeutics in human diseases. An evaluation of MSC function and applications with attention to detail in the preparation as well as quality control (QC and quality assurance (QA are only as good as the assays that are developed. In vivo measures of efficacy and potency require an appreciation of the overall pathophysiology of the model and standardization of outcome measures. The new concepts of how MSC’s participate in the tissue regeneration and wound repair process and further, how this is impacted by estimates of efficacy and potency Are important new topics. In this regard,,, this chapter will review some of the in vitro and in vivo assays for MSC function and activity and their application to the clinical arena.

Stem cell-derived angiogenic/vasculogenic cells: Possible therapies for tissue repair and tissue engineering

NARCIS (Netherlands)

Zwaginga, J. J.; Doevendans, P.

2003-01-01

1. The recent ability to isolate stem cells and study their specific capacity of self-renewal with the formation of different cell types has opened up exciting vistas to help the repair of damaged tissue and even the formation of new tissue. In the present review, we deal with the characteristics

Tissue-engineered bone constructed in a bioreactor for repairing critical-sized bone defects in sheep.

Science.gov (United States)

Li, Deqiang; Li, Ming; Liu, Peilai; Zhang, Yuankai; Lu, Jianxi; Li, Jianmin

2014-11-01

Repair of bone defects, particularly critical-sized bone defects, is a considerable challenge in orthopaedics. Tissue-engineered bones provide an effective approach. However, previous studies mainly focused on the repair of bone defects in small animals. For better clinical application, repairing critical-sized bone defects in large animals must be studied. This study investigated the effect of a tissue-engineered bone for repairing critical-sized bone defect in sheep. A tissue-engineered bone was constructed by culturing bone marrow mesenchymal-stem-cell-derived osteoblast cells seeded in a porous β-tricalcium phosphate ceramic (β-TCP) scaffold in a perfusion bioreactor. A critical-sized bone defect in sheep was repaired with the tissue-engineered bone. At the eighth and 16th week after the implantation of the tissue-engineered bone, X-ray examination and histological analysis were performed to evaluate the defect. The bone defect with only the β-TCP scaffold served as the control. X-ray showed that the bone defect was successfully repaired 16 weeks after implantation of the tissue-engineered bone; histological sections showed that a sufficient volume of new bones formed in β-TCP 16 weeks after implantation. Eight and 16 weeks after implantation, the volume of new bones that formed in the tissue-engineered bone group was more than that in the β-TCP scaffold group (P bone improved osteogenesis in vivo and enhanced the ability to repair critical-sized bone defects in large animals.

Digital design of scaffold for mandibular defect repair based on tissue engineering.

Science.gov (United States)

Liu, Yun-feng; Zhu, Fu-dong; Dong, Xing-tao; Peng, Wei

2011-09-01

Mandibular defect occurs more frequently in recent years, and clinical repair operations via bone transplantation are difficult to be further improved due to some intrinsic flaws. Tissue engineering, which is a hot research field of biomedical engineering, provides a new direction for mandibular defect repair. As the basis and key part of tissue engineering, scaffolds have been widely and deeply studied in regards to the basic theory, as well as the principle of biomaterial, structure, design, and fabrication method. However, little research is targeted at tissue regeneration for clinic repair operations. Since mandibular bone has a special structure, rather than uniform and regular structure in existing studies, a methodology based on tissue engineering is proposed for mandibular defect repair in this paper. Key steps regarding scaffold digital design, such as external shape design and internal microstructure design directly based on triangular meshes are discussed in detail. By analyzing the theoretical model and the measured data from the test parts fabricated by rapid prototyping, the feasibility and effectiveness of the proposed methodology are properly verified. More works about mechanical and biological improvements need to be done to promote its clinical application in future.

Digital design of scaffold for mandibular defect repair based on tissue engineering

Institute of Scientific and Technical Information of China (English)

Yun-feng LIU; Fu-dong ZHU; Xing-tao DONG; Wei PENG

2011-01-01

Mandibular defect occurs more frequently in recent years,and clinical repair operations via bone transplantation are difficult to be further improved due to some intrinsic flaws.Tissue engineering,which is a hot research field of biomedical engineering,provides a new direction for mandibular defect repair.As the basis and key part of tissue engineering,scaffolds have been widely and deeply studied in regards to the basic theory,as well as the principle of biomaterial,structure,design,and fabrication method.However,little research is targeted at tissue regeneration for clinic repair operations.Since mandibular bone has a special structure,rather than uniform and regular structure in existing studies,a methodology based on tissue engineering is proposed for mandibular defect repair in this paper.Key steps regarding scaffold digital design,such as external shape design and internal microstructure design directly based on triangular meshes are discussed in detail.By analyzing the theoretical model and the measured data from the test parts fabricated by rapid prototyping,the feasibility and effectiveness of the proposed methodology are properly verified.More works about mechanical and biological improvements need to be done to promote its clinical application in future.

Transcriptional profiling differences for articular cartilage and repair tissue in equine joint surface lesions

Directory of Open Access Journals (Sweden)

Stromberg Arnold J

2009-09-01

Full Text Available Abstract Background Full-thickness articular cartilage lesions that reach to the subchondral bone yet are restricted to the chondral compartment usually fill with a fibrocartilage-like repair tissue which is structurally and biomechanically compromised relative to normal articular cartilage. The objective of this study was to evaluate transcriptional differences between chondrocytes of normal articular cartilage and repair tissue cells four months post-microfracture. Methods Bilateral one-cm2 full-thickness defects were made in the articular surface of both distal femurs of four adult horses followed by subchondral microfracture. Four months postoperatively, repair tissue from the lesion site and grossly normal articular cartilage from within the same femorotibial joint were collected. Total RNA was isolated from the tissue samples, linearly amplified, and applied to a 9,413-probe set equine-specific cDNA microarray. Eight paired comparisons matched by limb and horse were made with a dye-swap experimental design with validation by histological analyses and quantitative real-time polymerase chain reaction (RT-qPCR. Results Statistical analyses revealed 3,327 (35.3% differentially expressed probe sets. Expression of biomarkers typically associated with normal articular cartilage and fibrocartilage repair tissue corroborate earlier studies. Other changes in gene expression previously unassociated with cartilage repair were also revealed and validated by RT-qPCR. Conclusion The magnitude of divergence in transcriptional profiles between normal chondrocytes and the cells that populate repair tissue reveal substantial functional differences between these two cell populations. At the four-month postoperative time point, the relative deficiency within repair tissue of gene transcripts which typically define articular cartilage indicate that while cells occupying the lesion might be of mesenchymal origin, they have not recapitulated differentiation to

Engineering dextran-based scaffolds for drug delivery and tissue repair

Science.gov (United States)

Sun, Guoming; Mao, Jeremy J

2015-01-01

Owing to its chemically reactive hydroxyl groups, dextran can be modified with different functional groups to form spherical, tubular and 3D network structures. The development of novel functional scaffolds for efficient controlled release and tissue regeneration has been a major research interest, and offers promising therapeutics for many diseases. Dextran-based scaffolds are naturally biodegradable and can serve as bioactive carriers for many protein biomolecules. The reconstruction of the in vitro microenvironment with proper signaling cues for large-scale tissue regenerative scaffolds has yet to be fully developed, and remains a significant challenge in regenerative medicine. This paper will describe recent advances in dextran-based polymers and scaffolds for controlled release and tissue engineering. Special attention is given to the development of dextran-based hydrogels that are precisely manipulated with desired structural properties and encapsulated with defined angiogenic growth factors for therapeutic neovascularization, as well as their potential for wound repair. PMID:23210716

Experiment K-7-29: Connective Tissue Studies. Part 3; Rodent Tissue Repair: Skeletal Muscle

Science.gov (United States)

Stauber, W.; Fritz, V. K.; Burkovskaya, T. E.; Ilyina-Kakueva, E. I.

1994-01-01

Myofiber injury-repair was studied in the rat gastrocnemius following a crush injury to the lower leg prior to flight in order to understand if the regenerative responses of muscles are altered by the lack of gravitational forces during Cosmos 2044 flight. After 14 days of flight, the gastrocnemius muscle was removed from the 5 injured flight rodents and various Earth-based treatment groups for comparison. The Earth-based animals consisted of three groups of five rats with injured muscles from a simulated, tail-suspended, and vivarium as well as an uninjured basal group. The gastrocnemius muscle from each was evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations following injury. In general the repair process was somewhat similar in all injured muscle samples with regard to extracellular matrix organization and myofiber regeneration. Small and large myofibers were present with a newly organized extracellular matrix indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with no enlarged area of non-muscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well differentiated with more macrophages and blood vessels in the repair region but small myofibers and proteoglycans, nevertheless, were in their usual configuration. Thus, myofiber repair did vary in muscles from the different groups, but for the most part, resulted in functional muscle tissue.

Mathematical models of soft tissue injury repair : towards understanding musculoskeletal disorders

OpenAIRE

Dunster, Joanne L.

2012-01-01

The process of soft tissue injury repair at the cellular lew I can be decomposed into three phases: acute inflammation including coagulation, proliferation and remodelling. While the later phases are well understood the early phase is less so. We produce a series of new mathematical models for the early phases coagulation and inflammation. The models produced are relevant not only to soft tissue injury repair but also to the many disease states in which coagulation and inflammation play a rol...

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.

HYDROGEL-BASED NANOCOMPOSITES OF THERAPEUTIC PROTEINS FOR TISSUE REPAIR.

Science.gov (United States)

Zhu, Suwei; Segura, Tatiana

2014-05-01

The ability to design artificial extracellular matrices as cell instructive scaffolds has opened the door to technologies capable of studying cell fates in vitro and to guide tissue repair in vivo . One main component of the design of artificial extracellular matrices is the incorporation of protein-based biochemical cues to guide cell phenotypes and multicellular organizations. However, promoting the long-term bioactivity, controlling the bioavailability and understanding how the physical presentations of these proteins impacts cellular fates are among the challenges of the field. Nanotechnolgy has advanced to meet the challenges of protein therapeutics. For example, the approaches to incorporating proteins into tissue repairing scaffolds have ranged from bulk encapsulations to smart nanodepots that protect proteins from degradations and allow opportunities for controlled release.

Native-tissue repair of isolated primary rectocele compared with nonabsorbable mesh

DEFF Research Database (Denmark)

Madsen, Lene Duch; Nussler, Emil; Kesmodel, Ulrik Schioler

2017-01-01

and included 3988 women with a primary operation for rectocele between 2006 and 2014: 3908 women had native-tissue repair, 80 were operated with nonabsorbable mesh. No concurrent operations were performed. Pre- and perioperative data were collected from doctors and patients. Patient-reported outcomes were......INTRODUCTION: We evaluated patient-reported outcomes and complications after treatment of isolated primary rectocele in routine health-care settings using native-tissue repair or nonabsorbable mesh. METHODS: We used prospective data from the Swedish National Register for Gynaecological Surgery...

Tissue and cellular biomechanics during corneal wound injury and repair.

Science.gov (United States)

Raghunathan, Vijay Krishna; Thomasy, Sara M; Strøm, Peter; Yañez-Soto, Bernardo; Garland, Shaun P; Sermeno, Jasmyne; Reilly, Christopher M; Murphy, Christopher J

2017-08-01

Corneal wound healing is an enormously complex process that requires the simultaneous cellular integration of multiple soluble biochemical cues, as well as cellular responses to the intrinsic chemistry and biophysical attributes associated with the matrix of the wound space. Here, we document how the biomechanics of the corneal stroma are altered through the course of wound repair following keratoablative procedures in rabbits. Further we documented the influence that substrate stiffness has on stromal cell mechanics. Following corneal epithelial debridement, New Zealand white rabbits underwent phototherapeutic keratectomy (PTK) on the right eye (OD). Wound healing was monitored using advanced imaging modalities. Rabbits were euthanized and corneas were harvested at various time points following PTK. Tissues were characterized for biomechanics with atomic force microscopy and with histology to assess inflammation and fibrosis. Factor analysis was performed to determine any discernable patterns in wound healing parameters. The matrix associated with the wound space was stiffest at 7days post PTK. The greatest number of inflammatory cells were observed 3days after wounding. The highest number of myofibroblasts and the greatest degree of fibrosis occurred 21days after wounding. While all clinical parameters returned to normal values 400days after wounding, the elastic modulus remained greater than pre-surgical values. Factor analysis demonstrated dynamic remodeling of stroma occurs between days 10 and 42 during corneal stromal wound repair. Elastic modulus of the anterior corneal stroma is dramatically altered following PTK and its changes coincide initially with the development of edema and inflammation, and later with formation of stromal haze and population of the wound space with myofibroblasts. Factor analysis demonstrates strongest correlation between elastic modulus, myofibroblasts, fibrosis and stromal haze thickness, and between edema and central corneal

Epithelial-mesenchymal transition in tissue repair and fibrosis.

Science.gov (United States)

Stone, Rivka C; Pastar, Irena; Ojeh, Nkemcho; Chen, Vivien; Liu, Sophia; Garzon, Karen I; Tomic-Canic, Marjana

2016-09-01

The epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including the loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics that confer migratory capacity. EMT and its converse, MET (mesenchymal-epithelial transition), are integral stages of many physiologic processes and, as such, are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes (the resident skin epithelial cells) migrate across the wound bed to restore the epidermal barrier. Moreover, EMT plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblasts arise from cells of the epithelial lineage in response to injury but are pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the faulty repair of fibrotic wounds might identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. Graphical Abstract Model for injury-triggered EMT activation in physiologic wound repair (left) and fibrotic wound healing (right).

Matrix metalloproteinase-8 overexpression prevents proper tissue repair

DEFF Research Database (Denmark)

Danielsen, Patricia L; Holst, Anders V; Maltesen, Henrik R

2011-01-01

The collagenolytic matrix metalloproteinase-8 (MMP-8) is essential for normal tissue repair but is often overexpressed in wounds with disrupted healing. Our aim was to study the impact of a local excess of this neutrophil-derived proteinase on wound healing using recombinant adenovirus...

Advances in biologic augmentation for rotator cuff repair

Science.gov (United States)

Patel, Sahishnu; Gualtieri, Anthony P.; Lu, Helen H.; Levine, William N.

2016-01-01

Rotator cuff tear is a very common shoulder injury that often necessitates surgical intervention for repair. Despite advances in surgical techniques for rotator cuff repair, there is a high incidence of failure after surgery because of poor healing capacity attributed to many factors. The complexity of tendon-to-bone integration inherently presents a challenge for repair because of a large biomechanical mismatch between the tendon and bone and insufficient regeneration of native tissue, leading to the formation of fibrovascular scar tissue. Therefore, various biological augmentation approaches have been investigated to improve rotator cuff repair healing. This review highlights recent advances in three fundamental approaches for biological augmentation for functional and integrative tendon–bone repair. First, the exploration, application, and delivery of growth factors to improve regeneration of native tissue is discussed. Second, applications of stem cell and other cell-based therapies to replenish damaged tissue for better healing is covered. Finally, this review will highlight the development and applications of compatible biomaterials to both better recapitulate the tendon–bone interface and improve delivery of biological factors for enhanced integrative repair. PMID:27750374

Factors predicting rotator cuff retears: an analysis of 1000 consecutive rotator cuff repairs.

Science.gov (United States)

Le, Brian T N; Wu, Xiao L; Lam, Patrick H; Murrell, George A C

2014-05-01

The rate of retears after rotator cuff repair varies from 11% to 94%. A retear is associated with poorer subjective and objective clinical outcomes than intact repair. This study was designed to determine which preoperative and/or intraoperative factors held the greatest association with retears after arthroscopic rotator cuff repair. Cohort study; Level of evidence, 3. This study retrospectively evaluated 1000 consecutive patients who had undergone a primary rotator cuff repair by a single surgeon using an arthroscopic inverted-mattress knotless technique and who had undergone an ultrasound evaluation 6 months after surgery to assess repair integrity. Exclusion criteria included previous rotator cuff repair on the same shoulder, incomplete repair, and repair using a synthetic polytetrafluoroethylene patch. All patients had completed the modified L'Insalata Questionnaire and underwent a clinical examination before surgery. Measurements of tear size, tear thickness, associated shoulder injury, tissue quality, and tendon mobility were recorded intraoperatively. The overall retear rate at 6 months after surgery was 17%. Retears occurred in 27% of full-thickness tears and 5% of partial-thickness tears (P < .0001). The best independent predictors of retears were anteroposterior tear length (correlation coefficient r = 0.41, P < .0001), tear size area (r = 0.40, P < .0001), mediolateral tear length (r = 0.34, P < .0001), tear thickness (r = 0.29, P < .0001), age at surgery (r = 0.27, P < .0001), and operative time (r = 0.18, P < .0001). These factors produced a predictive model for retears: logit P = (0.039 × age at surgery in years) + (0.027 × tear thickness in %) + (1 × anteroposterior tear length in cm) + (0.76 × mediolateral tear length in cm) - (0.17 × tear size area in cm(2)) + (0.018 × operative time in minutes) -9.7. Logit P can be transformed into P, which is the chance of retears at 6 months after surgery. A rotator cuff retear is a multifactorial process

Single-stage soft tissue reconstruction and orbital fracture repair for complex facial injuries.

Science.gov (United States)

Wu, Peng Sen; Matoo, Reshvin; Sun, Hong; Song, Li Yuan; Kikkawa, Don O; Lu, Wei

2017-02-01

Orbital fractures with open periorbital wounds cause significant morbidity. Timing of debridement with fracture repair and soft tissue reconstruction is controversial. This study focuses on the efficacy of early single-stage repair in combined bony and soft tissue injuries. Retrospective review. Twenty-three patients with combined open soft tissue wounds and orbital fractures were studied for single-stage orbital reconstruction and periorbital soft tissue repair. Inclusion criteria were open soft tissue wounds with clinical and radiographic evidence of orbital fractures and repair performed within 48 h after injury. Surgical complications and reconstructive outcomes were assessed over 6 months. The main outcome measures were enophthalmos, pre- and post-CT imaging of orbits, scar evaluation, presence of diplopia, and eyelid position. Enophthalmos was corrected in 16/19 cases and improved in 3/19 cases. 3D reconstruction of CT images showed markedly improved orbital alignment with objective measurements of the optic foramen to cornea distance (mm) in reconstructed orbits relative to intact orbits of 0.66, 95% confidence interval [CI] (lower 0.33, upper 0.99) mm. The mean baseline of Stony Brook Scar Evaluation Scale was 0.6, 95%CI (0.30-0.92), and for 6 months, the mean score was 3.4, 95%CI (3.05-3.73). Residual diplopia in secondary gazes was present in two patients; one patient had ectropion. Complications included one case of local wound infection. An early single-stage repair of combined soft tissue and orbital fractures yields satisfactory functional and aesthetic outcomes. Complications are low and likely related to trauma severity. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Quantitative assessment of optical properties in healthy cartilage and repair tissue by optical coherence tomography and histology (Conference Presentation)

Science.gov (United States)

Jansen, Sanne M. A.; Cernohorsky, Paul; de Bruin, Daniel M.; van der Pol, Edwin; Savci-Heijink, Cemile D.; Strackee, Simon D.; Faber, Dirk J.; van Leeuwen, Ton G.

2016-02-01

Quantification of the OCT signal is an important step toward clinical implementation of a diagnostic tool in cartilage imaging. Discrimination of structural cartilage differences in patients with osteoarthritis is critical, yet challenging. This study assesses the variation in the optical attenuation coefficient (μOCT) between healthy cartilage, repair tissue, bone and layers within repair tissue in a controlled setting. OCT and histology was used to assess goat talus articular surfaces in which central osteochondral defects were created. Exact matches of OCT and histology were selected for research. μOCT measurements were taken from healthy cartilage, repair tissue and bone. Measured μOCT in healthy cartilage was higher compared to both repair tissue and bone tissue. Two possible mechanisms for the difference in attenuation were investigated. We studied morphological parameters in terms of nucleus count, nucleus size and inter-nucleus distance. Collagen content in healthy cartilage and repair tissue was assessed using polarization microscopy. Quantitative analysis of the nuclei did not demonstrate a difference in nucleus size and count between healthy cartilage and repair tissue. In healthy cartilage, cells were spaced farther apart and had a lower variation in local nuclear density compared to repair tissue. Polarization microscopy suggested higher collagen content in healthy cartilage compared to repair tissue. μOCT measurements can distinguish between healthy cartilage, repair tissue and bone. Results suggest that cartilage OCT attenuation measurements could be of great impact in clinical diagnostics of osteoarthritis.

Advances and Perspectives on Tissue Repair and Healing

Science.gov (United States)

Pinheiro, Antonio L. B.; Marques, Aparecida M. C.; de Sousa, Ana Paula C.; Aciole, Jouber M. S.; Soares, Luiz G. P.

2011-08-01

Wound healing involves local and systemic responses that reflect the etiology of the lesion, type of tissue, systemic condition and others. Despite being essentially the same for different wounds, the pattern of healing may change due to intrinsic and/or extrinsic factors. The type of tissue has also to be considered. Several therapeutic approaches have been used to improve healing including phototherapies such as Laser, LEDs and Lamps. Their effects on soft and mineralized tissues are well reported. The choice of appropriated parameters is essential for the results of the treatment and includes wavelength, power density, energy, duration and frequency of application and others. We studied the effects of different types of light on the healing of both soft and mineralized tissues using different models. We found that the use of Laser and polarized light are effective on improving the healing of diabetic and undernourished animals. We also found that Laser light is capable of improving the healing of drug-induced impairment and on increasing the survival rate of flaps on both diabetic and non-diabetic animals. We have also studied and shown the influence of the laser parameters on the healing of surgical and laser wounds. Lately we verified the positive effect of LEDs on healing. We used Laser/LED light for improving bone healing in conditions such as in dental implants, autologous grafts, biomaterials and fractures. From these reports and our own experience we have no doubt whatsoever that the use of phototherapies, carried out with appropriate parameters, promotes quicker tissue repair.

Mesenchymal Stem Cells in Tissue Growth and Repair

OpenAIRE

Kalinina, N.I.; Sysoeva, V.Yu.; Rubina, K.A.; Parfenova, Ye.V.; Tkachuk, V.A.

2011-01-01

It has been established in the recent several decades that stem cells play a crucial role in tissue renewal and regeneration. Mesenchymal stem cells (MSCs) are part of the most important population of adult stem cells. These cells have hereby been identified for the very first time and subsequently isolated from bone marrow stroma. Bone marrow-derived MSCs have been believed to play the role of a source of cells for the renewal and repair of connective tissues, including bone, cartilage and a...

Evaluation of cartilage repair tissue in the knee and ankle joint using sodium magnetic resonance imaging at 7 Tesla

International Nuclear Information System (INIS)

Zbyn, S.

2015-01-01

Articular cartilage of adults shows no or very limited intrinsic capacity for self-repair. Since untreated chondral defects often progress to osteoarthritis, symptomatic defects should be treated. Different cartilage repair procedures have been developed with the goal to restore joint function and prevent further cartilage degeneration by providing repair tissue of the same structure, composition, and biomechanical properties as native cartilage. Various cartilage repair procedures have been developed; including bone marrow stimulation (BMS) techniques such as microfracture (MFX), cell-based techniques such as matrix-associated autologous chondrocyte transplantation (MACT), and others. Since biopsies of cartilage repair tissue are invasive and cannot be repeated, a noninvasive method is needed that could follow-up the quality of cartilage and repair tissue. Negatively charged glycosaminoglycans (GAG) are very important for cartilage function as they attract positive ions such as sodium. The high concentration of ions in cartilage is responsible for osmotic pressure providing cartilage its resilience to compression. Since GAGs are counterbalanced by sodium ions, sodium magnetic resonance imaging (MRI) was validated as a sensitive method for the in vivo evaluation of GAG concentration in native cartilage but not for repair tissue. Thus, the main goal of this thesis was to optimize and validate sodium 7 Tesla MRI for the evaluation of cartilage repair tissue quality in patients after different cartilage repair surgeries in the knee and ankle joint. In our studies, sodium MRI was used for the first time for the clinical evaluation of cartilage repair tissue. A strong correlation found between sodium imaging and dGEMRIC (another GAG-sensitive technique) in patients after MACT on femoral cartilage proved sensitivity of sodium MRI to GAG changes in native cartilage and repair tissue in vivo. Comparison between BMS and MACT patients showed significantly lower sodium values

The Vascular Niche in Tissue Repair: A Therapeutic Target for Regeneration

OpenAIRE

Rivera, Francisco J.; Silva, Maria Elena; Aigner, Ludwig

2017-01-01

Editorial on the Research Topic The Vascular Niche in Tissue Repair: A Therapeutic Target for Regeneration In mammals, although regeneration is quite restricted to a number of tissues and organs, this particular healing process is possible through the existence of tissue-resident stem/progenitor cells. Upon injury, these cells are activated, they proliferate, migrate, and differentiate into tissue-specific cells and functionally replace the damaged or lost cells. Besides this, angio...

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.

The tissue injury and repair in cancer radiotherapy. A concept of tissue architecture and radio sensitivity

Energy Technology Data Exchange (ETDEWEB)

Matsuzawa, T [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer

1975-06-01

One of the difficulties in cancer radiotherapy arises from the fact that the tissue tolerance dose is much smaller than the tumor lethal dose. In our opinion the former depends upon the tolerance of the endothelial cell of the blood vessel in the normal tissue. In this introduction, a new concept regarding the estimation of tissue radiosensitivity was described, and the possible significance of the mode of radiation injury and the repair capability of normal tissue in the cancer radiotheraphy was discussed.

Tissue localization of human trefoil factors 1, 2, and 3

DEFF Research Database (Denmark)

Madsen, Jens; Nielsen, Ole; Tornøe, Ida

2007-01-01

Trefoil factors (TTFs) are small, compact proteins coexpressed with mucins in the gastrointestinal tract. Three trefoil factors are known in mammals: TFF1, TFF2, and TFF3. They are implicated to play diverse roles in maintenance and repair of the gastrointestinal channel. We compared the expression...... pattern of the three trefoil factors analyzing mRNA from a panel of 20 human tissues by conventional reverse transcriptase (RT) PCR and, in addition, by real-time PCR. These findings were supported by immunohistochemical analysis of paraffin-embedded human tissues using rabbit polyclonal antibodies raised...... against these factors. TFF1 showed highest expression in the stomach and colon, whereas TFF2 and TFF3 showed highest expression in stomach and colon, respectively. All three TFFs were found in the ducts of pancreas. Whereas TFF2 was found to be restricted to these two tissues, the structurally more...

Pulp and periodontal tissue repair - regeneration or tissue metaplasia after dental trauma. A review

DEFF Research Database (Denmark)

Andreasen, Jens O

2012-01-01

Healing subsequent to dental trauma is known to be very complex, a result explained by the variability of the types of dental trauma (six luxations, nine fracture types, and their combinations). On top of that, at least 16 different cellular systems get involved in more severe trauma types each o...... of tissue replaces the injured). In this study, a review is given of the impact of trauma to various dental tissues such as alveolar bone, periodontal ligament, cementum, Hertvigs epithelial root sheath, and the pulp....... of them with a different potential for healing with repair, i.e. (re-establishment of tissue continuity without functional restitution) and regeneration (where the injured or lost tissue is replaced with new tissue with identical tissue anatomy and function) and finally metaplasia (where a new type...

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

Solid emulsion gel as a vehicle for delivery of polyunsaturated fatty acids: implications for tissue repair, dermal angiogenesis and wound healing.

Science.gov (United States)

Shingel, Kirill I; Faure, Marie-Pierre; Azoulay, Laurent; Roberge, Christophe; Deckelbaum, Richard J

2008-10-01

The paper describes preparation and biological characterization of the solid hybrid biomaterial that was designed for cell-targeted lipid delivery in healing tissues. The material referred to as 'solid emulsion gel' combines a protein-stabilized lipid emulsion and a hydrogel structure in a single compartment. The potential of the omega-3 (n-3)-fatty acids rich solid emulsion gel for tissue repair applications was investigated at the macro-, micro-, molecular and gene expression levels, using human fibroblasts and endothelial cells and a porcine model of full-thickness wounds. Being non-cytotoxic in vitro and in vivo, the biomaterial was found to affect cell metabolism, modulate expression of certain genes, stimulate early angiogenesis and promote wound repair in vivo. The neovascular response in vivo was correlated with upregulated expression of the genes involved in lipid transport (e.g. adipophilin), anti-apoptosis (e.g. heat shock proteins, haem oxygenase 1) and angiogenesis (vascular endothelial growth factor, placental growth factor). Collectively, the results of this study provide first evidence that the angiogenic response provided by solid emulsion gel-mediated delivery of n-3 fatty acids is an alternative to the topical administration of exogenous growth factors or gene therapy, and can be advantageously used for the stimulation of tissue repair in complex wounds. Copyright (c) 2008 John Wiley & Sons, Ltd.

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.

Prediction of cartilaginous tissue repair after knee joint distraction

NARCIS (Netherlands)

van der Woude, J A D; Welsing, P M; van Roermund, P M; Custers, R J H; Kuchuk, N O; Lafeber, F P J G G

2016-01-01

BACKGROUND: For young patients (<65years), knee joint distraction (KJD) may be a joint-saving treatment option for end-stage knee osteoarthritis. Distracting the femur from the tibia by five millimeters for six to eight weeks using an external fixation frame results in cartilaginous tissue repair,

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.

Use of NASA Bioreactor in Engineering Tissue for Bone Repair

Science.gov (United States)

Duke, Pauline

1998-01-01

This study was proposed in search for a new alternative for bone replacement or repair. Because the systems commonly used in repair of bony defects form bone by going through a cartilaginous phase, implantation of a piece of cartilage could enhance the healing process by having a more advanced starting point. However, cartilage has seldom been used to replace bone due, in part, to the limitations in conventional culture systems that did not allow production of enough tissue for implants. The NASA-developed bioreactors known as STLV (Slow Turning Lateral Vessel) provide homogeneous distribution of cells, nutrients, and waste products, with less damaging turbulence and shear forces than conventional systems. Cultures under these conditions have higher growth rates, viability, and longevity, allowing larger "tissue-like" aggregates to form, thus opening the possibilities of producing enough tissue for implantation, along with the inherent advantages of in vitro manipulations. To assure large numbers of cells and to eliminate the use of timed embryos, we proposed to use an immortalized mouse limb bud cell line as the source of cells.

Analysis of DNA vulnerability to damage, repair and degradation in tissues of irradiated animals

International Nuclear Information System (INIS)

Ryabchenko, N.I.; Ivannik, B.P.

1982-01-01

Single-strand and paired ruptures of DNA were found to result in appearance of locally denaturated areas in its secondary structure and to disordered protein-DNA interaction. It was shown with the use of the viscosimeter method of measuring the molecular mass of single stranded high-polymeric DNA that cells of various tissues by the intensity of DNA repair can be divided into two groups, rapid- and slow-repair ones. Tissue specificity of enzyme function of the repair systems and systems responsible for post-irradiation DNA degradation depends on the activity of endonucleases synthesized by the cells both in health and in their irradiation-induced synthesis

Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain

International Nuclear Information System (INIS)

Wei, Y T; Tian, W M; Yu, X; Cui, F Z; Hou, S P; Xu, Q Y; Lee, In-Seop

2007-01-01

A biocompatible hydrogel of hyaluronic acid with the neurite-promoting peptide sequence of IKVAV was synthesized. The characterization of the hydrogel shows an open porous structure and a large surface area available for cell interaction. Its ability to promote tissue repair and axonal regeneration in the lesioned rat cerebrum is also evaluated. After implantation, the polymer hydrogel repaired the tissue defect and formed a permissive interface with the host tissue. Axonal growth occurred within the microstructure of the network. Within 6 weeks the polymer implant was invaded by host-derived tissue, glial cells, blood vessels and axons. Such a hydrogel matrix showed the properties of neuron conduction. It has the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost tissue

Epithelial-Mesenchymal Transition in Tissue Repair and Fibrosis

Science.gov (United States)

Stone, Rivka C.; Pastar, Irena; Ojeh, Nkemcho; Chen, Vivien; Liu, Sophia; Garzon, Karen I.; Tomic-Canic, Marjana

2016-01-01

Epithelial-mesenchymal transition (EMT) describes the global process by which stationary epithelial cells undergo phenotypic changes, including loss of cell-cell adhesion and apical-basal polarity, and acquire mesenchymal characteristics which confer migratory capacity. EMT and its converse, MET (mesenchymal-to-epithelial transition), are integral stages of many physiologic processes, and as such are tightly coordinated by a host of molecular regulators. Converging lines of evidence have identified EMT as a component of cutaneous wound healing, during which otherwise stationary keratinocytes - the resident skin epithelial cells - migrate across the wound bed to restore the epidermal barrier. Moreover, EMT also plays a role in the development of scarring and fibrosis, as the matrix-producing myofibroblast arises from cells of epithelial lineage in response to injury but is pathologically sustained instead of undergoing MET or apoptosis. In this review, we summarize the role of EMT in physiologic repair and pathologic fibrosis of tissues and organs. We conclude that further investigation into the contribution of EMT to the impaired repair of fibrotic wounds may identify components of EMT signaling as common therapeutic targets for impaired healing in many tissues. PMID:27461257

Effect-independent measures of tissue response to fractionated radiation

International Nuclear Information System (INIS)

Thames, H.D.

1984-01-01

Tissue repair factors are measures of sparing from dose fractionation, in the absence of proliferation. A desirable feature of any repair factor is that it be independent of the level of injury induced in the tissue, since otherwise the comparison of tissues on the basis of the factor would not be meaningful. The repair factors F/sub R/ and F/sub rec/ are increasing functions of D/sub 1/, and depend on level of skin reaction after fractionated radiation. By contrast, β/α is effect-independent as a measure of repair capacity in skin, gut, and bone marrow. For late fibrotic reactions in the kidney, there was an increase in β/α with increased levels of injury that was statistically insignificant. The halftime, T/sub 1/2/, for intracellular repair processes in tissues is a measure of repair kinetics. Effect-independence is defend for T/sub 1/2/ as independence from size of dose per fraction. T/sub 1/2/ is independent of fraction size in skin, gut, and spinal cord, and is longer (1.5 hours) in the late-reacting tissues (lung and spinal cord) than in those that react acutely (less than 1 hour), with skin as the exception (1.3 hours). Therefore, early and late-responding normal tissues may be distinguished in terms of both repair capacity and repair kinetics: repair is slower in late-responding tissues, which are also more sensitive to changes in dose fractionation

Tissue repair genes: the TiRe database and its implication for skin wound healing

OpenAIRE

Yanai, Hagai; Budovsky, Arie; Tacutu, Robi; Barzilay, Thomer; Abramovich, Amir; Ziesche, Rolf; Fraifeld, Vadim E.

2016-01-01

Wound healing is an inherent feature of any multicellular organism and recent years have brought about a huge amount of data regarding regular and abnormal tissue repair. Despite the accumulated knowledge, modulation of wound healing is still a major biomedical challenge, especially in advanced ages. In order to collect and systematically organize what we know about the key players in wound healing, we created the TiRe (Tissue Repair) database, an online collection of genes and proteins that ...

NOD-Like Receptors in Intestinal Homeostasis and Epithelial Tissue Repair

Science.gov (United States)

Parlato, Marianna; Yeretssian, Garabet

2014-01-01

The intestinal epithelium constitutes a dynamic physical barrier segregating the luminal content from the underlying mucosal tissue. Following injury, the epithelial integrity is restored by rapid migration of intestinal epithelial cells (IECs) across the denuded area in a process known as wound healing. Hence, through a sequence of events involving restitution, proliferation and differentiation of IECs the gap is resealed and homeostasis reestablished. Relapsing damage followed by healing of the inflamed mucosa is a hallmark of several intestinal disorders including inflammatory bowel diseases (IBD). While several regulatory peptides, growth factors and cytokines stimulate restitution of the epithelial layer after injury, recent evidence in the field underscores the contribution of innate immunity in controlling this process. In particular, nucleotide-binding and oligomerization domain-like receptors (NLRs) play critical roles in sensing the commensal microbiota, maintaining homeostasis, and regulating intestinal inflammation. Here, we review the process of intestinal epithelial tissue repair and we specifically focus on the impact of NLR-mediated signaling mechanisms involved in governing epithelial wound healing during disease. PMID:24886810

Nerve autografts and tissue-engineered materials for the repair of peripheral nerve injuries: a 5-year bibliometric analysis

Directory of Open Access Journals (Sweden)

Yuan Gao

2015-01-01

Full Text Available With advances in biomedical methods, tissue-engineered materials have developed rapidly as an alternative to nerve autografts for the repair of peripheral nerve injuries. However, the materials selected for use in the repair of peripheral nerve injuries, in particular multiple injuries and large-gap defects, must be chosen carefully. Various methods and materials for protecting the healthy tissue and repairing peripheral nerve injuries have been described, and each method or material has advantages and disadvantages. Recently, a large amount of research has been focused on tissue-engineered materials for the repair of peripheral nerve injuries. Using the keywords "pe-ripheral nerve injury", "autotransplant", "nerve graft", and "biomaterial", we retrieved publications using tissue-engineered materials for the repair of peripheral nerve injuries appearing in the Web of Science from 2010 to 2014. The country with the most total publications was the USA. The institutions that were the most productive in this field include Hannover Medical School (Germany, Washington University (USA, and Nantong University (China. The total number of publications using tissue-engineered materials for the repair of peripheral nerve injuries grad-ually increased over time, as did the number of Chinese publications, suggesting that China has made many scientific contributions to this field of research.

Prognostic factors in sensory recovery after digital nerve repair

OpenAIRE

Bulut, Tugrul; Akgun, Ulas; Citlak, Atilla; Aslan, Cihan; Sener, Ufuk; Sener, Muhittin

2018-01-01

Objective: The prognostic factors that affect sensory nerve recovery after digital nerve repair are variable because of nonhomogeneous data, subjective tests, and different assessment/scoring methods. The aim of this study was to evaluate the success of sensory nerve recovery after digital nerve repair and to investigate the prognostic factors in sensorial healing.Methods: Ninety-six digital nerve repairs of 63 patients were retrospectively evaluated. All nerves were repaired with end-to-end ...

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.

Role of the immune system in cardiac tissue damage and repair following myocardial infarction.

Science.gov (United States)

Saparov, Arman; Ogay, Vyacheslav; Nurgozhin, Talgat; Chen, William C W; Mansurov, Nurlan; Issabekova, Assel; Zhakupova, Jamilya

2017-09-01

The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation. At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair. It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.

An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode

Science.gov (United States)

Doni, Andrea; Musso, Tiziana; Morone, Diego; Bastone, Antonio; Zambelli, Vanessa; Sironi, Marina; Castagnoli, Carlotta; Cambieri, Irene; Stravalaci, Matteo; Pasqualini, Fabio; Laface, Ilaria; Valentino, Sonia; Tartari, Silvia; Ponzetta, Andrea; Maina, Virginia; Barbieri, Silvia S.; Tremoli, Elena; Catapano, Alberico L.; Norata, Giuseppe D.; Bottazzi, Barbara; Garlanda, Cecilia

2015-01-01

Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity. PMID:25964372

Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

International Nuclear Information System (INIS)

Curtis, Carol D; Thorngren, Daniel L; Nardulli, Ann M

2010-01-01

During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue. We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells

Traumatic hallux varus repair utilizing a soft-tissue anchor: a case report.

Science.gov (United States)

Labovitz, J M; Kaczander, B I

2000-01-01

Hallux varus is usually iatrogenic in nature; however, congenital and acquired etiologies have been described in the literature. The authors present a case of traumatic hallux varus secondary to rupture of the adductor tendon. Surgical correction was performed using a soft tissue anchor for maintenance of the soft tissues utilized for repair.

DNA Checkpoint and Repair Factors Are Nuclear Sensors for Intracellular Organelle Stresses—Inflammations and Cancers Can Have High Genomic Risks

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Huihong Zeng

2018-05-01

Full Text Available Under inflammatory conditions, inflammatory cells release reactive oxygen species (ROS and reactive nitrogen species (RNS which cause DNA damage. If not appropriately repaired, DNA damage leads to gene mutations and genomic instability. DNA damage checkpoint factors (DDCF and DNA damage repair factors (DDRF play a vital role in maintaining genomic integrity. However, how DDCFs and DDRFs are modulated under physiological and pathological conditions are not fully known. We took an experimental database analysis to determine the expression of 26 DNA DDCFs and 42 DNA DDRFs in 21 human and 20 mouse tissues in physiological/pathological conditions. We made the following significant findings: (1 Few DDCFs and DDRFs are ubiquitously expressed in tissues while many are differentially regulated.; (2 the expression of DDCFs and DDRFs are modulated not only in cancers but also in sterile inflammatory disorders and metabolic diseases; (3 tissue methylation status, pro-inflammatory cytokines, hypoxia regulating factors and tissue angiogenic potential can determine the expression of DDCFs and DDRFs; (4 intracellular organelles can transmit the stress signals to the nucleus, which may modulate the cell death by regulating the DDCF and DDRF expression. Our results shows that sterile inflammatory disorders and cancers increase genomic instability, therefore can be classified as pathologies with a high genomic risk. We also propose a new concept that as parts of cellular sensor cross-talking network, DNA checkpoint and repair factors serve as nuclear sensors for intracellular organelle stresses. Further, this work would lead to identification of novel therapeutic targets and new biomarkers for diagnosis and prognosis of metabolic diseases, inflammation, tissue damage and cancers.

Factors affecting healing after arthroscopic rotator cuff repair

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Abtahi, Amir M; Granger, Erin K; Tashjian, Robert Z

2015-01-01

Rotator cuff repair has been shown to have good long-term results. Unfortunately, a significant proportion of repairs still fail to heal. Many factors, both patient and surgeon related, can influence healing after repair. Older age, larger tear size, worse muscle quality, greater muscle-tendon unit retraction, smoking, osteoporosis, diabetes and hypercholesterolemia have all shown to negatively influence tendon healing. Surgeon related factors that can influence healing include repair construct-single vs double row, rehabilitation, and biologics including platelet rich plasma and mesenchymal stem cells. Double-row repairs are biomechanically stronger and have better healing rates compared with single-row repairs although clinical outcomes are equivalent between both constructs. Slower, less aggressive rehabilitation programs have demonstrated improved healing with no negative effect on final range of motion and are therefore recommended after repair of most full thickness tears. Additionally no definitive evidence supports the use of platelet rich plasma or mesenchymal stem cells regarding improvement of healing rates and clinical outcomes. Further research is needed to identify effective biologically directed augmentations that will improve healing rates and clinical outcomes after rotator cuff repair. PMID:25793161

Genipin crosslinker releasing sutures for improving the mechanical/repair strength of damaged connective tissue.

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Sundararaj, Sharath; Slusarewicz, Paul; Brown, Matt; Hedman, Thomas

2017-11-01

The most common mode of surgical repair of ruptured tendons and ligaments involves the use of sutures for reattachment. However, there is a high incidence of rerupture and repair failure due to pulling out of the suture material from the damaged connective tissue. The main goal of this research was to achieve a localized delivery of crosslinking agent genipin (GP) from rapid-release biodegradable coatings on sutures, for strengthening the repair of ruptured connective tissue. Our hypothesis is that GP released from the suture coating will lead to exogenous crosslinking of native connective tissue resulting in beneficial effects on clinically relevant mechanical parameters such as tear resistance, tissue strength, and energy required to rupture the tissue (toughness). Sutures were successfully coated with a biodegradable polymer layer loaded with the crosslinking agent genipin, without compromising the mechanical properties of the suture. The rapid-release of genipin was achieved under both in vitro and ex vivo conditions. Exogenous crosslinking using these genipin releasing sutures was demonstrated using equine tendons. The tendons treated with genipin releasing sutures showed significant improvement in failure load, energy required for pull-out failure, and stiffness. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2199-2205, 2017. © 2016 Wiley Periodicals, Inc.

Apparatus for enhancing tissue repair in mammals

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Goodwin, Thomas J. (Inventor); Parker, Clayton R. (Inventor)

2007-01-01

An apparatus is disclosed for enhancing tissue repair in mammals, with the apparatus comprising: a sleeve for encircling a portion of a mammalian body part, said sleeve comprising an electrically conductive coil capable of generating an electromagnetic field when an electrical current is applied thereto, means for supporting the sleeve on the mammalian body part; and means for supplying the electrically conductive coil with a square wave time varying electrical current sufficient to create a time varying electromagnetic force of from approximately 0.05 gauss to 0.05 gauss within the interior of the coil in order that when the sleeve is placed on a mammalian body part and the time varying electromagnetic force of from approximately 0.05 gauss to 0.05 gauss is generated on the mammalian body part for an extended period of time, tissue regeneration within the mammalian body part is increased to a rate in excess of the normal tissue regeneration rate that would occur without application of the time varying electromagnetic force.

Definition of pertinent parameters for the evaluation of articular cartilage repair tissue with high-resolution magnetic resonance imaging

International Nuclear Information System (INIS)

Marlovits, Stefan; Striessnig, Gabriele; Resinger, Christoph T.; Aldrian, Silke M.; Vecsei, Vilmos; Imhof, Herwig; Trattnig, Siegfried

2004-01-01

To evaluate articular cartilage repair tissue after biological cartilage repair, we propose a new technique of non-invasive, high-resolution magnetic resonance imaging (MRI) and define a new classification system. For the definition of pertinent variables the repair tissue of 45 patients treated with three different techniques for cartilage repair (microfracture, autologous osteochondral transplantation, and autologous chondrocyte transplantation) was analyzed 6 and 12 months after the procedure. High-resolution imaging was obtained with a surface phased array coil placed over the knee compartment of interest and adapted sequences were used on a 1 T MRI scanner. The analysis of the repair tissue included the definition and rating of nine pertinent variables: the degree of filling of the defect, the integration to the border zone, the description of the surface and structure, the signal intensity, the status of the subchondral lamina and subchondral bone, the appearance of adhesions and the presence of synovitis. High-resolution MRI, using a surface phased array coil and specific sequences, can be used on every standard 1 or 1.5 T MRI scanner according to the in-house standard protocols for knee imaging in patients who have had cartilage repair procedures without substantially prolonging the total imaging time. The new classification and grading system allows a subtle description and suitable assessment of the articular cartilage repair tissue

Magnetization transfer analysis of cartilage repair tissue: a preliminary study

International Nuclear Information System (INIS)

Palmieri, F.; Keyzer, F. de; Maes, F.; Breuseghem, I. van

2006-01-01

To evaluate the magnetization transfer ratio (MTR) after two different cartilage repair procedures, and to compare these data with the MTR of normal cartilage. Twenty-seven patients with a proven cartilage defect were recruited: 13 were treated with autologous chondrocyte implantation (ACI) and 14 were treated with the microfracture technique (MFR). All patients underwent MRI examinations with MT-sequences before the surgical treatment, after 12 months (26 patients) and after 24 months (11 patients). Eleven patients received a complete follow-up study at all three time points (five of the ACI group and six of the MFR group). All images were transferred to a workstation to calculate MTR images. For every MT image set, different ROIs were delineated by two radiologists. Means were calculated per ROI type in the different time frames and in both groups of cartilage repair. The data were analyzed with unpaired t- and ANOVA tests, and by calculating Pearson's correlation coefficient. No significant differences were found in the MTR of fatty bone marrow, muscle and normal cartilage in the different time frames. There was a significant but small difference between the MTR of normal cartilage and the cartilage repair area after 12 months for both procedures. After 24 months, the MTR of ACI repaired cartilage (0.31±0.07) was not significantly different from normal cartilage MTR (0.34±0.05). The MTR of MFR repaired cartilage (0.28±0.02), still showed a significant difference from normal cartilage. The differences between damaged and repaired cartilage MTR are too small to enable MT-imaging to be a useful tool for postoperative follow-up of cartilage repair procedures. There is, however, an evolution towards normal MTR-values in the cartilage repair tissue (especially after ACI repair). (orig.)

Development of biodegradable hyper-branched tissue adhesives for the repair of meniscus tears

NARCIS (Netherlands)

Bochynska, A. I.; Van Tienen, T. G.; Hannink, G.; Buma, P.; Grijpma, D. W.

2016-01-01

Meniscus tears are one of the most commonly occurring injuries of the knee joint. Current meniscus repair techniques are challenging and do not bring fully satisfactory results. Tissue adhesives are a promising alternative, since they are easy to apply and cause minimal tissue trauma. In this study,

Hypospadias repair using laser tissue soldering (LTS): preliminary results of a prospective randomized study

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Kirsch, Andrew J.; Cooper, Christopher S.; Canning, Douglas A.; Snyder, Howard M., III; Zderic, Stephen A.

1998-07-01

Purpose: The purpose of this study was to evaluate laser tissue soldering using an 808 nm diode laser and wavelength- matched human albumin solder for urethral surgery in children. Methods: Currently, 30 boys, ages 3 months to 8 years were randomized to standard suturing (n equals 22) or 'sutureless' laser hypospadias repair (n equals 18). Laser soldering was performed with a human albumin solder doped with indocyanine green dye (2.5 mg/ml) using a laser power output of 0.5 W, pulse duration of 0.5 sec, and interval of 0.1 sec. Power density was approximately 16 W/cm2. In the laser group, sutures were used for tissue alignment only. At the time of surgery, neourethral and penile lengths, operative time for urethral repair, and number of sutures/throws were measured. Postoperatively, patients were examined for complications of wound healing, stricture, or fistula formation. Results: Mean age, severity of urethral defect, type of repair, and neourethra length were equivalent between the two groups. Operative time was significantly faster for laser soldering in both simple (1.6 plus or minus 0.21 min, p less than 0.001) and complex (5.4 plus or minus 0.28 min, p less than 0.0001) hypospadias repairs compared to controls (10.6 plus or minus 1.4 min and 27.8 plus or minus 2.9 min, respectively). The mean number of sutures used in the laser group for simple and complex repairs (3.3 plus or minus 0.3 and 8.1 plus or minus 0.64, respectively) were significantly (p less than 0.0001) less than for controls (8.2 plus or minus 0.84 and 20 plus or minus 2.3, respectively). Followup was between 3 months and 14 months. The overall complication rate in the laser group (11%) was lower than the controls (23%). However, statistical significance (p less than 0.05) was achieved only for the subgroup of patients undergoing simple repairs (LTS, 100% success versus suturing, 69% success). Conclusions: These preliminary results indicate that laser tissue soldering for hypospadias repair

Potential of Osteoblastic Cells Derived from Bone Marrow and Adipose Tissue Associated with a Polymer/Ceramic Composite to Repair Bone Tissue.

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Freitas, Gileade P; Lopes, Helena B; Almeida, Adriana L G; Abuna, Rodrigo P F; Gimenes, Rossano; Souza, Lucas E B; Covas, Dimas T; Beloti, Marcio M; Rosa, Adalberto L

2017-09-01

One of the tissue engineering strategies to promote bone regeneration is the association of cells and biomaterials. In this context, the aim of this study was to evaluate if cell source, either from bone marrow or adipose tissue, affects bone repair induced by osteoblastic cells associated with a membrane of poly(vinylidene-trifluoroethylene)/barium titanate (PVDF-TrFE/BT). Mesenchymal stem cells (MSC) were isolated from rat bone marrow and adipose tissue and characterized by detection of several surface markers. Also, both cell populations were cultured under osteogenic conditions and it was observed that MSC from bone marrow were more osteogenic than MSC from adipose tissue. The bone repair was evaluated in rat calvarial defects implanted with PVDF-TrFE/BT membrane and locally injected with (1) osteoblastic cells differentiated from MSC from bone marrow, (2) osteoblastic cells differentiated from MSC from adipose tissue or (3) phosphate-buffered saline. Luciferase-expressing osteoblastic cells derived from bone marrow and adipose tissue were detected in bone defects after cell injection during 25 days without difference in luciferin signal between cells from both sources. Corroborating the in vitro findings, osteoblastic cells from bone marrow combined with the PVDF-TrFE/BT membrane increased the bone formation, whereas osteoblastic cells from adipose tissue did not enhance the bone repair induced by the membrane itself. Based on these findings, it is possible to conclude that, by combining a membrane with cells in this rat model, cell source matters and that bone marrow could be a more suitable source of cells for therapies to engineer bone.

Cell-based and biomaterial approaches to connective tissue repair

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Stalling, Simone Suzette

Connective tissue injuries of skin, tendon and ligament, heal by a reparative process in adults, filling the wound site with fibrotic, disorganized scar tissue that poorly reflects normal tissue architecture or function. Conversely, fetal skin and tendon have been shown to heal scarlessly. Complete regeneration is not intrinsically ubiquitous to all fetal tissues; fetal diaphragmatic and gastrointestinal injuries form scars. In vivo studies suggest that the presence of fetal fibroblasts is essential for scarless healing. In the orthopaedic setting, adult anterior cruciate ligament (ACL) heals poorly; however, little is known about the regenerative capacity of fetal ACL or fetal ACL fibroblasts. We characterized in vitro wound healing properties of fetal and adult ACL fibroblasts demonstrating that fetal ACL fibroblasts migrate faster and elaborate greater quantities of type I collagen, suggesting the healing potential of the fetal ACL may not be intrinsically poor. Similar to fetal ACL fibroblasts, fetal dermal fibroblasts also exhibit robust cellular properties. We investigated the age-dependent effects of dermal fibroblasts on tendon-to-bone healing in rat supraspinatus tendon injuries, a reparative injury model. We hypothesized delivery of fetal dermal fibroblasts would increase tissue organization and mechanical properties in comparison to adult dermal fibroblasts. However, at 1 and 8 weeks, the presence of dermal fibroblasts, either adult or fetal, had no significant effect on tissue histology or mechanical properties. There was a decreasing trend in cross-sectional area of repaired tendons treated with fetal dermal fibroblasts in comparison to adult, but this finding was not significant in comparison to controls. Finally, we synthesized a novel polysaccharide, methacrylated methylcellulose (MA-MC), and fabricated hydrogels using a well-established photopolymerization technique. We characterized the physical and mechanical properties of MA-MC hydrogels in

Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage

NARCIS (Netherlands)

Rutgers, M.; van Pelt, M.J.; Dhert, W.J.A.; Creemers, L.B.; Saris, D.B.F.

2010-01-01

Osteoarthritis and Cartilage Volume 18, Issue 1, January 2010, Pages 12-23 -------------------------------------------------------------------------------- Review Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage M. Rutgers†, M.J.P. van Pelt†,

ADENOSINE RECEPTOR STIMULATION BY POLYDEOXYRIBONUCLEOTIDE IMPROVES TISSUE REPAIR AND SYMPTOMOLOGY IN EXPERIMENTAL COLITIS.

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Giovanni Pallio

2016-08-01

Full Text Available Activation of the adenosine receptor pathway has been demonstrated to be effective in improving tissue remodelling and blunting the inflammatory response. Active colitis is characterized by an intense inflammatory reaction resulting in extensive tissue damage. Symptomatic improvement requires both control of the inflammatory process and repair and remodelling of damaged tissues. We investigated the ability of an A2A receptor agonist, polydeoxyribonucleotide (PDRN, to restore tissue structural integrity in two experimental colitis models using male Sprague-Dawley rats. In the first model, colitis was induced with a single intra-colonic instillation of dinitro-benzene-sulfonic acid (DNBS, 25mg diluted in 0.8ml 50% ethanol. After 6 hrs, animals were randomized to receive either PDRN (8mg/kg/i.p., or PDRN + the A2A antagonist (DMPX; 10mg/kg/i.p., or vehicle (0.8 ml saline solution daily. In the second model, dextran sodium sulphate (DSS was dissolved in drinking water at a concentration of 8%. Control animals received standard drinking water. After 24 hrs animals were randomized to receive PDRN or PDRN+DMPX as described above. Rats were sacrificed 7 days after receiving DNBS or 5 days after DSS. In both experimental models of colitis, PDRN ameliorated the clinical symptoms and weight loss associated with disease as well as promoted the histological repair of damaged tissues. Moreover, PDRN reduced expression of inflammatory cytokines, myeloperoxydase activity, and malondialdheyde. All these effects were abolished by the concomitant administration of the A2a antagonist DMPX. Our study suggests that PDRN may represent a promising treatment for improving tissue repair during inflammatory bowel diseases.

DNA double-strand break repair of blood lymphocytes and normal tissues analysed in a preclinical mouse model: implications for radiosensitivity testing.

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Rübe, Claudia E; Grudzenski, Saskia; Kühne, Martin; Dong, Xiaorong; Rief, Nicole; Löbrich, Markus; Rübe, Christian

2008-10-15

Radiotherapy is an effective cancer treatment, but a few patients suffer severe radiation toxicities in neighboring normal tissues. There is increasing evidence that the variable susceptibility to radiation toxicities is caused by the individual genetic predisposition, by subtle mutations, or polymorphisms in genes involved in cellular responses to ionizing radiation. Double-strand breaks (DSB) are the most deleterious form of radiation-induced DNA damage, and DSB repair deficiencies lead to pronounced radiosensitivity. Using a preclinical mouse model, the highly sensitive gammaH2AX-foci approach was tested to verify even subtle, genetically determined DSB repair deficiencies known to be associated with increased normal tissue radiosensitivity. By enumerating gammaH2AX-foci in blood lymphocytes and normal tissues (brain, lung, heart, and intestine), the induction and repair of DSBs after irradiation with therapeutic doses (0.1-2 Gy) was investigated in repair-proficient and repair-deficient mouse strains in vivo and blood samples irradiated ex vivo. gammaH2AX-foci analysis allowed to verify the different DSB repair deficiencies; even slight impairments caused by single polymorphisms were detected similarly in both blood lymphocytes and solid tissues, indicating that DSB repair measured in lymphocytes is valid for different and complex organs. Moreover, gammaH2AX-foci analysis of blood samples irradiated ex vivo was found to reflect repair kinetics measured in vivo and, thus, give reliable information about the individual DSB repair capacity. gammaH2AX analysis of blood and tissue samples allows to detect even minor genetically defined DSB repair deficiencies, affecting normal tissue radiosensitivity. Future studies will have to evaluate the clinical potential to identify patients more susceptible to radiation toxicities before radiotherapy.

Apparatus and method for enhancing tissue repair in mammals

Science.gov (United States)

Goodwin, Thomas J. (Inventor); Parker, Clayton R. (Inventor)

2009-01-01

An apparatus is introduced for the use of enhancing tissue repair in mammals. The apparatus includes a sleeve; an electrically conductive coil; a sleeve support; an electrical circuit configured to supply the coil with a square wave time varying electrical current sufficient to create approximately 0.05 gauss to 0.5 gauss. When in use, the sleeve of the apparatus is placed on a mammalian body part and the time varying electromagnetic force of from approximately 0.05 gauss to 0.5 gauss is generated on the mammalian body for an extended period of time so that the tissue is encouraged to be regenerated in the mammalian body part at a rate in excess of the normal tissue regeneration rate relative to regeneration without application of the time varying electromagnetic force.

Arthroscopic Partial Repair of Irreparable Rotator Cuff Tears: Preoperative Factors Associated With Outcome Deterioration Over 2 Years.

Science.gov (United States)

Shon, Min Soo; Koh, Kyoung Hwan; Lim, Tae Kang; Kim, Won Ju; Kim, Kyung Cheon; Yoo, Jae Chul

2015-08-01

Arthroscopic partial repair is a treatment option in irreparable large-to-massive rotator cuff tears without arthritic changes. However, there are indications that arthroscopic partial repair does not yield satisfactory outcomes. To report the clinical and radiographic results of arthroscopic partial repairs in patients with irreparable large-to-massive cuff tears. In addition, an analysis was performed regarding preoperative factors that may influence patient outcomes and patient-rated satisfaction over time. Case series; Level of evidence, 4. From 2005 to 2011, a total of 31 patients who underwent arthroscopic partial repair for irreparable large-to-massive cuff tears were retrospectively evaluated. Partial repair was defined as posterior cuff tissue repair with or without subscapularis tendon repair to restore the transverse force couple of the cuff. Pain visual analog scale (PVAS), questionnaire results (American Shoulder and Elbow Surgeons [ASES] and Simple Shoulder Test [SST]), and radiographic changes (acromiohumeral distance and degenerative change) were assessed preoperatively, at first follow-up (roughly 1 year postoperatively), and at final follow-up (>2 years postoperatively). Patients rated their satisfaction level at each postoperative follow-up as well. Preoperative factors that might influence outcomes, such as patient demographics, tear size, and fatty infiltration, were investigated. The preoperative, first follow-up, and final follow-up results for mean PVAS (5.13, 2.13, and 3.16, respectively) and questionnaires (ASES: 41.97, 76.37, and 73.78; SST: 3.61, 6.33, and 6.07, respectively) improved significantly (all P .05) from the first to the final follow-up. Among preoperative factors, fatty infiltration of the teres minor was identified as the only statistically significant factor affecting patient-rated satisfaction (P = .007). This study showed that arthroscopic partial repair may produce initial improvement in selected outcomes at 2-year

Disrupted G1 to S phase clearance via cyclin signaling impairs liver tissue repair in thioacetamide-treated type 1 diabetic rats

International Nuclear Information System (INIS)

Devi, Sachin S.; Mehendale, Harihara M.

2005-01-01

Previously we reported that a nonlethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats because of irreversible acute liver injury owing to inhibited hepatic tissue repair, primarily due to blockage of G 0 to S phase progression of cell division cycle. On the other hand, DB rats receiving 30 mg TA/kg exhibited equal initial liver injury and delayed tissue repair compared to nondiabetic (NDB) rats receiving 300 mg TA/kg, resulting in a delay in recovery from liver injury and survival. The objective of the present study was to test the hypothesis that impaired cyclin-regulated progression of G 1 to S phase of the cell cycle may explain inhibited liver tissue repair, hepatic failure, and death, contrasted with delayed liver tissue repair but survival observed in the DB rats receiving 300 in contrast to 30 mg TA/kg. In the TA-treated NDB rats sustained MAPKs and cyclin expression resulted in higher phosphorylation of retinoblastoma (pRb), explaining prompt tissue repair and survival. In contrast, DB rats receiving the same dose of TA (300 mg/kg) exhibited suppressed MAPKs and cyclin expression that led to inhibition of pRb, inhibited tissue repair, and death. On the other hand, DB rats receiving 30 mg TA/kg exhibited delayed up regulation of MAPK signaling that delayed the expression of CD1 and pRb, explaining delayed stimulation of tissue repair observed in this group. In conclusion, the hepatotoxicant TA has a dose-dependent adverse effect on cyclin-regulated pRb signaling: the lower dose causes a recoverable delay, whereas the higher dose inhibits it with corresponding effect on the ultimate outcomes on hepatic tissue repair; this dose-dependent adverse effect is substantially shifted to the left of the dose response curve in diabetes

Cell and biomolecule delivery for tissue repair and regeneration in the central nervous system.

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Elliott Donaghue, Irja; Tam, Roger; Sefton, Michael V; Shoichet, Molly S

2014-09-28

Tissue engineering frequently involves cells and scaffolds to replace damaged or diseased tissue. It originated, in part, as a means of effecting the delivery of biomolecules such as insulin or neurotrophic factors, given that cells are constitutive producers of such therapeutic agents. Thus cell delivery is intrinsic to tissue engineering. Controlled release of biomolecules is also an important tool for enabling cell delivery since the biomolecules can enable cell engraftment, modulate inflammatory response or otherwise benefit the behavior of the delivered cells. We describe advances in cell and biomolecule delivery for tissue regeneration, with emphasis on the central nervous system (CNS). In the first section, the focus is on encapsulated cell therapy. In the second section, the focus is on biomolecule delivery in polymeric nano/microspheres and hydrogels for the nerve regeneration and endogenous cell stimulation. In the third section, the focus is on combination strategies of neural stem/progenitor cell or mesenchymal stem cell and biomolecule delivery for tissue regeneration and repair. In each section, the challenges and potential solutions associated with delivery to the CNS are highlighted. Copyright © 2014 Elsevier B.V. All rights reserved.

Method of tissue repair using a composite material

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Hutchens, Stacy A.; Woodward, Jonathan; Evans, Barbara R.; O' Neill, Hugh M.

2016-03-01

A composite biocompatible hydrogel material includes a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa. A calcium comprising salt is disposed in at least some of the pores. The porous polymer matrix can comprise cellulose, including bacterial cellulose. The composite can be used as a bone graft material. A method of tissue repair within the body of animals includes the steps of providing a composite biocompatible hydrogel material including a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa, and inserting the hydrogel material into cartilage or bone tissue of an animal, wherein the hydrogel material supports cell colonization in vitro for autologous cell seeding.

Method of tissue repair using a composite material

Science.gov (United States)

Hutchens, Stacy A; Woodward, Jonathan; Evans, Barbara R; O'Neill, Hugh M

2014-03-18

A composite biocompatible hydrogel material includes a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa. A calcium comprising salt is disposed in at least some of the pores. The porous polymer matrix can comprise cellulose, including bacterial cellulose. The composite can be used as a bone graft material. A method of tissue repair within the body of animals includes the steps of providing a composite biocompatible hydrogel material including a porous polymer matrix, the polymer matrix including a plurality of pores and providing a Young's modulus of at least 10 GPa, and inserting the hydrogel material into cartilage or bone tissue of an animal, wherein the hydrogel material supports cell colonization in vitro for autologous cell seeding.

Radiation Exposure in Endovascular Infra-Renal Aortic Aneurysm Repair and Factors that Influence It

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Rui Machado

Full Text Available Abstract Objective: The endovascular repair of aortic abdominal aneurysms exposes the patients and surgical team to ionizing radiation with risk of direct tissue damage and induction of gene mutation. This study aims to describe our standard of radiation exposure in endovascular aortic aneurysm repair and the factors that influence it. Methods: Retrospective analysis of a prospective database of patients with abdominal infra-renal aortic aneurysms submitted to endovascular repair. This study evaluated the radiation doses (dose area product (DAP, fluoroscopy durations and their relationships to the patients, aneurysms, and stent-graft characteristics. Results: This study included 127 patients with a mean age of 73 years. The mean DAP was 4.8 mGy.m2, and the fluoroscopy time was 21.8 minutes. Aortic bilateral iliac aneurysms, higher body mass index, aneurysms with diameters larger than 60 mm, necks with diameters larger than 28 mm, common iliac arteries with diameters larger than 20 mm, and neck angulations superior to 50 degrees were associated with an increased radiation dose. The number of anatomic risk factors present was associated with increased radiation exposure and fluoroscopy time, regardless of the anatomical risk factors. Conclusion: The radiation exposure during endovascular aortic aneurysm repair is significant (mean DAP 4.8 mGy.m2 with potential hazards to the surgical team and the patients. The anatomical characteristics of the aneurysm, patient characteristics, and the procedure's technical difficulty were all related to increased radiation exposure during endovascular aortic aneurysm repair procedures. Approximately 40% of radiation exposure can be explained by body mass index, neck angulation, aneurysm diameter, neck diameter, and aneurysm type.

The influence of environmental factors on bone tissue engineering.

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Szpalski, Caroline; Sagebin, Fabio; Barbaro, Marissa; Warren, Stephen M

2013-05-01

Bone repair and regeneration are dynamic processes that involve a complex interplay between the substrate, local and systemic cells, and the milieu. Although each constituent plays an integral role in faithfully recreating the skeleton, investigators have long focused their efforts on scaffold materials and design, cytokine and hormone administration, and cell-based therapies. Only recently have the intangible aspects of the milieu received their due attention. In this review, we highlight the important influence of environmental factors on bone tissue engineering. Copyright © 2012 Wiley Periodicals, Inc.

Tissue repair in myxobacteria: A cooperative strategy to heal cellular damage.

Science.gov (United States)

Vassallo, Christopher N; Wall, Daniel

2016-04-01

Damage repair is a fundamental requirement of all life as organisms find themselves in challenging and fluctuating environments. In particular, damage to the barrier between an organism and its environment (e.g. skin, plasma membrane, bacterial cell envelope) is frequent because these organs/organelles directly interact with the external world. Here, we discuss the general strategies that bacteria use to cope with damage to their cell envelope and their repair limits. We then describe a novel damage-coping mechanism used by multicellular myxobacteria. We propose that cell-cell transfer of membrane material within a population serves as a wound-healing strategy and provide evidence for its utility. We suggest that--similar to how tissues in eukaryotes have evolved cooperative methods of damage repair--so too have some bacteria that live a multicellular lifestyle. © 2016 WILEY Periodicals, Inc.

Meta-analysis of prognostic factors for amputation following surgical repair of lower extremity vascular trauma.

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Perkins, Z B; Yet, B; Glasgow, S; Cole, E; Marsh, W; Brohi, K; Rasmussen, T E; Tai, N R M

2015-04-01

Lower extremity vascular trauma (LEVT) is a major cause of amputation. A clear understanding of prognostic factors for amputation is important to inform surgical decision-making, patient counselling and risk stratification. The aim was to develop an understanding of prognostic factors for amputation following surgical repair of LEVT. A systematic review was conducted to identify potential prognostic factors. Bayesian meta-analysis was used to calculate an absolute (pooled proportion) and relative (pooled odds ratio, OR) measure of the amputation risk for each factor. Forty-five studies, totalling 3187 discrete LEVT repairs, were included. The overall amputation rate was 10·0 (95 per cent credible interval 7·4 to 13·1) per cent. Significant prognostic factors for secondary amputation included: associated major soft tissue injury (26 versus 8 per cent for no soft tissue injury; OR 5·80), compartment syndrome (28 versus 6 per cent; OR 5·11), multiple arterial injuries (18 versus 9 per cent; OR 4·85), duration of ischaemia exceeding 6 h (24 versus 5 per cent; OR 4·40), associated fracture (14 versus 2 per cent; OR 4·30), mechanism of injury (blast 19 per cent, blunt 16 per cent, penetrating 5 per cent), anatomical site of injury (iliac 18 per cent, popliteal 14 per cent, tibial 10 per cent, femoral 4 per cent), age over 55 years (16 versus 9 per cent; OR 3·03) and sex (men 7 per cent versus women 8 per cent; OR 0·64). Shock and nerve or venous injuries were not significant prognostic factors for secondary amputation. A significant proportion of patients who undergo lower extremity vascular trauma repair will require secondary amputation. This meta-analysis describes significant prognostic factors needed to inform surgical judgement, risk assessment and patient counselling. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

Repair of dense connective tissues via biomaterial-mediated matrix reprogramming of the wound interface.

Science.gov (United States)

Qu, Feini; Pintauro, Michael P; Haughan, Joanne E; Henning, Elizabeth A; Esterhai, John L; Schaer, Thomas P; Mauck, Robert L; Fisher, Matthew B

2015-01-01

Repair of dense connective tissues in adults is limited by their intrinsic hypocellularity and is exacerbated by a dense extracellular matrix (ECM) that impedes cellular migration to and local proliferation at the wound site. Conversely, healing in fetal tissues occurs due in part to an environment conducive to cell mobility and division. Here, we investigated whether the application of a degradative enzyme, collagenase, could reprogram the adult wound margin to a more fetal-like state, and thus abrogate the biophysical impediments that hinder migration and proliferation. We tested this concept using the knee meniscus, a commonly injured structure for which few regenerative approaches exist. To focus delivery and degradation to the wound interface, we developed a system in which collagenase was stored inside poly(ethylene oxide) (PEO) electrospun nanofibers and released upon hydration. Through a series of in vitro and in vivo studies, our findings show that partial digestion of the wound interface improves repair by creating a more compliant and porous microenvironment that expedites cell migration to and/or proliferation at the wound margin. This innovative approach of targeted manipulation of the wound interface, focused on removing the naturally occurring barriers to adult tissue repair, may find widespread application in the treatment of injuries to a variety of dense connective tissues. Copyright © 2014 Elsevier Ltd. All rights reserved.

Factors Influencing Choice of Inguinal Hernia Repair Technique ...

African Journals Online (AJOL)

Background: Inguinal hernia repair surgery is one of the most frequently performed surgical procedures worldwide. This study sought to highlight factors that may influence decisions concerning inguinal hernia repair techniques. Methods: This descriptive crosssectional study was carried out in September 2014 among ...

Prognostic factors in sensory recovery after digital nerve repair.

Science.gov (United States)

Bulut, Tuğrul; Akgün, Ulaş; Çıtlak, Atilla; Aslan, Cihan; Şener, Ufuk; Şener, Muhittin

2016-01-01

The prognostic factors that affect sensory nerve recovery after digital nerve repair are variable because of nonhomogeneous data, subjective tests, and different assessment/scoring methods. The aim of this study was to evaluate the success of sensory nerve recovery after digital nerve repair and to investigate the prognostic factors in sensorial healing. Ninety-six digital nerve repairs of 63 patients were retrospectively evaluated. All nerves were repaired with end-to-end neurorraphy. The static two-point discrimination (s2PD) and Semmes Weinstein monofilament (SWM) tests were performed to evaluate sensory recovery. The association between prognostic factors such as gender, age, involved digit, time from injury to repair, length of follow-up, smoking, concomitant injuries, type of injury, and sensory recovery results were assessed. The s2PD test demonstrated excellent results in 26 nerves (27%), good results in 61 nerves (64%), and poor results in 9 nerves (9%). The results of the SWM test according to Imai classification showed that 31 nerves (32%) were normal, light touch was diminished in 38 nerves (40%), protective sensation was diminished in 17 nerves (18%), loss of protective sensation occurred in 5 nerves (5%), and 5 nerves (5%) were anesthetic. There was a negative relationship between age, smoking, concomitant injuries, and sensory recovery. Our results demonstrate that concomitant tendon, bone and vascular injuries, older age, and smoking were associated with worse sensory nerve recovery results. However, all digital nerve injuries should be repaired, regardless of these prognostic factors.

Development of biodegradable hyper-branched tissue adhesives for the repair of meniscus tears.

Science.gov (United States)

Bochyńska, A I; Van Tienen, T G; Hannink, G; Buma, P; Grijpma, D W

2016-03-01

Meniscus tears are one of the most commonly occurring injuries of the knee joint. Current meniscus repair techniques are challenging and do not bring fully satisfactory results. Tissue adhesives are a promising alternative, since they are easy to apply and cause minimal tissue trauma. In this study, a series of amphiphilic copolymers based on polyethylene glycol, trimethylene carbonate and citric acid were synthesized and subsequently end-functionalized with hexamethylene diisocyanate to form reactive adhesive materials. The shear adhesive strength of the networks to bovine meniscus tissue measured in a lap-shear adhesion test ranged between 20 and 80 kPa, which was better than for fibrin glue (10 kPa). The elastic modulus of the networks depended on composition and was in the same range as that of human meniscus. Cell compatibility was assessed using Alamar Blue staining after incubation of the bovine meniscus cells with different concentrations of the glues for 7 days. Cell viability was not affected after adding up to 3mg of the adhesive/mL of medium. The proposed materials are suitable candidates to be used as resorbable tissue adhesives for meniscus repair. They have excellent mechanical and adhesive properties that can be adjusted by varying the composition of the copolymers. Meniscal tears often occur and current treatment strategies do not bring fully satisfactory results. Use of biodegradable tissue adhesives would be an interesting option, but currently available adhesives are not suited due to toxicity or poor mechanical properties. Here, we describe the development of novel biodegradable, hyper-branched, adhesive copolymers. These adhesives cure upon contact with water forming flexible networks. Their adhesion to bovine meniscus tissue was significantly better than that of clinically used fibrin glue. The tensile properties of the cured networks were in the same range of values of the human meniscus. When physiologically relevant amounts were added to

The transcription fidelity factor GreA impedes DNA break repair.

Science.gov (United States)

Sivaramakrishnan, Priya; Sepúlveda, Leonardo A; Halliday, Jennifer A; Liu, Jingjing; Núñez, María Angélica Bravo; Golding, Ido; Rosenberg, Susan M; Herman, Christophe

2017-10-12

Homologous recombination repairs DNA double-strand breaks and must function even on actively transcribed DNA. Because break repair prevents chromosome loss, the completion of repair is expected to outweigh the transcription of broken templates. However, the interplay between DNA break repair and transcription processivity is unclear. Here we show that the transcription factor GreA inhibits break repair in Escherichia coli. GreA restarts backtracked RNA polymerase and hence promotes transcription fidelity. We report that removal of GreA results in markedly enhanced break repair via the classic RecBCD-RecA pathway. Using a deep-sequencing method to measure chromosomal exonucleolytic degradation, we demonstrate that the absence of GreA limits RecBCD-mediated resection. Our findings suggest that increased RNA polymerase backtracking promotes break repair by instigating RecA loading by RecBCD, without the influence of canonical Chi signals. The idea that backtracked RNA polymerase can stimulate recombination presents a DNA transaction conundrum: a transcription fidelity factor that compromises genomic integrity.

Factors Influencing Choice of Inguinal Hernia Repair Technique

African Journals Online (AJOL)

This study sought to highlight factors that may influence ... Experienced peers play a major role in training on the various repair ... Reasons influencing choice of repair technique include training ... (after appendectomy) accounting for 10 to 15% of all surgical ..... in medical school [as undergraduate students or as residents].

[Application of the xenogenic acellular dermal matrix membrane application used in the postoperative tissue shortage repair].

Science.gov (United States)

Bai, Yanxia; Yan, Liying; Zhang, Shaoqiang; Shao, Yuan; Yao, Xiaobao; Li, Honghui; Zhao, Ruimin; Zhao, Qian; Zhang, Pengfei; Yang, Qi

2014-09-01

To observe the short-term and long-term curative effect of the xenogenic acellular dermal matrix membrane (or joint muscle flap transfer) application used in the 82 cases postoperative tissue shortage repair that after the head neck carcinoma resection. To held the 82 cases head neck carcinoma postoperative mucosa shortage repaired after resection by the xenogenic acellular dermal matrix membrane (or joint muscle flap transfer), 65 cases mucosa shortage wound be directly covered by the repair membrane and the other 17 cases mucosa shortage wound be repaired by the tranfered muscle tissue flap with the repair membrane covered; 53 cases underwent additional postoperative radiotherapy between 2-4 weeks and follow-up in 1, 3, 6, 12, 18, 24, 30, 36, 48, 60 months and observed the operation site repair process through the electronic laryngoscope, observed the patients respiration, swallow, phonation function. Seventy-seven cases patients operation incision reached I phase healing standard, another 5 cases patients operation incision reached II phase healing standard because of the wound infection and fully-recovered through the local wound drainage,dressing process. All the patients tracheal cannula,the stomach tube be extubated successfully and without the local cicatricial constriction occurred. Seventy-eight cases follow up period reached 1 year including 53 cases who underwent postoperative radiotherapy, 49 cases follow up period reached 3 years including 32 cases who underwent postoperative radiotherapy, 14 cases follow up period reached 5 years including 12 cases who underwent postoperative radiotherapy. The patients with static local lesions discovered no reaction such as exclusion, allergy. The application of xenogenic acellular dermal matrix membrane (or joint muscle flap transfer used in in the postoperative tissue shortage repair that after the head neck carcinoma resection have several advantage such as comparatively easily implementation, operation safety

Growth factor and proteinase profile of Vivostat® platelet-rich fibrin linked to tissue repair

DEFF Research Database (Denmark)

Ågren, Sven Per Magnus; Rasmussen, Karina; Pakkenberg, Bente

2014-01-01

. Leucocyte, erythrocyte and platelet counts in whole blood and fibrin-I were determined by automated haematology analyser. Platelet concentration in PRF was quantified manually by stereologic analysis of Giemsa-stained tissue sections, and the total content of five growth factors and MMP-9 by enzyme......·001]. MMP-9 was reduced 139-fold (P tissue regenerative applications....

Current Biomechanical Concepts for Rotator Cuff Repair

Science.gov (United States)

2013-01-01

For the past few decades, the repair of rotator cuff tears has evolved significantly with advances in arthroscopy techniques, suture anchors and instrumentation. From the biomechanical perspective, the focus in arthroscopic repair has been on increasing fixation strength and restoration of the footprint contact characteristics to provide early rehabilitation and improve healing. To accomplish these objectives, various repair strategies and construct configurations have been developed for rotator cuff repair with the understanding that many factors contribute to the structural integrity of the repaired construct. These include repaired rotator cuff tendon-footprint motion, increased tendon-footprint contact area and pressure, and tissue quality of tendon and bone. In addition, the healing response may be compromised by intrinsic factors such as decreased vascularity, hypoxia, and fibrocartilaginous changes or aforementioned extrinsic compression factors. Furthermore, it is well documented that torn rotator cuff muscles have a tendency to atrophy and become subject to fatty infiltration which may affect the longevity of the repair. Despite all the aforementioned factors, initial fixation strength is an essential consideration in optimizing rotator cuff repair. Therefore, numerous biomechanical studies have focused on elucidating the strongest devices, knots, and repair configurations to improve contact characteristics for rotator cuff repair. In this review, the biomechanical concepts behind current rotator cuff repair techniques will be reviewed and discussed. PMID:23730471

Ectopic bone formation during tissue-engineered cartilage repair using autologous chondrocytes and novel plasma-derived albumin scaffolds.

Science.gov (United States)

Robla Costales, David; Junquera, Luis; García Pérez, Eva; Gómez Llames, Sara; Álvarez-Viejo, María; Meana-Infiesta, Álvaro

2016-10-01

The aims of this study were twofold: first, to evaluate the production of cartilaginous tissue in vitro and in vivo using a novel plasma-derived scaffold, and second, to test the repair of experimental defects made on ears of New Zealand rabbits (NZr) using this approach. Scaffolds were seeded with chondrocytes and cultured in vitro for 3 months to check in vitro cartilage production. To evaluate in vivo cartilage production, a chondrocyte-seeded scaffold was transplanted subcutaneously to a nude mouse. To check in vivo repair, experimental defects made in the ears of five New Zealand rabbits (NZr) were filled with chondrocyte-seeded scaffolds. In vitro culture produced mature chondrocytes with no extracellular matrix (ECM). Histological examination of redifferentiated in vitro cultures showed differentiated chondrocytes adhered to scaffold pores. Subcutaneous transplantation of these constructs to a nude mouse produced cartilage, confirmed by histological study. Experimental cartilage repair in five NZr showed cartilaginous tissue repairing the defects, mixed with calcified areas of bone formation. It is possible to produce cartilaginous tissue in vivo and to repair experimental auricular defects by means of chondrocyte cultures and the novel plasma-derived scaffold. Further studies are needed to determine the significance of bone formation in the samples. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

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.

Detection of abnormalities in the superficial zone of cartilage repaired using a tissue engineered construct derived from synovial stem cells

Directory of Open Access Journals (Sweden)

W Ando

2012-09-01

Full Text Available The present study investigated the surface structure and mechanical properties of repair cartilage generated from a tissue engineered construct (TEC derived from synovial mesenchymal stem cells at six months post-implantation compared to those of uninjured cartilage. TEC-mediated repair tissue was cartilaginous with Safranin O staining, and had comparable macro-scale compressive properties with uninjured cartilage. However, morphological assessments revealed that the superficial zone of TEC-mediated tissue was more fibrocartilage-like, in contrast to the middle or deep zones that were more hyaline cartilage-like with Safranin O staining. Histological scoring of the TEC-mediated tissue was significantly lower in the superficial zone than in the middle and deep zones. Scanning electron microscopy showed a thick tangential bundle of collagen fibres at the most superficial layer of uninjured cartilage, while no corresponding structure was detected at the surface of TEC-mediated tissue. Immunohistochemical analysis revealed that PRG4 was localised in the superficial area of uninjured cartilage, as well as the TEC-mediated tissue. Friction testing showed that the lubrication properties of the two tissues was similar, however, micro-indentation analysis revealed that the surface stiffness of the TEC-repair tissue was significantly lower than that of uninjured cartilage. Permeability testing indicated that the TEC-mediated tissue exhibited lower water retaining capacity than did uninjured cartilage, specifically at the superficial zone. Thus, TEC-mediated tissue exhibited compromised mechanical properties at the superficial zone, properties which need improvement in the future for maintenance of long term repair cartilage integrity.

Detection of abnormalities in the superficial zone of cartilage repaired using a tissue engineered construct derived from synovial stem cells.

Science.gov (United States)

Ando, Wataru; Fujie, Hiromichi; Moriguchi, Yu; Nansai, Ryosuke; Shimomura, Kazunori; Hart, David A; Yoshikawa, Hideki; Nakamura, Norimasa

2012-09-28

The present study investigated the surface structure and mechanical properties of repair cartilage generated from a tissue engineered construct (TEC) derived from synovial mesenchymal stem cells at six months post-implantation compared to those of uninjured cartilage. TEC-mediated repair tissue was cartilaginous with Safranin O staining, and had comparable macro-scale compressive properties with uninjured cartilage. However, morphological assessments revealed that the superficial zone of TEC-mediated tissue was more fibrocartilage-like, in contrast to the middle or deep zones that were more hyaline cartilage-like with Safranin O staining. Histological scoring of the TEC-mediated tissue was significantly lower in the superficial zone than in the middle and deep zones. Scanning electron microscopy showed a thick tangential bundle of collagen fibres at the most superficial layer of uninjured cartilage, while no corresponding structure was detected at the surface of TEC-mediated tissue. Immunohistochemical analysis revealed that PRG4 was localised in the superficial area of uninjured cartilage, as well as the TEC-mediated tissue. Friction testing showed that the lubrication properties of the two tissues was similar, however, micro-indentation analysis revealed that the surface stiffness of the TEC-repair tissue was significantly lower than that of uninjured cartilage. Permeability testing indicated that the TEC-mediated tissue exhibited lower water retaining capacity than did uninjured cartilage, specifically at the superficial zone. Thus, TEC-mediated tissue exhibited compromised mechanical properties at the superficial zone, properties which need improvement in the future for maintenance of long term repair cartilage integrity.

Injectable Biodegradable Polyurethane Scaffolds with Release of Platelet-derived Growth Factor for Tissue Repair and Regeneration

Science.gov (United States)

Hafeman, Andrea E.; Li, Bing; Yoshii, Toshitaka; Zienkiewicz, Katarzyna; Davidson, Jeffrey M.; Guelcher, Scott A.

2013-01-01

Purpose The purpose of this work was to investigate the effects of triisocyanate composition on the biological and mechanical properties of biodegradable, injectable polyurethane scaffolds for bone and soft tissue engineering. Methods Scaffolds were synthesized using reactive liquid molding techniques, and were characterized in vivo in a rat subcutaneous model. Porosity, dynamic mechanical properties, degradation rate, and release of growth factors were also measured. Results Polyurethane scaffolds were elastomers with tunable damping properties and degradation rates, and they supported cellular infiltration and generation of new tissue. The scaffolds showed a two-stage release profile of platelet-derived growth factor, characterized by a 75% burst release within the first 24 h and slower release thereafter. Conclusions Biodegradable polyurethanes synthesized from triisocyanates exhibited tunable and superior mechanical properties compared to materials synthesized from lysine diisocyanates. Due to their injectability, biocompatibility, tunable degradation, and potential for release of growth factors, these materials are potentially promising therapies for tissue engineering. PMID:18516665

Current Therapeutic Strategies for Adipose Tissue Defects/Repair Using Engineered Biomaterials and Biomolecule Formulations

Directory of Open Access Journals (Sweden)

Christopher M. Mahoney

2018-05-01

Full Text Available Tissue engineered scaffolds for adipose restoration/repair has significantly evolved in recent years. Patients requiring soft tissue reconstruction, caused by defects or pathology, require biomaterials that will restore void volume with new functional tissue. The gold standard of autologous fat grafting (AFG is not a reliable option. This review focuses on the latest therapeutic strategies for the treatment of adipose tissue defects using biomolecule formulations and delivery, and specifically engineered biomaterials. Additionally, the clinical need for reliable off-the-shelf therapies, animal models, and challenges facing current technologies are discussed.

Current Therapeutic Strategies for Adipose Tissue Defects/Repair Using Engineered Biomaterials and Biomolecule Formulations.

Science.gov (United States)

Mahoney, Christopher M; Imbarlina, Cayla; Yates, Cecelia C; Marra, Kacey G

2018-01-01

Tissue engineered scaffolds for adipose restoration/repair has significantly evolved in recent years. Patients requiring soft tissue reconstruction, caused by defects or pathology, require biomaterials that will restore void volume with new functional tissue. The gold standard of autologous fat grafting (AFG) is not a reliable option. This review focuses on the latest therapeutic strategies for the treatment of adipose tissue defects using biomolecule formulations and delivery, and specifically engineered biomaterials. Additionally, the clinical need for reliable off-the-shelf therapies, animal models, and challenges facing current technologies are discussed.

Laser-activated nano-biomaterials for tissue repair and controlled drug release

International Nuclear Information System (INIS)

Matteini, P; Ratto, F; Rossi, F; Pini, R

2014-01-01

We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds. (laser biophotonics)

Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

Science.gov (United States)

Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

2016-06-23

The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

[Feasibility of using connective tissue prosthesis for autoplastic repair of urinary bladder wall defects (an experimental study)].

Science.gov (United States)

Tyumentseva, N V; Yushkov, B G; Medvedeva, S Y; Kovalenko, R Y; Uzbekov, O K; Zhuravlev, V N

2016-12-01

Experiments on laboratory rats have shown the feasibility of autoplastic repair of urinary bladder wall defects using a connective-tissue capsule formed as the result of an inflammatory response to the presence of a foreign body. The formation of connective tissue prosthesis is characterized by developing fibrous connective tissue, ordering of collagen fibers, reducing the number of cells per unit area with a predominance of more mature cells - fibroblasts. With increasing time of observation, connective tissue prostheses were found to acquire a morphological structure similar to that of the urinary bladder wall. By month 12, the mucosa, the longitudinal and circular muscle layers were formed. The proposed method of partial autoplastic repair of urinary bladder wall is promising, has good long-term results, but requires further experimental studies.

Leucine Supplementation Accelerates Connective Tissue Repair of Injured Tibialis Anterior Muscle

Directory of Open Access Journals (Sweden)

Marcelo G. Pereira

2014-09-01

Full Text Available This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA. Young male Wistar rats were supplemented with leucine (1.35 g/kg per day; then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA of regenerating myofibers (p > 0.05 from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I and Smad2/3 in regenerating muscles (p < 0.05. Leucine also reduced neonatal myosin heavy chain (MyHC-n (p < 0.05, increased adult MyHC-II expression (p < 0.05 and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05. Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases.

Bioactive Polymeric Materials for Tissue Repair

Directory of Open Access Journals (Sweden)

Diane R. Bienek

2017-01-01

Full Text Available Bioactive polymeric materials based on calcium phosphates have tremendous appeal for hard tissue repair because of their well-documented biocompatibility. Amorphous calcium phosphate (ACP-based ones additionally protect against unwanted demineralization and actively support regeneration of hard tissue minerals. Our group has been investigating the structure/composition/property relationships of ACP polymeric composites for the last two decades. Here, we present ACP’s dispersion in a polymer matrix and the fine-tuning of the resin affects the physicochemical, mechanical, and biological properties of ACP polymeric composites. These studies illustrate how the filler/resin interface and monomer/polymer molecular structure affect the material’s critical properties, such as ion release and mechanical strength. We also present evidence of the remineralization efficacy of ACP composites when exposed to accelerated acidic challenges representative of oral environment conditions. The utility of ACP has recently been extended to include airbrushing as a platform technology for fabrication of nanofiber scaffolds. These studies, focused on assessing the feasibility of incorporating ACP into various polymer fibers, also included the release kinetics of bioactive calcium and phosphate ions from nanofibers and evaluate the biorelevance of the polymeric ACP fiber networks. We also discuss the potential for future integration of the existing ACP scaffolds into therapeutic delivery systems used in the precision medicine field.

Biomaterial applications in neural therapy and repair

Institute of Scientific and Technical Information of China (English)

Harmanvir Ghuman; Michel Modo

2017-01-01

The use of biomaterials,such as hydrogels,as a scaffold to deliver cells and drugs is becoming increasingly common to treat neurological conditions,including stroke.With a limited intrinsic ability to regenerate after injury,innovative tissue engineering strategies have shown the potential of biomaterials in facilitating neural tissue regeneration and functional recovery.Using biomaterials can not only promote the survival and integration of transplanted cells in the existing circuitry,but also support controlled site specific delivery of therapeutic drugs.This review aims to provide the reader an understanding of the brain tissue microenvironment after injury,biomaterial criteria that support tissue repair,commonly used natural and synthetic biomaterials,benefits of incorporating cells and neurotrophic factors,as well as the potential of endogenous neurogenesis in repairing the injured brain.

Immobilization and Application of Electrospun Nanofiber Scaffold-based Growth Factor in Bone Tissue Engineering.

Science.gov (United States)

Chen, Guobao; Lv, Yonggang

2015-01-01

Electrospun nanofibers have been extensively used in growth factor delivery and regenerative medicine due to many advantages including large surface area to volume ratio, high porosity, excellent loading capacity, ease of access and cost effectiveness. Their relatively large surface area is helpful for cell adhesion and growth factor loading, while storage and release of growth factor are essential to guide cellular behaviors and tissue formation and organization. In bone tissue engineering, growth factors are expected to transmit signals that stimulate cellular proliferation, migration, differentiation, metabolism, apoptosis and extracellular matrix (ECM) deposition. Bolus administration is not always an effective method for the delivery of growth factors because of their rapid diffusion from the target site and quick deactivation. Therefore, the integration of controlled release strategy within electrospun nanofibers can provide protection for growth factors against in vivo degradation, and can manipulate desired signal at an effective level with extended duration in local microenvironment to support tissue regeneration and repair which normally takes a much longer time. In this review, we provide an overview of growth factor delivery using biomimetic electrospun nanofiber scaffolds in bone tissue engineering. It begins with a brief introduction of different kinds of polymers that were used in electrospinning and their applications in bone tissue engineering. The review further focuses on the nanofiber-based growth factor delivery and summarizes the strategies of growth factors loading on the nanofiber scaffolds for bone tissue engineering applications. The perspectives on future challenges in this area are also pointed out.

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.

Adult Bone Marrow Mesenchymal Stem Cells Primed for fhe Repair of Damaged Cardiac Tissue After Myocardial Infarction

Science.gov (United States)

Marks, Edward D.

The burden of cardiovascular disease around the world is growing, despite improvements in hospital care and time to treatment. As more people survive an initial myocardial infarction (MI), the decompensated heart tissue is strained, leading to heart failure (HF) and an increased risk for a second MI. While extensive progress has been made in treating the symptoms after MI, including HF and angina, little success has come from repairing the damaged heart tissue to alleviate the progression to these end- stage symptoms. One promising area of regenerative research has been the use of adult stem cells, particularly from the bone marrow (BMSCs). These cells can differentiate towards the cardiac cell lineage in vitro while producing trophic factors that can repair damaged tissue. When placed in the heart after MI though, BMSCs have mixed results, producing profound changes in some patients but zero or even negative effects in others. In this report, we used BMSCs as a stem cell base for a regenerative medicine system for the repair of damaged cardiac tissue. These cells are seeded on a polycaprolactone nanoscaffolding support system, which provides a growth substrate for in vitro work, as well as a housing system for protected in vivo delivery. When the nanoscaffold is pre-coated with a novel combination of a cardiac protein, thymosin beta4 (Tbeta4), and a small molecule effector of the WNT protein pathway, IWP-2, BMSCs differentiated towards the cardiac lineage in as little as 24hours. When injected into rat hearts that have been given an ischemic MI, the nanoscaffolding system slowly dissolves, leaving the cells in place of the damaged cardiac tissue. After two weeks of monitoring, BMSCs are present within the damaged hearts, as evidenced by immunofluorescence and nanoparticle tracking. Injections of the nanoscaffolding/cell system led to robust healing of the rat hearts that had been given small- and medium- damage heart attacks, outperforming PBS sham and cell

The optimal fraction size in high-dose-rate brachytherapy: dependency on tissue repair kinetics and low-dose rate

International Nuclear Information System (INIS)

Sminia, Peter; Schneider, Christoph J.; Fowler, Jack F.

2002-01-01

Background and Purpose: Indications of the existence of long repair half-times on the order of 2-4 h for late-responding human normal tissues have been obtained from continuous hyperfractionated accelerated radiotherapy (CHART). Recently, these data were used to explain, on the basis of the biologically effective dose (BED), the potential superiority of fractionated high-dose rate (HDR) with large fraction sizes of 5-7 Gy over continuous low-dose rate (LDR) irradiation at 0.5 Gy/h in cervical carcinoma. We investigated the optimal fraction size in HDR brachytherapy and its dependency on treatment choices (overall treatment time, number of HDR fractions, and time interval between fractions) and treatment conditions (reference low-dose rate, tissue repair characteristics). Methods and Materials: Radiobiologic model calculations were performed using the linear-quadratic model for incomplete mono-exponential repair. An irradiation dose of 20 Gy was assumed to be applied either with HDR in 2-12 fractions or continuously with LDR for a range of dose rates. HDR and LDR treatment regimens were compared on the basis of the BED and BED ratio of normal tissue and tumor, assuming repair half-times between 1 h and 4 h. Results: With the assumption that the repair half-time of normal tissue was three times longer than that of the tumor, hypofractionation in HDR relative to LDR could result in relative normal tissue sparing if the optimum fraction size is selected. By dose reduction while keeping the tumor BED constant, absolute normal tissue sparing might therefore be achieved. This optimum HDR fraction size was found to be largely dependent on the LDR dose rate. On the basis of the BED NT/TUM ratio of HDR over LDR, 3 x 6.7 Gy would be the optimal HDR fractionation scheme for replacement of an LDR scheme of 20 Gy in 10-30 h (dose rate 2-0.67 Gy/h), while at a lower dose rate of 0.5 Gy/h, four fractions of 5 Gy would be preferential, still assuming large differences between tumor

Growth factor and proteinase profile of Vivostat® platelet-rich fibrin linked to tissue repair.

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Agren, M S; Rasmussen, K; Pakkenberg, B; Jørgensen, B

2014-07-01

Autologous platelet-rich fibrin (PRF(®)) is prepared by the automatic Vivostat(®) system. Conflicting results with Vivostat PRF in acute wound healing prompted us to examine its cellular and biomolecular composition. Specifically, platelets, selected growth factors and matrix metalloproteinase (MMP)-9 were quantified using novel analytical methods. Ten healthy non-thrombocytopenic volunteers donated blood for generation of intermediate fibrin-I and final PRF. Anticoagulated whole blood and serum procured in parallel served as baseline controls. Leucocyte, erythrocyte and platelet counts in whole blood and fibrin-I were determined by automated haematology analyser. Platelet concentration in PRF was quantified manually by stereologic analysis of Giemsa-stained tissue sections, and the total content of five growth factors and MMP-9 by enzyme-linked immunosorbent assays. The number of leucocytes and erythrocytes was reduced (P platelets increased (P fibrin-I versus whole blood. PRF contained 982 ± 206 × 10(9) platelets/l representing 3·9-fold (P platelet-derived growth factor (PDGF)-AB [2·5-fold, P PDGF-BB [1·6-fold, P vascular endothelial growth factor > basic fibroblast growth factor [75-fold, P platelet enrichment and biomolecular constituents may guide clinicians in their optimal use of Vivostat PRF for tissue regenerative applications. © 2013 International Society of Blood Transfusion.

Effects of "second-hand" smoke on structure and function of fibroblasts, cells that are critical for tissue repair and remodeling

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Yadav Madhav

2004-04-01

Full Text Available Abstract Background It is known that "second-hand" cigarette smoke leads to abnormal tissue repair and remodelling but the cellular mechanisms involved in these adverse effects are not well understood. Fibroblasts play a major role in repair and remodelling. They orchestrate these processes by proliferating, migrating, and secreting proteins such as, cytokines, growth factors and extracellular matrix molecules. Therefore, we focus our studies on the effects of "second-hand" cigarette smoke on the structure and function of these cells. Results We used sidestream whole (SSW smoke, a major component of "second-hand" smoke, primary embryonic fibroblasts, cells that behave very much like wound fibroblasts, and a variety of cellular and molecular approaches. We show that doses of smoke similar to those found in tissues cause cytoskeletal changes in the fibroblasts that may lead to a decrease in cell migration. In addition, we also show that these levels of cigarette smoke stimulate an increase in cell survival that is reflected in an increase and/or activation of stress/survival proteins such as cIL-8, grp78, PKB/Akt, p53, and p21. We further show that SSW affects the endomembrane system and that this effect is also accomplished by nicotine alone. Conclusions Taken together, our results suggest that: (i SSW may delay wound repair because of the inability of the fibroblasts to migrate into the wounded area, leading to an accumulation of these cells at the edge of the wound, thus preventing the formation of the healing tissue; (ii the increase in cell survival coupled to the decrease in cell migration can lead to a build-up of connective tissue, thereby causing fibrosis and excess scarring.

Repair and tissue engineering techniques for articular cartilage.

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Makris, Eleftherios A; Gomoll, Andreas H; Malizos, Konstantinos N; Hu, Jerry C; Athanasiou, Kyriacos A

2015-01-01

Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.

Degradability of injectable calcium sulfate/mineralized collagen-based bone repair material and its effect on bone tissue regeneration

International Nuclear Information System (INIS)

Chen, Zonggang; Kang, Lingzhi; Meng, Qing-Yuan; Liu, Huanye; Wang, Zhaoliang; Guo, Zhongwu; Cui, Fu-Zhai

2014-01-01

The nHAC/CSH composite is an injectable bone repair material with controllable injectability and self-setting properties prepared by introducing calcium sulfate hemihydrate (CSH) into mineralized collagen (nHAC). When mixed with water, the nHAC/CSH composites can be transformed into mineralized collagen/calcium sulfate dihydrate (nHAC/CSD) composites. The nHAC/CSD composites have good biocompatibility and osteogenic capability. Considering that the degradation behavior of bone repair material is another important factor for its clinical applications, the degradability of nHAC/CSD composites was studied. The results showed that the degradation ratio of the nHAC/CSD composites with lower nHAC content increased with the L/S ratio increase of injectable materials, but the variety of L/S ratio had no significant effect on the degradation ratio of the nHAC/CSD composites with higher nHAC content. Increasing nHAC content in the composites could slow down the degradation of nHAC/CSD composite. Setting accelerator had no significant effect on the degradability of nHAC/CSD composites. In vivo histological analysis suggests that the degradation rate of materials can match the growth rate of new mandibular bone tissues in the implanted site of rabbit. The regulable degradability of materials resulting from the special prescriptions of injectable nHAC/CSH composites will further improve the workability of nHAC/CSD composites. - Highlights: • The nHAC/CSH composite can be as an injectable bone repair material. • The L/S ratio and nHAC content have a significant effect on material degradability. • The degradability of bone materials can be regulated to match tissue repair. • The regulable degradability will further improve the workability of bone materials

Degradability of injectable calcium sulfate/mineralized collagen-based bone repair material and its effect on bone tissue regeneration

Energy Technology Data Exchange (ETDEWEB)

Chen, Zonggang, E-mail: chenzg@sdu.edu.cn [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Kang, Lingzhi [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Meng, Qing-Yuan [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China); Liu, Huanye [Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang 110001 (China); Wang, Zhaoliang [Jinan Military General Hospital of PLA, Jinan 250031 (China); Guo, Zhongwu, E-mail: zwguo@sdu.edu.cn [National Glycoengineering Research Center, Shandong University, Jinan 250100 (China); Cui, Fu-Zhai, E-mail: cuifz@mail.tsinghua.edu.cn [Department of Materials Science and Engineering, Tsinghua University, Beijing 100084 (China)

2014-12-01

The nHAC/CSH composite is an injectable bone repair material with controllable injectability and self-setting properties prepared by introducing calcium sulfate hemihydrate (CSH) into mineralized collagen (nHAC). When mixed with water, the nHAC/CSH composites can be transformed into mineralized collagen/calcium sulfate dihydrate (nHAC/CSD) composites. The nHAC/CSD composites have good biocompatibility and osteogenic capability. Considering that the degradation behavior of bone repair material is another important factor for its clinical applications, the degradability of nHAC/CSD composites was studied. The results showed that the degradation ratio of the nHAC/CSD composites with lower nHAC content increased with the L/S ratio increase of injectable materials, but the variety of L/S ratio had no significant effect on the degradation ratio of the nHAC/CSD composites with higher nHAC content. Increasing nHAC content in the composites could slow down the degradation of nHAC/CSD composite. Setting accelerator had no significant effect on the degradability of nHAC/CSD composites. In vivo histological analysis suggests that the degradation rate of materials can match the growth rate of new mandibular bone tissues in the implanted site of rabbit. The regulable degradability of materials resulting from the special prescriptions of injectable nHAC/CSH composites will further improve the workability of nHAC/CSD composites. - Highlights: • The nHAC/CSH composite can be as an injectable bone repair material. • The L/S ratio and nHAC content have a significant effect on material degradability. • The degradability of bone materials can be regulated to match tissue repair. • The regulable degradability will further improve the workability of bone materials.

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

Activation of factor VII bound to tissue factor: A key early step in the tissue factor pathway of blood coagulation

International Nuclear Information System (INIS)

Rao, L.V.M.; Rapaport, S.I.

1988-01-01

Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. The earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were made with purified factor VII, X, and tissue factor; in some experiments antithrombin III and heparin were added to prevent back-activation of factor VII. Factor X was activated at similar rates in reaction mixtures containing either VII or factor VIIa after an initial 30-sec lag with factor VII. In reaction mixtures with factor VII a linear activation of factor X was established several minutes before cleavage of 125 I-labeled factor VII to the two-chain activated molecule was demonstrable on gel profiles. These data suggest that factor VII/tissue factor cannot activate measurable amounts of factor X over several minutes. Overall, the results support the hypothesis that a rapid preferential activation of factor VII bound to tissue factor by trace amounts of factor Xa is a key early step in tissue factor-dependent blood coagulation

Activation of factor VII bound to tissue factor: a key early step in the tissue factor pathway of blood coagulation.

OpenAIRE

Rao, L V; Rapaport, S I

1988-01-01

Whether the factor VII/tissue factor complex that forms in tissue factor-dependent blood coagulation must be activated to factor VIIa/tissue factor before it can activate its substrates, factor X and factor IX, has been a difficult question to answer because the substrates, once activated, back-activate factor VII. Our earlier studies suggested that human factor VII/tissue factor cannot activate factor IX. Studies have now been extended to the activation of factor X. Reaction mixtures were ma...

HGF-transgenic MSCs can improve the effects of tissue self-repair in a rabbit model of traumatic osteonecrosis of the femoral head.

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Qian Wen

Full Text Available BACKGROUND: Osteonecrosis of the femoral head (ONFH is generally characterized as an irreversible disease and tends to cause permanent disability. Therefore, understanding the pathogenesis and molecular mechanisms of ONFH and developing effective therapeutic methods is critical for slowing the progress of the disease. METHODOLOGY/PRINCIPAL FINDINGS: In this study, an experimental rabbit model of early stage traumatic ONFH was established, validated, and used for an evaluation of therapy. Computed tomography (CT and magnetic resonance (MR imaging confirmed that this model represents clinical Association Research Circulation Osseous (ARCO phase I or II ONFH, which was also confirmed by the presence of significant tissue damage in osseous tissue and vasculature. Pathological examination detected obvious self-repair of bone tissue up to 2 weeks after trauma, as indicated by revascularization (marked by CD105 and expression of collagen type I (Col I, osteocalcin, and proliferating cell nuclear antigen. Transplantation of hepatocyte growth factor (HGF-transgenic mesenchymal stem cells (MSCs 1 week after trauma promoted recovery from ONFH, as evidenced by a reversed pattern of Col I expression compared with animals receiving no therapeutic treatment, as well as increased expression of vascular endothelial growth factor. CONCLUSIONS/SIGNIFICANCE: These results indicate that the transplantation of HGF-transgenic MSCs is a promising method for the treatment for ONFH and suggest that appropriate interference therapy during the tissue self-repair stage contributes to the positive outcomes. This study also provides a model for the further study of the ONFH etiology and therapeutic interventions.

Evaluation of the Risk Factors for a Rotator Cuff Retear After Repair Surgery.

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Lee, Yeong Seok; Jeong, Jeung Yeol; Park, Chan-Deok; Kang, Seung Gyoon; Yoo, Jae Chul

2017-07-01

A retear is a significant clinical problem after rotator cuff repair. However, no study has evaluated the retear rate with regard to the extent of footprint coverage. To evaluate the preoperative and intraoperative factors for a retear after rotator cuff repair, and to confirm the relationship with the extent of footprint coverage. Cohort study; Level of evidence, 3. Data were retrospectively collected from 693 patients who underwent arthroscopic rotator cuff repair between January 2006 and December 2014. All repairs were classified into 4 types of completeness of repair according to the amount of footprint coverage at the end of surgery. All patients underwent magnetic resonance imaging (MRI) after a mean postoperative duration of 5.4 months. Preoperative demographic data, functional scores, range of motion, and global fatty degeneration on preoperative MRI and intraoperative variables including the tear size, completeness of rotator cuff repair, concomitant subscapularis repair, number of suture anchors used, repair technique (single-row or transosseous-equivalent double-row repair), and surgical duration were evaluated. Furthermore, the factors associated with failure using the single-row technique and transosseous-equivalent double-row technique were analyzed separately. The retear rate was 7.22%. Univariate analysis revealed that rotator cuff retears were affected by age; the presence of inflammatory arthritis; the completeness of rotator cuff repair; the initial tear size; the number of suture anchors; mean operative time; functional visual analog scale scores; Simple Shoulder Test findings; American Shoulder and Elbow Surgeons scores; and fatty degeneration of the supraspinatus, infraspinatus, and subscapularis. Multivariate logistic regression analysis revealed patient age, initial tear size, and fatty degeneration of the supraspinatus as independent risk factors for a rotator cuff retear. Multivariate logistic regression analysis of the single-row group

Porous poly (lactic-co-glycolide) microsphere sintered scaffolds for tissue repair applications

International Nuclear Information System (INIS)

Wang Yingjun; Shi Xuetao; Ren Li; Wang Chunming; Wang Dongan

2009-01-01

In this paper, a new route to preparing porous poly (lactic-co-glycolide) (PLGA) scaffolds for bone tissue repair applications was developed. Novel porous PLGA scaffolds were fabricated via microsphere sintered technique and gas forming technique. Ammonium bicarbonate was used to regulate porosity of these porous scaffolds. Porosity of the scaffolds, and cell attachment, viability and proliferation on the scaffolds were evaluated. The results indicated that PLGA porous scaffolds were with the porosity from around 30% to 95% by regulating ammonium bicarbonate content from 0 to 10%. We also found that PLGA porous microsphere scaffolds benefited cell attachment and viability. Taken together, the achieved porous scaffolds have controlled porosity and also support mesenchymal stem cell proliferation, which could serve as potential scaffolds for bone repair applications.

True Lies: The Double Life of the Nucleotide Excision Repair Factors in Transcription and DNA Repair

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Nicolas Le May

2010-01-01

Full Text Available Nucleotide excision repair (NER is a major DNA repair pathway in eukaryotic cells. NER removes structurally diverse lesions such as pyrimidine dimers, arising upon UV irradiation or bulky chemical adducts, arising upon exposure to carcinogens and some chemotherapeutic drugs. NER defects lead to three genetic disorders that result in predisposition to cancers, accelerated aging, neurological and developmental defects. During NER, more than 30 polypeptides cooperate to recognize, incise, and excise a damaged oligonucleotide from the genomic DNA. Recent papers reveal an additional and unexpected role for the NER factors. In the absence of a genotoxic attack, the promoters of RNA polymerases I- and II-dependent genes recruit XPA, XPC, XPG, and XPF to initiate gene expression. A model that includes the growth arrest and DNA damage 45α protein (Gadd45α and the NER factors, in order to maintain the promoter of active genes under a hypomethylated state, has been proposed but remains controversial. This paper focuses on the double life of the NER factors in DNA repair and transcription and describes the possible roles of these factors in the RNA synthesis process.

Osteochondral Biopsy Analysis Demonstrates That BST-CarGel Treatment Improves Structural and Cellular Characteristics of Cartilage Repair Tissue Compared With Microfracture

Science.gov (United States)

Méthot, Stéphane; Changoor, Adele; Tran-Khanh, Nicolas; Hoemann, Caroline D.; Stanish, William D.; Restrepo, Alberto; Shive, Matthew S.; Buschmann, Michael D.

2016-01-01

Objective The efficacy and safety of BST-CarGel, a chitosan-based medical device for cartilage repair, was compared with microfracture alone at 1 year during a multicenter randomized controlled trial (RCT) in the knee. The quality of repair tissue of osteochondral biopsies collected from a subset of patients was compared using blinded histological assessments. Methods The international RCT evaluated repair tissue quantity and quality by 3-dimensional quantitative magnetic resonance imaging as co-primary endpoints at 12 months. At an average of 13 months posttreatment, 21/41 BST-CarGel and 17/39 microfracture patients underwent elective second look arthroscopies as a tertiary endpoint, during which ICRS (International Cartilage Repair Society) macroscopic scoring was carried out, and osteochondral biopsies were collected. Stained histological sections were evaluated by blinded readers using ICRS I and II histological scoring systems. Collagen organization was evaluated using a polarized light microscopy score. Results BST-CarGel treatment resulted in significantly better ICRS macroscopic scores (P = 0.0002) compared with microfracture alone, indicating better filling, integration, and tissue appearance. Histologically, BST-CarGel resulted in a significant improvement of structural parameters—Surface Architecture (P = 0.007) and Surface/Superficial Assessment (P = 0.042)—as well as cellular parameters—Cell Viability (P = 0.006) and Cell Distribution (P = 0.032). No histological parameters were significantly better for the microfracture group. BST-CarGel treatment also resulted in a more organized repair tissue with collagen stratification more similar to native hyaline cartilage, as measured by polarized light microscopy scoring (P = 0.0003). Conclusion Multiple and independent analyses in this biopsy substudy demonstrated that BST-CarGel treatment results in improved structural and cellular characteristics of repair tissue at 1 year posttreatment compared with

Mechanical properties of hyaline and repair cartilage studied by nanoindentation.

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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.

Concise Review: Mesenchymal Stem Cells Ameliorate Tissue Injury via Secretion of Tumor Necrosis Factor-α Stimulated Protein/Gene 6

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Zhigang He

2014-01-01

Full Text Available Numerous reports have described therapeutic benefits in various disease models after administration of the adult stem/progenitor cells from bone marrow or other tissues referred to as mesenchymal stem cells/multipotent mesenchymal stromal cells (MSCs. They all showed that one of the important effects of MSCs is to act against excessive inflammatory responses and repair the damaged tissues. The therapeutic benefits of MSCs were initially interpreted by their migration, engraftment, and differentiation into target tissues. However, remarkable anatomical structural repairs and functional improvements were increasingly observed with a small number of or even no MSCs in the injured tissues. This suggests that most beneficial effects are largely due to paracrine secretions or cell-to-cell contacts that have multiple effects involving modulation of inflammatory and immune responses. Currently, the therapeutic benefits of MSCs are in part explained by the cells being activated by signals from injured tissues to express an anti-inflammatory protein, tumor-necrosis-factor-α-induced protein 6. This important mechanism of action has attracted increasing attention, and therefore we conducted this review to summarize the latest research.

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

Repairable-conditionally repairable damage model based on dual Poisson processes.

Science.gov (United States)

Lind, B K; Persson, L M; Edgren, M R; Hedlöf, I; Brahme, A

2003-09-01

The advent of intensity-modulated radiation therapy makes it increasingly important to model the response accurately when large volumes of normal tissues are irradiated by controlled graded dose distributions aimed at maximizing tumor cure and minimizing normal tissue toxicity. The cell survival model proposed here is very useful and flexible for accurate description of the response of healthy tissues as well as tumors in classical and truly radiobiologically optimized radiation therapy. The repairable-conditionally repairable (RCR) model distinguishes between two different types of damage, namely the potentially repairable, which may also be lethal, i.e. if unrepaired or misrepaired, and the conditionally repairable, which may be repaired or may lead to apoptosis if it has not been repaired correctly. When potentially repairable damage is being repaired, for example by nonhomologous end joining, conditionally repairable damage may require in addition a high-fidelity correction by homologous repair. The induction of both types of damage is assumed to be described by Poisson statistics. The resultant cell survival expression has the unique ability to fit most experimental data well at low doses (the initial hypersensitive range), intermediate doses (on the shoulder of the survival curve), and high doses (on the quasi-exponential region of the survival curve). The complete Poisson expression can be approximated well by a simple bi-exponential cell survival expression, S(D) = e(-aD) + bDe(-cD), where the first term describes the survival of undamaged cells and the last term represents survival after complete repair of sublethal damage. The bi-exponential expression makes it easy to derive D(0), D(q), n and alpha, beta values to facilitate comparison with classical cell survival models.

Cellular response of healing tissue to DegraPol tube implantation in rabbit Achilles tendon rupture repair: an in vivo histomorphometric study.

Science.gov (United States)

Buschmann, Johanna; Meier-Bürgisser, Gabriella; Bonavoglia, Eliana; Neuenschwander, Peter; Milleret, Vincent; Giovanoli, Pietro; Calcagni, Maurizio

2013-05-01

In tendon rupture repair, improvements such as higher primary repair strength, anti-adhesion and accelerated healing are needed. We developed a potential carrier system of an electrospun DegraPol tube, which was tightly implanted around a transected and conventionally sutured rabbit Achilles tendon. Histomorphometric analysis of the tendon tissue 12 weeks postoperation showed that the tenocyte density, tenocyte morphology and number of inflammation zones were statistically equivalent, whether or not DegraPol tube was implanted; only the collagen fibres were slightly less parallelly orientated in the tube-treated case. Comparison of rabbits that were operated on both hind legs with ones that were operated on only one hind leg showed that there were significantly more inflammation zones in the two-leg cases compared to the one-leg cases, while the implantation of a DegraPol tube had no such adverse effects. These findings are a prerequisite for using DegraPol tube as a carrier system for growth factors, cytokines or stem cells in order to accelerate the healing process of tendon tissue. Copyright © 2012 John Wiley & Sons, Ltd.

Emergency repair of upper extremity large soft tissue and vascular injuries with flow-through anterolateral thigh free flaps.

Science.gov (United States)

Zhan, Yi; Fu, Guo; Zhou, Xiang; He, Bo; Yan, Li-Wei; Zhu, Qing-Tang; Gu, Li-Qiang; Liu, Xiao-Lin; Qi, Jian

2017-12-01

Complex extremity trauma commonly involves both soft tissue and vascular injuries. Traditional two-stage surgical repair may delay rehabilitation and functional recovery, as well as increase the risk of infections. We report a single-stage reconstructive surgical method that repairs soft tissue defects and vascular injuries with flow-through free flaps to improve functional outcomes. Between March 2010 and December 2016 in our hospital, 5 patients with severe upper extremity trauma received single-stage reconstructive surgery, in which a flow-through anterolateral thigh free flap was applied to repair soft tissue defects and vascular injuries simultaneously. Cases of injured artery were reconstructed with the distal trunk of the descending branch of the lateral circumflex femoral artery. A segment of adjacent vein was used if there was a second artery injury. Patients were followed to evaluate their functional recoveries, and received computed tomography angiography examinations to assess peripheral circulation. Two patients had post-operative thumb necrosis; one required amputation, and the other was healed after debridement and abdominal pedicle flap repair. The other 3 patients had no major complications (infection, necrosis) to the recipient or donor sites after surgery. All the patients had achieved satisfactory functional recovery by the end of the follow-up period. Computed tomography angiography showed adequate circulation in the peripheral vessels. The success of these cases shows that one-step reconstructive surgery with flow-through anterolateral thigh free flaps can be a safe and effective treatment option for patients with complex upper extremity trauma with soft tissue defects and vascular injuries. Copyright © 2017. Published by Elsevier Ltd.

Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits.

Science.gov (United States)

Wang, Z J; An, R Z; Zhao, J Y; Zhang, Q; Yang, J; Wang, J B; Wen, G Y; Yuan, X H; Qi, X W; Li, S J; Ye, X C

2014-06-18

After injury, inflammation, or degeneration, articular cartilage has limited self-repair ability. We aimed to explore the feasibility of repair of articular cartilage defects with tissue-engineered cartilage constructed by acellular cartilage matrices (ACMs) seeded with adipose-derived stem cells (ADSCs). The ADSCs were isolated from 3-month-old New Zealand albino rabbit by using collagenase and cultured and amplified in vitro. Fresh cartilage isolated from adult New Zealand albino rabbit were freeze-dried for 12 h and treated with Triton X-100, DNase, and RNase to obtain ACMs. ADSCs were seeded in the acellular cartilaginous matrix at 2x10(7)/mL, and cultured in chondrogenic differentiation medium for 2 weeks to construct tissue-engineered cartilage. Twenty-four New Zealand white rabbits were randomly divided into A, B, and C groups. Engineered cartilage was transplanted into cartilage defect position of rabbits in group A, group B obtained ACMs, and group C did not receive any transplants. The rabbits were sacrificed in week 12. The restored tissue was evaluated using macroscopy, histology, immunohistochemistry, and transmission electron microscopy (TEM). In the tissue-engineered cartilage group (group A), articular cartilage defects of the rabbits were filled with chondrocyte-like tissue with smooth surface. Immunohistochemistry showed type II-collagen expression and Alcian blue staining was positive. TEM showed chondrocytes in the recesses, with plenty of secretary matrix particles. In the scaffold group (group B), the defect was filled with fibrous tissue. No repaired tissue was found in the blank group (group C). Tissue-engineered cartilage using ACM seeded with ADSCs can help repair articular cartilage defects in rabbits.

The role of nuclear hormone receptors in cutaneous wound repair.

Science.gov (United States)

Rieger, Sandra; Zhao, Hengguang; Martin, Paige; Abe, Koichiro; Lisse, Thomas S

2015-01-01

The cutaneous wound repair process involves balancing a dynamic series of events ranging from inflammation, oxidative stress, cell migration, proliferation, survival and differentiation. A complex series of secreted trophic factors, cytokines, surface and intracellular proteins are expressed in a temporospatial manner to restore skin integrity after wounding. Impaired initiation, maintenance or termination of the tissue repair processes can lead to perturbed healing, necrosis, fibrosis or even cancer. Nuclear hormone receptors (NHRs) in the cutaneous environment regulate tissue repair processes such as fibroplasia and angiogenesis. Defects in functional NHRs and their ligands are associated with the clinical phenotypes of chronic non-healing wounds and skin endocrine disorders. The functional relationship between NHRs and skin niche cells such as epidermal keratinocytes and dermal fibroblasts is pivotal for successful wound closure and permanent repair. The aim of this review is to delineate the cutaneous effects and cross-talk of various nuclear receptors upon injury towards functional tissue restoration. Copyright © 2014 John Wiley & Sons, Ltd.

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.

Further proof of the plasticity of adult stem cells and their role in tissue repair

OpenAIRE

Prockop, Darwin J.

2003-01-01

In this issue, De Bari et al. (2003) present elegant data to counter the recent claims that adult stem cells have a limited plasticity. Further, they provide evidence that adult stem cells can seek out damaged tissues and repair them.

Factors affecting healing rates after arthroscopic double-row rotator cuff repair.

Science.gov (United States)

Tashjian, Robert Z; Hollins, Anthony M; Kim, Hyun-Min; Teefey, Sharlene A; Middleton, William D; Steger-May, Karen; Galatz, Leesa M; Yamaguchi, Ken

2010-12-01

Double-row arthroscopic rotator cuff repairs were developed to improve initial biomechanical strength of repairs to improve healing rates. Despite biomechanical improvements, failure of healing remains a clinical problem. To evaluate the anatomical results after double-row arthroscopic rotator cuff repair with ultrasound to determine postoperative repair integrity and the effect of various factors on tendon healing. Case series; Level of evidence, 4. Forty-eight patients (49 shoulders) who had a complete arthroscopic rotator cuff repair (double-row technique) were evaluated with ultrasound at a minimum of 6 months after surgery. Outcome was evaluated at a minimum of 1-year follow-up with standardized history and physical examination, visual analog scale for pain, active forward elevation, and preoperative and postoperative shoulder scores according to the system of the American Shoulder and Elbow Surgeons and the Simple Shoulder Test. Quantitative strength was measured postoperatively. Ultrasound and physical examinations were performed at a minimum of 6 months after surgery (mean, 16 months; range, 6 to 36 months) and outcome questionnaire evaluations at a minimum of 12 months after surgery (mean, 29 months; range, 12 to 55 months). Of 49 repairs, 25 (51%) were healed. Healing rates were 67% in single-tendon tears (16 of 24 shoulders) and 36% in multitendon tears (9 of 25 shoulders). Older age and longer duration of follow-up were correlated with poorer tendon healing (P repair (P rotator cuff repair. The biological limitation at the repair site, as reflected by the effects of age on healing, appears to be the most important factor influencing tendon healing, even after maximizing repair biomechanical strength with a double-row construct.

Galectin-7 is important for normal uterine repair following menstruation.

Science.gov (United States)

Evans, Jemma; Yap, Joanne; Gamage, Thillini; Salamonsen, Lois; Dimitriadis, Evdokia; Menkhorst, Ellen

2014-08-01

Menstruation involves the shedding of the functional layer of the endometrium in the absence of pregnancy. At sites where tissue shedding is complete, re-epithelialization of the tissue is essential for repair and termination of bleeding. The complement of growth factors that mediate post-menstrual endometrial repair are yet to be completely elucidated. Galectins regulate many cell functions important for post-menstrual repair, such as cell adhesion and migration. Galectin-7 has a well characterized role in re-epithelialization and wound healing. We hypothesized that galectin-7 would be important in re-epithelialization during post-menstrual repair. We aimed to identify endometrial expression of galectin-7 in women undergoing normal endometrial repair and in women with amenorrhoea who do not experience endometrial breakdown and repair, and to determine whether galectin-7 enhances endometrial re-epithelialization in vitro. Galectin-7 immunolocalized to the endometrial luminal and glandular epithelium during the late secretory and menstrual phases, and to decidualized stroma in regions exhibiting tissue breakdown. Immunostaining intensity was significantly reduced in the endometrium of women with amenorrhoea compared with normally cycling woman. ELISA identified galectin-7 in menstrual fluid at significantly elevated levels compared with matched peripheral plasma. Exogenous galectin-7 (2.5 µg/ml) significantly enhanced endometrial epithelial wound repair in vitro; this was abrogated by inhibition of integrin binding. Galectin-7 elevated epithelial expression of extracellular matrix-related molecules likely involved in repair including β-catenin, contactin and TGF-β1. In conclusion, galectin-7 is produced by the premenstrual and menstrual endometrium, where it accumulates in menstrual fluid and likely acts as a paracrine factor to facilitate post-menstrual endometrial re-epithelialization. © The Author 2014. Published by Oxford University Press on behalf of the

Repair in unicellular green algae under the chronic action of mutagenic factors

International Nuclear Information System (INIS)

Sergeeva, S.A.; Ptitsina, S.N.; Shevchenko, V.A.

1986-01-01

Repair of single-standed DNA breaks in different strains of unicellular green Chlamidomonas reinhardii algae under the chronic action of mutagenic factors after γ-radiation was studied. It is shown, that the highest DNA break repair efficiency is observed in M γ mt++ strain, resistant to radiation. Strains, sensitive to UV-rays, possess the same repair efficiency as a wild type strain. UVS-1 strain demonstrated a higher repair efficiency, than a wild type strain. All that gives evidence of the difference in Chlamidomonas reinhardii of repair ways, leading to repair of damages, induced by γ-radiation and UV-rays

In-situ crosslinkable and self-assembling elastin-like polypeptide block copolymers for cartilage tissue repair

Science.gov (United States)

Lim, Dong Woo

This work describes the development of genetically engineered elastin-like polypeptide (ELP) block copolymers as in-situ gelling scaffolds for cartilage tissue repair. The central hypothesis underlying this work is that ELP based biopolymers can be exploited as injectable biomaterials by rapid chemical crosslinking. To prove this, gene libraries encoding ELP having different molecular weights and amino acid sequences, and ELP block copolymers composed of various ELP blocks having diverse amino acid composition, length, and phase transition behavior were synthesized by recursive directional ligation, expressed in E. Coli and purified by inverse transition cycling. Mannich-type condensation of hydroxymethylphosphines (HMPs) with primary- and secondary-amines of amino acids was developed as a new crosslinking method of polypeptides. Chemically crosslinked ELP hydrogels were formed rapidly in an aqueous solution by reaction of ELPs containing periodic lysine residues with HMPs. The crosslinking density and mechanical property of the ELP hydrogels were controlled at the sequence level by varying the Lys density in ELPs composed of mono-block as well as by segregation of the Lys residues within specific blocks of tri-block architectures. Fibroblasts embedded in ELP hydrogels survived the crosslinking process and were viable after in vitro culture for at least 3 days. The DNA content of fibroblasts within the tri-block gels was significantly higher than that in the mono-block gels at day 3. These results suggest that the HMP crosslinked ELP block copolymer hydrogels show finely tuned mechanical properties and different microenvironments for cell viability as well as potential as in-situ crosslinkable biopolymers for tissue repair applications with load-bearing environments. As an alternative, rheological behavior of the ELP block copolymers and ELP-grafted hyaluronic acids (HAs) as artificial extracellular matrices (ECMs) showed that they were thermally aggregated into

Fibrinogen-Related Proteins in Tissue Repair: How a Unique Domain with a Common Structure Controls Diverse Aspects of Wound Healing.

Science.gov (United States)

Zuliani-Alvarez, Lorena; Midwood, Kim S

2015-05-01

Significance: Fibrinogen-related proteins (FRePs) comprise an intriguing collection of extracellular molecules, each containing a conserved fibrinogen-like globe (FBG). This group includes the eponymous fibrinogen as well as the tenascin, angiopoietin, and ficolin families. Many of these proteins are upregulated during tissue repair and exhibit diverse roles during wound healing. Recent Advances: An increasing body of evidence highlights the specific expression of a number of FRePs following tissue injury and infection. Upon induction, each FReP uses its FBG domain to mediate quite distinct effects that contribute to different stages of tissue repair, such as driving coagulation, pathogen detection, inflammation, angiogenesis, and tissue remodeling. Critical Issues: Despite a high degree of homology among FRePs, each contains unique sequences that enable their diversification of function. Comparative analysis of the structure and function of FRePs and precise mapping of regions that interact with a variety of ligands has started to reveal the underlying molecular mechanisms by which these proteins play very different roles using their common domain. Future Directions: Fibrinogen has long been used in the clinic as a synthetic matrix serving as a scaffold or a delivery system to aid tissue repair. Novel therapeutic strategies are now emerging that harness the use of other FRePs to improve wound healing outcomes. As we learn more about the underlying mechanisms by which each FReP contributes to the repair response, specific blockade, or indeed potentiation, of their function offers real potential to enable regulation of distinct processes during pathological wound healing.

Honey can repairing damage of liver tissue due to protein energy malnutrition through induction of endogenous stem cells.

Science.gov (United States)

Prasetyo, R Heru; Hestianah, Eka Pramyrtha

2017-06-01

This study was to evaluate effect of honey in repairing damage of liver tissue due to energy protein malnutrition and in mobilization of endogenous stem cells. Male mice model of degenerative liver was obtained through food fasting but still have drinking water for 5 days. It caused energy protein malnutrition and damage of liver tissue. The administration of 50% (v/v) honey was performed for 10 consecutive days, while the positive control group was fasted and not given honey and the negative control not fasted and without honey. Observations of regeneration the liver tissue based on histologically examination, observation of Hsp70 expression, and homing signal based on vascular endothelial growth factor-1 (VEGF-1) expression using immunohistochemistry technique. Observation on expression of CD34 and CD45 as the marker of auto mobilization of hematopoietic stem cells using flow cytometry technique. There is regeneration of the liver tissue due to protein energy malnutrition, decrease of Hsp70 expression, increase of VEGF-1 expression, and high expression of CD34 and CD45. Honey can improve the liver tissue based on: (1) Mobilization of endogenous stem cells (CD34 and CD45); (2) Hsp70 and VEGF-1 expressions as regeneration marker of improvement, and (3) regeneration histologically of liver tissue.

Tissue-engineering as an adjunct to pelvic reconstructive surgery

DEFF Research Database (Denmark)

Jangö, Hanna

of pelvic organ prolapse (POP) are warranted. Traditional native tissue repair may be associated with poor long-term outcome and augmentation with permanent polypropylene meshes is associated with frequent and severe adverse effects. Tissue-engineering is a regenerative strategy that aims at creating...... functional tissue using stem cells, scaffolds and trophic factors. The aim of this thesis was to investigate the potential adjunctive use of a tissue-engineering technique for pelvic reconstructive surgery using two synthetic biodegradable materials; methoxypolyethyleneglycol-poly(lactic-co-glycolic acid......) (MPEG-PLGA) and electrospun polycaprolactone (PCL) - with or without seeded muscle stem cells in the form of autologous fresh muscle fiber fragments (MFFs).To simulate different POP repair scenarios different animal models were used. In Study 1 and 2, MPEG-PLGA was evaluated in a native tissue repair...

Injury induces in vivo expression of platelet-derived growth factor (PDGF) and PDGF receptor mRNAs in skin epithelial cells and PDGF mRNA in connective tissue fibroblasts

International Nuclear Information System (INIS)

Antoniades, H.N.; Galanopoulos, T.; Neville-Golden, J.; Kiritsy, C.P.; Lynch, S.E.

1991-01-01

Platelet-derived growth factor (PDGF) stimulates many of the processes important in tissue repair, including proliferation of fibroblasts and synthesis of extracellular matrices. In this study, the authors have demonstrated with in situ hydridization and immunocytochemistry the reversible expression of 3-sis/PDGF-2 and PDGF receptor (PDGF-R) b mRNAs and their respective protein products in epithelial cells and fibroblasts following cutaneous injury in pigs. Epithelial cells in control, unwounded skin did not express c-sis and PDGF-R mRNAs, and fibroblasts expressed only PDGF-R mRNA. The expression levels in the injured site were correlated with the stage of tissue repair, being highest during the initial stages of the repair process and declining at the time of complete re-epithelialization and tissue remodeling. These studies provide a mulecular basis for understanding the mechanisms contributing to normal tissue repair. They suggest the possibility that a defect in these mechanisms may be associated with defective wound healing. It is also conceivable that chronic injury may induce irreversible gene expression leading to pathologic, unregulated cell growth

Evaluation and comparison of cartilage repair tissue of the patella and medial femoral condyle by using morphological MRI and biochemical zonal T2 mapping

International Nuclear Information System (INIS)

Welsch, Goetz H.; Mamisch, Tallal C.; Quirbach, Sebastian; Trattnig, Siegfried; Zak, Lukas; Marlovits, Stefan

2009-01-01

The objective of this study was to use advanced MR techniques to evaluate and compare cartilage repair tissue after matrix-associated autologous chondrocyte transplantation (MACT) in the patella and medial femoral condyle (MFC). Thirty-four patients treated with MACT underwent 3-T MRI of the knee. Patients were treated on either patella (n = 17) or MFC (n = 17) cartilage and were matched by age and postoperative interval. For morphological evaluation, the MR observation of cartilage repair tissue (MOCART) score was used, with a 3D-True-FISP sequence. For biochemical assessment, T2 mapping was prepared by using a multiecho spin-echo approach with particular attention to the cartilage zonal structure. Statistical evaluation was done by analyses of variance. The MOCART score showed no significant differences between the patella and MFC (p ≥ 0.05). With regard to biochemical T2 relaxation, higher T2 values were found throughout the MFC (p < 0.05). The zonal increase in T2 values from deep to superficial was significant for control cartilage (p < 0.001) and cartilage repair tissue (p < 0.05), with an earlier onset in the repair tissue of the patella. The assessment of cartilage repair tissue of the patella and MFC afforded comparable morphological results, whereas biochemical T2 values showed differences, possibly due to dissimilar biomechanical loading conditions. (orig.)

Genetic and physiological factors affecting repair and mutagenesis in yeast

International Nuclear Information System (INIS)

Lemontt, J.F.

1979-01-01

Current views of DNA repair and mutagenesis in the yeast Saccharomyces cerevisiae are discussed in the light of recent data, and with emphasis on the isolation and characterization of genetically well-defined mutations that affect DNA metabolism in general (including replication and recombination). Various pathways of repair are described particularly in relation to their involvement in mutagenic mechanisms. In addition to genetic control, certain physiological factors such as cell age, DNA replication, and the regulatory state of the mating-type locus, are shown to also play a role in repair and mutagenesis

Genetic and physiological factors affecting repair and mutagenesis in yeast

International Nuclear Information System (INIS)

Lemontt, J.F.

1979-01-01

Current views of DNA repair and mutagenesis in the yeast Saccharomyces cerevisiae are discussed in the light of recent data and with emphasis on the isolation and characterization of genetically well-defined mutations that affect DNA metabolism in general (including replication and recombination). Various pathways of repair are described, particularly in relation to their imvolvement in mutagenic mechanisms. In addition to genetic control, certain physiological factors such as cell age, DNA replication, and the regulatory state of the mating-type locus are shown to also play a role in repair and mutagenesis

Genetic and physiological factors affecting repair and mutagenesis in yeast

Energy Technology Data Exchange (ETDEWEB)

Lemontt, J F

1979-01-01

Current views of DNA repair and mutagenesis in the yeast Saccharomyces cerevisiae are discussed in the light of recent data, and with emphasis on the isolation and characterization of genetically well-defined mutations that affect DNA metabolism in general (including replication and recombination). Various pathways of repair are described particularly in relation to their involvement in mutagenic mechanisms. In addition to genetic control, certain physiological factors such as cell age, DNA replication, and the regulatory state of the mating-type locus, are shown to also play a role in repair and mutagenesis.

Genetic and physiological factors affecting repair and mutagenesis in yeast

Energy Technology Data Exchange (ETDEWEB)

Lemontt, J F

1979-01-01

Current views of DNA repair and mutagenesis in the yeast Saccharomyces cerevisiae are discussed in the light of recent data and with emphasis on the isolation and characterization of genetically well-defined mutations that affect DNA metabolism in general (including replication and recombination). Various pathways of repair are described, particularly in relation to their imvolvement in mutagenic mechanisms. In addition to genetic control, certain physiological factors such as cell age, DNA replication, and the regulatory state of the mating-type locus are shown to also play a role in repair and mutagenesis.

Immunohistochemical Expression of TGF-β1 and Osteonectin in engineered and Ca(OH2-repaired human pulp tissues

Directory of Open Access Journals (Sweden)

Luiz Alexandre CHISINI

Full Text Available Abstract The aim of the present study was to evaluate the expression of transforming growth factor-β1 (TGF-β1 and osteonectin (ON in pulp-like tissues developed by tissue engineering and to compare it with the expression of these proteins in pulps treated with Ca(OH2 therapy. Tooth slices were obtained from non-carious human third molars under sterile procedures. The residual periodontal and pulp soft tissues were removed. Empty pulp spaces of the tooth slice were filled with sodium chloride particles (250–425 µm. PLLA solubilized in 5% chloroform was applied over the salt particles. The tooth slice/scaffold (TS/S set was stored overnight and then rinsed thoroughly to wash out the salt. Scaffolds were previously sterilized with ethanol (100–70° and washed with phosphate-buffered saline (PBS. TS/S was treated with 10% EDTA and seeded with dental pulp stem cells (DPSC. Then, TS/S was implanted into the dorsum of immunodeficient mice for 28 days. Human third molars previously treated with Ca(OH2 for 90 days were also evaluated. Samples were prepared and submitted to histological and immunohistochemical (with anti-TGF-β1, 1:100 and anti-ON, 1:350 analyses. After 28 days, TS/S showed morphological characteristics similar to those observed in dental pulp treated with Ca(OH2. Ca(OH2-treated pulps showed the usual repaired pulp characteristics. In TS/S, newly formed tissues and pre-dentin was colored, which elucidated the expression of TGF-β1 and ON. Immunohistochemistry staining of Ca(OH2-treated pulps showed the same expression patterns. The extracellular matrix displayed a fibrillar pattern under both conditions. Regenerative events in the pulp seem to follow a similar pattern of TGF-β1 and ON expression as the repair processes.

Abnormal Base Excision Repair at Trinucleotide Repeats Associated with Diseases: A Tissue-Selective Mechanism

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Agathi-Vasiliki Goula

2013-07-01

Full Text Available More than fifteen genetic diseases, including Huntington’s disease, myotonic dystrophy 1, fragile X syndrome and Friedreich ataxia, are caused by the aberrant expansion of a trinucleotide repeat. The mutation is unstable and further expands in specific cells or tissues with time, which can accelerate disease progression. DNA damage and base excision repair (BER are involved in repeat instability and might contribute to the tissue selectivity of the process. In this review, we will discuss the mechanisms of trinucleotide repeat instability, focusing more specifically on the role of BER.

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...

Using radionuclide imaging for monitoring repairment of bone defect with tissue-engineered bone graft in rabbits

International Nuclear Information System (INIS)

Xia Changsuo; Ye Fagang; Zou Yunwen; Ji Shixiang; Wang Dengchun

2004-01-01

Objective: To observe the effect of tissue-engineered bone grafts in repairing bone defect in rabbits, and assess the value of radionuclide for monitoring the therapeutic effect of this approach. Methods: Bilateral radial defects of 15 mm in length in 24 rabbits were made. The tissue-engineered bone grafts (composite graft) contained bone marrow stromal cells (BMSCs) of rabbits and calcium phosphate cement (CPC) were grafted in left side defects, CPC only grafts (artificial bone graft) in right defects. After the operation, radionuclide was used to monitor the therapeutic effects at 4, 8 and 12 weeks. Results: 99 Tc m -methylene diphosphonic acid (MDP) radionuclide bone imaging indicated that there was more radionuclide accumulation in grafting region of composite than that of CPC. There was significant difference between 99 Tc m -MDP uptake of the region of interest (ROI) and scintillant counts of composite bone and the artificial bone (P<0.01). Conclusion: Tissue-engineered bone grafts is eligible for repairing radial bone defects, and radionuclide imaging may accurately monitor the revascularization and bone regeneration after the bone graft implantation. (authors)

Radiosensitivity and repair capacity of two xenografted human soft tissue sarcomas to photons and fast neutrons

International Nuclear Information System (INIS)

Budach, V.; Stuschke, M.; Budach, W.; Krause, U.; Streffer, C.; Sack, H.

1989-01-01

The radiation response, the relative biological effectiveness (RBE) and sublethal damage repair of two xenografted human soft tissue sarcomas after single doses and fractionated irradiation with 60 Co and 5.8 MeV fast neutrons are presented. (author)

Biomechanics and mechanobiology in functional tissue engineering

Science.gov (United States)

Guilak, Farshid; Butler, David L.; Goldstein, Steven A.; Baaijens, Frank P.T.

2014-01-01

The field of tissue engineering continues to expand and mature, and several products are now in clinical use, with numerous other preclinical and clinical studies underway. However, specific challenges still remain in the repair or regeneration of tissues that serve a predominantly biomechanical function. Furthermore, it is now clear that mechanobiological interactions between cells and scaffolds can critically influence cell behavior, even in tissues and organs that do not serve an overt biomechanical role. Over the past decade, the field of “functional tissue engineering” has grown as a subfield of tissue engineering to address the challenges and questions on the role of biomechanics and mechanobiology in tissue engineering. Originally posed as a set of principles and guidelines for engineering of load-bearing tissues, functional tissue engineering has grown to encompass several related areas that have proven to have important implications for tissue repair and regeneration. These topics include measurement and modeling of the in vivo biomechanical environment; quantitative analysis of the mechanical properties of native tissues, scaffolds, and repair tissues; development of rationale criteria for the design and assessment of engineered tissues; investigation of the effects biomechanical factors on native and repair tissues, in vivo and in vitro; and development and application of computational models of tissue growth and remodeling. Here we further expand this paradigm and provide examples of the numerous advances in the field over the past decade. Consideration of these principles in the design process will hopefully improve the safety, efficacy, and overall success of engineered tissue replacements. PMID:24818797

Biomimetic strategies for fracture repair: engineering the cell microenvironment for directed tissue formation

OpenAIRE

Vas, Wollis J.; Shah, Mittal; Al Hosni, Rawiya; Owen, Helen C.; Roberts, Scott J.

2017-01-01

Complications resulting from impaired fracture healing have major clinical implications on fracture management strategies. Novel concepts taken from developmental biology have driven research strategies towards the elaboration of regenerative approaches that can truly harness the complex cellular events involved in tissue formation and repair. Advances in polymer technology and a better understanding of naturally derived scaffolds have given rise to novel biomaterials with an increasing abili...

The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues

Directory of Open Access Journals (Sweden)

Naosuke Kamei

2017-01-01

Full Text Available Endothelial progenitor cells (EPCs derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regeneration in musculoskeletal and neural tissues including the bone, skeletal muscle, ligaments, spinal cord, and peripheral nerves. EPCs can be mobilized from bone marrow and recruited to injured tissue to contribute to neovascularization and tissue repair. In addition, EPCs or stem cell populations containing EPCs promote neovascularization and tissue repair through their differentiation to endothelial cells or tissue-specific cells, the upregulation of growth factors, and the induction and activation of endogenous stem cells. Human peripheral blood CD34(+ cells containing EPCs have been used in clinical trials of bone repair. Thus, EPCs are a promising cell source for the treatment of musculoskeletal and neural tissue injury.

Hydrogel derived from porcine decellularized nerve tissue as a promising biomaterial for repairing peripheral nerve defects.

Science.gov (United States)

Lin, Tao; Liu, Sheng; Chen, Shihao; Qiu, Shuai; Rao, Zilong; Liu, Jianghui; Zhu, Shuang; Yan, Liwei; Mao, Haiquan; Zhu, Qingtang; Quan, Daping; Liu, Xiaolin

2018-06-01

Decellularized matrix hydrogels derived from tissues or organs have been used for tissue repair due to their biocompatibility, tunability, and tissue-specific extracellular matrix (ECM) components. However, the preparation of decellularized peripheral nerve matrix hydrogels and their use to repair nerve defects have not been reported. Here, we developed a hydrogel from porcine decellularized nerve matrix (pDNM-G), which was confirmed to have minimal DNA content and retain collagen and glycosaminoglycans content, thereby allowing gelatinization. The pDNM-G exhibited a nanofibrous structure similar to that of natural ECM, and a ∼280-Pa storage modulus at 10 mg/mL similar to that of native neural tissues. Western blot and liquid chromatography tandem mass spectrometry analysis revealed that the pDNM-G consisted mostly of ECM proteins and contained primary ECM-related proteins, including fibronectin and collagen I and IV). In vitro experiments showed that pDNM-G supported Schwann cell proliferation and preserved cell morphology. Additionally, in a 15-mm rat sciatic nerve defect model, pDNM-G was combined with electrospun poly(lactic-acid)-co-poly(trimethylene-carbonate)conduits to bridge the defect, which did not elicit an adverse immune response and promoted the activation of M2 macrophages associated with a constructive remodeling response. Morphological analyses and electrophysiological and functional examinations revealed that the regenerative outcomes achieved by pDNM-G were superior to those by empty conduits and closed to those using rat decellularized nerve matrix allograft scaffolds. These findings indicated that pDNM-G, with its preserved ECM composition and nanofibrous structure, represents a promising biomaterial for peripheral nerve regeneration. Decellularized nerve allografts have been widely used to treat peripheral nerve injury. However, given their limited availability and lack of bioactive factors, efforts have been made to improve the efficacy

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.

Biological effect of pulsed dose rate brachytherapy with stepping sources if short half-times of repair are present in tissues

International Nuclear Information System (INIS)

Fowler, Jack F.; Limbergen, Erik F.M. van

1997-01-01

Purpose: To explore the possible increase of radiation effect in tissues irradiated by pulsed brachytherapy (PDR) for local tissue dose rates between those 'averaged over the whole pulse' and the instantaneous high dose rates close to the dwell positions. Increased effect is more likely for tissues with short half-times of repair of the order of a few minutes, similar to pulse durations. Methods and Materials: Calculations were done assuming the linear quadratic formula for radiation damage, in which only the dose-squared term is subject to exponential repair. The situation with two components of T (1(2)) is addressed. A constant overall time of 140 h and a constant total dose of 70 Gy were assumed throughout, the continuous low dose rate of 0.5 Gy/h (CLDR) providing the unitary standard effects for each PDR condition. Effects of dose rates ranging from 4 Gy/h to 120 Gy/h (HDR at 2 Gy/min) were studied, covering the gap in an earlier publication. Four schedules were examined: doses per pulse of 0.5, 1, 1.5, and 2 Gy given at repetition frequencies of 1, 2, 3, and 4 h, respectively, each with a range of assumed half-times of repair of 4 min to 1.5 h. Results are presented for late-responding tissues, the differences from CLDR being two or three times greater than for early-responding tissues and most tumors. Results: Curves are presented relating the ratio of increased biological effect (proportional to log cell kill) calculated for PDR relative to CLDR. Ratios as high as 1.5 can be found for large doses per pulse (2 Gy) if the half-time of repair in tissues is as short as a few minutes. The major influences on effect are dose per pulse, half-time of repair in tissue, and--when T (1(2)) is short--the instantaneous dose rate. Maximum ratios of PDR/CLDR occur when the dose rate is such that pulse duration is approximately equal to T (1(2)) . As dose rate in the pulse is increased, a plateau of effect is reached, for most T (1(2)) s, above 10 to 20 Gy/h, which is

A novel basalt fiber-reinforced polylactic acid composite for hard tissue repair.

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Chen, Xi; Li, Yan; Gu, Ning

2010-08-01

A basalt fiber (BF) was, for the first time, introduced into a poly(l-lactic acid) (PLLA) matrix as innovative reinforcement to fabricate composite materials for hard tissue repair. Firstly, BF/PLLA composites and pure PLLA were produced by the methods of solution blending and freeze drying. The results showed that basalt fibers can be uniformly dispersed in the PLLA matrix and significantly improve the mechanical properties and hydrophilicity of the PLLA matrix. The presence of basalt fibers may retard the polymer degradation rate and neutralize the acid degradation from PLLA. Osteoblasts were cultured in vitro to evaluate the cytocompatibility of the composite. An MTT assay revealed that osteoblasts proliferated well for 7 days and there was little difference found in their viability on both PLLA and BF/PLLA films, which was consistent with the alkaline phosphatase (ALP) activity results. A fluorescent staining observation showed that osteoblasts grew well on the composites. SEM images displayed that osteoblasts tended to grow along the fiber axis. The formation of mineralized nodules was observed on the films by Alizarin red S staining. These results suggest that the presence of basalt fibers does not noticeably affect osteoblastic behavior and the designed composites are osteoblast compatible. It is concluded that basalt fibers, as reinforcing fibers, may have promising applications in hard tissue repair.

A novel basalt fiber-reinforced polylactic acid composite for hard tissue repair

International Nuclear Information System (INIS)

Chen Xi; Li Yan; Gu Ning

2010-01-01

A basalt fiber (BF) was, for the first time, introduced into a poly(l-lactic acid) (PLLA) matrix as innovative reinforcement to fabricate composite materials for hard tissue repair. Firstly, BF/PLLA composites and pure PLLA were produced by the methods of solution blending and freeze drying. The results showed that basalt fibers can be uniformly dispersed in the PLLA matrix and significantly improve the mechanical properties and hydrophilicity of the PLLA matrix. The presence of basalt fibers may retard the polymer degradation rate and neutralize the acid degradation from PLLA. Osteoblasts were cultured in vitro to evaluate the cytocompatibility of the composite. An MTT assay revealed that osteoblasts proliferated well for 7 days and there was little difference found in their viability on both PLLA and BF/PLLA films, which was consistent with the alkaline phosphatase (ALP) activity results. A fluorescent staining observation showed that osteoblasts grew well on the composites. SEM images displayed that osteoblasts tended to grow along the fiber axis. The formation of mineralized nodules was observed on the films by Alizarin red S staining. These results suggest that the presence of basalt fibers does not noticeably affect osteoblastic behavior and the designed composites are osteoblast compatible. It is concluded that basalt fibers, as reinforcing fibers, may have promising applications in hard tissue repair.

Full incorporation of Strattice™ Reconstructive Tissue Matrix in a reinforced hiatal hernia repair: a case report

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Freedman Bruce E

2012-08-01

Full Text Available Abstract Introduction A non-cross-linked porcine acellular dermal matrix was used to reinforce an esophageal hiatal hernia repair. A second surgery was required 11 months later to repair a slipped Nissen; this allowed for examination of the hiatal hernia repair and showed the graft to be well vascularized and fully incorporated. Case presentation A 71-year-old Caucasian woman presented with substernal burning and significant dysphagia. An upper gastrointestinal series revealed a type III complex paraesophageal hiatal hernia. She underwent laparoscopic surgery to repair a hiatal hernia that was reinforced with a xenograft (Strattice™ Reconstructive Tissue Matrix, LifeCell, Branchburg, NJ, USA along with a Nissen fundoplication. A second surgery was required to repair a slipped Nissen; this allowed for examination of the hiatal repair and graft incorporation 11 months after the initial surgery. Conclusion In this case, a porcine acellular dermal matrix was an effective tool to reinforce the crural hiatal hernia repair. The placement of the mesh and method of fixation are believed to be crucial to the success of the graft. It was found to be well vascularized 11 months after the original placement with no signs of erosion, stricture, or infection. Further studies and long-term follow-up are required to support the findings of this case report.

Honey can repairing damage of liver tissue due to protein energy malnutrition through induction of endogenous stem cells

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R. Heru Prasetyo

2017-06-01

Full Text Available Aim: This study was to evaluate effect of honey in repairing damage of liver tissue due to energy protein malnutrition and in mobilization of endogenous stem cells. Materials and Methods: Male mice model of degenerative liver was obtained through food fasting but still have drinking water for 5 days. It caused energy protein malnutrition and damage of liver tissue. The administration of 50% (v/v honey was performed for 10 consecutive days, while the positive control group was fasted and not given honey and the negative control not fasted and without honey. Observations of regeneration the liver tissue based on histologically examination, observation of Hsp70 expression, and homing signal based on vascular endothelial growth factor-1 (VEGF-1 expression using immunohistochemistry technique. Observation on expression of CD34 and CD45 as the marker of auto mobilization of hematopoietic stem cells using flow cytometry technique. Results: There is regeneration of the liver tissue due to protein energy malnutrition, decrease of Hsp70 expression, increase of VEGF-1 expression, and high expression of CD34 and CD45. Conclusion: Honey can improve the liver tissue based on: (1 Mobilization of endogenous stem cells (CD34 and CD45; (2 Hsp70 and VEGF-1 expressions as regeneration marker of improvement, and (3 regeneration histologically of liver tissue.

Repair of full-thickness tendon injury using connective tissue progenitors efficiently derived from human embryonic stem cells and fetal tissues.

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Cohen, Shahar; Leshansky, Lucy; Zussman, Eyal; Burman, Michael; Srouji, Samer; Livne, Erella; Abramov, Natalie; Itskovitz-Eldor, Joseph

2010-10-01

The use of stem cells for tissue engineering (TE) encourages scientists to design new platforms in the field of regenerative and reconstructive medicine. Human embryonic stem cells (hESC) have been proposed to be an important cell source for cell-based TE applications as well as an exciting tool for investigating the fundamentals of human development. Here, we describe the efficient derivation of connective tissue progenitors (CTPs) from hESC lines and fetal tissues. The CTPs were significantly expanded and induced to generate tendon tissues in vitro, with ultrastructural characteristics and biomechanical properties typical of mature tendons. We describe a simple method for engineering tendon grafts that can successfully repair injured Achilles tendons and restore the ankle joint extension movement in mice. We also show the CTP's ability to differentiate into bone, cartilage, and fat both in vitro and in vivo. This study offers evidence for the possibility of using stem cell-derived engineered grafts to replace missing tissues, and sets a basic platform for future cell-based TE applications in the fields of orthopedics and reconstructive surgery.

Time-course expression of CNS inflammatory, neurodegenerative tissue repair markers and metallothioneins during experimental autoimmune encephalomyelitis

DEFF Research Database (Denmark)

Espejo, C; Penkowa, M; Demestre, M

2005-01-01

-inflammatory, neuroprotective, antioxidant proteins expressed during EAE and MS, in which they might play a protective role. The present study aimed to describe the expression profile of a group of inflammatory, neurodegenerative and tissue repair markers as well as metallothioneins during proteolipid protein-induced EAE...

A generalised formulation of the 'incomplete-repair' model for cell survival and tissue response to fractionated low dose-rate irradiation

International Nuclear Information System (INIS)

Nilsson, P.; Joiner, M.C.

1990-01-01

A generalized equation for cell survival or tissue effects after fractionated low dose-rate irradiations, when there is incomplete repair between fractions and significant repair during fractions, is derived in terms of the h- and g-functions of the 'incomplete-repair' (IR) model. The model is critically dependent on α/β, repair half-time, treatment time and interfraction interval, and should therefore be regarded primarily as a tool for the analysis of fractionation and dose-rate effects in carefully designed radiobiological experiments, although it should also be useful in exploring, in a general way, the feasibility of clinical treatment protocols using fractionated low dose-rate treatments. (author)

Preliminary Evaluation of Platelet Rich Fibrin-Mediated Tissue Repair in Immature Canine Pulpless Teeth.

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Wang, Qi Lin; Yang, Pan Pan; Ge, Li Hong; Liu, He

2016-03-01

To evaluate the use of platelet-rich fibrin (PRF) in the regenerative therapy of immature canine permanent teeth. Eight immature premolars of beagle dogs were pulp extracted and cleaned with irrigation, then divided into two groups of empty root canals and those filled with a PRF clot. All of the eight premolars were sealed with mineral trioxide aggregate and glass ionomer cement. Two premolars were left naturally grown as a positive control. The root development was assessed radiographically and histologically after 12 weeks. The radiological findings showed greater increases in the thickness of lateral dentinal wall in the PRF group than in the vacant group. Histologically, dental-associated mineral tissue, connective tissue, and bone-like mineral tissue grew into the root canals independent of PRF clot use. The PRF was able to increase the thickness of dental-associated mineral tissue. However, the vital tissue differed from the pulp dentin complex. Our study demonstrated the feasibility of using PRF-mediated regenerative therapy in pulpless immature teeth for improving tissue repair.

Nuclear survivin and its relationship to DNA damage repair genes in non-small cell lung cancer investigated using tissue array.

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Songliu Hu

Full Text Available To investigate the predictive role and association of nuclear survivin and the DNA double-strand breaks repair genes in non-small cell lung cancer (NSCLC: DNA-dependent protein kinase catalytic subunit (DNA-PKcs, Ku heterodimeric regulatory complex 70-KD subunit (Ku70 and ataxia-telangiectasia mutated (ATM.The protein expression of nuclear survivin, DNA-PKcs, Ku70 and ATM were investigated using immunohistochemistry in tumors from 256 patients with surgically resected NSCLC. Furthermore, we analyzed the correlation between the expression of nuclear survivin, DNA-PKcs, Ku70 and ATM. Univariate and multivariate analyses were performed to determine the prognostic factors that inuenced the overall survival and disease-free survival of NSCLC.The expression of nuclear survivin, DNA-PKcs, Ku70 and ATM was significantly higher in tumor tissues than in normal tissues. By dichotomizing the specimens as expressing low or high levels of nuclear survivin, nuclear survivin correlated significantly with the pathologic stage (P = 0.009 and lymph node status (P = 0.004. The nuclear survivin levels were an independent prognostic factor for both the overall survival and the disease-free survival in univariate and multivariate analyses. Patients with low Ku70 and DNA-PKcs expression had a greater benefit from radiotherapy than patients with high expression of Ku70 (P = 0.012 and DNA-PKcs (P = 0.02. Nuclear survivin expression positively correlated with DNA-PKcs (P<0.001 and Ku70 expression (P<0.001.Nuclear survivin may be a prognostic factor for overall survival in patients with resected stage I-IIIA NSCLC. DNA-PKcs and Ku70 could predict the effect of radiotherapy in patients with NSCLC. Nuclear survivin may also stimulates DNA double-strand breaks repair by its interaction with DNA-PKcs and Ku70.

Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.

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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

Changes in tissue morphology and collagen composition during the repair of cortical bone in the adult chicken.

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Glimcher, M J; Shapiro, F; Ellis, R D; Eyre, D R

1980-09-01

An animal model was developed to study the histology and collagen chemistry of healing cortical bone. A hole was cut through the cortex of the mid-shaft of the humerus of the adult chicken, which allowed for repair at a mechanically stable site. After one to two weeks the collagen of the repair tissue, which consisted principally of woven bone, contained almost three times as much hydroxylysine as the collagen of normal adult bone and thus resembled the collagen of embryonic long bones. By eight weeks, when lamellar one predominated, the hydroxylysine content had fallen to normal levels. Type I was the major genetic type of collagen present throughout. No type-II collagen, characteristic of cartilage, was detected; this was consistent with the histological findings. The results established that hydroxylysine-rich type-I collagen can be made by osteoblasts of adult animals as well as by those of embryos and early postnates. In order to understand the biological characteristics of fracture healing, it is vital to study not only the macroscopic organization of the repair tissue but also the chemical properties of its molecular components. The strength of healing fractured bone, and indeed of normal bone, depends largely on the properties of the structural protein collagen. To date, it is not known whether the collagen in healing fractures is the same as that in normal bone, or whether it has distinct chemical features that may suit it for bone repair.

Next Generation Tissue Engineering of Orthopedic Soft Tissue-to-Bone Interfaces

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Boys, Alexander J.; McCorry, Mary Clare; Rodeo, Scott; Bonassar, Lawrence J.; Estroff, Lara A.

2017-01-01

Soft tissue-to-bone interfaces are complex structures that consist of gradients of extracellular matrix materials, cell phenotypes, and biochemical signals. These interfaces, called entheses for ligaments, tendons, and the meniscus, are crucial to joint function, transferring mechanical loads and stabilizing orthopedic joints. When injuries occur to connected soft tissue, the enthesis must be re-established to restore function, but due to structural complexity, repair has proven challenging. Tissue engineering offers a promising solution for regenerating these tissues. This prospective review discusses methodologies for tissue engineering the enthesis, outlined in three key design inputs: materials processing methods, cellular contributions, and biochemical factors. PMID:29333332

Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

DEFF Research Database (Denmark)

Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

2008-01-01

Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...

Evaluation of phototherapy in the differentiation of mesenchymal stem cells in the tissue repair of rats submitted to a hyperlipidemic diet

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Oliveira, C. R. B.; Santos, L. S.; Silva, V. D. U.; Vitória, L. A.; Rodriguez, T. T.; Marques, A. M. C.; Xavier, F. C. A.; Ramalho, L.

2018-04-01

Obese people present a greater risk of developing other systemic diseases and comorbidities such as compromising the tissue repair process. Laser phototherapy can contribute to this repair by improving cellular functions, since stem cells may play an important role in repair due to their pluripotent potential. In this way, the influence of Laser Phototherapy (LP) was evaluated in the tissue repair of rats submitted to a hyperlipid diet through CD49 immunostaining for adipose stem cells. Forty-eight Wistar albinus rats were divided into two experimental groups: Standard Diet (SD) and Hyperlipid Diet (HD) for 20 weeks. After this period, excisional dorsal cutaneous wounds of 1 cm2 were made. The groups were subdivided into control and laser, the laser groups were irradiated (Diode Laser of Gallium and Aluminum Arsenide, λ660nm, 40mW, 6J / cm2) immediately after the surgery and every 48 hours. A group of rats were killed on day 7 and the other group on day 14 and the specimens processed by the immunohistochemical technique. The SD group presented antibodies marked with moderate to intense intensity, whereas in the HD group the weak staining for the time of 14 days prevailed. The irradiation protocol employed had no influence on the CD49 marker when compared to the control and irradiated groups over the same period. According to the methodology used and the results obtained it is concluded that laser light does not influence the recruitment of adipoderivative stem cells for the tissue repair process.

Capturing tissue repair in zebrafish larvae with time-lapse brightfield stereomicroscopy.

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Lisse, Thomas S; Brochu, Elizabeth A; Rieger, Sandra

2015-01-31

The zebrafish larval tail fin is ideal for studying tissue regeneration due to the simple architecture of the larval fin-fold, which comprises of two layers of skin that enclose undifferentiated mesenchyme, and because the larval tail fin regenerates rapidly within 2-3 days. Using this system, we demonstrate a method for capturing the repair dynamics of the amputated tail fin with time-lapse video brightfield stereomicroscopy. We demonstrate that fin amputation triggers a contraction of the amputation wound and extrusion of cells around the wound margin, leading to their subsequent clearance. Fin regeneration proceeds from proximal to distal direction after a short delay. In addition, developmental growth of the larva can be observed during all stages. The presented method provides an opportunity for observing and analyzing whole tissue-scale behaviors such as fin development and growth in a simple microscope setting, which is easily adaptable to any stereomicroscope with time-lapse capabilities.

Factors affecting rotator cuff healing after arthroscopic repair: osteoporosis as one of the independent risk factors.

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Chung, Seok Won; Oh, Joo Han; Gong, Hyun Sik; Kim, Joon Yub; Kim, Sae Hoon

2011-10-01

The prognostic factors associated with structural outcome after arthroscopic rotator cuff repair have not yet been fully determined. The hypothesis of this study was that bone mineral density (BMD) is an important prognostic factor affecting rotator cuff healing after arthroscopic cuff repair. Cohort study; Level of evidence, 3. Among 408 patients who underwent arthroscopic repair for full-thickness rotator cuff tear between January 2004 and July 2008, 272 patients were included whose postoperative cuff integrity was verified by computed tomography arthrography (CTA) or ultrasonography (USG) and simultaneously who were evaluated by various functional outcome instruments. The mean age at the time of operation was 59.5 ± 7.9 years. Postoperative CTA or USG was performed at a mean 13.0 ± 5.1 months after surgery, and the mean follow-up period was 37.2 ± 10.0 months (range, 24-65 months). The clinical, structural, and surgery-related factors affecting cuff integrity including BMD were analyzed using both univariate and multivariate analysis. Evaluation of postoperative cuff integrity was performed by musculoskeletal radiologists who were unaware of the present study. The failure rate of rotator cuff healing was 22.8% (62 of 272). The failure rate was significantly higher in patients with lower BMD (P cuff healing failure following arthroscopic rotator cuff repair. Bone mineral density, as well as FI of the infraspinatus and amount of retraction, was an independent determining factor affecting postoperative rotator cuff healing. Further studies with prospective, randomized, and controlled design are needed to confirm the relationship between BMD and postoperative rotator cuff healing.

MENISCAL REPAIR BY FIBROCARTILAGE - AN EXPERIMENTAL-STUDY IN THE DOG

NARCIS (Netherlands)

JANSEN, HWB; VETH, RPH; NIELSEN, HKL; DEGROOT, JH; PENNINGS, AJ; KUIJER, R

Longitudinal lesions in the avascular part of the dog's meniscus were repaired by implantation of a porous polyurethane. Ingrowing repair tissue was characterized by biochemical and immunological analysis. Histologically, repair tissue initially was composed of fibrous tissue containing type I

Novel applications of trophic factors, Wnt and WISP for neuronal repair and regeneration in metabolic disease

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Kenneth Maiese

2015-01-01

Full Text Available Diabetes mellitus affects almost 350 million individuals throughout the globe resulting in significant morbidity and mortality. Of further concern is the growing population of individuals that remain undiagnosed but are susceptible to the detrimental outcomes of this disorder. Diabetes mellitus leads to multiple complications in the central and peripheral nervous systems that include cognitive impairment, retinal disease, neuropsychiatric disease, cerebral ischemia, and peripheral nerve degeneration. Although multiple strategies are being considered, novel targeting of trophic factors, Wnt signaling, Wnt1 inducible signaling pathway protein 1, and stem cell tissue regeneration are considered to be exciting prospects to overcome the cellular mechanisms that lead to neuronal injury in diabetes mellitus involving oxidative stress, apoptosis, and autophagy. Pathways that involve insulin-like growth factor-1, fibroblast growth factor, epidermal growth factor, and erythropoietin can govern glucose homeostasis and are intimately tied to Wnt signaling that involves Wnt1 and Wnt1 inducible signaling pathway protein 1 (CCN4 to foster control over stem cell proliferation, wound repair, cognitive decline,β-cell proliferation, vascular regeneration, and programmed cell death. Ultimately, cellular metabolism through Wnt signaling is driven by primary metabolic pathways of the mechanistic target of rapamycin and AMP activated protein kinase. These pathways offer precise biological control of cellular metabolism, but are exquisitely sensitive to the different components of Wnt signaling. As a result, unexpected clinical outcomes can ensue and therefore demand careful translation of the mechanisms that govern neural repair and regeneration in diabetes mellitus.

Formation of tissue factor activity following incubation of recombinant human tissue factor apoprotein with plasma lipoproteins

International Nuclear Information System (INIS)

Sakai, T.; Kisiel, W.

1990-01-01

Incubation of recombinant human tissue factor apoprotein (Apo-TF) with human plasma decreased the recalcified clotting time of this plasma in a time-and dose-dependent manner suggesting relipidation of the Apo-TF by plasma lipoproteins. Incubation of Apo-TF with purified preparations of human very low density, low density and high density lipoproteins resulted in tissue factor activity in a clotting assay. The order of effectiveness was VLDL greater than LDL much greater than HDL. Tissue factor activity generated by incubation of a fixed amount of Apo-TF with plasma lipoproteins was lipoprotein concentration-dependent and saturable. The association of Apo-TF with lipoprotein particles was supported by gel filtration studies in which 125 I-Apo-TF coeluted with the plasma lipoprotein in the void volume of a Superose 6 column in the presence and absence of calcium ions. In addition, void-volume Apo-TF-lipoprotein fractions exhibited tissue factor activity. These results suggest that the factor VIII-bypassing activity of bovine Apo-TF observed in a canine hemophilic model may be due, in part, to its association with plasma lipoproteins and expression of functional tissue factor activity

Investigating the use of curcumin-loaded electrospun filaments for soft tissue repair applications

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Mouthuy PA

2017-05-01

Full Text Available Pierre-Alexis Mouthuy,1,2 Maja Somogyi Škoc,3 Ana Čipak Gašparović,1 Lidija Milković,1 Andrew J Carr,2 Neven Žarković1 1Laboratory for Oxidative Stress, Rudjer Boskovic Institute, Zagreb, Croatia; 2Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Medical Science Division, University of Oxford, Oxford, UK; 3Department of Materials, Fibres and Textile Testing, University of Zagreb, Zagreb, Croatia Abstract: Electrospun filaments represent a new generation of medical textiles with promising applications in soft tissue repair. A potential strategy to improve their design is to combine them with bioactive molecules. Curcumin, a natural compound found in turmeric, is particularly attractive for its antioxidant, anti-inflammatory, and antimicrobial properties. However, investigating the range of relevant doses of curcumin in materials designed for tissue regeneration has remained limited. In this paper, a wide range of curcumin concentrations was explored and the potential of the resulting materials for soft tissue repair applications was assessed. Polydioxanone (PDO filaments were prepared with various amounts of curcumin: 0%, 0.001%, 0.01%, 0.1%, 1%, and 10% (weight to weight ratio. The results from the present study showed that, at low doses (≤0.1%, the addition of curcumin has no influence on the spinning process or on the physicochemical properties of the filaments, whereas higher doses lead to smaller fiber diameters and improved mechanical properties. Moreover, filaments with 0.001% and 0.01% curcumin stimulate the metabolic activity and proliferation of normal human dermal fibroblasts (NHDFs compared with the no-filament control. However, this stimulation is not significant when compared to the control filaments (0%. Highly dosed filaments induce either the inhibition of proliferation (with 1% or cell apoptosis (with 10% as a result of the concentrations of curcumin found in the

The forked flap repair for hypospadias

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Anil Chadha

2012-01-01

Full Text Available Context: Despite the abundance of techniques for the repair of Hypospadias, its problems still persist and a satisfactory design to correct the penile curvature with the formation of neourethra from the native urethral tissue or genital or extragenital tissues, with minimal postoperative complications has yet to evolve. Aim: Persisting with such an endeavor, a new technique for the repair of distal and midpenile hypospadias is described. Materials and Methods: The study has been done in 70 cases over the past 11 years. The "Forked-Flap" repair is a single stage method for the repair of such Hypospadias with chordee. It takes advantage of the rich vascular communication at the corona and capitalizes on the established reliability of the meatal based flip-flap. The repair achieves straightening of the curvature of the penis by complete excision of chordee tissue from the ventral surface of the penis beneath the urethral plate. The urethra is reconstructed using the native plate with forked flap extensions and genital tissue relying on the concept of meatal based flaps. Water proofing by dartos tissue and reinforcement by Nesbit′s prepucial tissue transfer completes the one stage procedure. Statistical Analysis: An analysis of 70 cases of this single stage technique of repair of penile hypospadias with chordee, operated at 3 to 5 years of age over the past 11 years is presented. Results and Conclusion: The Forked Flap gives comparable and replicable results; except for a urethrocutaneous fistula rate of 4% no other complications were observed.

Effect-independent measures of tissue responses to fractionated irradiation

International Nuclear Information System (INIS)

Thames, H.D. Jr.

1984-01-01

Tissue repair factors measure the sparing that can be achieved from dose fractionation in the absence of proliferation. Four repair factors are analysed in these terms: Fsub(R),Fsub(rec), the ratio of linear-quadratic survival model parameters β/α and the half-time Tsub(1/2) for intracellular repair processes. Theoretically, Fsub(R) and Fsub(rec) are increasing functions of D 1 , and thus depend on level of effect. This is confirmed by analysis of skin reactions after multifractionated radiation. By contrast, β/α is effect-independent as a measure of repair capacity in skin, gut, and bone marrow, tissues for which it is reasonable to assume that survival of identifiable target cells is the primary determinant of the endpoint. For a functional endpoint not clearly connected with the depletion of a specific target-cell population (late fibrotic reactions in the kidney), there was an increase in β/α with increased levels of injury, but this was statistically insignificant. Tsub(1/2) is independent of fraction size in skin, gut, and spinal cord, and is longer (1.5 hours) in the late-reacting tissues (lung and spinal cord) than in those that react acutely (Tsub(1/2) less than 1 hour), with skin as the exception (Tsub(1/2) approx. 1.3 hours). (author)

Hematopoietic tissue repair under chronic low daily dose irradiation

International Nuclear Information System (INIS)

Seed, T.M.

1994-01-01

The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). We have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3-26.3 cGy d -1 ). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup (1), the failure to augment basic m-pair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments particularly marked within erythroid compartments. that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccomodated and either prone- or not prone to ML, subgroup 2 ampersand 3 appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high- tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity

Cell-based tissue engineering strategies used in the clinical repair of articular cartilage.

Science.gov (United States)

Huang, Brian J; Hu, Jerry C; Athanasiou, Kyriacos A

2016-08-01

One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of current research in the field, it is known that 90% of new drugs that advance past animal studies fail clinical trials. The objective of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cell-based tissue engineering strategies used in the clinical repair of articular cartilage

Science.gov (United States)

Huang, Brian J.; Hu, Jerry C.; Athanasiou, Kyriacos A.

2016-01-01

One of the most important issues facing cartilage tissue engineering is the inability to move technologies into the clinic. Despite the multitude of review articles on the paradigm of biomaterials, signals, and cells, it is reported that 90% of new drugs that advance past animal studies fail clinical trials (1). The intent of this review is to provide readers with an understanding of the scientific details of tissue engineered cartilage products that have demonstrated a certain level of efficacy in humans, so that newer technologies may be developed upon this foundation. Compared to existing treatments, such as microfracture or autologous chondrocyte implantation, a tissue engineered product can potentially provide more consistent clinical results in forming hyaline repair tissue and in filling the entirety of the defect. The various tissue engineering strategies (e.g., cell expansion, scaffold material, media formulations, biomimetic stimuli, etc.) used in forming these products, as collected from published literature, company websites, and relevant patents, are critically discussed. The authors note that many details about these products remain proprietary, not all information is made public, and that advancements to the products are continuously made. Nevertheless, by fully understanding the design and production processes of these emerging technologies, one can gain tremendous insight into how to best use them and also how to design the next generation of tissue engineered cartilage products. PMID:27177218

Biology and augmentation of tendon-bone insertion repair

Directory of Open Access Journals (Sweden)

Lui PPY

2010-08-01

Full Text Available Abstract Surgical reattachment of tendon and bone such as in rotator cuff repair, patellar-patella tendon repair and anterior cruciate ligament (ACL reconstruction often fails due to the failure of regeneration of the specialized tissue ("enthesis" which connects tendon to bone. Tendon-to-bone healing taking place between inhomogenous tissues is a slow process compared to healing within homogenous tissue, such as tendon to tendon or bone to bone healing. Therefore special attention must be paid to augment tendon to bone insertion (TBI healing. Apart from surgical fixation, biological and biophysical interventions have been studied aiming at regeneration of TBI healing complex, especially the regeneration of interpositioned fibrocartilage and new bone at the healing junction. This paper described the biology and the factors influencing TBI healing using patella-patellar tendon (PPT healing and tendon graft to bone tunnel healing in ACL reconstruction as examples. Recent development in the improvement of TBI healing and directions for future studies were also reviewed and discussed.

A biocompatible hybrid material with simultaneous calcium and strontium release capability for bone tissue repair

Energy Technology Data Exchange (ETDEWEB)

Almeida, J. Carlos [CICECO — Aveiro Institute of Materials, Department of Materials and Ceramic Engineering, University of Aveiro, 3810-193 Aveiro (Portugal); Wacha, András [Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar Tudósok körútja 2, Budapest 1117 (Hungary); Gomes, Pedro S. [Laboratory for Bone Metabolism and Regeneration, Faculdade de Medicina Dentária, Universidade do Porto (Portugal); Alves, Luís C. [C2TN, Instituto Superior Técnico, Universidade de Lisboa, E.N.10, 2695-066 Bobadela LRS (Portugal); Fernandes, M. Helena Vaz [CICECO — Aveiro Institute of Materials, Department of Materials and Ceramic Engineering, University of Aveiro, 3810-193 Aveiro (Portugal); Salvado, Isabel M. Miranda, E-mail: isabelmsalvado@ua.pt [CICECO — Aveiro Institute of Materials, Department of Materials and Ceramic Engineering, University of Aveiro, 3810-193 Aveiro (Portugal); Fernandes, M. Helena R. [Laboratory for Bone Metabolism and Regeneration, Faculdade de Medicina Dentária, Universidade do Porto (Portugal)

2016-05-01

The increasing interest in the effect of strontium in bone tissue repair has promoted the development of bioactive materials with strontium release capability. According to literature, hybrid materials based on the system PDMS–SiO{sub 2} have been considered a plausible alternative as they present a mechanical behavior similar to the one of the human bone. The main purpose of this study was to obtain a biocompatible hybrid material with simultaneous calcium and strontium release capability. A hybrid material, in the system PDMS–SiO{sub 2}–CaO–SrO, was prepared with the incorporation of 0.05 mol of titanium per mol of SiO{sub 2}. Calcium and strontium were added using the respective acetates as sources, following a sol–gel technique previously developed by the present authors. The obtained samples were characterized by FT-IR, solid-state NMR, and SAXS, and surface roughness was analyzed by 3D optical profilometry. In vitro studies were performed by immersion of the samples in Kokubo's SBF for different periods of time, in order to determine the bioactive potential of these hybrids. Surfaces of the immersed samples were observed by SEM, EDS and PIXE, showing the formation of calcium phosphate precipitates. Supernatants were analyzed by ICP, revealing the capability of the material to simultaneously fix phosphorus ions and to release calcium and strontium, in a concentration range within the values reported as suitable for the induction of the bone tissue repair. The material demonstrated to be cytocompatible when tested with MG63 osteoblastic cells, exhibiting an inductive effect on cell proliferation and alkaline phosphatase activity. - Highlights: • A hybrid PDMS–SiO{sub 2}–CaO–SrO material was prepared with the incorporation of Ti. • Sr was released in concentrations suitable for the induction of bone tissue repair. • The material demonstrated to be cytocompatible when tested with osteoblastic cells.

Endothelium trans differentiated from Wharton's jelly mesenchymal cells promote tissue regeneration: potential role of soluble pro-angiogenic factors.

Science.gov (United States)

Aguilera, Valeria; Briceño, Luis; Contreras, Hector; Lamperti, Liliana; Sepúlveda, Esperanza; Díaz-Perez, Francisca; León, Marcelo; Veas, Carlos; Maura, Rafael; Toledo, Jorge Roberto; Fernández, Paulina; Covarrubias, Ambart; Zuñiga, Felipe Andrés; Radojkovic, Claudia; Escudero, Carlos; Aguayo, Claudio

2014-01-01

Mesenchymal stem cells have a high capacity for trans-differentiation toward many adult cell types, including endothelial cells. Feto-placental tissue, such as Wharton's jelly is a potential source of mesenchymal stem cells with low immunogenic capacity; make them an excellent source of progenitor cells with a potential use for tissue repair. We evaluated whether administration of endothelial cells derived from mesenchymal stem cells isolated from Wharton's jelly (hWMSCs) can accelerate tissue repair in vivo. Mesenchymal stem cells were isolated from human Wharton's jelly by digestion with collagenase type I. Endothelial trans-differentiation was induced for 14 (hWMSC-End14d) and 30 (hWMSC-End30d) days. Cell phenotyping was performed using mesenchymal (CD90, CD73, CD105) and endothelial (Tie-2, KDR, eNOS, ICAM-1) markers. Endothelial trans-differentiation was demonstrated by the expression of endothelial markers and their ability to synthesize nitric oxide (NO). hWMSCs can be differentiated into adipocytes, osteocytes, chondrocytes and endothelial cells. Moreover, these cells show high expression of CD73, CD90 and CD105 but low expression of endothelial markers prior to differentiation. hWMSCs-End express high levels of endothelial markers at 14 and 30 days of culture, and also they can synthesize NO. Injection of hWMSC-End30d in a mouse model of skin injury significantly accelerated wound healing compared with animals injected with undifferentiated hWMSC or injected with vehicle alone. These effects were also observed in animals that received conditioned media from hWMSC-End30d cultures. These results demonstrate that mesenchymal stem cells isolated from Wharton's jelly can be cultured in vitro and trans-differentiated into endothelial cells. Differentiated hWMSC-End may promote neovascularization and tissue repair in vivo through the secretion of soluble pro-angiogenic factors.

Aberrant repair and fibrosis development in skeletal muscle

Directory of Open Access Journals (Sweden)

Mann Christopher J

2011-05-01

Full Text Available Abstract The repair process of damaged tissue involves the coordinated activities of several cell types in response to local and systemic signals. Following acute tissue injury, infiltrating inflammatory cells and resident stem cells orchestrate their activities to restore tissue homeostasis. However, during chronic tissue damage, such as in muscular dystrophies, the inflammatory-cell infiltration and fibroblast activation persists, while the reparative capacity of stem cells (satellite cells is attenuated. Abnormal dystrophic muscle repair and its end stage, fibrosis, represent the final common pathway of virtually all chronic neurodegenerative muscular diseases. As our understanding of the pathogenesis of muscle fibrosis has progressed, it has become evident that the muscle provides a useful model for the regulation of tissue repair by the local microenvironment, showing interplay among muscle-specific stem cells, inflammatory cells, fibroblasts and extracellular matrix components of the mammalian wound-healing response. This article reviews the emerging findings of the mechanisms that underlie normal versus aberrant muscle-tissue repair.

Tissue engineering and regenerative medicine: past, present, and future.

Science.gov (United States)

Salgado, António J; Oliveira, Joaquim M; Martins, Albino; Teixeira, Fábio G; Silva, Nuno A; Neves, Nuno M; Sousa, Nuno; Reis, Rui L

2013-01-01

Tissue and organ repair still represents a clinical challenge. Tissue engineering and regenerative medicine (TERM) is an emerging field focused on the development of alternative therapies for tissue/organ repair. This highly multidisciplinary field, in which bioengineering and medicine merge, is based on integrative approaches using scaffolds, cell populations from different sources, growth factors, nanomedicine, gene therapy, and other techniques to overcome the limitations that currently exist in the clinics. Indeed, its overall objective is to induce the formation of new functional tissues, rather than just implanting spare parts. This chapter aims at introducing the reader to the concepts and techniques of TERM. It begins by explaining how TERM have evolved and merged into TERM, followed by a short overview of some of its key aspects such as the combinations of scaffolds with cells and nanomedicine, scaffold processing, and new paradigms of the use of stem cells for tissue repair/regeneration, which ultimately could represent the future of new therapeutic approaches specifically aimed at clinical applications. © 2013 Elsevier Inc. All rights reserved.

The transcription factor GLI1 modulates the inflammatory response during pancreatic tissue remodeling.

Science.gov (United States)

Mathew, Esha; Collins, Meredith A; Fernandez-Barrena, Maite G; Holtz, Alexander M; Yan, Wei; Hogan, James O; Tata, Zachary; Allen, Benjamin L; Fernandez-Zapico, Martin E; di Magliano, Marina Pasca

2014-10-03

Pancreatic cancer, one of the deadliest human malignancies, is almost uniformly associated with a mutant, constitutively active form of the oncogene Kras. Studies in genetically engineered mouse models have defined a requirement for oncogenic KRAS in both the formation of pancreatic intraepithelial neoplasias, the most common precursor lesions to pancreatic cancer, and in the maintenance and progression of these lesions. Previous work using an inducible model allowing tissue-specific and reversible expression of oncogenic Kras in the pancreas indicates that inactivation of this GTPase at the pancreatic intraepithelial neoplasia stage promotes pancreatic tissue repair. Here, we extend these findings to identify GLI1, a transcriptional effector of the Hedgehog pathway, as a central player in pancreatic tissue repair upon Kras inactivation. Deletion of a single allele of Gli1 results in improper stromal remodeling and perdurance of the inflammatory infiltrate characteristic of pancreatic tumorigenesis. Strikingly, this partial loss of Gli1 affects activated fibroblasts in the pancreas and the recruitment of immune cells that are vital for tissue recovery. Analysis of the mechanism using expression and chromatin immunoprecipitation assays identified a subset of cytokines, including IL-6, mIL-8, Mcp-1, and M-csf (Csf1), as direct GLI1 target genes potentially mediating this phenomenon. Finally, we demonstrate that canonical Hedgehog signaling, a known regulator of Gli1 activity, is required for pancreas recovery. Collectively, these data delineate a new pathway controlling tissue repair and highlight the importance of GLI1 in regulation of the pancreatic microenvironment during this cellular process. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Aging and DNA repair capability. [Review

Energy Technology Data Exchange (ETDEWEB)

Tice, R R

1977-01-01

A review of the literature on DNA repair processes in relation to aging is presented under the following headings: DNA repair processes; age-related occurrence of unrepaired DNA lesions; DNA repair capability as a function of age; tissue-specific DNA repair capability; acceleration of the aging process by exposure to DNA damaging agents; human genetic syndromes; and longevity and DNA repair processes. (HLW)

Tissue Engineering Strategies in Ligament Regeneration

Directory of Open Access Journals (Sweden)

Caglar Yilgor

2012-01-01

Full Text Available Ligaments are dense fibrous connective tissues that connect bones to other bones and their injuries are frequently encountered in the clinic. The current clinical approaches in ligament repair and regeneration are limited to autografts, as the gold standard, and allografts. Both of these techniques have their own drawbacks that limit the success in clinical setting; therefore, new strategies are being developed in order to be able to solve the current problems of ligament grafting. Tissue engineering is a novel promising technique that aims to solve these problems, by producing viable artificial ligament substitutes in the laboratory conditions with the potential of transplantation to the patients with a high success rate. Direct cell and/or growth factor injection to the defect site is another current approach aiming to enhance the repair process of the native tissue. This review summarizes the current approaches in ligament tissue engineering strategies including the use of scaffolds, their modification techniques, as well as the use of bioreactors to achieve enhanced regeneration rates, while also discussing the advances in growth factor and cell therapy applications towards obtaining enhanced ligament regeneration.

Diabetic mice are protected from normally lethal nephrotoxicity of S-1,2-dichlorovinyl-L-cysteine (DCVC): role of nephrogenic tissue repair

International Nuclear Information System (INIS)

Dnyanmote, Ankur V.; Sawant, Sharmilee P.; Lock, Edward A.; Latendresse, John R.; Warbritton, Alan A.; Mehendale, Harihara M.

2006-01-01

Streptozotocin (STZ)-induced diabetic (DB) rats are protected from nephrotoxicity of gentamicin, cisplatin and mercuric chloride, although the mechanisms remain unclear. Ninety percent of DB mice receiving a LD90 dose (75 mg/kg, ip) of S-1,2-dichlorovinyl-L-cysteine (DCVC) survived in contrast to only 10% of the nondiabetic (NDB) mice surviving the same dose. We tested the hypothesis that the mechanism of protection is upregulated tissue repair. In the NDB mice, DCVC produced steep temporal increases in blood urea nitrogen (BUN) and plasma creatinine, which were associated with proximal tubular cell (PTC) necrosis, acute renal failure (ARF), and death within 48 h. In contrast, in the DB mice, BUN and creatinine increased less steeply, declining after 36 h to completely resolve by 96 h. HPLC analysis of plasma and urine revealed that DB did not alter the toxicokinetics of DCVC. Furthermore, activity of renal cysteine conjugate β-lyase, the enzyme that bioactivates DCVC, was unaltered in DB mice, undermining the possibility of lower bioactivation of DCVC leading to lower injury. [3H]-thymidine pulse labeling and PCNA analysis indicated an early onset and sustained nephrogenic tissue repair in DCVC-treated DB mice. BRDU immunohistochemistry revealed a fourfold increase in the number of cells in S-phase in the DB kidneys even without exposure to DCVC. Blocking the entry of cells into S-phase by antimitotic intervention using colchicine abolished stimulated nephrogenic tissue repair and nephroprotection. These findings suggest that preplacement of S-phase cells in the kidney due to diabetes is critical in mitigating the progression of DCVC-initiated renal injury by upregulation of tissue repair, leading to survival of the DB mice by avoiding acute renal failure

High fat diet accelerates cartilage repair in DBA/1 mice.

Science.gov (United States)

Wei, Wu; Bastiaansen-Jenniskens, Yvonne M; Suijkerbuijk, Mathijs; Kops, Nicole; Bos, Pieter K; Verhaar, Jan A N; Zuurmond, Anne-Marie; Dell'Accio, Francesco; van Osch, Gerjo J V M

2017-06-01

Obesity is a well-known risk factor for osteoarthritis, but it is unknown what it does on cartilage repair. Here we investigated whether a high fat diet (HFD) influences cartilage repair in a mouse model of cartilage repair. We fed DBA/1 mice control or HFD (60% energy from fat). After 2 weeks, a full thickness cartilage defect was made in the trochlear groove. Mice were sacrificed, 1, 8, and 24 weeks after operation. Cartilage repair was evaluated on histology. Serum glucose, insulin and amyloid A were measured 24 h before operation and at endpoints. Immunohistochemical staining was performed on synovium and adipose tissue to evaluate macrophage infiltration and phenotype. One week after operation, mice on HFD had defect filling with fibroblast-like cells and more cartilage repair as indicated by a lower Pineda score. After 8 weeks, mice on a HFD still had a lower Pineda score. After 24 weeks, no mice had complete cartilage repair and we did not detect a significant difference in cartilage repair between diets. Bodyweight was increased by HFD, whereas serum glucose, amyloid A and insulin were not influenced. Macrophage infiltration and phenotype in adipose tissue and synovium were not influenced by HFD. In contrast to common wisdom, HFD accelerated intrinsic cartilage repair in DBA/1 mice on the short term. Resistance to HFD induced inflammatory and metabolic changes could be associated with accelerated cartilage repair. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1258-1264, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

The roles of connective tissue growth factor in the development of anastomotic esophageal strictures.

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Zhao, Haibin; Zhao, Lingna; Zhou, Zhihua; Wu, Yaoyi

2015-08-12

The aim of this study was to investigate the roles of connective tissue growth factor (CTGF) in the development of anastomotic strictures after surgical repair of the esophagus. Tissues collected from the patients were divided into three groups based on the results of endoscopy and clinical grading. Patients without dysphagia after esophagectomy were used as the control population. The protein levels of CTGF, TGF-β1, Smad2, and Smad4 were determined by immunohistochemistry (IHC) and western blot analyses, while the mRNA levels of the two growth factors were evaluated by real-time polymerase chain reaction. Compared with the control group, significantly increased (p tissues collected from the patients with stenosis were significantly up-regulated (p < 0.05) as compared with those from the control group. In addition, the levels of Smad2 and Smad4 protein were also significantly increased (p < 0.05) with the increasing severity of stenosis, and the protein levels were positively correlated with the levels of CTGF (r = 0.59, p < 0.05) and TGF-β1 (r = 0.63, p < 0.05). Inhibition of CTGF protein or mRNA expression may be a distinctive and effective therapy for the treatment of postoperative anastomotic strictures.

Metallothionein-I overexpression alters brain inflammation and stimulates brain repair in transgenic mice with astrocyte-targeted interleukin-6 expression

DEFF Research Database (Denmark)

Penkowa, Milena; Camats, Jordi; Giralt, Mercedes

2003-01-01

injury, such as a cryolesion, demonstrate a neuroprotective role of IL-6. Thus, the GFAP-IL-6 mice showed faster tissue repair and decreased oxidative stress and apoptosis compared with control litter-mate mice. The neuroprotective factors metallothionein-I+II (MT-I+II) were upregulated by the cryolesion...... the inflammatory response, decreased oxidative stress and apoptosis significantly, and increased brain tissue repair in comparison with either GFAP-IL-6 or control litter-mate mice. Overall, the results demonstrate that brain MT-I+II proteins are fundamental neuroprotective factors....

The Acid-Secreting Parietal Cell as an Endocrine Source of Sonic Hedgehog During Gastric Repair

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Engevik, Amy C.; Feng, Rui; Yang, Li

2013-01-01

Sonic Hedgehog (Shh) has been shown to regulate wound healing in various tissues. Despite its known function in tissue regeneration, the role of Shh secreted from the gastric epithelium during tissue repair in the stomach remains unknown. Here we tested the hypothesis that Shh secreted from the acid-secreting parietal cell is a fundamental circulating factor that drives gastric repair. A mouse model expressing a parietal cell-specific deletion of Shh (PC-ShhKO) was generated using animals bearing loxP sites flanking exon 2 of the Shh gene (Shhflx/flx) and mice expressing a Cre transgene under the control of the H+,K+-ATPase β-subunit promoter. Shhflx/flx, the H+,K+-ATPase β-subunit promoter, and C57BL/6 mice served as controls. Ulcers were induced via acetic acid injury. At 1, 2, 3, 4, 5, and 7 days after the ulcer induction, gastric tissue and blood samples were collected. Parabiosis experiments were used to establish the effect of circulating Shh on ulcer repair. Control mice exhibited an increased expression of Shh in the gastric tissue and plasma that correlated with the repair of injury within 7 days after surgery. PC-ShhKO mice showed a loss of ulcer repair and reduced Shh tissue and plasma concentrations. In a parabiosis experiment whereby a control mouse was paired with a PC-ShhKO littermate and both animals subjected to gastric injury, a significant increase in the circulating Shh was measured in both parabionts. Elevated circulating Shh concentrations correlated with the repair of gastric ulcers in the PC-ShhKO parabionts. Therefore, the acid-secreting parietal cell within the stomach acts as an endocrine source of Shh during repair. PMID:24092639

Magnetic Resonance Imaging of Cartilage Repair

Science.gov (United States)

Trattnig, Siegfried; Winalski, Carl S.; Marlovits, Stephan; Jurvelin, Jukka S.; Welsch, Goetz H.; Potter, Hollis G.

2011-01-01

Articular cartilage lesions are a common pathology of the knee joint, and many patients may benefit from cartilage repair surgeries that offer the chance to avoid the development of osteoarthritis or delay its progression. Cartilage repair surgery, no matter the technique, requires a noninvasive, standardized, and high-quality longitudinal method to assess the structure of the repair tissue. This goal is best fulfilled by magnetic resonance imaging (MRI). The present article provides an overview of the current state of the art of MRI of cartilage repair. In the first 2 sections, preclinical and clinical MRI of cartilage repair tissue are described with a focus on morphological depiction of cartilage and the use of functional (biochemical) MR methodologies for the visualization of the ultrastructure of cartilage repair. In the third section, a short overview is provided on the regulatory issues of the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) regarding MR follow-up studies of patients after cartilage repair surgeries. PMID:26069565

Risk Factors for the Postoperative Recurrence of Instability After Arthroscopic Bankart Repair in Athletes

OpenAIRE

Nakagawa, Shigeto; Mae, Tatsuo; Sato, Seira; Okimura, Shinichiro; Kuroda, Miki

2017-01-01

Background: Several risk factors for the postoperative recurrence of instability after arthroscopic Bankart repair have been reported, but there have been few detailed investigations of the specific risk factors in relation to the type of sport. Purpose: This study investigated the postoperative recurrence of instability after arthroscopic Bankart repair without additional reinforcement procedures in competitive athletes, including athletes with a large glenoid defect. The purpose of this stu...

Effect of laser wavelength and protein solder concentration on acute tissue repair using laser welding: initial results in a canine ureter model.

Science.gov (United States)

Wright, E J; Poppas, D P

1997-01-01

Successful tissue approximation can be performed using low power laser energy combined with human albumin solder. In vitro studies were undertaken to investigate the acute repair strengths achieved using different laser wavelengths. Furthermore, we evaluated the change in repair strength with that resulted from changes in protein solder concentration. Intraluminal bursting pressure following ureterotomy repair was measured for the following laser wavelengths: 532, 808, 1,320, 2,100, and 10,600 nm. The tissue absorption characteristics of the 808-nm diode and the KTP-532-nm lasers required the addition of the exogenous chromophores indocyanine green and fluorescein, respectively. A 40% human albumin solder was incorporated in the repair of a 1.0-cm longitudinal defect in the canine ureter. Following determination of an optimal welding wavelength, human albumin solder of varying concentrations (25%, 38%, 45%, and 50%) were prepared and tested. The 1,320-nm YAG laser achieved the highest acute bursting pressure and was the most effective in this model. Of the concentrations of albumin tested, 50% human albumin yielded the greatest bursting pressures. We conclude that of the laser wavelengths evaluated, the 1,320-nm YAG achieves the strongest tissue weld in the acute ex vivo dog ureter model. In addition, when this laser system is used, the acute strength of a photothermal weld appears to be directly proportional to the concentration of human albumin solder in the range of 25 to 50%.

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.

Native tissue repair or transvaginal mesh for recurrent vaginal prolapse: what are the long-term outcomes?

Science.gov (United States)

Ow, Lin Li; Lim, Yik N; Dwyer, Peter L; Karmakar, Debjyoti; Murray, Christine; Thomas, Elizabeth; Rosamilia, Anna

2016-09-01

The objective of this study was to assess outcomes in native tissue (NT) and transvaginal mesh (TVM) repair in women with recurrent prolapse. A retrospective two-group observational study of 237 women who underwent prolapse repair after failed NT repair in two tertiary hospitals. A primary outcome of "success" was defined using a composite outcome of no vaginal bulge symptoms, no anatomical recurrence in the same compartment beyond the hymen (0 cm on POPQ) and no surgical re-treatment for prolapse in the same compartment. Secondary outcomes assessed included re-operation for prolapse in the same compartment, dyspareunia and mesh-related complications. Of a total of 336 repairs, 196 were performed in the anterior compartment and 140 in the posterior compartment. Compared with the TVM groups, women undergoing repeat NT repair were more likely to experience anatomical recurrence (anterior 40.9 % vs 25 %, p = 0.02, posterior 25.3 % vs 7.5 %, p = 0.01), report vaginal bulge (anterior 34.1 % vs 12 %, p mesh exposure were 9.3 % anteriorly and 15.1 % posteriorly. Although the number of women requiring a prolapse re-operation is lower in the TVM group, the overall re-operation rate was not significantly different when procedures to correct mesh complications were included. Although the success rate is better with the use of TVM for recurrent prolapse, the total re-operation rates are similar when mesh complication-related surgeries are included.

Effect of low-level laser therapy on tissue repair after dental extraction in rats administered zoledronic acid and dexamethasone

Science.gov (United States)

Weber, João Batista Blessmann; Camilotti, Renata Stifelman; Jasper, Juliana; Casagrande, Liliane Cristina Onofre; Maito, Fábio Luiz Dal Moro

2017-05-01

Bisphosphonates (BPs) are being increasingly used for the treatment of metabolic and oncological pathologies involving the skeletal system. Because of the severity of the BP associated osteonecrosis of the jaws, the difficulties of treatment, and patient discomfort, additional support methods for their management are needed. Laser therapy has an easy handling, photobiostimulator effect on tissues healing, so it can be considered a preferred therapy. The aim of this study was to evaluate the influence of low-level laser therapy in the 685- and 830-nm wavelength in the healing process of the bone and soft tissues in rats under BP therapy [zoledronic acid (ZA)] and dexamethasone concomitantly that underwent a surgery for the extraction of upper molars. There were statistically significant differences in the clinical evaluation of the wound and the weight of the animals. Regarding the histological evaluation, it was possible to observe the different maturations of the healing stage between groups. The effect of drug therapy with ZA and dexamethasone in the bone tissue repair process induces osteonecrosis of the jaw in rats and slows down the healing process. In the laser groups, at the stipulated dosimetry, a positive influence on the bone and soft tissue repair process was observed.

Biomaterial-mediated strategies targeting vascularization for bone repair.

Science.gov (United States)

García, José R; García, Andrés J

2016-04-01

Repair of non-healing bone defects through tissue engineering strategies remains a challenging feat in the clinic due to the aversive microenvironment surrounding the injured tissue. The vascular damage that occurs following a bone injury causes extreme ischemia and a loss of circulating cells that contribute to regeneration. Tissue-engineered constructs aimed at regenerating the injured bone suffer from complications based on the slow progression of endogenous vascular repair and often fail at bridging the bone defect. To that end, various strategies have been explored to increase blood vessel regeneration within defects to facilitate both tissue-engineered and natural repair processes. Developments that induce robust vascularization will need to consolidate various parameters including optimization of embedded therapeutics, scaffold characteristics, and successful integration between the construct and the biological tissue. This review provides an overview of current strategies as well as new developments in engineering biomaterials to induce reparation of a functional vascular supply in the context of bone repair.

Endovascular Repair of Thoracoabdominal and Arch Aneurysms in Patients with Connective Tissue Disease Using Branched and Fenestrated Devices.

Science.gov (United States)

Clough, Rachel E; Martin-Gonzalez, Teresa; Van Calster, Katrien; Hertault, Adrien; Spear, Rafaëlle; Azzaoui, Richard; Sobocinski, Jonathan; Haulon, Stéphan

2017-10-01

Prophylactic open surgery is the standard practice in patients with connective tissue and thoracoabdominal aortic aneurysm (TAAA) and aortic arch disease. Branched and fenestrated devices offer a less invasive alternative but there are concerns regarding the durability of the repair and the effect of the stent graft on the fragile aortic wall. The aim of this study is to evaluate mid-term outcomes of fenestrated and/or branched endografting in patients with connective tissue disease. All patients with connective tissue disease who underwent TAAA or arch aneurysm repair using a fenestrated and/or branched endograft in a single, high-volume center between 2004 and 2015 were included. Ruptured aneurysms and acute aortic dissections were excluded from this study, but not chronic aortic dissections. In total, 427 (403 pararenal and TAAAs, and 24 arch aneurysms) endovascular interventions were performed during the study period. Of these, 17 patients (4%) (16 TAAAs, 1 arch) had connective tissue disease. All patients were classified as unfit for open repair. The mean age was 51 ± 8 years. Thirteen patients with TAAA were treated with a fenestrated, 1 with a branched, and 2 with a combined fenestrated/branch device. A double inner branch device was used to treat the arch aneurysm. The technical success rate was 100% with no incidence of early mortality, spinal cord ischemia, stroke, or further dissection. Postoperative deterioration in renal function was seen in 3 patients (18.8%) and no hemodialysis was required. The mean follow-up was 3.4 years (0.3-7.4). Aneurysm sac shrinkage was seen in 35% of patients (6/17) and the sac diameter remained stable in 65% of patients (11/17). No sac or sealing zone enlargement was observed in any of the patients and there were no conversions to open repair. Reintervention was required in 1 patient at 2 years for bilateral renal artery occlusion (successful fibrinolysis). One type II endoleak (lumbar) is under surveillance and 1 type

Factors modifying 3-aminobenzamide cytotoxicity in normal and repair-deficient human fibroblasts

International Nuclear Information System (INIS)

Boorstein, R.J.; Pardee, A.B.

1984-01-01

3-Aminobenzamide (3-AB), an inhibitor of poly(ADP-ribosylation), is lethal to human fibroblasts with damaged DNA. Its cytotoxicity was determined relative to a number of factors including the types of lesions, the kinetics of repair, and the availability of alternative repair systems. A variety of alkylating agent, UV or gamma irradiation, or antimetabolites were used to create DNA lesions. 3-AB enhanced lethality with monofunctional alkylating agents only. Within this class of compounds, methylmethanesulfonate (MMS) treatments made cells more sensitive to 3-AB than did treatment with methylnitrosourea (MNU) or methylnitronitrosoguanidine (MNNG). 3-AB interfered with a dynamic repair process lasting several days, since human fibroblasts remained sensitive to 3-AB for 36-48 hours following MMS treatment. During this same interval 3-AB caused these cells to arrest in G 2 phase. Alkaline elution analysis also revealed that this slow repair was delayed further by 3-AB. Human mutant cell defective in DNA repair differed in their responses to 3-AB. Greater lethality with 3-AB could be dependent on inability of the mutant cells to repair damage by other processes

DNA double strand break repair pathway plays a significant role in determining the radiotherapy induced normal tissue toxicity among head-and-neck and breast cancer

International Nuclear Information System (INIS)

Sadashiva, Satish Rao Bola; Mumbrekar, Kamalesh Dattaram; Venkatesh, Goutham Hassan; Fernandes, Donald Jerard; Bejadi, Vadhiraja Manjunath; Kapaettu, Satyamoorthy

2014-01-01

The ability to predict individual risk of radiotherapy induced normal tissue complications prior to the therapy may give an opportunity to personalize the treatment aiming improved therapeutic effect and quality of life. Therefore, predicting the risk of developing acute reactions before the initiation of radiation therapy may serve as a potential biomarker. DNA double-strand break (DSB) induction and its repair kinetics in lymphocytes of Head-and-Neck (n = 183) and Breast cancer (n = 132) patients undergoing chemoradiation or radiation therapy alone were analyzed by performing γ-H2AX foci, neutral comet and a modified neutral filter elution assay. Candidate radioresponsive genes like DNA repair, antioxidant pathway, profibrotic cytokine genes were screened for the common variants for their association with normal tissue toxicity outcome. Patients were stratified as non-over responders (NOR) and over responders (OR) based on their Radiation Therapy Oncology Group grading for normal tissue adverse reactions. Our results suggest that DSB repair plays a major role in the development of normal tissue adverse reactions in H and N and Breast cancer patients. The cellular (γ-H2AX analysis) and SNP analysis may have the potential to be developed into a clinically useful predictive assay for identifying the normal tissue over reactors

DNA Repair Alterations in Children With Pediatric Malignancies: Novel Opportunities to Identify Patients at Risk for High-Grade Toxicities

International Nuclear Information System (INIS)

Ruebe, Claudia E.; Fricke, Andreas; Schneider, Ruth; Simon, Karin; Kuehne, Martin; Fleckenstein, Jochen; Graeber, Stefan; Graf, Norbert; Ruebe, Christian

2010-01-01

Purpose: To evaluate, in a pilot study, the phosphorylated H2AX (γH2AX) foci approach for identifying patients with double-strand break (DSB) repair deficiencies, who may overreact to DNA-damaging cancer therapy. Methods and Materials: The DSB repair capacity of children with solid cancers was analyzed compared with that of age-matched control children and correlated with treatment-related normal-tissue responses (n = 47). Double-strand break repair was investigated by counting γH2AX foci in blood lymphocytes at defined time points after irradiation of blood samples. Results: Whereas all healthy control children exhibited proficient DSB repair, 3 children with tumors revealed clearly impaired DSB repair capacities, and 2 of these repair-deficient children developed life-threatening or even lethal normal-tissue toxicities. The underlying mutations affecting regulatory factors involved in DNA repair pathways were identified. Moreover, significant differences in mean DSB repair capacity were observed between children with tumors and control children, suggesting that childhood cancer is based on genetic alterations affecting DSB repair function. Conclusions: Double-strand break repair alteration in children may predispose to cancer formation and may affect children's susceptibility to normal-tissue toxicities. Phosphorylated H2AX analysis of blood samples allows one to detect DSB repair deficiencies and thus enables identification of children at risk for high-grade toxicities.

Specific patient-related prognostic factors for rotator cuff repair : a systematic review

NARCIS (Netherlands)

Heerspink, Frederik O. Lambers; Dorrestijn, Oscar; van Raay, Jos J. A. M.; Diercks, Ron L.

Background: Many studies that describe factors affecting outcome in primary rotator cuff repair (RCR) have been published, but so far there is no review that summarizes them. This systematic review was conducted to identify prognostic factors influencing functional (clinical) outcome and

Trabecular bone structure and strength - remodelling and repair

DEFF Research Database (Denmark)

Mosekilde, Lis; Ebbesen, Ebbe Nils; Erikstrup, Lise Tornvig

2000-01-01

vertical and horizontal struts reaching a certain magnitude and thereby inducing buckling under compression. 4) Microdamage and microfractures will occur - mainly in these very loaded vertical struts. The microfractures will be repaired by microcallus formation, and these calluses will later be removed...... can never be isolated in vivo, other factors need to be investigated: The interplay between the cortical shell and the trabecular network; transmission of load; the interplay between soft tissues (cartilage, connective tissue, muscle) and bone; the shock absorbing capacity of the discs...

Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair

Science.gov (United States)

Agarwal, Rachit; García, Andrés J.

2015-01-01

Bone tissue has a remarkable ability to regenerate and heal itself. However, large bone defects and complex fractures still present a significant challenge to the medical community. Current treatments center on metal implants for structural and mechanical support and auto- or allo-grafts to substitute long bone defects. Metal implants are associated with several complications such as implant loosening and infections. Bone grafts suffer from donor site morbidity, reduced bioactivity, and risk of pathogen transmission. Surgical implants can be modified to provide vital biological cues, growth factors and cells in order to improve osseointegration and repair of bone defects. Here we review strategies and technologies to engineer metal surfaces to promote osseointegration with the host tissue. We also discuss strategies for modifying implants for cell adhesion and bone growth via integrin signaling and growth factor and cytokine delivery for bone defect repair. PMID:25861724

Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

DEFF Research Database (Denmark)

Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

2008-01-01

Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...... and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers. Udgivelsesdato: 2008-Feb...

Prospective study of single-stage repair of contaminated hernias using a biologic porcine tissue matrix: the RICH Study.

Science.gov (United States)

Itani, Kamal M F; Rosen, Michael; Vargo, Daniel; Awad, Samir S; Denoto, George; Butler, Charles E

2012-09-01

In the presence of contamination, the repair of a ventral incisional hernia (VIH) is challenging. The presence of comorbidities poses an additional risk for postoperative wound events and hernia recurrence. To date, very few studies describe the outcomes of VIH repair in this high-risk population. A prospective, multicenter, single-arm, the Repair of Infected or Contaminated Hernias study was performed to study the clinical outcomes of open VIH repair of contaminated abdominal defects with a non-cross-linked, porcine, acellular dermal matrix, Strattice. Of 85 patients who consented to participate, 80 underwent open VIH repair with Strattice. Hernia defects were 'clean-contaminated' (n = 39), 'contaminated' (n = 39), or 'dirty' (n = 2), and the defects were classified as grade 3 (n = 60) or grade 4 (n = 20). The midline was restored, and primary closure was achieved in 64 patients; the defect was bridged in 16 patients. At 24 months, 53 patients (66%) experienced 95 wound events. There were 28 unique, infection-related events in 24 patients. Twenty-two patients experienced seromas, all but 5 of which were transient and required no intervention. No unanticipated adverse events occurred, and no tissue matrix required complete excision. There were 22 hernia (28%) recurrences by month 24. There was no correlation between infection-related events and hernia recurrence. The use of the intact, non-cross-linked, porcine, acellular dermal matrix, Strattice, in the repair of contaminated VIH in high-risk patients allowed for successful, single-stage reconstruction in >70% of patients followed for 24 months after repair. Published by Mosby, Inc.

Is glans penis width a risk factor for complications after hypospadias repair?

Science.gov (United States)

Faasse, M A; Johnson, E K; Bowen, D K; Lindgren, B W; Maizels, M; Marcus, C R; Jovanovic, B D; Yerkes, E B

2016-08-01

Recent studies have suggested that a smaller glans penis size may be associated with a higher likelihood of complications after hypospadias repair. Accurate identification of risk factors other than the well-understood variable of meatal location would allow development of better prognostic models and individualized risk stratification. To test the hypothesis that a smaller width of the glans penis predicts adverse outcomes after hypospadias surgery. Prospectively recorded clinical data were reviewed from a single-institution registry of primary hypospadias repairs performed between 2011 and 2014. Follow-up records were examined for occurrence of complications. Urethroplasty complications were defined to include meatal stenosis, dehiscence, urethrocutaneous fistula, urethral stricture, and/or urethral diverticulum. The subset of meatal stenosis and dehiscence were regarded as glanular complications. Regression analyses were performed to determine association between glans width and occurrence of complications. Because pre-operative androgen stimulation is known to increase glans penis size, separate subgroup analyses were included of patients with and without pre-operative use of testosterone cream. A total of 159 patients met criteria for inclusion in the study cohort: 140 patients underwent a single-stage repair, while 19 patients had a two-stage repair. The median glans penis width was 15 mm (range 10-22). Eighty-four patients (53%) received testosterone cream pre-operatively and had a significantly wider glans penis than the 75 patients who did not (median 15.5 vs 14 mm; P penis width was not a risk factor for complications after hypospadias repair. This finding differs from the results of other recent studies and encourages further research into the value of measuring penile parameters in patients undergoing hypospadias repair. Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Tissue repair genes: the TiRe database and its implication for skin wound healing.

Science.gov (United States)

Yanai, Hagai; Budovsky, Arie; Tacutu, Robi; Barzilay, Thomer; Abramovich, Amir; Ziesche, Rolf; Fraifeld, Vadim E

2016-04-19

Wound healing is an inherent feature of any multicellular organism and recent years have brought about a huge amount of data regarding regular and abnormal tissue repair. Despite the accumulated knowledge, modulation of wound healing is still a major biomedical challenge, especially in advanced ages. In order to collect and systematically organize what we know about the key players in wound healing, we created the TiRe (Tissue Repair) database, an online collection of genes and proteins that were shown to directly affect skin wound healing. To date, TiRe contains 397 entries for four organisms: Mus musculus, Rattus norvegicus, Sus domesticus, and Homo sapiens. Analysis of the TiRe dataset of skin wound healing-associated genes showed that skin wound healing genes are (i) over-conserved among vertebrates, but are under-conserved in invertebrates; (ii) enriched in extracellular and immuno-inflammatory genes; and display (iii) high interconnectivity and connectivity to other proteins. The latter may provide potential therapeutic targets. In addition, a slower or faster skin wound healing is indicative of an aging or longevity phenotype only when assessed in advanced ages, but not in the young. In the long run, we aim for TiRe to be a one-station resource that provides researchers and clinicians with the essential data needed for a better understanding of the mechanisms of wound healing, designing new experiments, and the development of new therapeutic strategies. TiRe is freely available online at http://www.tiredb.org.

Soft tissue reinforcement interposition flaps in hypospadias repair

Directory of Open Access Journals (Sweden)

Singh R

2007-01-01

Full Text Available Purpose: To discuss the role and mechanism of action of soft tissue reinforcement interposition flaps (STRIFs in hypospadias repairs (reinforced hypospadiac urethroplasties. Materials and Methods: Between 2000-2005, 120 consecutive hypospadiacs (distal 85, mid 20, proximal 15, who underwent primary reinforced urethroplasties employing different types of STRIFs, were retrospectively analyzed. The STRIFs were highly vascular soft tissue pedicled flaps (devoid of epithelium interposed between neo-urethras and the covering skin to reinforce the neo-urethras against fistula formation. The STRIFs were harvested, without much donor site deformity, from: preputial skin, penile skin and scrotal skin by de-epithelialization. Those from Buck′s fascia, corpus spongiosum and tunica vaginalis are STRIFs without epithelium anyway, therefore do not need de-epithelialization. Redo urethroplasties and micropenises were not included. Seven patients were excluded because they had incomplete follow-up. The remaining 113 (distal 84, mid 17, proximal 12 were followed up for nine to 40 months for number, size, location, spontaneous closure and persistence of urethro-cutaneous fistula (UCF, and other complications with regard to the severity of hypospadias, method of neourethral re-construction, types of STRIFs employed and skin cover used. A total of 158 STRIFs and 124 skin covers were used in 113 hypospadiac urethroplasties. Results: The first surgery was curative in 74 (65% of 113 patients. In the remaining 39 (35%, various complications included 12 urethro-cutaneous fistulas (UCFs, 10 urethral strictures, six cases each of penile torsion and meatal stenosis and five cases each of superficial necrosis and poor cosmesis. Of these 39 patients, 25 (64% recovered with conservative treatment and 14 (36% required re-operation, i.e. UCFs and strictures in four cases each and penile torsion, meatal stenosis and dog-ears in two cases each. All the 12 UCFs were single

Mediator MED23 Links Pigmentation and DNA Repair through the Transcription Factor MITF.

Science.gov (United States)

Xia, Min; Chen, Kun; Yao, Xiao; Xu, Yichi; Yao, Jiaying; Yan, Jun; Shao, Zhen; Wang, Gang

2017-08-22

DNA repair is related to many physiological and pathological processes, including pigmentation. Little is known about the role of the transcriptional cofactor Mediator complex in DNA repair and pigmentation. Here, we demonstrate that Mediator MED23 plays an important role in coupling UV-induced DNA repair to pigmentation. The loss of Med23 specifically impairs the pigmentation process in melanocyte-lineage cells and in zebrafish. Med23 deficiency leads to enhanced nucleotide excision repair (NER) and less DNA damage following UV radiation because of the enhanced expression and recruitment of NER factors to chromatin for genomic stability. Integrative analyses of melanoma cells reveal that MED23 controls the expression of a melanocyte master regulator, Mitf, by modulating its distal enhancer activity, leading to opposing effects on pigmentation and DNA repair. Collectively, the Mediator MED23/MITF axis connects DNA repair to pigmentation, thus providing molecular insights into the DNA damage response and skin-related diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Role of DNA damage and repair as predeterminant factor in the development of radiotherapy induced acute adverse reactions

International Nuclear Information System (INIS)

Satish Rao, B.S.; Kamalesh, D.M.; Goutham, H.V.; Donald, J.F.; Sharan, Krishna; Vadhiraja, B.M.; Satyamoorthy, K.

2013-01-01

Radiotherapy induced normal tissue toxicity is one of the major limitations for the compromised the therapeutic outcome and also worsens the quality of life of survivors. Further, the clinical experience demonstrated inter-individual variability with respect to their normal tissue toxicity. Therefore, the discovery of contributing key factors of variability or predicting the risk of developing acute reactions before the initiation of radiation therapy may serve as a powerful predictive biomarker for individualizing radiotherapy, anticipating increased therapeutic effect. DNA double-strand break (DSB) induction and its repair in lymphocytes of head-and-neck and breast cancer patients undergoing chemoradiation or radiation therapy alone were analyzed by performing γ-H2AX foci, neutral comet and a modified neutral filter elution assays. Treatment induced normal tissue adverse reactions (acute skin reaction, oral mucositis) were assessed by the criteria of Radiation Therapy Oncology Group. The residual damage (RD) at 6 hrs of post irradiation was used as parameters to measure cellular radiosensitivity and for its correlation with radiotherapy induced acute reactions in patients stratified as non-over responders (NOR) and over responders (OR). A large inter-individual variation in the radiosensitivity was observed in the cancer individuals with respect to their lymphocyte radiosensitivity and the severity of normal tissue adverse reactions. There was a significant difference in RD (p<0.05) between the NOR and OR in breast cancer radiotherapy. Further, the increased normal tissue toxicity such as oral mucositis and skin reactions was associated with the reduced DSB repair (p<0.05) in head-and-neck cancer patients. The percentile analysis was found to be useful in predicting the OR amongst the head-and-neck cancer patients. Our results suggest that γ-H2AX analysis may have its potential to be developed into a clinically useful predictive assay for identifying the

CARTILAGE CONSTRUCTS ENGINEERED FROM CHONDROCYTES OVEREXPRESSING IGF-I IMPROVE THE REPAIR OF OSTEOCHONDRAL DEFECTS IN A RABBIT MODEL

Science.gov (United States)

Madry, Henning; Kaul, Gunter; Zurakowski, David; Vunjak-Novakovic, Gordana; Cucchiarini, Magali

2015-01-01

Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes over expressing a human insulin-like growth factor I (IGF-I) gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-over expressing chondrocytes markedly improved osteochondral repair compared with control (lacZ) constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects. PMID:23588785

Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model

Directory of Open Access Journals (Sweden)

H Madry

2013-04-01

Full Text Available Tissue engineering combined with gene therapy is a promising approach for promoting articular cartilage repair. Here, we tested the hypothesis that engineered cartilage with chondrocytes overexpressing a human insulin-like growth factor I (IGF-I gene can enhance the repair of osteochondral defects, in a manner dependent on the duration of cultivation. Genetically modified chondrocytes were cultured on biodegradable polyglycolic acid scaffolds in dynamic flow rotating bioreactors for either 10 or 28 d. The resulting cartilaginous constructs were implanted into osteochondral defects in rabbit knee joints. After 28 weeks of in vivo implantation, immunoreactivity to ß-gal was detectable in the repair tissue of defects that received lacZ constructs. Engineered cartilaginous constructs based on IGF-I-overexpressing chondrocytes markedly improved osteochondral repair compared with control (lacZ constructs. Moreover, IGF-I constructs cultivated for 28 d in vitro significantly promoted osteochondral repair vis-à-vis similar constructs cultivated for 10 d, leading to significantly decreased osteoarthritic changes in the cartilage adjacent to the defects. Hence, the combination of spatially defined overexpression of human IGF-I within a tissue-engineered construct and prolonged bioreactor cultivation resulted in most enhanced articular cartilage repair and reduction of osteoarthritic changes in the cartilage adjacent to the defect. Such genetically enhanced tissue engineering provides a versatile tool to evaluate potential therapeutic genes in vivo and to improve our comprehension of the development of the repair tissue within articular cartilage defects. Insights gained with additional exploration using this model may lead to more effective treatment options for acute cartilage defects.

Opening of the inward rectifier potassium channel alleviates maladaptive tissue repair following myocardial infarction.

Science.gov (United States)

Liu, Chengfang; Liu, Enli; Luo, Tiane; Zhang, Weifang; He, Rongli

2016-08-01

Activation of the inward rectifier potassium current (IK1) channel has been reported to be associated with suppression of ventricular arrhythmias. In this study, we tested the hypothesis that opening of the IK1 channel with zacopride (ZAC) was involved in the modulation of tissue repair after myocardial infarction. Sprague-Dawley rats were subject to coronary artery ligation and ZAC was administered intraperitoneally (15 µg/kg/day) for 28 days. Compared with the ischemia group, treatment with ZAC significantly reduced the ratio of heart/body weight and the cross-sectional area of cardiomyocytes, suggesting less cardiac hypertrophy. ZAC reduced the accumulation of collagen types I and III, accompanied with decrease of collagen area, which were associated with a reduction of collagen deposition in the fibrotic myocardium. Echocardiography showed improved cardiac function, evidenced by the reduced left ventricular end-diastolic dimension and left ventricular end-systolic dimension, and the increased ejection fraction and fractional shortening in ZAC-treated animals (all P < 0.05 vs. ischemia group). In coincidence with these changes, ZAC up-regulated the protein level of the IK1 channel and down-regulated the phosphorylation of mammalian target of rapamycin (mTOR) and 70-kDa ribosomal protein S6 (p70S6) kinase. Administration of chloroquine alone, an IK1 channel antagonist, had no effect on all the parameters measured, but significantly blocked the beneficial effects of ZAC on cardiac repair. In conclusion, opening of the IK1 channel with ZAC inhibits maladaptive tissue repair and improves cardiac function, potentially mediated by the inhibition of ischemia-activated mTOR-p70S6 signaling pathway via the IK1 channel. So the development of pharmacological agents specifically targeting the activation of the IK1 channel may protect the heart against myocardial ischemia-induced cardiac dysfunction. © The Author 2016. Published by Oxford University Press on behalf of

The application of lesion sterilization and tissue repair 3Mix-MP for treating rat's dental pulp tissue

Directory of Open Access Journals (Sweden)

Raditya Nugroho

2015-03-01

Full Text Available Background: Lesion sterilization and tissue repair (LSTR 3Mix-MP are three broad-spectrum antibiotics, including metronidazole, ciprofloxacin and minocycline are mixed with propylene glycol or macrogol. There is the possibility ofthe healing process that marked proliferation ofnew blood vessels and proliferation offibroblasts in the treatment ofirreversible pulpitis by pulp capping LSTR 3MixMP because of  the principle of the method LSTR 3Mix-MP is to kill bacteria. Purpose: The purpose of this study to prove the effect of LSTR 3Mix-MP on chronic inflammation and the healing process in rat dental pulp tissue in vivo. Methods: Rattus norvegicus anaesthetized by using ketamine and xylazine dissolved in sterile isotonic saline solution (0.2 ml/50gr mm on the upper right thigh. Cavity preparation class I to perforation by using a low speed tapered diamond round bur. In the treatment group, rats were treated 3Mix-MP at a dose of10 mg and then covered with glass ionomer cement for 7 days on the pulp that has been opened for 3 days. The control group treated with saline irrigation on the pulp that has been opened for 3 days. Rats were killed after seven days, and then made preparations pulp tissue to count the number oflymphocytes, macrophages, plasma cells, blood vessels, and fibroblasts Results: There is an increase in the average number ofmacrophage cells, plasma, and fibroblasts; and decreased lymphocytes and blood vessels in the treated group exposure LSTR 3Mix-MP. Conclusion:LSTR 3Mix-MP can reduce chronic inflammation process and enhance the healing process in rat dental pulp tissue.

Novel Stem Cell Therapies for Applications to Wound Healing and Tissue Repair.

Science.gov (United States)

Grada, Ayman; Falanga, Vincent

2016-10-26

The number of individuals with chronic cutaneous wounds has been increasing worldwide due to an aging population, diabetes, obesity, and cardiovascular disease. In the United States, almost seven million Americans have chronic skin ulcers. Many therapeutic approaches have been used. However, the treatment outcomes are not always ideal because of failure to achieve complete wound closure in around 60% of cases, scarring, and high rate of recurrence. Therefore, there is a need for more effective therapies. Stem cells offer promising possibilities. Pre-clinical studies have shown that bone- or adipose tissue-derived mesenchymal stem cells (MSCs) have a competitive advantage over other types of stem cells due to their better defined multipotent differentiating potential, paracrine effects, immunomodulatory properties, and safety. However, large controlled clinical trials are needed to examine the capabilities of MSCs in humans and to assess their safety profile. In this review, we highlight emerging treatments in tissue regeneration and repair and provide some perspectives on how to translate current knowledge about stem cells-both multipotent and pluripotent-into viable clinical approaches for treating patients with difficult to heal wounds.

Mesh complications and failure rates after transvaginal mesh repair compared with abdominal or laparoscopic sacrocolpopexy and to native tissue repair in treating apical prolapse.

Science.gov (United States)

Dandolu, Vani; Akiyama, Megumi; Allenback, Gayle; Pathak, Prathamesh

2017-02-01

Our objective was to quantitate the extent of complications and failure rate for apical prolapse repair with transvaginal mesh (TVM) use versus sacrocolpopexy over a minimum of 2 years of follow-up. Truven CCAE and Medicare Supplemental databases 2008-2013 were used for analysis. Patients with apical prolapse repair via transvaginal mesh (TVMR), abdominal sacrocolpopexy (ASCP), laparoscopic sacrocolpopexy (LSCP), or native tissue repair (NTR) and continuously enrolled for years were in the study cohort. Surgical failures were identified by reoperation for any prolapse or subsequent use of pessary. SAS® 9.3 was used for analysis. Mesh removal/revision was reported highest in TVMR (5.1 %), followed by LSCP (1.7 %) and ASCP (1.2 %). In those with concomitant sling, combined rates for mesh/sling revision were high, at 9.0 % in TVMR + sling, 5.6 % in ASCP + sling, and 4.5 % LSCP + sling. Sling-alone cases reported a 3.5 % revision rate. Pelvic pain (16.4-22.7 %) and dyspareunia (5.6-7.5 %) were high in all three approaches for apical prolapse repairs. Reoperation for apical prolapse was more common for TVMR (2.9 %) compared with NTR (2.3 %) [odds ratio (OR) 1.27; confidence interval (CI) 1.1-1.47; p 0.002]. Both ASCP and LSCP were superior to NTR (ASCP 1.5 %, OR 0.63, CI 0.46-0.86; p 0.003) and LSCP 1.8 % (OR 0.79, CI 0.62-1.01; p 0.07). Overall prolapse recurrence, as indicated by any compartment surgery for prolapse and/or pessary use, was also noted highest in TVMR (5.9 % OR 1.23, CI 1.11-1.36; p mesh is used for repair, mesh revision is highest with TVMR and lowest with ASCP.

Stem Cells and Gene Therapy for Cartilage Repair

OpenAIRE

Longo, Umile Giuseppe; Petrillo, Stefano; Franceschetti, Edoardo; Berton, Alessandra; Maffulli, Nicola; Denaro, Vincenzo

2012-01-01

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, sur...

Tissue engineering and the use of stem/progenitor cells for airway epithelium repair

Directory of Open Access Journals (Sweden)

GM Roomans

2010-06-01

Full Text Available Stem/progenitor cells can be used to repair defects in the airway wall, resulting from e.g., tumors, trauma, tissue reactions following long-time intubations, or diseases that are associated with epithelial damage. Several potential sources of cells for airway epithelium have been identified. These can be divided into two groups. The first group consists of endogenous progenitor cells present in the respiratory tract. This group can be subdivided according to location into (a a ductal cell type in the submucosal glands of the proximal trachea, (b basal cells in the intercartilaginous zones of the lower trachea and bronchi, (c variant Clara cells (Clarav-cells in the bronchioles and (d at the junctions between the bronchioles and the alveolar ducts, and (e alveolar type II cells. This classification of progenitor cell niches is, however, controversial. The second group consists of exogenous stem cells derived from other tissues in the body. This second group can be subdivided into: (a embryonic stem (ES cells, induced pluripotent stem (iPS cells, or amniotic fluid stem cells, (b side-population cells from bone marrow or epithelial stem cells present in bone marrow or circulation and (c fat-derived mesenchymal cells. Airway epithelial cells can be co-cultured in a system that includes a basal lamina equivalent, extracellular factors from mesenchymal fibroblasts, and in an air-liquid interface system. Recently, spheroid-based culture systems have been developed. Several clinical applications have been suggested: cystic fibrosis, acute respiratory distress syndrome, chronic obstructive lung disease, pulmonary fibrosis, pulmonary edema, and pulmonary hypertension. Clinical applications so far are few, but include subglottic stenosis, tracheomalacia, bronchiomalacia, and emphysema.

International Cartilage Repair Society (ICRS) Recommended Guidelines for Histological Endpoints for Cartilage Repair Studies in Animal Models and Clinical Trials

Science.gov (United States)

Hoemann, Caroline; Kandel, Rita; Roberts, Sally; Saris, Daniel B.F.; Creemers, Laura; Mainil-Varlet, Pierre; Méthot, Stephane; Hollander, Anthony P.; Buschmann, Michael D.

2011-01-01

Cartilage repair strategies aim to resurface a lesion with osteochondral tissue resembling native cartilage, but a variety of repair tissues are usually observed. Histology is an important structural outcome that could serve as an interim measure of efficacy in randomized controlled clinical studies. The purpose of this article is to propose guidelines for standardized histoprocessing and unbiased evaluation of animal tissues and human biopsies. Methods were compiled from a literature review, and illustrative data were added. In animal models, treatments are usually administered to acute defects created in healthy tissues, and the entire joint can be analyzed at multiple postoperative time points. In human clinical therapy, treatments are applied to developed lesions, and biopsies are obtained, usually from a subset of patients, at a specific time point. In striving to standardize evaluation of structural endpoints in cartilage repair studies, 5 variables should be controlled: 1) location of biopsy/sample section, 2) timing of biopsy/sample recovery, 3) histoprocessing, 4) staining, and 5) blinded evaluation with a proper control group. Histological scores, quantitative histomorphometry of repair tissue thickness, percentage of tissue staining for collagens and glycosaminoglycan, polarized light microscopy for collagen fibril organization, and subchondral bone integration/structure are all relevant outcome measures that can be collected and used to assess the efficacy of novel therapeutics. Standardized histology methods could improve statistical analyses, help interpret and validate noninvasive imaging outcomes, and permit cross-comparison between studies. Currently, there are no suitable substitutes for histology in evaluating repair tissue quality and cartilaginous character. PMID:26069577

Promoting tissue regeneration by modulating the immune system.

Science.gov (United States)

Julier, Ziad; Park, Anthony J; Briquez, Priscilla S; Martino, Mikaël M

2017-04-15

The immune system plays a central role in tissue repair and regeneration. Indeed, the immune response to tissue injury is crucial in determining the speed and the outcome of the healing process, including the extent of scarring and the restoration of organ function. Therefore, controlling immune components via biomaterials and drug delivery systems is becoming an attractive approach in regenerative medicine, since therapies based on stem cells and growth factors have not yet proven to be broadly effective in the clinic. To integrate the immune system into regenerative strategies, one of the first challenges is to understand the precise functions of the different immune components during the tissue healing process. While remarkable progress has been made, the immune mechanisms involved are still elusive, and there is indication for both negative and positive roles depending on the tissue type or organ and life stage. It is well recognized that the innate immune response comprising danger signals, neutrophils and macrophages modulates tissue healing. In addition, it is becoming evident that the adaptive immune response, in particular T cell subset activities, plays a critical role. In this review, we first present an overview of the basic immune mechanisms involved in tissue repair and regeneration. Then, we highlight various approaches based on biomaterials and drug delivery systems that aim at modulating these mechanisms to limit fibrosis and promote regeneration. We propose that the next generation of regenerative therapies may evolve from typical biomaterial-, stem cell-, or growth factor-centric approaches to an immune-centric approach. Most regenerative strategies have not yet proven to be safe or reasonably efficient in the clinic. In addition to stem cells and growth factors, the immune system plays a crucial role in the tissue healing process. Here, we propose that controlling the immune-mediated mechanisms of tissue repair and regeneration may support

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.

Stratification of surgical site infection by operative factors and comparison of infection rates after hernia repair.

Science.gov (United States)

Olsen, Margaret A; Nickel, Katelin B; Wallace, Anna E; Mines, Daniel; Fraser, Victoria J; Warren, David K

2015-03-01

To investigate whether operative factors are associated with risk of surgical site infection (SSI) after hernia repair. Retrospective cohort study. Patients Commercially insured enrollees aged 6 months-64 years with International Classification of Diseases, Ninth Revision, Clinical Modification procedure or Current Procedural Terminology, fourth edition, codes for inguinal/femoral, umbilical, and incisional/ventral hernia repair procedures from January 1, 2004, through December 31, 2010. SSIs within 90 days after hernia repair were identified by diagnosis codes. The χ2 and Fisher exact tests were used to compare SSI incidence by operative factors. A total of 119,973 hernia repair procedures were analyzed. The incidence of SSI differed significantly by anatomic site, with rates of 0.45% (352/77,666) for inguinal/femoral, 1.16% (288/24,917) for umbilical, and 4.11% (715/17,390) for incisional/ventral hernia repair. Within anatomic sites, the incidence of SSI was significantly higher for open versus laparoscopic inguinal/femoral (0.48% [295/61,142] vs 0.34% [57/16,524], P=.020) and incisional/ventral (4.20% [701/16,699] vs 2.03% [14/691], P=.005) hernia repairs. The rate of SSI was higher following procedures with bowel obstruction/necrosis than procedures without obstruction/necrosis for open inguinal/femoral (0.89% [48/5,422] vs 0.44% [247/55,720], Poperative factors may facilitate accurate comparison of SSI rates between facilities.

DNA damage repair and radiosensitivity

International Nuclear Information System (INIS)

Suzuki, Norio

2003-01-01

Tailored treatment is not new in radiotherapy; it has been the major subject for the last 20-30 years. Radiation responses and RBE (relative biological effectiveness) depend on assay systems, endpoints, type of tissues and tumors, radiation quality, dose rate, dose fractionation, physiological and environmental factors etc, Latent times to develop damages also differ among tissues and endpoints depending on doses and radiation quality. Recent progress in clarification of radiation induced cell death, especially of apoptotic cell death, is quite important for understanding radiosensitivity of tumor cure process as well as of tumorigenesis. Apoptotic cell death as well as dormant cells had been unaccounted and missed into a part of reproductive cell death. Another area of major progress has been made in clarifying repair mechanisms of radiation damage, i.e., non-homologous end joining (NHEJ) and homologous recombinational repair (HRR). New approaches and developments such as cDNA or protein micro arrays and so called informatics in addition to basic molecular biological analysis are expected to aid identifying molecules and their roles in signal transduction pathways, which are multi-factorial and interactive each other being involved in radiation responses. (authors)

Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration

DEFF Research Database (Denmark)

Hjortoe, Gertrud M; Petersen, Lars C; Albrektsen, Tatjana

2004-01-01

Tissue factor (TF), the cellular receptor for factor VIIa (FVIIa), besides initiating blood coagulation, is believed to play an important role in tissue repair, inflammation, angiogenesis, and tumor metastasis. Like TF, the chemokine interleukin-8 (IL-8) is shown to play a critical role...... in these processes. To elucidate the potential mechanisms by which TF contributes to tumor invasion and metastasis, we investigated the effect of FVIIa on IL-8 expression and cell migration in a breast carcinoma cell line, MDA-MB-231, a cell line that constitutively expresses abundant TF. Expression of IL-8 m......RNA in MDA-MB-231 cells was markedly up-regulated by plasma concentrations of FVII or an equivalent concentration of FVIIa (10 nM). Neither thrombin nor other proteases involved in hemostasis were effective in stimulating IL-8 in these cells. Increased transcriptional activation of the IL-8 gene...

Accumulation of DNA Double-Strand Breaks in Normal Tissues After Fractionated Irradiation

International Nuclear Information System (INIS)

Ruebe, Claudia E.; Fricke, Andreas; Wendorf, Juliane; Stuetzel, Annika; Kuehne, Martin; Ong, Mei Fang; Lipp, Peter; Ruebe, Christian

2010-01-01

Purpose: There is increasing evidence that genetic factors regulating the recognition and/or repair of DNA double-strand breaks (DSBs) are responsible for differences in radiosensitivity among patients. Genetically defined DSB repair capacities are supposed to determine patients' individual susceptibility to develop adverse normal tissue reactions after radiotherapy. In a preclinical murine model, we analyzed the impact of different DSB repair capacities on the cumulative DNA damage in normal tissues during the course of fractionated irradiation. Material and Methods: Different strains of mice with defined genetic backgrounds (SCID -/- homozygous, ATM -/- homozygous, ATM +/- heterozygous, and ATM +/+ wild-type mice) were subjected to single (2 Gy) or fractionated irradiation (5 x 2 Gy). By enumerating γH2AX foci, the formation and rejoining of DSBs were analyzed in organs representative of both early-responding (small intestine) and late-responding tissues (lung, kidney, and heart). Results: In repair-deficient SCID -/- and ATM -/- homozygous mice, large proportions of radiation-induced DSBs remained unrepaired after each fraction, leading to the pronounced accumulation of residual DNA damage after fractionated irradiation, similarly visible in early- and late-responding tissues. The slight DSB repair impairment of ATM +/- heterozygous mice was not detectable after single-dose irradiation but resulted in a significant increase in unrepaired DSBs during the fractionated irradiation scheme. Conclusions: Radiation-induced DSBs accumulate similarly in acute- and late-responding tissues during fractionated irradiation, whereas the whole extent of residual DNA damage depends decisively on the underlying genetically defined DSB repair capacity. Moreover, our data indicate that even minor impairments in DSB repair lead to exceeding DNA damage accumulation during fractionated irradiation and thus may have a significant impact on normal tissue responses in clinical

Imaging of cartilage repair procedures

International Nuclear Information System (INIS)

Sanghvi, Darshana; Munshi, Mihir; Pardiwala, Dinshaw

2014-01-01

The rationale for cartilage repair is to prevent precocious osteoarthritis in untreated focal cartilage injuries in the young and middle-aged population. The gamut of surgical techniques, normal postoperative radiological appearances, and possible complications have been described. An objective method of recording the quality of repair tissue is with the magnetic resonance observation of cartilage repair tissue (MOCART) score. This scoring system evaluates nine parameters that include the extent of defect filling, border zone integration, signal intensity, quality of structure and surface, subchondral bone, subchondral lamina, and records presence or absence of synovitis and adhesions. The five common techniques of cartilage repair currently offered include bone marrow stimulation (microfracture or drilling), mosaicplasty, synthetic resorbable scaffold grafts, osteochondral allograft transplants, and autologous chondrocyte implantation (ACI). Complications of cartilage repair procedures that may be demonstrated on magnetic resonance imaging (MRI) include plug loosening, graft protuberance, graft depression, and collapse in mosaicplasty, graft hypertrophy in ACI, and immune response leading to graft rejection, which is more common with synthetic grafts and cadaveric allografts

Recurrent Tricuspid Insufficiency: Is the Surgical Repair Technique a Risk Factor?

OpenAIRE

Kara, Ibrahim; Koksal, Cengiz; Cakalagaoglu, Canturk; Sahin, Muslum; Yanartas, Mehmet; Ay, Yasin; Demir, Serdar

2013-01-01

This study compares the medium-term results of De Vega, modified De Vega, and ring annuloplasty techniques for the correction of tricuspid insufficiency and investigates the risk factors for recurrent grades 3 and 4 tricuspid insufficiency after repair.

Wound repair and regeneration: Mechanisms, signaling, and translation

Science.gov (United States)

Eming, Sabine A.; Martin, Paul; Tomic-Canic, Marjana

2015-01-01

The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body’s natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies. PMID:25473038

Cell-Based Strategies for Meniscus Tissue Engineering

Science.gov (United States)

Niu, Wei; Guo, Weimin; Han, Shufeng; Zhu, Yun; Liu, Shuyun; Guo, Quanyi

2016-01-01

Meniscus injuries remain a significant challenge due to the poor healing potential of the inner avascular zone. Following a series of studies and clinical trials, tissue engineering is considered a promising prospect for meniscus repair and regeneration. As one of the key factors in tissue engineering, cells are believed to be highly beneficial in generating bionic meniscus structures to replace injured ones in patients. Therefore, cell-based strategies for meniscus tissue engineering play a fundamental role in meniscal regeneration. According to current studies, the main cell-based strategies for meniscus tissue engineering are single cell type strategies; cell coculture strategies also were applied to meniscus tissue engineering. Likewise, on the one side, the zonal recapitulation strategies based on mimicking meniscal differing cells and internal architectures have received wide attentions. On the other side, cell self-assembling strategies without any scaffolds may be a better way to build a bionic meniscus. In this review, we primarily discuss cell seeds for meniscus tissue engineering and their application strategies. We also discuss recent advances and achievements in meniscus repair experiments that further improve our understanding of meniscus tissue engineering. PMID:27274735

Understanding Magnetic Resonance Imaging of Knee Cartilage Repair: A Focus on Clinical Relevance.

Science.gov (United States)

Hayashi, Daichi; Li, Xinning; Murakami, Akira M; Roemer, Frank W; Trattnig, Siegfried; Guermazi, Ali

2017-06-01

The aims of this review article are (a) to describe the principles of morphologic and compositional magnetic resonance imaging (MRI) techniques relevant for the imaging of knee cartilage repair surgery and their application to longitudinal studies and (b) to illustrate the clinical relevance of pre- and postsurgical MRI with correlation to intraoperative images. First, MRI sequences that can be applied for imaging of cartilage repair tissue in the knee are described, focusing on comparison of 2D and 3D fast spin echo and gradient recalled echo sequences. Imaging features of cartilage repair tissue are then discussed, including conventional (morphologic) MRI and compositional MRI techniques. More specifically, imaging techniques for specific cartilage repair surgery techniques as described above, as well as MRI-based semiquantitative scoring systems for the knee cartilage repair tissue-MR Observation of Cartilage Repair Tissue and Cartilage Repair OA Knee Score-are explained. Then, currently available surgical techniques are reviewed, including marrow stimulation, osteochondral autograft, osteochondral allograft, particulate cartilage allograft, autologous chondrocyte implantation, and others. Finally, ongoing research efforts and future direction of cartilage repair tissue imaging are discussed.

Augmentation of Rotator Cuff Repair With Soft Tissue Scaffolds

Science.gov (United States)

Thangarajah, Tanujan; Pendegrass, Catherine J.; Shahbazi, Shirin; Lambert, Simon; Alexander, Susan; Blunn, Gordon W.

2015-01-01

Background Tears of the rotator cuff are one of the most common tendon disorders. Treatment often includes surgical repair, but the rate of failure to gain or maintain healing has been reported to be as high as 94%. This has been substantially attributed to the inadequate capacity of tendon to heal once damaged, particularly to bone at the enthesis. A number of strategies have been developed to improve tendon-bone healing, tendon-tendon healing, and tendon regeneration. Scaffolds have received considerable attention for replacement, reconstruction, or reinforcement of tendon defects but may not possess situation-specific or durable mechanical and biological characteristics. Purpose To provide an overview of the biology of tendon-bone healing and the current scaffolds used to augment rotator cuff repairs. Study Design Systematic review; Level of evidence, 4. Methods A preliminary literature search of MEDLINE and Embase databases was performed using the terms rotator cuff scaffolds, rotator cuff augmentation, allografts for rotator cuff repair, xenografts for rotator cuff repair, and synthetic grafts for rotator cuff repair. Results The search identified 438 unique articles. Of these, 214 articles were irrelevant to the topic and were therefore excluded. This left a total of 224 studies that were suitable for analysis. Conclusion A number of novel biomaterials have been developed into biologically and mechanically favorable scaffolds. Few clinical trials have examined their effect on tendon-bone healing in well-designed, long-term follow-up studies with appropriate control groups. While there is still considerable work to be done before scaffolds are introduced into routine clinical practice, there does appear to be a clear indication for their use as an interpositional graft for large and massive retracted rotator cuff tears and when repairing a poor-quality degenerative tendon. PMID:26665095

Injectable systems and implantable conduits for peripheral nerve repair

International Nuclear Information System (INIS)

Lin, Yen-Chih; Marra, Kacey G

2012-01-01

Acute sensory problems following peripheral nerve injury include pain and loss of sensation. Approximately 360 000 people in the United States suffer from upper extremity paralytic syndromes every year. Restoration of sufficient functional recovery after long-gap peripheral nerve damage remains a clinical challenge. Potential nerve repair therapies have increased in the past decade as the field of tissue engineering expands. The following review describes the use of biomaterials in nerve tissue engineering. Namely, the use of both synthetic and natural biomaterials, including non-degradable and degradable nerve grafts, is addressed. The enhancement of axonal regeneration can be achieved by further modification of the nerve guides. These approaches include injectable hydrogel fillers, controlled drug delivery systems, and cell incorporation. Hydrogels are a class of liquid–gel biomaterials with high water content. Injectable and gelling hydrogels can serve as growth factor delivery vehicles and cell carriers for tissue engineering applications. While natural hydrogels and polymers are suitable for short gap nerve repair, the use of polymers for relatively long gaps remains a clinical challenge. (paper)

Magnetic resonance observation of cartilage repair tissue (MOCART) for the evaluation of autologous chondrocyte transplantation: Determination of interobserver variability and correlation to clinical outcome after 2 years

International Nuclear Information System (INIS)

Marlovits, Stefan; Singer, Philipp; Zeller, Philip; Mandl, Irena; Haller, Joerg; Trattnig, Siegfried

2006-01-01

In an observational study, the validity and reliability of magnetic resonance imaging (MRI) for the assessment of autologous chondrocyte transplantation (ACT) in the knee joint was determined. Two years after implantation, high-resolution MRI was used to analyze the repair tissue with nine pertinent variables. A complete filling of the defect was found in 61.5%, and a complete integration of the border zone to the adjacent cartilage in 76.9%. An intact subchondral lamina was present in 84.6% and an intact subchondral bone was present in 61.5%. Isointense signal intensities of the repair tissue compared to the adjacent native cartilage were seen in 92.3%. To evaluate interobserver variability, a reliability analysis with the determination of the intraclass correlation coefficient (ICC) was calculated. An 'almost perfect' agreement, with an ICC value >0.81, was calculated in 8 of 9 variables. The clinical outcome after 2 years showed the visual analog score (VAS) at 2.62 (S.D. ±0.65). The values for the knee injury and osteoarthritis outcome score (KOOS) subgroups were 68.29 (±23.90) for pain, 62.09 (±14.62) for symptoms, 75.45 (±21.91) for ADL function, 52.69 (±28.77) for sport and 70.19 (±22.41) for knee-related quality of life. The clinical scores were correlated with the MRI variables. A statistically significant correlation was found for the variables 'filling of the defect,' 'structure of the repair tissue,' 'changes in the subchondral bone,' and 'signal intensities of the repair issue'. High resolution MRI and well-defined MRI variables are a reliable, reproducible and accurate tool for assessing cartilage repair tissue

Five-Year Follow-up of Knee Joint Distraction: Clinical Benefit and Cartilaginous Tissue Repair in an Open Uncontrolled Prospective Study.

Science.gov (United States)

van der Woude, Jan-Ton A D; Wiegant, Karen; van Roermund, Peter M; Intema, Femke; Custers, Roel J H; Eckstein, Felix; van Laar, Jaap M; Mastbergen, Simon C; Lafeber, Floris P J G

2017-07-01

Objective In end-stage knee osteoarthritis, total knee arthroplasty (TKA) may finally become inevitable. At a relatively young age, this comes with the risk of future revision surgery. Therefore, in these cases, joint preserving surgery such as knee joint distraction (KJD) is preferred. Here we present 5-year follow-up data of KJD. Design Patients ( n = 20; age cartilaginous tissue repair that provides a long-term tissue structure benefit as compared to natural progression. Level of evidence, II.

Neural crest stem cell population in craniomaxillofacial development and tissue repair

Directory of Open Access Journals (Sweden)

M La Noce

2014-10-01

Full Text Available Neural crest cells, delaminating from the neural tube during migration, undergo an epithelial-mesenchymal transition and differentiate into several cell types strongly reinforcing the mesoderm of the craniofacial body area – giving rise to bone, cartilage and other tissues and cells of this human body area. Recent studies on craniomaxillofacial neural crest-derived cells have provided evidence for the tremendous plasticity of these cells. Actually, neural crest cells can respond and adapt to the environment in which they migrate and the cranial mesoderm plays an important role toward patterning the identity of the migrating neural crest cells. In our experience, neural crest-derived stem cells, such as dental pulp stem cells, can actively proliferate, repair bone and give rise to other tissues and cytotypes, including blood vessels, smooth muscle, adipocytes and melanocytes, highlighting that their use in tissue engineering is successful. In this review, we provide an overview of the main pathways involved in neural crest formation, delamination, migration and differentiation; and, in particular, we concentrate our attention on the translatability of the latest scientific progress. Here we try to suggest new ideas and strategies that are needed to fully develop the clinical use of these cells. This effort should involve both researchers/clinicians and improvements in good manufacturing practice procedures. It is important to address studies towards clinical application or take into consideration that studies must have an effective therapeutic prospect for humans. New approaches and ideas must be concentrated also toward stem cell recruitment and activation within the human body, overcoming the classical grafting.

Effects of chronic severe pulmonary regurgitation and percutaneous valve repair on right ventricular geometry and contractility assessed by tissue Doppler echocardiography

DEFF Research Database (Denmark)

Kjaergaard, Jesper; Iversen, Kasper K; Vejlstrup, Niels G

2010-01-01

Pulmonary regurgitation (PR) following repair of right ventricular (RV) outflow obstruction is related to slowly progressive RV dilatation and heart failure and will eventually require surgical intervention, but optimal timing of pulmonary valve replacement is challenging. Tissue Doppler based...

The mitochondrial transcription factor A functions in mitochondrial base excision repair

DEFF Research Database (Denmark)

Canugovi, Chandrika; Maynard, Scott; Bayne, Anne-Cécile V

2010-01-01

Mitochondrial transcription factor A (TFAM) is an essential component of mitochondrial nucleoids. TFAM plays an important role in mitochondrial transcription and replication. TFAM has been previously reported to inhibit nucleotide excision repair (NER) in vitro but NER has not yet been detected i...

E2F1 and p53 Transcription Factors as Accessory Factors for Nucleotide Excision Repair

Directory of Open Access Journals (Sweden)

David G. Johnson

2012-10-01

Full Text Available Many of the biochemical details of nucleotide excision repair (NER have been established using purified proteins and DNA substrates. In cells however, DNA is tightly packaged around histones and other chromatin-associated proteins, which can be an obstacle to efficient repair. Several cooperating mechanisms enhance the efficiency of NER by altering chromatin structure. Interestingly, many of the players involved in modifying chromatin at sites of DNA damage were originally identified as regulators of transcription. These include ATP-dependent chromatin remodelers, histone modifying enzymes and several transcription factors. The p53 and E2F1 transcription factors are well known for their abilities to regulate gene expression in response to DNA damage. This review will highlight the underappreciated, transcription-independent functions of p53 and E2F1 in modifying chromatin structure in response to DNA damage to promote global NER.

Biology and augmentation of tendon-bone insertion repair

OpenAIRE

Lui, PPY; Zhang, P; Chan, KM; Qin, L

2010-01-01

Abstract Surgical reattachment of tendon and bone such as in rotator cuff repair, patellar-patella tendon repair and anterior cruciate ligament (ACL) reconstruction often fails due to the failure of regeneration of the specialized tissue ("enthesis") which connects tendon to bone. Tendon-to-bone healing taking place between inhomogenous tissues is a slow process compared to healing within homogenous tissue, such as tendon to tendon or bone to bone healing. Therefore special attention must be ...

EGR1 induces tenogenic differentiation of tendon stem cells and promotes rabbit rotator cuff repair.

Science.gov (United States)

Tao, Xu; Liu, Junpeng; Chen, Lei; Zhou, You; Tang, Kanglai

2015-01-01

The rate of healing failure after surgical repair of chronic rotator cuff tears is considerably high. The aim of this study was to investigate the function of the zinc finger transcription factor early growth response 1 (EGR1) in the differentiation of tendon stem cells (TSCs) and in tendon formation, healing, and tendon tear repair using an animal model of rotator cuff repair. Tenocyte, adipocyte, osteocyte, and chondrocyte differentiation as well as the expression of related genes were determined in EGR1-overexpressing TSCs (EGR1-TSCs) using tissue-specific staining, immunofluorescence staining, quantitative PCR, and western blotting. A rabbit rotator cuff repair model was established, and TSCs and EGR1-TSCs in a fibrin glue carrier were applied onto repair sites. The rabbits were sacrificed 8 weeks after repair operation, and tissues were histologically evaluated and tenocyte-related gene expression was determined. EGR1 induced tenogenic differentiation of TSCs and inhibited non-tenocyte differentiation of TSCs. Furthermore, EGR1 promoted tendon repair in a rabbit model of rotator cuff injury. The BMP12/Smad1/5/8 signaling pathway was involved in EGR1-induced tenogenic differentiation and rotator cuff tendon repair. EGR1 plays a key role in tendon formation, healing, and repair through BMP12/Smad1/5/8 pathway. EGR1-TSCs is a promising treatment for rotator cuff tendon repair surgeries. © 2015 S. Karger AG, Basel.

EGR1 Induces Tenogenic Differentiation of Tendon Stem Cells and Promotes Rabbit Rotator Cuff Repair

Directory of Open Access Journals (Sweden)

Xu Tao

2015-01-01

Full Text Available Background/Aims: The rate of healing failure after surgical repair of chronic rotator cuff tears is considerably high. The aim of this study was to investigate the function of the zinc finger transcription factor early growth response 1 (EGR1 in the differentiation of tendon stem cells (TSCs and in tendon formation, healing, and tendon tear repair using an animal model of rotator cuff repair. Methods: Tenocyte, adipocyte, osteocyte, and chondrocyte differentiation as well as the expression of related genes were determined in EGR1-overexpressing TSCs (EGR1-TSCs using tissue-specific staining, immunofluorescence staining, quantitative PCR, and western blotting. A rabbit rotator cuff repair model was established, and TSCs and EGR1-TSCs in a fibrin glue carrier were applied onto repair sites. The rabbits were sacrificed 8 weeks after repair operation, and tissues were histologically evaluated and tenocyte-related gene expression was determined. Results: EGR1 induced tenogenic differentiation of TSCs and inhibited non-tenocyte differentiation of TSCs. Furthermore, EGR1 promoted tendon repair in a rabbit model of rotator cuff injury. The BMP12/Smad1/5/8 signaling pathway was involved in EGR1-induced tenogenic differentiation and rotator cuff tendon repair. Conclusion: EGR1 plays a key role in tendon formation, healing, and repair through BMP12/Smad1/5/8 pathway. EGR1-TSCs is a promising treatment for rotator cuff tendon repair surgeries.

DNA repair and cancer

International Nuclear Information System (INIS)

Rathore, Shakuntla; Joshi, Pankaj Kumar; Gaur, Sudha

2012-01-01

DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecule that encode it's genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many one million individual molecular lesions per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions include potentially harmful mutation in cell's genome which affect the survival of it's daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. Inherited mutation that affect DNA repair genes are strongly associated with high cancer risks in humans. Hereditary non polyposis colorectal cancer (HNPCC) is strongly associated with specific mutation in the DNA mismatch repair pathway. BRCA1, BRCA2 two famous mutation conferring a hugely increased risk of breast cancer on carrier, are both associated with a large number of DNA repair pathway, especially NHEJ and homologous recombination. Cancer therapy procedures such as chemotherapy and radiotherapy work by overwhelming the capacity of the cell to repair DNA damage, resulting in cell death. Cells that are most rapidly dividing most typically cancer cells are preferentially affected. The side effect is that other non-cancerous but rapidly dividing cells such as stem cells in the bone marrow are also affected. Modern cancer treatment attempt to localize the DNA damage to cells and tissue only associated with cancer, either by physical means (concentrating the therapeutic agent in the region of the tumor) or by biochemical means (exploiting a feature unique to cancer cells in the body). (author)

Activation of 125I-Factor IX and 125I-Factor X: Effect of tissue factor and Factor VII, Factor Xsub(a) and thrombin

International Nuclear Information System (INIS)

Oesterud, B.; Rapaport, S.I.

Activation of Factor IX and Factor X was studied by adding 125 I-Factor IX or 125 I-Factor X to reaction mixtures and quantitating cleavage products by reduced sodium dodecylsulfate gel electrophoresis. Thrombin failed to activate Factors IX or X; Factor Xsub(a) produced insignificant amounts of cleavage products of both factors. In contrast, the reaction product of tissue factor and Factor VII cleaved large amounts of both Factor IX and Factor X in purified systems and in plasma. In incubation mixtures of plasma containing added 125 I-Factor IX or 125 I-Factor X, tissue factor and Ca 2+ ions, the percentage of total radioactivity in the heavy chain peak of 125 I-IXsub(a) and the heavy chain of 125 I-Xsub(a) increased at a similar rate. When the tissue factor was diluted, similar curves were obtained for percent cleavage of 125 I-Factor IX and percent cleavage of 125 I-Factor X plotted against tissue factor concentration. These findings support the hypothesis that activation of Factor IX by the tissue factor-Factor VII reaction product represents a physiologically significant step in normal haemostasis. (author)

The long-term behavior of lightweight and heavyweight meshes used to repair abdominal wall defects is determined by the host tissue repair process provoked by the mesh.

Science.gov (United States)

Pascual, Gemma; Hernández-Gascón, Belén; Rodríguez, Marta; Sotomayor, Sandra; Peña, Estefania; Calvo, Begoña; Bellón, Juan M

2012-11-01

Although heavyweight (HW) or lightweight (LW) polypropylene (PP) meshes are widely used for hernia repair, other alternatives have recently appeared. They have the same large-pore structure yet are composed of polytetrafluoroethylene (PTFE). This study compares the long-term (3 and 6 months) behavior of meshes of different pore size (HW compared with LW) and composition (PP compared with PTFE). Partial defects were created in the lateral wall of the abdomen in New Zealand White rabbits and then repaired by the use of a HW or LW PP mesh or a new monofilament, large-pore PTFE mesh (Infinit). At 90 and 180 days after implantation, tissue incorporation, gene and protein expression of neocollagens (reverse transcription-polymerase chain reaction/immunofluorescence), macrophage response (immunohistochemistry), and biomechanical strength were determined. Shrinkage was measured at 90 days. All three meshes induced good host tissue ingrowth, yet the macrophage response was significantly greater in the PTFE implants (P .05). Host collagen deposition is mesh pore size dependent whereas the macrophage response induced is composition dependent with a greater response shown by PTFE. In the long term, macroporous meshes show comparable biomechanical behavior regardless of their pore size or composition. Copyright © 2012 Mosby, Inc. All rights reserved.

More efficient repair of DNA double-strand breaks in skeletal muscle stem cells compared to their committed progeny

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Leyla Vahidi Ferdousi

2014-11-01

Full Text Available The loss of genome integrity in adult stem cells results in accelerated tissue aging and is possibly cancerogenic. Adult stem cells in different tissues appear to react robustly to DNA damage. We report that adult skeletal stem (satellite cells do not primarily respond to radiation-induced DNA double-strand breaks (DSBs via differentiation and exhibit less apoptosis compared to other myogenic cells. Satellite cells repair these DNA lesions more efficiently than their committed progeny. Importantly, non-proliferating satellite cells and post-mitotic nuclei in the fiber exhibit dramatically distinct repair efficiencies. Altogether, reduction of the repair capacity appears to be more a function of differentiation than of the proliferation status of the muscle cell. Notably, satellite cells retain a high efficiency of DSB repair also when isolated from the natural niche. Finally, we show that repair of DSB substrates is not only very efficient but, surprisingly, also very accurate in satellite cells and that accurate repair depends on the key non-homologous end-joining factor DNA-PKcs.

More efficient repair of DNA double-strand breaks in skeletal muscle stem cells compared to their committed progeny.

Science.gov (United States)

Vahidi Ferdousi, Leyla; Rocheteau, Pierre; Chayot, Romain; Montagne, Benjamin; Chaker, Zayna; Flamant, Patricia; Tajbakhsh, Shahragim; Ricchetti, Miria

2014-11-01

The loss of genome integrity in adult stem cells results in accelerated tissue aging and is possibly cancerogenic. Adult stem cells in different tissues appear to react robustly to DNA damage. We report that adult skeletal stem (satellite) cells do not primarily respond to radiation-induced DNA double-strand breaks (DSBs) via differentiation and exhibit less apoptosis compared to other myogenic cells. Satellite cells repair these DNA lesions more efficiently than their committed progeny. Importantly, non-proliferating satellite cells and post-mitotic nuclei in the fiber exhibit dramatically distinct repair efficiencies. Altogether, reduction of the repair capacity appears to be more a function of differentiation than of the proliferation status of the muscle cell. Notably, satellite cells retain a high efficiency of DSB repair also when isolated from the natural niche. Finally, we show that repair of DSB substrates is not only very efficient but, surprisingly, also very accurate in satellite cells and that accurate repair depends on the key non-homologous end-joining factor DNA-PKcs. Copyright © 2014. Published by Elsevier B.V.

Arthroscopic Hip Labral Repair: The Iberian Suture Technique

OpenAIRE

Stubbs, Allston J.; Andersen, Jason S.; Mannava, Sandeep; Wooster, Benjamin M.; Howse, Elizabeth A.; Winter, S. Bradley

2014-01-01

Arthroscopic hip labral repair has beneficial short-term outcomes; however, debate exists regarding ideal surgical labral repair technique. This technical note presents an arthroscopic repair technique that uses intrasubstance labral suture passage to restore the chondrolabral interface. This “Iberian suture technique” allows for an anatomic repair while posing minimal risk of damage to the labral and chondral tissues.

Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

Science.gov (United States)

Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

2015-07-01

It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

Magnetic resonance observation of cartilage repair tissue (MOCART) for the evaluation of autologous chondrocyte transplantation: Determination of interobserver variability and correlation to clinical outcome after 2 years

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; Singer, Philipp [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Zeller, Philip [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Mandl, Irena [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Haller, Joerg [Department of Radiology, Hanusch Hospital, Heinrich-Collin-Strasse, A-1140 Vienna (Austria); Trattnig, Siegfried [Department of Radiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)

2006-01-15

In an observational study, the validity and reliability of magnetic resonance imaging (MRI) for the assessment of autologous chondrocyte transplantation (ACT) in the knee joint was determined. Two years after implantation, high-resolution MRI was used to analyze the repair tissue with nine pertinent variables. A complete filling of the defect was found in 61.5%, and a complete integration of the border zone to the adjacent cartilage in 76.9%. An intact subchondral lamina was present in 84.6% and an intact subchondral bone was present in 61.5%. Isointense signal intensities of the repair tissue compared to the adjacent native cartilage were seen in 92.3%. To evaluate interobserver variability, a reliability analysis with the determination of the intraclass correlation coefficient (ICC) was calculated. An 'almost perfect' agreement, with an ICC value >0.81, was calculated in 8 of 9 variables. The clinical outcome after 2 years showed the visual analog score (VAS) at 2.62 (S.D. {+-}0.65). The values for the knee injury and osteoarthritis outcome score (KOOS) subgroups were 68.29 ({+-}23.90) for pain, 62.09 ({+-}14.62) for symptoms, 75.45 ({+-}21.91) for ADL function, 52.69 ({+-}28.77) for sport and 70.19 ({+-}22.41) for knee-related quality of life. The clinical scores were correlated with the MRI variables. A statistically significant correlation was found for the variables 'filling of the defect,' 'structure of the repair tissue,' 'changes in the subchondral bone,' and 'signal intensities of the repair issue'. High resolution MRI and well-defined MRI variables are a reliable, reproducible and accurate tool for assessing cartilage repair tissue.

Management strategies, early results, benefits, and risk factors of laparoscopic repair of perforated peptic ulcer.

Science.gov (United States)

Lunevicius, Raimundas; Morkevicius, Matas

2005-10-01

The primary goal of this study was to describe epidemiology and management strategies of the perforated duodenal ulcer, as well as the most common methods of laparoscopic perforated duodenal ulcer repair. The secondary goal was to demonstrate the value of prospective and retrospective studies regarding the early results of surgery and the risk factors. The tertiary goal was to emphasize the benefits of this operation, and the fourth goal was to clarify the possible risk factors associated with laparoscopic repair of the duodenal ulcer. The Medline/Pubmed database was used. Review was done after evaluation of 96 retrieved full-text articles. Thirteen prospective and twelve retrospective studies were selected, grouped, and summarized. The spectrum of the retrospective studies' results are as follows: median overall morbidity rate 10.5 %, median conversion rate 7%, median hospital stay 7 days, and median postoperative mortality rate 0%. The following is the spectrum of results of the prospective studies: median overall morbidity rate was slightly less (6%); the median conversion rate was higher (15%); the median hospital stay was shorter (5 days) and the postoperative mortality was higher (3%). The risk factors identified were the same. Shock, delayed presentation (> 24 hours), confounding medical condition, age > 70 years, poor laparoscopic expertise, ASA III-IV, and Boey score should be considered preoperative laparoscopic repair risk factors. Each of these factors independently should qualify as a criterion for open repair due to higher intraoperative risks as well as postoperative morbidity. Inadequate ulcer localization, large perforation size (defined by some as > 6 mm diameter, and by others as > 10 mm), and ulcers with friable edges are also considered as conversion risk factors.

Muscle Tissue Engineering Using Gingival Mesenchymal Stem Cells Encapsulated in Alginate Hydrogels Containing Multiple Growth Factors.

Science.gov (United States)

Ansari, Sahar; Chen, Chider; Xu, Xingtian; Annabi, Nasim; Zadeh, Homayoun H; Wu, Benjamin M; Khademhosseini, Ali; Shi, Songtao; Moshaverinia, Alireza

2016-06-01

Repair and regeneration of muscle tissue following traumatic injuries or muscle diseases often presents a challenging clinical situation. If a significant amount of tissue is lost the native regenerative potential of skeletal muscle will not be able to grow to fill the defect site completely. Dental-derived mesenchymal stem cells (MSCs) in combination with appropriate scaffold material, present an advantageous alternative therapeutic option for muscle tissue engineering in comparison to current treatment modalities available. To date, there has been no report on application of gingival mesenchymal stem cells (GMSCs) in three-dimensional scaffolds for muscle tissue engineering. The objectives of the current study were to develop an injectable 3D RGD-coupled alginate scaffold with multiple growth factor delivery capacity for encapsulating GMSCs, and to evaluate the capacity of encapsulated GMSCs to differentiate into myogenic tissue in vitro and in vivo where encapsulated GMSCs were transplanted subcutaneously into immunocompromised mice. The results demonstrate that after 4 weeks of differentiation in vitro, GMSCs as well as the positive control human bone marrow mesenchymal stem cells (hBMMSCs) exhibited muscle cell-like morphology with high levels of mRNA expression for gene markers related to muscle regeneration (MyoD, Myf5, and MyoG) via qPCR measurement. Our quantitative PCR analyzes revealed that the stiffness of the RGD-coupled alginate regulates the myogenic differentiation of encapsulated GMSCs. Histological and immunohistochemical/fluorescence staining for protein markers specific for myogenic tissue confirmed muscle regeneration in subcutaneous transplantation in our in vivo animal model. GMSCs showed significantly greater capacity for myogenic regeneration in comparison to hBMMSCs (p alginate hydrogel with multiple growth factor delivery capacity is a promising candidate for muscle tissue engineering.

Radiation-induced DNA damage in tumors and normal tissues. II. Influence of dose, residual DNA damage and physiological factors in oxygenated cells

International Nuclear Information System (INIS)

Zhang, H.; Wheeler, K.T.

1994-01-01

Detection and quantification of hypoxic cells in solid tumors is important for many experimental and clinical situations. Several laboratories, including ours, have suggested that assays which measure radiation-induced DNA strand breaks and DNA-protein crosslinks (DPCs) might be used to detect or quantify hypoxic cells in tumors and normal tissues. Recently, we demonstrated the feasibility of using an alkaline elution assay that measures strand breaks and DPCs to detect and/or quantify hypoxic cells in tissues. For this approach to be valid, DPCs must not be formed to any great extent in irradiated oxygenated cells, and the formation and repair of strand breaks and DPCs in oxygenated cells must not be modified appreciably by physiological factors (e.g., temperature, pH and nutrient depletion) that are often found in solid tumors. To address these issues, two sets of experiments were performed. In one set of experiments, oxygenated 9L cells in tissue culture, subcutaneous 9L tumors and rat cerebella were irradiated with doses of 15 or 50 Gy and allowed to repair until the residual strand break damage was low enough to detect DPCs. In another set of experiments, oxygenated exponentially growing or plateau-phase 9L cells in tissue culture were irradiated with a dose of 15 Gy at 37 or 20 degrees C, while the cells were maintained at a pH of either 6.6 or 7.3. DNA-protein crosslinks were formed in oxygenated cells about 100 times less efficiently than in hypoxic cells. In addition, temperature, pH, nutrient depletion and growth phase did not appreciably alter the formation and repair of strand breaks or the formation of DPCs in oxygenated 9L cells. These results support the use of this DNA damage assay for the detection and quantification of hypoxic cells in solid tumors. 27 refs., 5 tabs

[Decellularized fish skin: characteristics that support tissue repair].

Science.gov (United States)

Magnússon, Skúli; Baldursson, Baldur Tumi; Kjartansson, Hilmar; Thorlacius, Guðný Ella; Axelsson, Ívar; Rolfsson, Óttar; Petersen, Pétur Henry; Sigurjónsson, Guðmundur Fertram

2015-12-01

Acellular fish skin of the Atlantic cod (Gadus morhua) is being used to treat chronic wounds. The prevalence of diabetes and the comorbidity of chronic wounds is increasing globally. The aim of the study was to assess the biocompatibility and biological characteristics of acellular fish skin, important for tissue repair. The structure of the acellular fish skin was examined with microscopy. Biocompatibility of the graft was conducted by a specialized certified laboratory. Protein extracts from the material were analyzed using gel electrophoresis. Cytokine levels were measured with an enzyme linked immunosorbent assay (ELISA). Angiogenic properties were assessed with a chick chorioallantoic membrane (chick CAM) assay. The structure of acellular fish skin is porous and the material is biocompatible. Electrophoresis revealed proteins around the size 115-130 kDa, indicative of collagens. The material did not have significant effect on IL-10, IL-12p40, IL-6 or TNF-α secretion from monocytes or macrophages. Acellular fish skin has significant effect on angiogenesis in the chick CAM assay. The acellular fish skin is not toxic and is not likely to promote inflammatory responses. The graft contains collagen I, promotes angiogenesis and supports cellular ingrowth. Compared to similar products made from mammalian sources, acellular fish skin does not confer a disease risk and contains more bioactive compounds, due to less severe processing.

Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair.

Science.gov (United States)

Zhou, Feifei; Zhang, Xianzhu; Cai, Dandan; Li, Jun; Mu, Qin; Zhang, Wei; Zhu, Shouan; Jiang, Yangzi; Shen, Weiliang; Zhang, Shufang; Ouyang, Hong Wei

2017-11-01

The demand of favorable scaffolds has increased for the emerging cartilage tissue engineering. Chondroitin sulfate (CS) and silk fibroin have been investigated and reported with safety and excellent biocompatibility as tissue engineering scaffolds. However, the rapid degradation rate of pure CS scaffolds presents a challenge to effectively recreate neo-tissue similar to natural articular cartilage. Meanwhile the silk fibroin is well used as a structural constituent material because its remarkable mechanical properties, long-lasting in vivo stability and hypoimmunity. The application of composite silk fibroin and CS scaffolds for joint cartilage repair has not been well studied. Here we report that the combination of silk fibroin and CS could synergistically promote articular cartilage defect repair. The silk fibroin (silk) and silk fibroin/CS (silk-CS) scaffolds were fabricated with salt-leaching, freeze-drying and crosslinking methodologies. The biocompatibility of the scaffolds was investigated in vitro by cell adhesion, proliferation and migration with human articular chondrocytes. We found that silk-CS scaffold maintained better chondrocyte phenotype than silk scaffold; moreover, the silk-CS scaffolds reduced chondrocyte inflammatory response that was induced by interleukin (IL)-1β, which is in consistent with the well-documented anti-inflammatory activities of CS. The in vivo cartilage repair was evaluated with a rabbit osteochondral defect model. Silk-CS scaffold induced more neo-tissue formation and better structural restoration than silk scaffold after 6 and 12weeks of implantation in ICRS histological evaluations. In conclusion, we have developed a silk fibroin/ chondroitin sulfate scaffold for cartilage tissue engineering that exhibits immuno-inhibition property and can improve the self-repair capacity of cartilage. Severe cartilage defect such as osteoarthritis (OA) is difficult to self-repair because of its avascular, aneural and alymphatic nature

Tissue Engineering-based Therapeutic Strategies for Vocal Fold Repair and Regeneration

Science.gov (United States)

Li, Linqing; Stiadle, Jeanna M.; Lau, Hang K.; Zerdoum, Aidan B.; Jia, Xinqiao; L.Thibeault, Susan; Kiick, Kristi L.

2016-01-01

Vocal folds are soft laryngeal connective tissues with distinct layered structures and complex multicomponent matrix compositions that endow phonatory and respiratory functions. This delicate tissue is easily damaged by various environmental factors and pathological conditions, altering vocal biomechanics and causing debilitating vocal disorders that detrimentally affect the daily lives of suffering individuals. Modern techniques and advanced knowledge of regenerative medicine have led to a deeper understanding of the microstructure, microphysiology, and micropathophysiology of vocal fold tissues. State-of-the-art materials ranging from extracecullar-matrix (ECM)-derived biomaterials to synthetic polymer scaffolds have been proposed for the prevention and treatment of voice disorders including vocal fold scarring and fibrosis. This review intends to provide a thorough overview of current achievements in the field of vocal fold tissue engineering, including the fabrication of injectable biomaterials to mimic in vitro cell microenvironments, novel designs of bioreactors that capture in vivo tissue biomechanics, and establishment of various animal models to characterize the in vivo biocompatibility of these materials. The combination of polymeric scaffolds, cell transplantation, biomechanical stimulation, and delivery of antifibrotic growth factors will lead to successful restoration of functional vocal folds and improved vocal recovery in animal models, facilitating the application of these materials and related methodologies in clinical practice. PMID:27619243

Indentation Damage and Crack Repair in Human Enamel*

OpenAIRE

Rivera, C.; Arola, D.; Ossa, A.

2013-01-01

Tooth enamel is the hardest and most highly mineralized tissue in the human body. While there have been a number of studies aimed at understanding the hardness and crack growth resistance behavior of this tissue, no study has evaluated if cracks in this tissue undergo repair. In this investigation the crack repair characteristics of young human enamel were evaluated as a function of patient gender and as a function of the distance from the Dentin Enamel Junction (DEJ). Cracks were introduced ...

Tissue Engineering Using Transfected Growth-Factor Genes

Science.gov (United States)

Madry, Henning; Langer, Robert S.; Freed, Lisa E.; Trippel, Stephen; Vunjak-Novakovic, Gordana

2005-01-01

A method of growing bioengineered tissues includes, as a major component, the use of mammalian cells that have been transfected with genes for secretion of regulator and growth-factor substances. In a typical application, one either seeds the cells onto an artificial matrix made of a synthetic or natural biocompatible material, or else one cultures the cells until they secrete a desired amount of an extracellular matrix. If such a bioengineered tissue construct is to be used for surgical replacement of injured tissue, then the cells should preferably be the patient s own cells or, if not, at least cells matched to the patient s cells according to a human-leucocyteantigen (HLA) test. The bioengineered tissue construct is typically implanted in the patient's injured natural tissue, wherein the growth-factor genes enhance metabolic functions that promote the in vitro development of functional tissue constructs and their integration with native tissues. If the matrix is biodegradable, then one of the results of metabolism could be absorption of the matrix and replacement of the matrix with tissue formed at least partly by the transfected cells. The method was developed for articular chondrocytes but can (at least in principle) be extended to a variety of cell types and biocompatible matrix materials, including ones that have been exploited in prior tissue-engineering methods. Examples of cell types include chondrocytes, hepatocytes, islet cells, nerve cells, muscle cells, other organ cells, bone- and cartilage-forming cells, epithelial and endothelial cells, connective- tissue stem cells, mesodermal stem cells, and cells of the liver and the pancreas. Cells can be obtained from cell-line cultures, biopsies, and tissue banks. Genes, molecules, or nucleic acids that secrete factors that influence the growth of cells, the production of extracellular matrix material, and other cell functions can be inserted in cells by any of a variety of standard transfection techniques.

Vascular endothelial growth factor/bone morphogenetic protein-2 bone marrow combined modification of the mesenchymal stem cells to repair the avascular necrosis of the femoral head

Science.gov (United States)

Ma, Xiao-Wei; Cui, Da-Ping; Zhao, De-Wei

2015-01-01

Vascular endothelial cell growth factor (VEGF) combined with bone morphogenetic protein (BMP) was used to repair avascular necrosis of the femoral head, which can maintain the osteogenic phenotype of seed cells, and effectively secrete VEGF and BMP-2, and effectively promote blood vessel regeneration and contribute to formation and revascularization of tissue engineered bone tissues. To observe the therapeutic effect on the treatment of avascular necrosis of the femoral head by using bone marrow mesenchymal stem cells (BMSCs) modified by VEGF-165 and BMP-2 in vitro. The models were avascular necrosis of femoral head of rabbits on right leg. There groups were single core decompression group, core decompression + BMSCs group, core decompression + VEGF-165/BMP-2 transfect BMSCs group. Necrotic bone was cleared out under arthroscope. Arthroscopic observation demonstrated that necrotic bone was cleared out in each group, and fresh blood flowed out. Histomorphology determination showed that blood vessel number and new bone area in the repair region were significantly greater at various time points following transplantation in the core decompression + VEGF-165/BMP-2 transfect BMSCs group compared with single core decompression group and core decompression + BMSCs group (P < 0.05). These suggested that VEGF-165/BMP-2 gene transfection strengthened osteogenic effects of BMSCs, elevated number and quality of new bones and accelerated the repair of osteonecrosis of the femoral head. PMID:26629044

Indentation Damage and Crack Repair in Human Enamel*

Science.gov (United States)

Rivera, C.; Arola, D.; Ossa, A.

2013-01-01

Tooth enamel is the hardest and most highly mineralized tissue in the human body. While there have been a number of studies aimed at understanding the hardness and crack growth resistance behavior of this tissue, no study has evaluated if cracks in this tissue undergo repair. In this investigation the crack repair characteristics of young human enamel were evaluated as a function of patient gender and as a function of the distance from the Dentin Enamel Junction (DEJ). Cracks were introduced via microindentation along the prism direction and evaluated as a function of time after the indentation. Microscopic observations indicated that the repair of cracks began immediately after crack initiation and reaches saturation after approximately 48 hours. During this process he crack length decreased up to 10% of the initial length, and the largest degree of reduction occurred in the deep enamel, nearest the DEJ. In addition, it was found that the degree of repair was significantly greater in the enamel of female patients. PMID:23541701

The stem cell secretome and its role in brain repair.

Science.gov (United States)

Drago, Denise; Cossetti, Chiara; Iraci, Nunzio; Gaude, Edoardo; Musco, Giovanna; Bachi, Angela; Pluchino, Stefano

2013-12-01

Compelling evidence exists that non-haematopoietic stem cells, including mesenchymal (MSCs) and neural/progenitor stem cells (NPCs), exert a substantial beneficial and therapeutic effect after transplantation in experimental central nervous system (CNS) disease models through the secretion of immune modulatory or neurotrophic paracrine factors. This paracrine hypothesis has inspired an alternative outlook on the use of stem cells in regenerative neurology. In this paradigm, significant repair of the injured brain may be achieved by injecting the biologics secreted by stem cells (secretome), rather than implanting stem cells themselves for direct cell replacement. The stem cell secretome (SCS) includes cytokines, chemokines and growth factors, and has gained increasing attention in recent years because of its multiple implications for the repair, restoration or regeneration of injured tissues. Thanks to recent improvements in SCS profiling and manipulation, investigators are now inspired to harness the SCS as a novel alternative therapeutic option that might ensure more efficient outcomes than current stem cell-based therapies for CNS repair. This review discusses the most recent identification of MSC- and NPC-secreted factors, including those that are trafficked within extracellular membrane vesicles (EVs), and reflects on their potential effects on brain repair. It also examines some of the most convincing advances in molecular profiling that have enabled mapping of the SCS. Copyright © 2013 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Both base excision repair and nucleotide excision repair in humans are influenced by nutritional factors.

Science.gov (United States)

Brevik, Asgeir; Karlsen, Anette; Azqueta, Amaya; Tirado, Anna Estaban; Blomhoff, Rune; Collins, Andrew

2011-01-01

Lack of reliable assays for DNA repair has largely prevented measurements of DNA repair from being included in human biomonitoring studies. Using newly developed modifications of the comet assay we tested whether a fruit- and antioxidant-rich plant-based intervention could affect base excision repair (BER) and nucleotide excision repair (NER) in a group of 102 male volunteers. BER and NER repair capacities were measured in lymphocytes before and after a dietary intervention lasting 8 weeks. The study had one control group, one group consuming three kiwifruits per day and one group consuming a variety of antioxidant-rich fruits and plant products in addition to their normal diet. DNA strand breaks were reduced following consumption of both kiwifruits (13%, p = 0.05) and antioxidant-rich plant products (20%, p = 0.02). Increased BER (55%, p = 0.01) and reduced NER (-39%, p plant products. Reduced NER was also observed in the kiwifruit group (-38%, p = 0.05), but BER was not affected in this group. Here we have demonstrated that DNA repair is affected by diet and that modified versions of the comet assay can be used to assess activity of different DNA repair pathways in human biomonitoring studies. Copyright © 2010 John Wiley & Sons, Ltd.

Connective tissue photodamage in the hairless mouse is partially reversible

International Nuclear Information System (INIS)

Kligman, L.H.

1987-01-01

Photodamaged connective tissue in animal and human skin is characterized by excessive accumulations of elastic fibers, loss of mature collagen, concomitant overproduction of new collagen, and greatly increased levels of glycosaminoglycans. Formerly considered irreversible changes, we recently showed in hairless mice, post irradiation, that a band of normal connective tissue was laid down subepidermally. The present studies focused on 2 aspects of this repair: whether repair would occur if animals were protected by sunscreens after dermal damage was induced and irradiation continued; whether retinoic acid could enhance the repair process. To examine the first aspect, albino hairless mice were irradiated with Westinghouse FS 20 sunlamps thrice weekly for 30 weeks. Sunscreens of high sun-protection factors were applied after 10 and 20 weeks. Not only was further damage prevented, but the damage incurred before sunscreen application was repaired. This appeared as subepidermal reconstruction zones containing normal, mature collagen and a network of fine elastic fibers. The second aspect was examined by applying 0.05% retinoic acid, topically, to animals preirradiated for 10 weeks. In contrast to controls treated with vehicle, the reconstruction zone was significantly wider in retinoic acid-treated mice. The enhanced repair was dose-related

Surgical management of colorectal injuries: colostomy or primary repair?

Science.gov (United States)

Papadopoulos, V N; Michalopoulos, A; Apostolidis, S; Paramythiotis, D; Ioannidis, A; Mekras, A; Panidis, S; Stavrou, G; Basdanis, G

2011-10-01

Several factors have been considered important for the decision between diversion and primary repair in the surgical management of colorectal injuries. The aim of this study is to clarify whether patients with colorectal injuries need diversion or not. From 2008 to 2010, ten patients with colorectal injuries were surgically treated by primary repair or by a staged repair. The patients were five men and five women, with median age 40 years (20-55). Two men and two women had rectal injuries, while 6 patients had colon injuries. The mechanism of trauma in two patients was firearm injuries, in two patients was a stab injury, in four patients was a motor vehicle accident, in one woman was iatrogenic injury during vaginal delivery, and one case was the transanal foreign body insertion. Primary repair was possible in six patients, while diversion was necessary in four patients. Primary repair should be attempted in the initial surgical management of all penetrating colon and intraperitoneal rectal injuries. Diversion of colonic injuries should only be considered if the colon tissue itself is inappropriate for repair due to severe edema or ischemia. The role of diversion in the management of unrepaired extraperitoneal rectal injuries and in cases with anal sphincter injuries is mandatory.

DNA damage and repair in plants

International Nuclear Information System (INIS)

Britt, A.B.

1996-01-01

The biological impact of any DNA damaging agent is a combined function of the chemical nature of the induced lesions and the efficiency and accuracy of their repair. Although much has been learned frommicrobes and mammals about both the repair of DNA damage and the biological effects of the persistence of these lesions, much remains to be learned about the mechanism and tissue-specificity of repair in plants. This review focuses on recent work on the induction and repair of DNA damage in higher plants, with special emphasis on UV-induced DNA damage products. (author)

Cloning and characterization of p52, the fifth subunit of the core of transcription/repair factor TFIIH.

NARCIS (Netherlands)

J.C. Marinoni; R. Roy (Richard); W. Vermeulen (Wim); P. Miniou; Y. Lutz; G. Weeda (Geert); T. Seroz; D.M. Gomez (Denise Molina); J.H.J. Hoeijmakers (Jan); J-M. Egly (Jean-Marc)

1997-01-01

textabstractTFIIH is a multiprotein factor involved in transcription and DNA repair and is implicated in DNA repair/transcription deficiency disorders such as xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Eight out of the nine genes encoding the subunits forming TFIIH have

Photothermal effects of laser tissue soldering

International Nuclear Information System (INIS)

McNally, K.M.; Sorg, B.S.; Welch, A.J.; Dawes, J.M.; Owen, E.R.

1999-01-01

Low-strength anastomoses and thermal damage of tissue are major concerns in laser tissue welding techniques where laser energy is used to induce thermal changes in the molecular structure of the tissues being joined, hence allowing them to bond together. Laser tissue soldering, on the other hand, is a bonding technique in which a protein solder is applied to the tissue surfaces to be joined, and laser energy is used to bond the solder to the tissue surfaces. The addition of protein solders to augment tissue repair procedures significantly reduces the problems of low strength and thermal damage associated with laser tissue welding techniques. Investigations were conducted to determine optimal solder and laser parameters for tissue repair in terms of tensile strength, temperature rise and damage and the microscopic nature of the bonds formed. An in vitro study was performed using an 808 nm diode laser in conjunction with indocyanine green (ICG)-doped albumin protein solders to repair bovine aorta specimens. Liquid and solid protein solders prepared from 25% and 60% bovine serum albumin (BSA), respectively, were compared. The efficacy of temperature feedback control in enhancing the soldering process was also investigated. Increasing the BSA concentration from 25% to 60% greatly increased the tensile strength of the repairs. A reduction in dye concentration from 2.5mgml -1 to 0.25mgml -1 was also found to result in an increase in tensile strength. Increasing the laser irradiance and thus surface temperature resulted in an increased severity of histological injury. Thermal denaturation of tissue collagen and necrosis of the intimal layer smooth muscle cells increased laterally and in depth with higher temperatures. The strongest repairs were produced with an irradiance of 6.4Wcm -2 using a solid protein solder composed of 60% BSA and 0.25mgml -1 ICG. Using this combination of laser and solder parameters, surface temperatures were observed to reach 85±5 deg. C with a

Hydrogels That Allow and Facilitate Bone Repair, Remodeling, and Regeneration.

Science.gov (United States)

Short, Aaron R; Koralla, Deepthi; Deshmukh, Ameya; Wissel, Benjamin; Stocker, Benjamin; Calhoun, Mark; Dean, David; Winter, Jessica O

2015-10-28

Bone defects can originate from a variety of causes, including trauma, cancer, congenital deformity, and surgical reconstruction. Success of the current "gold standard" treatment (i.e., autologous bone grafts) is greatly influenced by insufficient or inappropriate bone stock. There is thus a critical need for the development of new, engineered materials for bone repair. This review describes the use of natural and synthetic hydrogels as scaffolds for bone tissue engineering. We discuss many of the advantages that hydrogels offer as bone repair materials, including their potential for osteoconductivity, biodegradability, controlled growth factor release, and cell encapsulation. We also discuss the use of hydrogels in composite devices with metals, ceramics, or polymers. These composites are useful because of the low mechanical moduli of hydrogels. Finally, the potential for thermosetting and photo-cross-linked hydrogels as three-dimensionally (3D) printed, patient-specific devices is highlighted. Three-dimensional printing enables controlled spatial distribution of scaffold materials, cells, and growth factors. Hydrogels, especially natural hydrogels present in bone matrix, have great potential to augment existing bone tissue engineering devices for the treatment of critical size bone defects.

Surface-modified polymers for cardiac tissue engineering.

Science.gov (United States)

Moorthi, Ambigapathi; Tyan, Yu-Chang; Chung, Tze-Wen

2017-09-26

Cardiovascular disease (CVD), leading to myocardial infarction and heart failure, is one of the major causes of death worldwide. The physiological system cannot significantly regenerate the capabilities of a damaged heart. The current treatment involves pharmacological and surgical interventions; however, less invasive and more cost-effective approaches are sought. Such new approaches are developed to induce tissue regeneration following injury. Hence, regenerative medicine plays a key role in treating CVD. Recently, the extrinsic stimulation of cardiac regeneration has involved the use of potential polymers to stimulate stem cells toward the differentiation of cardiomyocytes as a new therapeutic intervention in cardiac tissue engineering (CTE). The therapeutic potentiality of natural or synthetic polymers and cell surface interactive factors/polymer surface modifications for cardiac repair has been demonstrated in vitro and in vivo. This review will discuss the recent advances in CTE using polymers and cell surface interactive factors that interact strongly with stem cells to trigger the molecular aspects of the differentiation or formulation of cardiomyocytes for the functional repair of heart injuries or cardiac defects.

Repair mechanisms and exposure standards

International Nuclear Information System (INIS)

Mills, W.A.

1978-01-01

The following topics are discussed; public policy for setting radiation standards; use of linear, nonthreshold theory in setting radiation standards; dose-rate dependence; occupational exposure to radiation; radon inhalation from radium in the soil in the vicinity of the phosphate industry; relation of repair mechanisms for cell survival to cancer induction; application of information on genetic repair to humans and to cancer induction; importance of repair processes in radiation protection standards; corrective factors for repair processes; relation of repair processes to age, sex, and other factors; and population distribution in radiosensitivity

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.

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.

HGFA Is an Injury-Regulated Systemic Factor that Induces the Transition of Stem Cells into GAlert

Directory of Open Access Journals (Sweden)

Joseph T. Rodgers

2017-04-01

Full Text Available Summary: The activation of quiescent stem cells into the cell cycle is a key step in initiating the process of tissue repair. We recently reported that quiescent stem cells can transition into GAlert, a cellular state in which they have an increased functional ability to activate and participate in tissue repair. However, the precise molecular signals that induce GAlert in stem cells have remained elusive. Here, we show that the injury-induced regulation of hepatocyte growth factor (HGF proteolytic processing via the systemic protease, hepatocyte growth factor activator (HGFA, stimulates GAlert in skeletal muscle stem cells (MuSCs and fibro-adipogenic progenitors (FAPs. We demonstrate that administering active HGFA to animals is sufficient to induce GAlert in stem cells throughout the body and to significantly accelerate the processes of stem cell activation and tissue repair. Our data suggest that factors that induce GAlert will have broad therapeutic applications for regenerative medicine and wound healing. : Rodgers et al. show that HGFA is a systemic protease that is activated by tissue injury and relays a signal to stem cells in non-injured tissues that induces their transition into a primed, “GAlert” state in which they possess an enhanced potential to activate and repair tissue damage. Keywords: satellite cells, muscle stem cells, fibro-adipogenic progenitors, HGFA, HGF, mTORC1, cMet, stem cell quiescence, stem cell activation, GAlert

The Bright and the Dark Sides of DNA Repair in Stem Cells

OpenAIRE

Frosina, Guido

2010-01-01

DNA repair is a double-edged sword in stem cells. It protects normal stem cells in both embryonic and adult tissues from genetic damage, thus allowing perpetuation of intact genomes into new tissues. Fast and efficient DNA repair mechanisms have evolved in normal stem and progenitor cells. Upon differentiation, a certain degree of somatic mutations becomes more acceptable and, consequently, DNA repair dims. DNA repair turns into a problem when stem cells transform and become cancerous. Tran...

Predictive Factors for Mortality and Morbidity of Ruptured Abdominal Aortic Aneurysm Repair

Directory of Open Access Journals (Sweden)

Manabu Shiraishi

2012-04-01

Conclusions: Emergency open repair can be safely performed in patients for infrarenal rAAA. In particular, we identified specific independent predictive factors of clinical examination and laboratory studies for mortality, major morbidity and renal insufficiency. [Arch Clin Exp Surg 2012; 1(2.000: 94-101

Modeling collagen remodeling in tissue engineered cardiovascular tissues

NARCIS (Netherlands)

Soares, A.L.F.

2012-01-01

Commonly, heart valve replacements consist of non-living materials lacking the ability to grow, repair and remodel. Tissue engineering (TE) offers a promising alternative to these replacement strategies since it can overcome its disadvantages. The technique aims to create an autologous living tissue

Analysis of acetylation stoichiometry suggests that SIRT3 repairs nonenzymatic acetylation lesions

DEFF Research Database (Denmark)

Weinert, Brian T; Moustafa, Tarek; Iesmantavicius, Vytautas

2015-01-01

or suppresses acetylation. Using quantitative mass spectrometry, we measured acetylation stoichiometry in mouse liver tissue and found that SIRT3 suppressed acetylation to a very low stoichiometry at its target sites. By examining acetylation changes in the liver, heart, brain, and brown adipose tissue...... of fasted mice, we found that SIRT3-targeted sites were mostly unaffected by fasting, a dietary manipulation that is thought to regulate metabolism through SIRT3-dependent deacetylation. Globally increased mitochondrial acetylation in fasted liver tissue, higher stoichiometry at mitochondrial acetylation...... functions as a protein repair factor that removes acetylation lesions from lysine residues....

Determination of bone and tissue concentrations of teicoplanin mixed with hydroxyapatite cement to repair cortical defects.

Science.gov (United States)

Eggenreich, K; Zeipper, U; Schwendenwein, E; Hadju, S; Kaltenecker, G; Laslo, I; Lang, S; Roschger, P; Vecsei, V; Wintersteiger, R

2002-01-01

A highly specific and sensitive isocratic reversed-phase high performance liquid chromatography (HPLC) method for the determination of the major component of teicoplanin in tissue is reported. Comparing fluorescamine and o-phthalaldehyde (OPA) as derivatizing agents, the derivative formed with the latter exhibits superior fluorescence intensity allowing detection of femtomole quantities. Pretreatment for tissue samples is by solid-phase extraction which uses Bakerbond PolarP C(18) cartridges and gives effective clean up from endogenous by-products. Linearity was given from 0.6 to 100 ng per injection. The coefficient of variation did not exceed 5.8% for both interday and intraday assays. It was found that when bone defects are repaired with a hydroxyapatite-teicoplanin mixture, the antibiotic does not degrade, even when it is in the cement for several months. The stability of teicoplanin in bone cement was determined fluorodensitometrically.

Disease related tissue damage and subsequent changes in fillet structure

DEFF Research Database (Denmark)

of the fish and subsequent a reduction in price. Despite this, the impact of infectious diseases on the meat quality and the mechanisms behind are poorly investigated. Wound repair is a dynamic, interactive response to tissue injury that involves a complex interaction and cross talk of various cell types......, extracellular matrix molecules, soluble mediators and cytokines. In order to describe the molecular mechanisms and processes of wound repair, a panel of genes covering immunological factors and tissue regeneration were used to measure changes at the mRNA level following mechanical tissue damage in rainbow trout...... (Oncorhynchus mykiss). Needle disrupted muscle tissue was sampled at different time points and subject to real-time RT-PCR for measuring the expression of the genes IL-1β, IL-8, IL-10, TGF-β, Myostatin-1ab, MMP-2, CTGF, Collagen-1α, VEGF, iNOS, Arg-2 and FGF. The results showed an initial phase with up...

Measurement of DNA base and nucleotide excision repair activities in mammalian cells and tissues using the comet assay - A methodological overview

Czech Academy of Sciences Publication Activity Database

Azqueta, A.; Langie, S. A. S.; Slyšková, Jana; Collins, A. R.

2013-01-01

Roč. 12, č. 11 (2013), s. 1007-1010 ISSN 1568-7864 Grant - others:EU FP6(XE) LSHB-CT-2006-037575 Institutional support: RVO:68378041 Keywords : comet assay * base excision repair * nucleotide excision repair Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.362, year: 2013

Stroke Repair via Biomimicry of the Subventricular Zone

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Rita Matta

2018-03-01

Full Text Available Stroke is among the leading causes of death and disability worldwide, 85% of which are ischemic. Current stroke therapies are limited by a narrow effective therapeutic time and fail to effectively complete the recovery of the damaged area. Magnetic resonance imaging of the subventricular zone (SVZ following infarct/stroke has allowed visualization of new axonal connections and projections being formed, while new immature neurons migrate from the SVZ to the peri-infarct area. Such studies suggest that the SVZ is a primary source of regenerative cells for the repair and regeneration of stroke-damaged neurons and tissue. Therefore, the development of tissue engineered scaffolds that serve as a bioreplicative SVZ niche would support the survival of multiple cell types that reside in the SVZ. Essential to replication of the human SVZ microenvironment is the establishment of microvasculature that regulates both the healthy and stroke-injured blood–brain barrier, which is dysregulated poststroke. In order to reproduce this niche, understanding how cells interact in this environment is critical, in particular neural stem cells, endothelial cells, pericytes, ependymal cells, and microglia. Remodeling and repair of the matrix-rich SVZ niche by endogenous reparative mechanisms may then support functional recovery when enhanced by an artificial niche that supports the survival and proliferation of migrating vascular and neuronal cells. Critical considerations to mimic this area include an understanding of resident cell types, delivery method, and the use of biocompatible materials. Controlling stem cell survival, differentiation, and migration are key factors to consider when transplanting stem cells. Here, we discuss the role of the SVZ architecture and resident cells in the promotion and enhancement of endogenous repair mechanisms. We elucidate the interplay between the extracellular matrix composition and cell interactions prior to and following stroke

Stroke Repair via Biomimicry of the Subventricular Zone

Science.gov (United States)

Matta, Rita; Gonzalez, Anjelica L.

2018-03-01

Stroke is among the leading causes of death and disability worldwide, 85% of which are ischemic. Current stroke therapies are limited by a narrow effective therapeutic time and fail to effectively complete the recovery of the damaged area. Magnetic resonance imaging of the subventricular zone (SVZ) following infarct/stroke has allowed visualization of new axonal connections and projections being formed, while new immature neurons migrate from the SVZ to the peri-infarct area. Such studies suggest that the SVZ is a primary source of regenerative cells for the repair and regeneration of stroke-damaged neurons and tissue. Therefore, the development of tissue engineered scaffolds that serve as a bioreplicative SVZ niche would support the survival of multiple cell types that reside in the SVZ. Essential to replication of the human SVZ microenvironment is the establishment of microvasculature that regulates both the healthy and stroke-injured blood brain barrier, which is dysregulated post-stroke. In order to reproduce this niche, understanding how cells interact in this environment is critical, in particular neural stem cells, endothelial cells, pericytes, ependymal cells, and microglia. Remodeling and repair of the matrix-rich SVZ niche by endogenous reparative mechanisms may then support functional recovery when enhanced by an artificial niche that supports the survival and proliferation of migrating vascular and neuronal cells. Critical considerations to mimic this area include an understanding of resident cell types, delivery method, and the use of biocompatible materials. Controlling stem cell survival, differentiation, and migration are key factors to consider when transplanting stem cells. Here, we discuss the role of the SVZ architecture and resident cells in the promotion and enhancement of endogenous repair mechanisms. We elucidate the interplay between the extracellular matrix composition and cell interactions prior to and following stroke. Lastly, we review

Biocompatibility Evaluation of EndoSequence Root Repair Paste in the Connective Tissue of Rats.

Science.gov (United States)

Taha, Nessrin A; Safadi, Rima A; Alwedaie, Manal S

2016-10-01

The aim of this study was to evaluate the subcutaneous connective tissue response to EndoSequence root repair paste (Brasseler, Savannah, GA) compared with mineral trioxide aggregate (MTA). Thirty-six Wistar rats each received 3 sterile tubes, containing 1 of the tested materials and control. The animals were killed 1, 3 and 6 weeks after implantation. The specimens were evaluated histologically for type of inflammation, intensity and extent of inflammatory cells, foreign body reaction, fibrous capsule thickness, perivascular fragments, calcific deposits and vascular congestion. EndoSequence provoked severe inflammation after 1 week, which was significantly different from MTA and control (P ˂ .05), with fragmented particles and foreign body reaction. MTA showed tissue-tolerance features almost comparable to control. EndoSequence was significantly more irritating than MTA and control at 1 and 3 weeks in terms of severity and extent of inflammation. After 6 weeks it displayed more biocompatible characteristics. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

DNA-damage foci to detect and characterize DNA repair alterations in children treated for pediatric malignancies.

Directory of Open Access Journals (Sweden)

Nadine Schuler

Full Text Available PURPOSE: In children diagnosed with cancer, we evaluated the DNA damage foci approach to identify patients with double-strand break (DSB repair deficiencies, who may overreact to DNA-damaging radio- and chemotherapy. In one patient with Fanconi anemia (FA suffering relapsing squamous cell carcinomas of the oral cavity we also characterized the repair defect in biopsies of skin, mucosa and tumor. METHODS AND MATERIALS: In children with histologically confirmed tumors or leukemias and healthy control-children DSB repair was investigated by counting γH2AX-, 53BP1- and pATM-foci in blood lymphocytes at defined time points after ex-vivo irradiation. This DSB repair capacity was correlated with treatment-related normal-tissue responses. For the FA patient the defective repair was also characterized in tissue biopsies by analyzing DNA damage response proteins by light and electron microscopy. RESULTS: Between tumor-children and healthy control-children we observed significant differences in mean DSB repair capacity, suggesting that childhood cancer is based on genetic alterations affecting DNA repair. Only 1 out of 4 patients with grade-4 normal-tissue toxicities revealed an impaired DSB repair capacity. The defective DNA repair in FA patient was verified in irradiated blood lymphocytes as well as in non-irradiated mucosa and skin biopsies leading to an excessive accumulation of heterochromatin-associated DSBs in rapidly cycling cells. CONCLUSIONS: Analyzing human tissues we show that DSB repair alterations predispose to cancer formation at younger ages and affect the susceptibility to normal-tissue toxicities. DNA damage foci analysis of blood and tissue samples allows one to detect and characterize DSB repair deficiencies and enables identification of patients at risk for high-grade toxicities. However, not all treatment-associated normal-tissue toxicities can be explained by DSB repair deficiencies.

Indentation damage and crack repair in human enamel.

Science.gov (United States)

Rivera, C; Arola, D; Ossa, A

2013-05-01

Tooth enamel is the hardest and most highly mineralized tissue in the human body. While there have been a number of studies aimed at understanding the hardness and crack growth resistance behavior of this tissue, no study has evaluated if cracks in this tissue undergo repair. In this investigation the crack repair characteristics of young human enamel were evaluated as a function of patient gender and as a function of the distance from the Dentin Enamel Junction (DEJ). Cracks were introduced via microindentation along the prism direction and evaluated as a function of time after the indentation. Microscopic observations indicated that the repair of cracks began immediately after crack initiation and reaches saturation after approximately 48 h. During this process he crack length decreased up to 10% of the initial length, and the largest degree of reduction occurred in the deep enamel, nearest the DEJ. In addition, it was found that the degree of repair was significantly greater in the enamel of female patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Validation of the IDS Octeia ELISA for the determination of insulin-like growth factor 1 in equine serum and tendon tissue extracts

DEFF Research Database (Denmark)

Lygren, Tone; Schjerling, Peter; Jacobsen, Stine

2013-01-01

BACKGROUND: Insulin-like growth factor (IGF-1) is an important mediator of tissue repair in horses. OBJECTIVES: The aim of the study was to evaluate whether IGF-1 could be measured reliably in equine serum and tendon tissue extracts, using an IGF-1 ELISA kit developed for human serum and plasma...... diluted equine serum samples and tendon tissue extracts. The recovery of IGF-1 was evaluated in serum and tendon tissue extracts spiked with known amounts of IGF-1. RESULTS: The range of IGF-1 released using the manufacturer's pretreatment was between 23% and 56% of the amount released using the gly...... with serum, and 72 ± 15% when diluted with PBS. The recovery after dilution was 108 ± 17% in tendon tissue extracts. Recovery from serum spiked with a fixed amount of IGF-1 was 101 ± 5% and 99 ± 7% from tendon tissue samples. CONCLUSIONS: The IDS Octeia IGF-1 ELISA kit can be used for measuring IGF-1...

When is cartilage repair successful?

International Nuclear Information System (INIS)

Raudner, M.; Roehrich, S.; Zalaudek, M.; Trattnig, S.; Schreiner, M.M.

2017-01-01

Focal cartilage lesions are a cause of long-term disability and morbidity. After cartilage repair, it is crucial to evaluate long-term progression or failure in a reproducible, standardized manner. This article provides an overview of the different cartilage repair procedures and important characteristics to look for in cartilage repair imaging. Specifics and pitfalls are pointed out alongside general aspects. After successful cartilage repair, a complete, but not hypertrophic filling of the defect is the primary criterion of treatment success. The repair tissue should also be completely integrated to the surrounding native cartilage. After some months, the transplants signal should be isointense compared to native cartilage. Complications like osteophytes, subchondral defects, cysts, adhesion and chronic bone marrow edema or joint effusion are common and have to be observed via follow-up. Radiological evaluation and interpretation of postoperative changes should always take the repair method into account. (orig.) [de

Vancomycin pre-treatment impairs tissue healing in experimental colitis: Importance of innate lymphoid cells.

Science.gov (United States)

Zhao, Di; Cai, Chenwen; Zheng, Qing; Jin, Shuang; Song, Dongjuan; Shen, Jun; Ran, Zhihua

2017-01-29

The interplay between luminal microbes and innate immunity during colonic epithelial repair has been well noted. At the same time, antibiotic has widely been used during flare-ups of ulcerative colitis. The possible effects of luminal microbiota disruption caused by antibiotics usage on epithelial repairing have been scarcely discussed. Innate lymphoid cells (ILCs) embedded in the lamina propria can be modulated by gut microbes, resulting in altered colonic IL-22/pSTAT3 levels, which is considered a prominent molecular axis in tissue repairing after epithelium damage. This study aimed to investigate whether antibiotics could interfere with ILCs-dependent tissue repair. Dextran sodium sulfate (DSS)-induced colitis was established in mice pre-treated with reagent of different antibiotic spectrum. Both morphological and molecular markers of tissue repair after DSS cessation were detected. ILCs population and function status were also recorded. Further attention was paid to the response of dendritic cells after antibiotics treatment, which were claimed to regulate colonic ILC3s in an IL-23 dependent way. Using of vancomycin resulted in delayed tissue repairing after experimental colitis. Both colonic IL-22/pSTAT3 axis and ILC3 population were found decreased in this situation. Vancomycin treatment diminished the upstream IL-23 and producer dendritic cell population. The reduced dendritic cell number may due to inadequate chemokines and colony-stimulating factors supply. Presence of vancomycin-sensitive microbiota is required for the maturation of ILC3-activating dendritic cells hence maintain the sufficient IL-22/pSTAT3 level in the colon during tissue healing. Manipulation of colonic microbiota may help achieve colonic mucosal healing post inflammation and injury. Copyright © 2016. Published by Elsevier Inc.

Macrophage diversity in renal injury and repair

NARCIS (Netherlands)

Ricardo, Sharon D.; van Goor, Harry; Eddy, Allison A.

Monocyte-derived macrophages can determine the outcome of the immune response and whether this response contributes to tissue repair or mediates tissue destruction. In addition to their important role in immune-mediated renal disease and host defense, macrophages play a fundamental role in tissue

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

Shining Light on Nanotechnology to Help Repair and Regeneration

Science.gov (United States)

Gupta, Asheesh; Avci, Pinar; Sadasivam, Magesh; Chandran, Rakkiyappan; Parizotto, Nivaldo; Vecchio, Daniela; Antunes-Melo, Wanessa C; Dai, Tianhong; Chiang, Long Y.; Hamblin, Michael R.

2012-01-01

Phototherapy can be used in two completely different but complementary therapeutic applications. While low level laser (or light) therapy (LLLT) uses red or near-infrared light alone to reduce inflammation, pain and stimulate tissue repair and regeneration, photodynamic therapy (PDT) uses the combination of light plus non-toxic dyes (called photosensitizers) to produce reactive oxygen species that can kill infectious microorganisms and cancer cells or destroy unwanted tissue (neo-vascularization in the choroid, atherosclerotic plaques in the arteries). The recent development of nanotechnology applied to medicine (nanomedicine) has opened a new front of advancement in the field of phototherapy and has provided hope for the development of nanoscale drug delivery platforms for effective killing of pathological cells and to promote repair and regeneration. Despite the well-known beneficial effects of phototherapy and nanomaterials in producing the killing of unwanted cells and promoting repair and regeneration, there are few reports that combine all three elements i.e. phototherapy, nanotechnology and, tissue repair and regeneration. However, these areas in all possible binary combinations have been addressed by many workers. The present review aims at highlighting the combined multi-model applications of phototherapy, nanotechnology and, reparative and regeneration medicine and outlines current strategies, future applications and limitations of nanoscale-assisted phototherapy for the management of cancers, microbial infections and other diseases, and to promote tissue repair and regeneration. PMID:22951919

Heparanase enhances the generation of activated factor X in the presence of tissue factor and activated factor VII.

Science.gov (United States)

Nadir, Yona; Brenner, Benjamin; Fux, Liat; Shafat, Itay; Attias, Judith; Vlodavsky, Israel

2010-11-01

Heparanase is an endo-β-D-glucuronidase dominantly involved in tumor metastasis and angiogenesis. Recently, we demonstrated that heparanase is involved in the regulation of the hemostatic system. Our hypothesis was that heparanase is directly involved in activation of the coagulation cascade. Activated factor X and thrombin were studied using chromogenic assays, immunoblotting and thromboelastography. Heparanase levels were measured by enzyme-linked immunosorbent assay. A potential direct interaction between tissue factor and heparanase was studied by co-immunoprecipitation and far-western assays. Interestingly, addition of heparanase to tissue factor and activated factor VII resulted in a 3- to 4-fold increase in activation of the coagulation cascade as shown by increased activated factor X and thrombin production. Culture medium of human embryonic kidney 293 cells over-expressing heparanase and its derivatives increased activated factor X levels in a non-enzymatic manner. When heparanase was added to pooled normal plasma, a 7- to 8-fold increase in activated factor X level was observed. Subsequently, we searched for clinical data supporting this newly identified role of heparanase. Plasma samples from 35 patients with acute leukemia at presentation and 20 healthy donors were studied for heparanase and activated factor X levels. A strong positive correlation was found between plasma heparanase and activated factor X levels (r=0.735, P=0.001). Unfractionated heparin and an inhibitor of activated factor X abolished the effect of heparanase, while tissue factor pathway inhibitor and tissue factor pathway inhibitor-2 only attenuated the procoagulant effect. Using co-immunoprecipitation and far-western analyses it was shown that heparanase interacts directly with tissue factor. Overall, our results support the notion that heparanase is a potential modulator of blood hemostasis, and suggest a novel mechanism by which heparanase increases the generation of activated

Fibroblast growth factor 2 and DNA repair involvement in the keratinocyte stem cells response to ionizing radiation

International Nuclear Information System (INIS)

Harfouche, L'Emira Ghida

2010-02-01

Keratinocyte stem cells (KSCs) from the human inter follicular epidermis are regarded as the major target to radiation during radiotherapy. We found herein that KSCs are more resistant to ionizing radiation than their direct progeny, and presented more rapid DNA damage repair kinetics than the progenitors. Furthermore, we provided evidence describing the effect of fibroblast growth factor 2 (FGF2) signaling on the ability of KSCs and progenitors to repair damaged DNA. Despite our knowledge of the fact, that FGF is an anti-apoptotic factor in multiple cell types, the direct link between DNA repair and FGF2 signaling has rarely been shown. Existence of such link is an important issue with implications not only to stem cell field but also to cancer therapy. (author)

An evaluation of Admedus' tissue engineering process-treated (ADAPT) bovine pericardium patch (CardioCel) for the repair of cardiac and vascular defects.

Science.gov (United States)

Strange, Geoff; Brizard, Christian; Karl, Tom R; Neethling, Leon

2015-03-01

Tissue engineers have been seeking the 'Holy Grail' solution to calcification and cytotoxicity of implanted tissue for decades. Tissues with all of the desired qualities for surgical repair of congenital heart disease (CHD) are lacking. An anti-calcification tissue engineering process (ADAPT TEP) has been developed and applied to bovine pericardium (BP) tissue (CardioCel, AdmedusRegen Pty Ltd, Perth, WA, Australia) to eliminate cytotoxicity, improve resistance to acute and chronic inflammation, reduce calcification and facilitate controlled tissue remodeling. Clinical data in pediatric patients, and additional pre-market authorized prescriber data demonstrate that CardioCel performs extremely well in the short term and is safe and effective for a range of congenital heart deformations. These data are supported by animal studies which have shown no more than normal physiologic levels of calcification, with good durability, biocompatibility and controlled healing.

Right Ventricular Outflow Tract Stenting in Tetralogy of Fallot Infants With Risk Factors for Early Primary Repair.

Science.gov (United States)

Sandoval, Juan Pablo; Chaturvedi, Rajiv R; Benson, Lee; Morgan, Gareth; Van Arsdell, Glen; Honjo, Osami; Caldarone, Christopher; Lee, Kyong-Jin

2016-12-01

Tetralogy of Fallot with cyanosis requiring surgical repair in early infancy reflects poor anatomy and is associated with more clinical instability and longer hospitalization than those who can be electively repaired later. We bridged symptomatic infants with risk factors for early primary repair by right ventricular outflow tract stenting (stent). Four groups of tetralogy of Fallot with confluent central pulmonary arteries were studied: stent group (n=42), primary repair (aged 3mo group; n=45). Stent patients had the smallest pulmonary arteries with a median (95% credible intervals) Nakata index (mm 2 /m 2 ) of 79 (66-85) compared with the early-PA 139 (129-154), early-PS 136 (121-153), and surg>3mo 167 (153-200) groups. Only stent infants required unifocalization of aortopulmonary collaterals (17%). Stent and early-PA infants had younger age and lower weight than early-PS infants. Stent infants had the most multiple comorbidities. Stenting allowed deferral of complete surgical repair to an age (6 months), weight (6.3 [5.8-7.0] kg), and Nakata index (147 [132-165]) similar to the low-risk surg>3mo group. The 3 early treatment groups had similar intensive care unit/hospital stays and high reintervention rates in the first 12 months after repair, compared with the surg>3mo group. Right ventricular outflow tract stenting of symptomatic tetralogy of Fallot with poor anatomy (small pulmonary arteries) and adverse factors (multiple comorbidities, low weight) relieves cyanosis and defers surgical repair. This allowed pulmonary arterial and somatic growth with clinical results comparable to early surgical repair in more favorable patients. © 2016 American Heart Association, Inc.

Vaginal native tissue repair versus transvaginal mesh repair for apical prolapse: how utilizing different methods of analysis affects the estimated trade-off between reoperation for mesh exposure/erosion and reoperation for recurrent prolapse.

Science.gov (United States)

Dieter, Alexis A; Willis-Gray, Marcella G; Weidner, Alison C; Visco, Anthony G; Myers, Evan R

2015-05-01

Informed decision-making about optimal surgical repair of apical prolapse with vaginal native tissue (NT) versus transvaginal mesh (TVM) requires understanding the balance between the potential "harm" of mesh-related complications and the potential "benefit" of reducing prolapse recurrence. Synthesis of data from observational studies is required and the current literature shows that the average follow-up for NT repair is significantly longer than for TVM repair. We examined this harm/benefit balance. We hypothesized that using different methods of analysis to incorporate follow-up time would affect the balance of outcomes. We used a Markov state transition model to estimate the cumulative 24-month probabilities of reoperation for mesh exposure/erosion or for recurrent prolapse after either NT or TVM repair. We used four different analytic approaches to estimate probability distributions ranging from simple pooled proportions to a random effects meta-analysis using study-specific events per patient-time. As variability in follow-up time was accounted for better, the balance of outcomes became more uncertain. For TVM repair, the incremental ratio of number of operations for mesh exposure/erosion per single reoperation for recurrent prolapse prevented increased progressively from 1.4 to over 100 with more rigorous analysis methods. The most rigorous analysis showed a 70% probability that TVM would result in more operations for recurrent prolapse repair than NT. Based on the best available evidence, there is considerable uncertainty about the harm/benefit trade-off between NT and TVM for apical prolapse repair. Future studies should incorporate time-to-event analyses, with greater standardization of reporting, in order to better inform decision-making.

Expression of various growth factors for cell proliferation and cytodifferentiation during fracture repair of bone

Directory of Open Access Journals (Sweden)

M Fukuda

2009-12-01

Full Text Available We examined immunohistochemically the fracture repair process in rat tibial bone using antibodies to PCNA, BMP2, TGF-b 1,-2,-3, TGF-b R1,- R2, bFGF, bFGFR, PDGF, VEGF, and S-100. The peak level of cell proliferation as revealed by PCNA labelling appeared first in primitive mesenchymal cells and inflammatory cells at the fracture edges and neighboring periosteum at 2-days after fracture, followed by the peaks of periosteal primitive fibroblasts and chondroblasts, which appeared at fracture edges at 3- and 4-days after fracture, respectively. BMP2 was weakly positive in primitive mesenchymal cells, osteoblasts and chondroblasts. At 3-days post-fracture, periosteal osteoblasts produced osteoid tissue and callus with marrow spaces lined by osteoblasts and osteoclasts, and all primitive mesenchymal cells and osteoblasts were positive for TGF-b 1,-2,-3, and TGF-b R1,-R2. They were also positive for vascular growth factors bFGF, FGFR and PDGF, but negative for VEGF, and the peak of PCNA labelling of vascular endothelial cells in the marrow space was delayed to 4-days after fracture. Chondroblasts at fracture edges produced hypertrophic chondrocytes at 5-days after fracture and they were positive for TGF-b 1,-2,-3, and TGF-b R1,-R2. Primitive chondroblasts were positive for vascular growth factors VEGF as well as bFGF, FGFR, and the peak of PCNA labelling of vascular endothelial cells in the cartilage was at 5-days after fracture. Hypertrophic chondrocytes were also positive for these growth factors but negative for bFGF and bFGFR. S-100 protein-induced calcification was only positive on chondroblasts and hypertrophic chondrocytes. At 7-days after fracture, bone began to be formed from the cartilage at fracture edges, by a process similar to bone formation in the growth plate. Enchondral ossification established a bridge between both fracture edges and periosteal membranous ossification encompassed the fracture site like a sheath at 14- day after

Arthroscopic repair of partial-thickness and small full-thickness rotator cuff tears: tendon quality as a prognostic factor for repair integrity.

Science.gov (United States)

Chung, Seok Won; Kim, Jae Yoon; Yoon, Jong Pil; Lyu, Seong Hwa; Rhee, Sung Min; Oh, Se Bong

2015-03-01

The healing failure rate is high for partial-thickness or small full-thickness rotator cuff tears. To retrospectively evaluate and compare outcomes after arthroscopic repair of high-grade partial-thickness and small full-thickness rotator cuff tears and factors affecting rotator cuff healing. Cohort study; Level of evidence, 3. Included in the study were 55 consecutive patients (mean age, 57.9 ± 7.2 years) who underwent arthroscopic repair for high-grade partial-thickness (n = 34) and small full-thickness (n = 21) rotator cuff tears. The study patients also underwent magnetic resonance imaging (MRI) preoperatively and computed tomography arthrography (CTA) at least 6 months postoperatively, and their functional outcomes were evaluated preoperatively and at the last follow-up (>24 months). All partial-thickness tears were repaired after being converted to full-thickness tears; thus, the repair process was almost the same as for small full-thickness tears. The tendinosis of the torn tendon was graded from the MRI images using a 4-point scale, and the reliabilities were assessed. The outcomes between high-grade partial-thickness tears that were converted to small full-thickness tears and initially small full-thickness tears were compared, and factors affecting outcomes were evaluated. The inter- and intraobserver reliabilities of the tendinosis grade were good (intraclass correlation coefficient, 0.706 and 0.777, respectively). Failure to heal as determined by CTA was observed in 12 patients with a high-grade partial-thickness tear (35.3%; complete failure in 4 and partial failure in 8) and in 3 patients with a small full-thickness tear (14.3%; complete failure in 1 and partial failure in 2). The patients with high-grade partial-thickness rotator cuff tears showed a higher tendinosis grade than did those with small full-thickness tears (P = .014), and the severity of the tendinosis was related to the failure to heal (P = .037). Tears with a higher tendinosis grade

Arthroscopic suture bridge rotator cuff repair: functional outcome, repair integrity, and preoperative factors related to postoperative outcome.

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Rimmke, Nathan; Maerz, Tristan; Cooper, Ross; Yadavalli, Sailaja; Anderson, Kyle

2016-01-01

To assess the retear rate, retear size and location, the clinical impact of a retear, and preoperative patient factors related to postoperative outcome after arthroscopic suture bridge rotator cuff repair. Fifty six patients with an isolated, full-thickness supraspinatus tendon tear who underwent arthroscopic suture bridge rotator cuff repair were retrospectively identified. Patients were evaluated and rotator cuff integrity was assessed using ultrasonography. Visual analog score (VAS), the American Shoulder and Elbow Surgeon (ASES) score, shoulder range of motion and strength were used for clinical evaluation. Retears were assessed for size and location on ultrasonography. Forty two patients (75%) aged a mean 59.7 ± 8.6 years (range 41-79 years) were available for follow-up at a mean 13.5 months. Postoperative evaluation indicated significant improvements in ASES score (49.76 ± 18.2 to 86.57 ± 13.4, P rotation ROM (44.13° ± 12.0 to 52.09° ± 12.0, P = 0.003). The retear rate was 14.28% (6/42). Patients with retears were not older (P = 0.526) but had a larger preoperative tear size (3.25 cm ± 0.5 vs. 2.05 cm ± 0.48, P rotation ROM (P = 0.002), and internal rotation strength (P = 0.004). Arthroscopic suture bridge repair provides good clinical results with a low retear rate. The duration of preoperative symptoms was associated with postoperative outcome, indicating that delaying surgery may result in inferior outcomes. IV, Case Series.

Calcium-phosphate matrix with or without TGF-β3 improves tendon-bone healing after rotator cuff repair.

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Kovacevic, David; Fox, Alice J; Bedi, Asheesh; Ying, Liang; Deng, Xiang-Hua; Warren, Russell F; Rodeo, Scott A

2011-04-01

Rotator cuff tendon heals by formation of an interposed zone of fibrovascular scar tissue. Recent studies demonstrate that transforming growth factor-beta 3 (TGF-β(3)) is associated with tissue regeneration and "scarless" healing, in contrast to scar-mediated healing that occurs with TGF-β(1). Delivery of TGF-β(3) in an injectable calcium-phosphate matrix to the healing tendon-bone interface after rotator cuff repair will result in increased attachment strength secondary to improved bone formation and collagen organization and reduced scar formation of the healing enthesis. Controlled laboratory study. Ninety-six male Sprague-Dawley rats underwent unilateral detachment of the supraspinatus tendon followed by acute repair using transosseous suture fixation. Animals were allocated into 1 of 3 groups: (1) repair alone (controls, n = 32), (2) repair augmented by application of an osteoconductive calcium-phosphate (Ca-P) matrix only (n = 32), or (3) repair augmented with Ca-P matrix + TGF-β(3) (2.75 µg) at the tendon-bone interface (n = 32). Animals were euthanized at either 2 weeks or 4 weeks postoperatively. Biomechanical testing of the supraspinatus tendon-bone complex was performed at 2 and 4 weeks (n = 8 per group). Microcomputed tomography was utilized to quantitate bone microstructure at the repair site. The healing tendon-bone interface was evaluated with histomorphometry and immunohistochemical localization of collagen types I (COLI) and III (COLIII). Statistical analysis was performed using 2-way analysis of variance with significance set at P repair site is associated with new bone formation, increased fibrocartilage, and improved collagen organization at the healing tendon-bone interface in the early postoperative period after rotator cuff repair. The addition of TGF-β(3) significantly improved strength of the repair at 4 weeks postoperatively and resulted in a more favorable COLI/COLIII ratio. The delivery of TGF-β(3) with an injectable Ca-P matrix

Engineering Complex Tissues

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MIKOS, ANTONIOS G.; HERRING, SUSAN W.; OCHAREON, PANNEE; ELISSEEFF, JENNIFER; LU, HELEN H.; KANDEL, RITA; SCHOEN, FREDERICK J.; TONER, MEHMET; MOONEY, DAVID; ATALA, ANTHONY; VAN DYKE, MARK E.; KAPLAN, DAVID; VUNJAK-NOVAKOVIC, GORDANA

2010-01-01

This article summarizes the views expressed at the third session of the workshop “Tissue Engineering—The Next Generation,” which was devoted to the engineering of complex tissue structures. Antonios Mikos described the engineering of complex oral and craniofacial tissues as a “guided interplay” between biomaterial scaffolds, growth factors, and local cell populations toward the restoration of the original architecture and function of complex tissues. Susan Herring, reviewing osteogenesis and vasculogenesis, explained that the vascular arrangement precedes and dictates the architecture of the new bone, and proposed that engineering of osseous tissues might benefit from preconstruction of an appropriate vasculature. Jennifer Elisseeff explored the formation of complex tissue structures based on the example of stratified cartilage engineered using stem cells and hydrogels. Helen Lu discussed engineering of tissue interfaces, a problem critical for biological fixation of tendons and ligaments, and the development of a new generation of fixation devices. Rita Kandel discussed the challenges related to the re-creation of the cartilage-bone interface, in the context of tissue engineered joint repair. Frederick Schoen emphasized, in the context of heart valve engineering, the need for including the requirements derived from “adult biology” of tissue remodeling and establishing reliable early predictors of success or failure of tissue engineered implants. Mehmet Toner presented a review of biopreservation techniques and stressed that a new breakthrough in this field may be necessary to meet all the needs of tissue engineering. David Mooney described systems providing temporal and spatial regulation of growth factor availability, which may find utility in virtually all tissue engineering and regeneration applications, including directed in vitro and in vivo vascularization of tissues. Anthony Atala offered a clinician’s perspective for functional tissue

Carbon nanotubes in neuroregeneration and repair.

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Fabbro, Alessandra; Prato, Maurizio; Ballerini, Laura

2013-12-01

In the last decade, we have experienced an increasing interest and an improved understanding of the application of nanotechnology to the nervous system. The aim of such studies is that of developing future strategies for tissue repair to promote functional recovery after brain damage. In this framework, carbon nanotube based technologies are emerging as particularly innovative tools due to the outstanding physical properties of these nanomaterials together with their recently documented ability to interface neuronal circuits, synapses and membranes. This review will discuss the state of the art in carbon nanotube technology applied to the development of devices able to drive nerve tissue repair; we will highlight the most exciting findings addressing the impact of carbon nanotubes in nerve tissue engineering, focusing in particular on neuronal differentiation, growth and network reconstruction. © 2013.

Histological and MR quantitative analysis of repaired tissue following microfracture treatment for knee joint osteochondritis dissecans in rabbit models

International Nuclear Information System (INIS)

Tao Hongyue; Chen Shuang; Feng Xiaoyuan; Wang Zhan; Li Hong; Hua Yinghui; Chen Zhongqing

2013-01-01

Objective: To quantitatively analyze the histological and MR images of repaired tissue (RT) following microfracture for knee joint osteochondritis dissecans (OCD) in rabbit models at different time points, make comparisons with the RT performances of joint debridement, explore the efficiency of the microfracture treatment for OCD. Methods: Twenty-seven New Zealand rabbits were randomly assigned into 3 groups (sacrificed at the end of 3, 5 and 7 weeks post-operation respectively), with 9 in each group. For each rabbit, one knee joint was made into an OCD model. In each group, 6 were for microfracture treatment, and the other 3 were for joint debridement as control. MR scan, which mainly included sequences of 3D double echo steady state sequence (3D-DESS) and T_2-mapping, was taken at 3, 5 and 7 weeks postoperation. The thickness index and T_2 value index of RT were calculated and T_2-mapping of repaired region was drafted. Then the operation sites were removed to make histological sections of HE and Masson staining. The modified O'Driscoll score system was employed to make semi-quantitative evaluation for the histological performance of RT. Comparisons were made with respect to MR and histological findings between two treatments at each time point using unpaired Student t test. Effects of two treatments were evaluated longitudinally by comparing the results of three time points using one-way ANOVA. Results: The post-operation thickness indexes of two groups increased gradually (F = 33.940, 28.841, P < 0.05), T_2 value indexes decreased (F = 80.183, 206.206, P < 0.05), and O'driscoll scores increased gradually (F = 29.867, 17.167, P < 0.05). At each time point, the thickness index of microfracture was higher than that of debridement group (3-week: 0.743 ± 0.048 vs 0.624 ± 0.013, t = 4.077; 5-week: 0.813 ± 0.031 vs 0.734 ± 0.015, t = 4.107; 7-week: 0.972 ± 0.064 vs 0.777 ± 0.039, t = 4.782; P < 0.05), and the defects of microfracture in 7-week group were almost

Potential Roles of Dental Pulp Stem Cells in Neural Regeneration and Repair

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Luo, Lihua; Wang, Xiaoyan; Key, Brian; Lee, Bae Hoon

2018-01-01

This review summarizes current advances in dental pulp stem cells (DPSCs) and their potential applications in the nervous diseases. Injured adult mammalian nervous system has a limited regenerative capacity due to an insufficient pool of precursor cells in both central and peripheral nervous systems. Nerve growth is also constrained by inhibitory factors (associated with central myelin) and barrier tissues (glial scarring). Stem cells, possessing the capacity of self-renewal and multicellular differentiation, promise new therapeutic strategies for overcoming these impediments to neural regeneration. Dental pulp stem cells (DPSCs) derive from a cranial neural crest lineage, retain a remarkable potential for neuronal differentiation, and additionally express multiple factors that are suitable for neuronal and axonal regeneration. DPSCs can also express immunomodulatory factors that stimulate formation of blood vessels and enhance regeneration and repair of injured nerve. These unique properties together with their ready accessibility make DPSCs an attractive cell source for tissue engineering in injured and diseased nervous systems. In this review, we interrogate the neuronal differentiation potential as well as the neuroprotective, neurotrophic, angiogenic, and immunomodulatory properties of DPSCs and its application in the injured nervous system. Taken together, DPSCs are an ideal stem cell resource for therapeutic approaches to neural repair and regeneration in nerve diseases. PMID:29853908

Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

NARCIS (Netherlands)

Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

2017-01-01

Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor beta induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

Connective tissue growth factor regulates fibrosis-associated renal lymphangiogenesis

NARCIS (Netherlands)

Kinashi, Hiroshi; Falke, Lucas L.; Nguyen, Tri Q.; Bovenschen, Niels; Aten, Jan; Leask, Andrew; Ito, Yasuhiko; Goldschmeding, Roel

2017-01-01

Lymphangiogenesis is correlated with the degree of renal interstitial fibrosis. Pro-fibrotic transforming growth factor β induces VEGF-C production, the main driver of lymphangiogenesis. Connective tissue growth factor (CTGF) is an important determinant of fibrotic tissue remodeling, but its

[Repair of soft tissue defect in hand or foot with lobulated medial sural artery perforator flap].

Science.gov (United States)

Fengjing, Zhao; Jianmin, Yao; Xingqun, Zhang; Liang, Ma; Longchun, Zhang; Yibo, Xu; Peng, Wang; Zhen, Zhu

2015-11-01

To explore the clinical effect of the lobulated medial sural artery perforator flap in repairing soft tissue defect in hand or foot. Since March 2012 to September 2014, 6 cases with soft tissue defects in hands or feet were treated by lobulated medial sural artery flaps pedicled with 1st musculo-cutaneous perforator and 2st musculo-cutaneous perforator of the medial sural artery. The size of the flaps ranged from 4.5 cm x 10.0 cm to 6.0 cm x 17.0 cm. 5 cases of lobulated flap survived smoothly, only 1 lobulated flap had venous articulo, but this flap also survived after the articulo was removed by vascular exploration. All flaps had desirable appearance and sensation and the two-point discrimination was 6 mm in mean with 4 to 12 months follow-up (average, 7 months). Linear scar was left in donor sites in 3 cases and skin scar in 3 cases. There was no malfunction in donor sites. Lobulated medial sural artery perforator flap is feasible and ideal method for the treatment of soft tissue defect in hand or foot with satisfactory effect.

Meniscal repair following meniscectomy: Mechanism and protective effect

International Nuclear Information System (INIS)

Berjon, J.J.; Munuera, L.; Calvo, M.

1990-01-01

Meniscal repair was studied to evaluate the mechanism and its potential protective effects on the articular cartilage in an experimental model consisting of 68 knees of adult dogs on which five different types of medial meniscectomy were performed. The results were assessed by macroscopic, microangiographic, and histological methods, after a sequential follow-up period of 10-450 days. Two different mechanisms of meniscal repair were observed, depending on whether meniscal section had been performed in vascular (total meniscectomy) or avascular (subtotal or partial meniscectomy) zones. It was also observed that the repaired meniscal tissue does not prevent articular cartilage degeneration. This is more closely related to the size of the meniscal fragment preserved at meniscetomy. Due to the biomechanical importance of the meniscus and the lack of functional relevance of the repaired meniscal tissue, the most conservative approach possible to meniscectomy is recommended. (orig.)

Spinal Cord Repair with Engineered Nervous Tissue

Science.gov (United States)

2014-04-01

ganglia ( DRG ) and axons that can be stretch-grown to a length necessary to bridge extensive lesions. In current studies, we have optimized in vivo...survival of DRGs up to 6 weeks post-transplant. If successful, this approach will provide an alternative or additional means to repair large spinal...lesions. 15. SUBJECT TERMS- none listed 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF

Multiple functions of gingival and mucoperiosteal fibroblasts in oral wound healing and repair.

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Chiquet, Matthias; Katsaros, Christos; Kletsas, Dimitris

2015-06-01

Fibroblasts are cells of mesenchymal origin. They are responsible for the production of most extracellular matrix in connective tissues and are essential for wound healing and repair. In recent years, it has become clear that fibroblasts from different tissues have various distinct traits. Moreover, wounds in the oral cavity heal under very special environmental conditions compared with skin wounds. Here, we reviewed the current literature on the various interconnected functions of gingival and mucoperiosteal fibroblasts during the repair of oral wounds. The MEDLINE database was searched with the following terms: (gingival OR mucoperiosteal) AND fibroblast AND (wound healing OR repair). The data gathered were used to compare oral fibroblasts with fibroblasts from other tissues in terms of their regulation and function during wound healing. Specifically, we sought answers to the following questions: (i) what is the role of oral fibroblasts in the inflammatory response in acute wounds; (ii) how do growth factors control the function of oral fibroblasts during wound healing; (iii) how do oral fibroblasts produce, remodel and interact with extracellular matrix in healing wounds; (iv) how do oral fibroblasts respond to mechanical stress; and (v) how does aging affect the fetal-like responses and functions of oral fibroblasts? The current state of research indicates that oral fibroblasts possess unique characteristics and tightly controlled specific functions in wound healing and repair. This information is essential for developing new strategies to control the intraoral wound-healing processes of the individual patient. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma

International Nuclear Information System (INIS)

Morrison, S.A.; Jesty, J.

1984-01-01

A comparism was made of the tissue factor-dependent activation of tritium-labeled factor IX and factor X in a human plasma system and a study was made of the role of proteases known to stimulate factor VII activity. Plasma was defibrinated by heating and depleted of its factors IX and X by passing it through antibody columns. Addition of human brain thromboplastin, Ca2+, and purified 3H-labeled factor X to the plasma resulted, after a short lag, in burst-like activation of the factor X, measured as the release of radiolabeled activation peptide. The progress of activation was slowed by both heparin and a specific inhibitor of factor Xa but factor X activation could not be completely abolished by such inhibitors. In the case of 3H-factor IX activation, the rate also increased for approximately 3 min after addition of thromboplastin, but was not subsequently curtailed. A survey of proteases implicated as activators of factor VII in other settings showed that both factor Xa and factor IXa could accelerate the activation of factor IX. However, factor Xa was unique in obliterating activation when present at concentrations greater than approximately 1 nM. Heparin inhibited the tissue factor-dependent activation of factor IX almost completely, apparently through the effect of antithrombin on the feedback reactions of factors Xa and IXa on factor VII. These results suggest that a very tight, biphasic control of factor VII activity exists in human plasma, which is modulated mainly by factor Xa. At saturation of factor VIIa/tissue factor, factor IX activation was significantly more rapid than was previously found in bovine plasma under similar conditions. The activation of factor X at saturation was slightly more rapid than in bovine plasma, despite the presence of heparin

Effect of Cell Seeding Density and Inflammatory Cytokines on Adipose Tissue-Derived Stem Cells: an in Vitro Study

NARCIS (Netherlands)

Sukho, P. (Panithi); J. Kirpensteijn (Jolle); Hesselink, J.W. (Jan Willem); G.J.V.M. van Osch (Gerjo); F. Verseijden (Femke); Y.M. Bastiaansen-Jenniskens (Yvonne)

2017-01-01

textabstractAdipose tissue-derived stem cells (ASCs) are known to be able to promote repair of injured tissue via paracrine factors. However, the effect of cell density and inflammatory cytokines on the paracrine ability of ASCs remains largely unknown. To investigate these effects, ASCs were

Tension (re)builds: Biophysical mechanisms of embryonic wound repair.

Science.gov (United States)

Zulueta-Coarasa, Teresa; Fernandez-Gonzalez, Rodrigo

2017-04-01

Embryonic tissues display an outstanding ability to rapidly repair wounds. Epithelia, in particular, serve as protective layers that line internal organs and form the skin. Thus, maintenance of epithelial integrity is of utmost importance for animal survival, particularly at embryonic stages, when an immune system has not yet fully developed. Rapid embryonic repair of epithelial tissues is conserved across species, and involves the collective migration of the cells around the wound. The migratory cell behaviours associated with wound repair require the generation and transmission of mechanical forces, not only for the cells to move, but also to coordinate their movements. Here, we review the forces involved in embryonic wound repair. We discuss how different force-generating structures are assembled at the molecular level, and the mechanisms that maintain the balance between force-generating structures as wounds close. Finally, we describe the mechanisms that cells use to coordinate the generation of mechanical forces around the wound. Collective cell movements and their misregulation have been associated with defective tissue repair, developmental abnormalities and cancer metastasis. Thus, we propose that understanding the role of mechanical forces during embryonic wound closure will be crucial to develop therapeutic interventions that promote or prevent collective cell movements under pathological conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The importance of residues 195-206 of human blood clotting factor VII in the interaction of factor VII with tissue factor

International Nuclear Information System (INIS)

Wildgoose, P.; Kisiel, W.; Kazim, A.L.

1990-01-01

Previous studies indicated that human and bovine factor VII exhibit 71% amino acid sequence identity. In the present study, competition binding experiments revealed that the interaction of human factor VII with cell-surface human tissue factor was not inhibited by 100-fold molar excess of bovine factor VII. This finding indicated that bovine and human factor VII are not structurally homologous in the region(s) where human factor VII interacts with human tissue factor. On this premise, the authors synthesized three peptides corresponding to regions of human factor VII that exhibited marked structural dissimilarity to bovine factor VII; these regions of dissimilarity included residues 195-206, 263-274, and 314-326. Peptide 195-206 inhibited the interaction of factor VII with cell-surface tissue factor and the activation of factor X by a complex of factor VIIa and tissue factor half-maximally at concentrations of 1-2 mM. A structurally rearranged form of peptide 195-206 containing an aspartimide residue inhibited these reactions half-maximally at concentrations of 250-300 μM. In contrast, neither peptide 263-274 nor peptide 314-326, at 2 mM concentration, significantly affected either factor VIIa interaction with tissue factor or factor VIIa-mediated activation of factor X. The data provide presumptive evidence that residues 195-206 of human factor VII are involved in the interaction of human factor VII with the extracellular domain of human tissue factor apoprotein

A new concept of endometriosis and adenomyosis: tissue injury and repair (TIAR).

Science.gov (United States)

Leyendecker, Gerhard; Wildt, Ludwig

2011-03-01

Pelvic endometriosis, deeply infiltrating endometriosis and uterine adenomyosis share a common pathophysiology and may be integrated into the physiological mechanism and new nosological concept of 'tissue injury and repair' (TIAR) and may, in this context, just represent the extreme of a basically physiological, estrogen-related mechanism that is pathologically exaggerated in an extremely estrogen-sensitive reproductive organ. The acronym TIAR describes a fundamental and apparently ubiquitous biological system that becomes operative in mesenchymal tissues following tissue injury and, upon activation, results in the local production of estradiol. Endometriosis and adenomyosis are caused by trauma. In the spontaneously developing disease, chronic uterine peristaltic activity or phases of hyperperistalsis induce, at the endometrial-myometrial interface near the fundo-cornual raphe, microtraumatisations, with activation of the TIAR mechanism. With ongoing traumatisations, such sites of inflammation might accumulate and the increasingly produced estrogens interfere in a paracrine fashion with ovarian control over uterine peristaltic activity, resulting in permanent hyperperistalsis and a self-perpetuation of the disease process. Overt autotraumatisation of the uterus with dislocation of fragments of basal endometrium into the peritoneal cavity and infiltration of basal endometrium into the depth of the myometrial wall ensues. In most cases of endometriosis/adenomyosis a causal event early in the reproductive period of life must be postulated, rapidly leading to archimetral hyperestrogenism and uterine hyperperistalsis. In late premenopausal adenomyosis such an event might not have occurred. However, as indicated by the high prevalence of the disease, it appears to be unavoidable that, with time, chronic normoperistalsis throughout the reproductive period of life accumulates to the same extent of microtraumatisation. With activation of the TIAR mechanism followed by

Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization

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Jianfeng Zhang

2015-06-01

Full Text Available Background/Aims: Transplantation of mesenchymal stem cells (MSCs improves post-injury cardiac muscle repair using ill-defined mechanisms. Recently, we have shown that production and secretion of placental growth factor (PLGF by MSCs play a critical role in the MSCs-mediated post-injury cardiac muscle repair. In this study, we addressed the underlying molecular mechanisms, focusing specifically on the interactions between MSCs, macrophages and endothelial cells. Methods: We isolated macrophages (BM-MΦ from mouse bone-marrow derived cells based on F4/80 expression by flow cytometry. BM-MΦ were treated with different doses of PLGF. Cell number was analyzed by a MTT assay. Macrophage polarization was examined based on CD206 expression by flow cytometry. PLGF levels in macrophage subpopulations were analyzed by RT-qPCR and ELISA. Effects of macrophages on vascularization were evaluated by a collagen gel assay using Human umbilical vein endothelial cells (HUVECs co-cultured with PLGF-treated macrophages. Results: PLGF did not increase macrophage number, but dose-dependently polarized macrophages into a M2 subpopulation. M2 macrophages expressed high levels of PLGF. PLGF-polarized M2 macrophages significantly increased tubular structures in the collagen gel assay. Conclusion: Our data suggest that MSCs-derived PLGF may induce macrophage polarization into a M2 subpopulation, which in turn releases more PLGF to promote local neovascularization for augmenting post-injury cardiac muscle repair. This study thus sheds novel light on the role of PLGF in cardiac muscle regeneration.

The age factor in axonal repair after spinal cord injury: A focus on neuron-intrinsic mechanisms.

Science.gov (United States)

Geoffroy, Cédric G; Meves, Jessica M; Zheng, Binhai

2017-06-23

Age is an important consideration for recovery and repair after spinal cord injury. Spinal cord injury is increasingly affecting the middle-aged and aging populations. Despite rapid progress in research to promote axonal regeneration and repair, our understanding of how age can modulate this repair is rather limited. In this review, we discuss the literature supporting the notion of an age-dependent decline in axonal growth after central nervous system (CNS) injury. While both neuron-intrinsic and extrinsic factors are involved in the control of axon growth after injury, here we focus on possible intrinsic mechanisms for this age-dependent decline. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

THE POWER FACTOR IMPROVING OF THE MOTORS IN ENTERPRISES WITH REPAIR OF RAILWAY EQUIPMENT

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O. L. Marenych

2008-03-01

Full Text Available In this article the following problem has been considered: ways of power factor increase for electric drives installed at the railway machinery repair enterprises with taking into account the specific conditions of technological processes.

Radiation repair models for clinical application.

Science.gov (United States)

Dale, Roger G

2018-02-28

A number of newly emerging clinical techniques involve non-conventional patterns of radiation delivery which require an appreciation of the role played by radiation repair phenomena. This review outlines the main models of radiation repair, focussing on those which are of greatest clinical usefulness and which may be incorporated into biologically effective dose assessments. The need to account for the apparent "slowing-down" of repair rates observed in some normal tissues is also examined, along with a comparison of the relative merits of the formulations which can be used to account for such phenomena. Jack Fowler brought valuable insight to the understanding of radiation repair processes and this article includes reference to his important contributions in this area.

Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

Directory of Open Access Journals (Sweden)

Xiaolin He

Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

Quantitative Methods for Measuring Repair Rates and Innate-Immune Cell Responses in Wounded Mouse Skin.

Science.gov (United States)

Li, Zhi; Gothard, Elizabeth; Coles, Mark C; Ambler, Carrie A

2018-01-01

In skin wounds, innate-immune cells clear up tissue debris and microbial contamination, and also secrete cytokines and other growth factors that impact repair process such as re-epithelialization and wound closure. After injury, there is a rapid influx and efflux of immune cells at wound sites, yet the function of each innate cell population in skin repair is still under investigation. Flow cytometry is a valuable research tool for detecting and quantifying immune cells; however, in mouse back skin, the difficulty in extracting immune cells from small area of skin due to tissue complexity has made cytometric analysis an underutilized tool. In this paper, we provide detailed methods on the digestion of lesion-specific skin without disrupting antigen expression followed by multiplex cell staining that allows for identification of seven innate-immune populations, including rare subsets such as group-3 innate lymphoid cells (ILC3s), by flow-cytometry analysis. Furthermore, when studying the functions of immune cells to tissue repair an important metric to monitor is size of the wound opening. Normal wounds close steadily albeit at non-linear rates, while slow or stalled wound closure can indicate an underlying problem with the repair process. Calliper measurements are difficult and time-consuming to obtain and can require repeated sedation of experimental animals. We provide advanced methods for measuring of wound openness; digital 3D image capture and semi-automated image processing that allows for unbiased, reliable measurements that can be taken repeatedly over time.

Effect of Cell Seeding Density and Inflammatory Cytokines on Adipose Tissue-Derived Stem Cells : an in Vitro Study

NARCIS (Netherlands)

Sukho, Panithi; Kirpensteijn, Jolle; Hesselink, Jan Willem; van Osch, Gerjo J V M; Verseijden, Femke; Bastiaansen-Jenniskens, Yvonne M

Adipose tissue-derived stem cells (ASCs) are known to be able to promote repair of injured tissue via paracrine factors. However, the effect of cell density and inflammatory cytokines on the paracrine ability of ASCs remains largely unknown. To investigate these effects, ASCs were cultured in 8000

Stepwise Total Aortic Repairs With Fenestrated Endografts in a Patient With Loeys-Dietz Syndrome.

Science.gov (United States)

Hashizume, Kenichi; Shimizu, Hideyuki; Honda, Masanori; Inoue, Shinya; Takaki, Hidenobu; Hayashi, Kanako; Kaneyama, Hiroaki

2017-07-01

Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder (CTD) caused by mutations in the gene encoding transforming growth factor-β receptors Ⅰ and Ⅱ. Patients with LDS manifest spontaneous aneurysms and dissections of the aorta and peripheral artery. We report a successful treatment with a hybrid endovascular repair for a rapidly expanding thoracoabdominal aneurysm in a 41-year-old woman affected by LDS. To overcome the difficulties of anatomical and surgical repair, we applied an original strategy using surgeon-modified fenestrated endografts. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Repairing organs: lessons from intestine and liver.

Science.gov (United States)

Gehart, Helmuth; Clevers, Hans

2015-06-01

The concept of organ regeneration has fascinated humanity from ancient mythology to modern science fiction. Recent advances offer the potential to soon bring such technology within the grasp of clinical medicine. Rapidly expanding insights into the intrinsic repair processes of the intestine and liver have uncovered significant plasticity in epithelial tissues. Harnessing this knowledge, researchers have recently created culture systems that enable the expansion of stem cells into transplantable tissue in vitro. Here we discuss how the growing tool set of stem cell biology can bring organ repair from fictitious narrative to medical practice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evolution of Autologous Chondrocyte Repair and Comparison to Other Cartilage Repair Techniques

Directory of Open Access Journals (Sweden)

Ashvin K. Dewan

2014-01-01

Full Text Available Articular cartilage defects have been addressed using microfracture, abrasion chondroplasty, or osteochondral grafting, but these strategies do not generate tissue that adequately recapitulates native cartilage. During the past 25 years, promising new strategies using assorted scaffolds and cell sources to induce chondrocyte expansion have emerged. We reviewed the evolution of autologous chondrocyte implantation and compared it to other cartilage repair techniques. Methods. We searched PubMed from 1949 to 2014 for the keywords “autologous chondrocyte implantation” (ACI and “cartilage repair” in clinical trials, meta-analyses, and review articles. We analyzed these articles, their bibliographies, our experience, and cartilage regeneration textbooks. Results. Microfracture, abrasion chondroplasty, osteochondral grafting, ACI, and autologous matrix-induced chondrogenesis are distinguishable by cell source (including chondrocytes and stem cells and associated scaffolds (natural or synthetic, hydrogels or membranes. ACI seems to be as good as, if not better than, microfracture for repairing large chondral defects in a young patient’s knee as evaluated by multiple clinical indices and the quality of regenerated tissue. Conclusion. Although there is not enough evidence to determine the best repair technique, ACI is the most established cell-based treatment for full-thickness chondral defects in young patients.

[Role of connective tissue growth factor (CTGF) in proliferation and migration of pancreatic cancer cells].

Science.gov (United States)

Bai, Yu-chun; Kang, Quan; Luo, Qing; Wu, Dao-qi; Ye, Wei-xia; Lin, Xue-mei; Zhao, Yong

2011-10-01

To explore the expression of connective tissue growth factor (CTGF) in pancreatic cancer and its influence on the proliferation and migration of cancer cells. The expression of CTGF in pancreatic cell line PANC-1 cells was analyzed by real-time PCR and in pancreatic carcinoma (50 cases) tissues by immunohistochemistry. The ability of proliferation and migration in vitro of PANC-1 cells was tested by MTT assay, scratch test and Boyden chamber test after the CTGF gene was overexpressed by Ad5-CTGF or silenced with Ad5-siCTGF transfection. CTGF was overexpressed in both pancreatic cancer cells and tissues. Overxpression of CTGF leads to increased proliferation and migration of PANC-1 cells. The CTGF-transfected PANC-1 cells showed apparent stronger proliferation ability and scratch-repair ability than that of empty vector controls. The results of Boyden chamber test showed that there were 34 cells/field (200× magnificantion) of the CTGF-transfected overexpressing cells, much more than the 11 cells/field of the empty vector control cells; and 6 cells/microscopic field of the Ad5-siCTGF-transfected silenced cells, much less than the 15 cells/field of the control cells. CTGF is overexpressed in both pancreatic cancer cells in vitro and in vivo, indicating that it may play an important role in the cell proliferation and migration in pancreatic cancer.

Harnessing the potential of biomaterials for brain repair after stroke

Science.gov (United States)

Tuladhar, Anup; Payne, Samantha L.; Shoichet, Molly S.

2018-03-01

Stroke is a devastating disease for which no clinical treatment exists to regenerate lost tissue. Strategies for brain repair in animal models of stroke include the delivery of drug or cell-based therapeutics; however, the complex anatomy and functional organization of the brain presents many challenges. Biomaterials may alleviate some of these challenges by providing a scaffold, localizing the therapy to the site of action, and/or modulating cues to brain cells. Here, the challenges associated with delivery of therapeutics to the brain and the biomaterial strategies used to overcome these challenges are described. For example, innovative hydrogel delivery systems have been designed to provide sustained trophic factor delivery for endogenous repair and to support transplanted cell survival and integration. Novel treatments, such as electrical stimulation of transplanted cells and the delivery of factors for the direct reprogramming of astrocytes into neurons, may be further enhanced by biomaterial delivery systems. Ultimately, improved clinical translation will be achieved by combining clinically relevant therapies with biomaterials strategies.

Neutron kerma factors, and water equivalence of some tissue substitutes

International Nuclear Information System (INIS)

Singh, V. P.; Badiger, N. M.; Vega C, H. R.

2014-08-01

The kerma factors and kerma relative to air and water of 24 compounds used as tissue substitutes were calculated for neutron energy from 2.53 x 10 -8 up to 29 MeV. The kerma ratio of the tissue substitutes relative to air and water were calculated by the ratio of kerma factors of the tissue substitute to air and water respectively. The water equivalence of the selected tissue substitutes was observed above neutron energies 100 eV. Kerma ratio relative to the air for Poly-vinylidene fluoride and Teflon are found to be nearest to unity in very low energy (up to 1 eV) and above 63 eV respectively. It was found that the natural rubber as a water equivalent tissue substitute compound. The results of the kerma factors in our investigation shows a very good agreement with those published in ICRU-44. We found that at higher neutron energies, the kerma factors and kerma ratios of the selected tissue substitute compounds are approximately same, but differences are large for energies below 100 eV. (Author)

Recurrent tricuspid insufficiency: is the surgical repair technique a risk factor?

Science.gov (United States)

Kara, Ibrahim; Koksal, Cengiz; Cakalagaoglu, Canturk; Sahin, Muslum; Yanartas, Mehmet; Ay, Yasin; Demir, Serdar

2013-01-01

This study compares the medium-term results of De Vega, modified De Vega, and ring annuloplasty techniques for the correction of tricuspid insufficiency and investigates the risk factors for recurrent grades 3 and 4 tricuspid insufficiency after repair. In our clinic, 93 patients with functional tricuspid insufficiency underwent surgical tricuspid repair from May 2007 through October 2010. The study was retrospective, and all the data pertaining to the patients were retrieved from hospital records. Functional capacity, recurrent tricuspid insufficiency, and risk factors aggravating the insufficiency were analyzed for each patient. In the medium term (25.4 ± 10.3 mo), the rates of grades 3 and 4 tricuspid insufficiency in the De Vega, modified De Vega, and ring annuloplasty groups were 31%, 23.1%, and 6.1%, respectively. Logistic regression analysis revealed that chronic obstructive pulmonary disease, left ventricular dysfunction (ejection fraction, tricuspid insufficiency. Medium-term survival was 90.6% for the De Vega group, 96.3% for the modified De Vega group, and 97.1% for the ring annuloplasty group. Ring annuloplasty provided the best relief from recurrent tricuspid insufficiency when compared with DeVega annuloplasty. Modified De Vega annuloplasty might be a suitable alternative to ring annuloplasty when rings are not available.

Engineering a multimodal nerve conduit for repair of injured peripheral nerve

Science.gov (United States)

Quigley, A. F.; Bulluss, K. J.; Kyratzis, I. L. B.; Gilmore, K.; Mysore, T.; Schirmer, K. S. U.; Kennedy, E. L.; O'Shea, M.; Truong, Y. B.; Edwards, S. L.; Peeters, G.; Herwig, P.; Razal, J. M.; Campbell, T. E.; Lowes, K. N.; Higgins, M. J.; Moulton, S. E.; Murphy, M. A.; Cook, M. J.; Clark, G. M.; Wallace, G. G.; Kapsa, R. M. I.

2013-02-01

Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate

Cell Based Meniscal Repair Using an Aligned Bioactive Nanofibrous Sheath

Science.gov (United States)

2017-07-01

to subsequently guide tissue regeneration , for example, by seeded tissue progenitor cells . To achieve this objective, the first step is to develop...AWARD NUMBER: W81XWH-15-1-0104 TITLE: Cell -Based Meniscal Repair Using an Aligned Bioactive Nanofibrous Sheath PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER Cell -Based Meniscal Repair Using an Aligned Bioactive Nanofibrous Sheath 5b. GRANT NUMBER W81XWH-15-1-0104 5c. PROGRAM

Transport of beta-aminopropionitrile through intact skin or scar tissue

International Nuclear Information System (INIS)

Gibeault, J.D.; Cravens, R.B. Jr.; Chvapil, M.

1989-01-01

A lathyrogen, [ 14 C]aminopropionitrile (beta APN), was administered to 34 rats either in K-Y jelly or saline vehicles onto intact shaven skin or onto a healed splinted deep excision wound. The dynamics of beta APN transport and content in the skin or repair tissue was observed after 2, 5, 8, and 24 hr of topical administration. The repair tissue quickly absorbed the lathyrogen and reached maximum at the 2-hr sampling. The content of beta APN in the repair tissue was twice as high as that in K-Y jelly vehicle and remained high and stable for at least 24 hr only when beta APN was administered through a saline vehicle. The transport of beta APN through intact skin, irrespective of the vehicle tested, was slow and continuously increased. The study showed that almost 20% of the beta APN administered onto the wounded skin area was transported into the repair tissue within 2 hr. We suggest that, due to the absence of epidermal stratum corneum from the repair tissue, drugs, such as beta APN, penetrate quickly into the wound

Platelet-rich plasma, plasma rich in growth factors and simvastatin in the regeneration and repair of alveolar bone.

Science.gov (United States)

Rivera, César; Monsalve, Francisco; Salas, Juan; Morán, Andrea; Suazo, Iván

2013-12-01

Platelet preparations promote bone regeneration by inducing cell migration, proliferation and differentiation in the area of the injury, which are essential processes for regeneration. In addition, several studies have indicated that simvastatin (SIMV), widely used for the treatment of hypercholesterolemia, stimulates osteogenesis. The objective of this study was to evaluate the effects of treatment with either platelet-rich plasma (PRP) or plasma rich in growth factors (PRGF) in combination with SIMV in the regeneration and repair of alveolar bone. The jaws of Sprague Dawley rats (n=18) were subjected to rotary instrument-induced bone damage (BD). Animals were divided into six groups: BD/H 2 O (n=3), distilled water without the drug and alveolar bone damage; BD/H 2 O/PRP (n=3), BD and PRP; BD/H 2 O/PRGF (n=3), BD and PRGF; BD/SIMV (n=3), BD and water with SIMV; BD/SIMV/PRP (n=3), BD, PRP and SIMV; and BD/SIMV/PRGF (n=3), BD, PRGF and SIMV. Conventional histological analysis (hematoxylin and eosin staining) revealed that the BD/SIMV group showed indicators for mature bone tissue, while the BD/SIMV/PRP and BD/SIMV/PRGF groups showed the coexistence of indicators for mature and immature bone tissue, with no statistical differences between the platelet preparations. Simvastatin did not improve the effect of platelet-rich plasma and plasma rich in growth factors. It was not possible to determine which platelet preparation produced superior effects.

Local delivery of glial cell line-derived neurotrophic factor improves facial nerve regeneration after late repair.

Science.gov (United States)

Barras, Florian M; Kuntzer, Thierry; Zurn, Anne D; Pasche, Philippe

2009-05-01

Facial nerve regeneration is limited in some clinical situations: in long grafts, by aged patients, and when the delay between nerve lesion and repair is prolonged. This deficient regeneration is due to the limited number of regenerating nerve fibers, their immaturity and the unresponsiveness of Schwann cells after a long period of denervation. This study proposes to apply glial cell line-derived neurotrophic factor (GDNF) on facial nerve grafts via nerve guidance channels to improve the regeneration. Two situations were evaluated: immediate and delayed grafts (repair 7 months after the lesion). Each group contained three subgroups: a) graft without channel, b) graft with a channel without neurotrophic factor; and c) graft with a GDNF-releasing channel. A functional analysis was performed with clinical observation of facial nerve function, and nerve conduction study at 6 weeks. Histological analysis was performed with the count of number of myelinated fibers within the graft, and distally to the graft. Central evaluation was assessed with Fluoro-Ruby retrograde labeling and Nissl staining. This study showed that GDNF allowed an increase in the number and the maturation of nerve fibers, as well as the number of retrogradely labeled neurons in delayed anastomoses. On the contrary, after immediate repair, the regenerated nerves in the presence of GDNF showed inferior results compared to the other groups. GDNF is a potent neurotrophic factor to improve facial nerve regeneration in grafts performed several months after the nerve lesion. However, GDNF should not be used for immediate repair, as it possibly inhibits the nerve regeneration.

Electrical stimulation enhances cell migration and integrative repair in the meniscus

Science.gov (United States)

Yuan, Xiaoning; Arkonac, Derya E.; Chao, Pen-hsiu Grace; Vunjak-Novakovic, Gordana

2014-01-01

Electrical signals have been applied towards the repair of articular tissues in the laboratory and clinical settings for over seventy years. We focus on healing of the meniscus, a tissue essential to knee function with limited innate repair potential, which has been largely unexplored in the context of electrical stimulation. Here we demonstrate for the first time that electrical stimulation enhances meniscus cell migration and integrative tissue repair. We optimize pulsatile direct current electrical stimulation parameters on cells at the micro-scale, and apply these to healing of full-thickness defects in explants at the macro-scale. We report increased expression of the adenosine A2b receptor in meniscus cells after stimulation at the micro- and macro-scale, and propose a role for A2bR in meniscus electrotransduction. Taken together, these findings advance our understanding of the effects of electrical signals and their mechanisms of action, and contribute to developing electrotherapeutic strategies for meniscus repair. PMID:24419206

A two-compartment mechanochemical model of the roles of transforming growth factor and tissue tension in dermal wound healing

KAUST Repository

Murphy, Kelly E.

2011-03-01

The repair of dermal tissue is a complex process of interconnected phenomena, where cellular, chemical and mechanical aspects all play a role, both in an autocrine and in a paracrine fashion. Recent experimental results have shown that transforming growth factor -β (TGF β) and tissue mechanics play roles in regulating cell proliferation, differentiation and the production of extracellular materials. We have developed a 1D mathematical model that considers the interaction between the cellular, chemical and mechanical phenomena, allowing the combination of TGF β and tissue stress to inform the activation of fibroblasts to myofibroblasts. Additionally, our model incorporates the observed feature of residual stress by considering the changing zero-stress state in the formulation for effective strain. Using this model, we predict that the continued presence of TGF β in dermal wounds will produce contractures due to the persistence of myofibroblasts; in contrast, early elimination of TGF β significantly reduces the myofibroblast numbers resulting in an increase in wound size. Similar results were obtained by varying the rate at which fibroblasts differentiate to myofibroblasts and by changing the myofibroblast apoptotic rate. Taken together, the implication is that elevated levels of myofibroblasts is the key factor behind wounds healing with excessive contraction, suggesting that clinical strategies which aim to reduce the myofibroblast density may reduce the appearance of contractures. © 2010 Elsevier Ltd.

A two-compartment mechanochemical model of the roles of transforming growth factor and tissue tension in dermal wound healing

KAUST Repository

Murphy, Kelly E.; Hall, Cameron L.; McCue, Scott W.; Sean McElwain, D.L.

2011-01-01

The repair of dermal tissue is a complex process of interconnected phenomena, where cellular, chemical and mechanical aspects all play a role, both in an autocrine and in a paracrine fashion. Recent experimental results have shown that transforming growth factor -β (TGF β) and tissue mechanics play roles in regulating cell proliferation, differentiation and the production of extracellular materials. We have developed a 1D mathematical model that considers the interaction between the cellular, chemical and mechanical phenomena, allowing the combination of TGF β and tissue stress to inform the activation of fibroblasts to myofibroblasts. Additionally, our model incorporates the observed feature of residual stress by considering the changing zero-stress state in the formulation for effective strain. Using this model, we predict that the continued presence of TGF β in dermal wounds will produce contractures due to the persistence of myofibroblasts; in contrast, early elimination of TGF β significantly reduces the myofibroblast numbers resulting in an increase in wound size. Similar results were obtained by varying the rate at which fibroblasts differentiate to myofibroblasts and by changing the myofibroblast apoptotic rate. Taken together, the implication is that elevated levels of myofibroblasts is the key factor behind wounds healing with excessive contraction, suggesting that clinical strategies which aim to reduce the myofibroblast density may reduce the appearance of contractures. © 2010 Elsevier Ltd.

Tissue-engineered rhesus monkey nerve grafts for the repair of long ulnar nerve defects: similar outcomes to autologous nerve grafts

Directory of Open Access Journals (Sweden)

Chang-qing Jiang

2016-01-01

Full Text Available Acellular nerve allografts can help preserve normal nerve structure and extracellular matrix composition. These allografts have low immunogenicity and are more readily available than autologous nerves for the repair of long-segment peripheral nerve defects. In this study, we repaired a 40-mm ulnar nerve defect in rhesus monkeys with tissue-engineered peripheral nerve, and compared the outcome with that of autograft. The graft was prepared using a chemical extract from adult rhesus monkeys and seeded with allogeneic Schwann cells. Pathomorphology, electromyogram and immunohistochemistry findings revealed the absence of palmar erosion or ulcers, and that the morphology and elasticity of the hypothenar eminence were normal 5 months postoperatively. There were no significant differences in the mean peak compound muscle action potential, the mean nerve conduction velocity, or the number of neurofilaments between the experimental and control groups. However, outcome was significantly better in the experimental group than in the blank group. These findings suggest that chemically extracted allogeneic nerve seeded with autologous Schwann cells can repair 40-mm ulnar nerve defects in the rhesus monkey. The outcomes are similar to those obtained with autologous nerve graft.

Tissue-engineered rhesus monkey nerve gratfs for the repair of long ulnar nerve defects：similar outcomes to autologous nerve gratfs

Institute of Scientific and Technical Information of China (English)

Chang-qing Jiang; Jun Hu; Jian-ping Xiang; Jia-kai Zhu; Xiao-lin Liu; Peng Luo

2016-01-01

Acellular nerve allogratfs can help preserve normal nerve structure and extracellular matrix composition. These allogratfs have low immu-nogenicity and are more readily available than autologous nerves for the repair of long-segment peripheral nerve defects. In this study, we repaired a 40-mm ulnar nerve defect in rhesus monkeys with tissue-engineered peripheral nerve, and compared the outcome with that of autogratf. The gratf was prepared using a chemical extract from adult rhesus monkeys and seeded with allogeneic Schwann cells. Pathomo-rphology, electromyogram and immunohistochemistry ifndings revealed the absence of palmar erosion or ulcers, and that the morphology and elasticity of the hypothenar eminence were normal 5 months postoperatively. There were no signiifcant differences in the mean peak compound muscle action potential, the mean nerve conduction velocity, or the number of neuroiflaments between the experimental and control groups. However, outcome was signiifcantly better in the experimental group than in the blank group. These ifndings suggest that chemically extracted allogeneic nerve seeded with autologous Schwann cells can repair 40-mm ulnar nerve defects in the rhesus monkey. The outcomes are similar to those obtained with autologous nerve gratf.

MR imaging of cartilage and its repair in the knee - a review

International Nuclear Information System (INIS)

Trattnig, S.; Welsch, G.W.; Domayer, S.; Mosher, T.; Eckstein, F.

2009-01-01

Chondral injuries are common lesions of the knee joint, and many patients could benefit from cartilage repair. Widespread cartilage repair techniques require sophisticated noninvasive follow-up using MRI. In addition to the precise morphological assessment of this area of cartilage repair, the cartilage's biochemical constitution can be determined using biochemical MRI techniques. The combination of the clinical outcome after cartilage repair together with the morphological and biochemical description of the cartilage repair tissue as well as the surrounding cartilage can lead to an optimal follow-up evaluation. The present article on MR imaging techniques of cartilage repair focuses on morphological description and scoring using techniques from conventional 2D through advanced isotropic 3D MRI sequences. Furthermore the ultrastructure of the repair tissue and the surrounding cartilage is evaluated in-vivo by biochemical T1-delayed gadolinium enhanced MRI of cartilage (dGEMRIC), T2 relaxation, and diffusion-weighted imaging techniques. (orig.)

The influence of combined treatment of Cd, and γ-irradiation on DNA damage and repair in lymphoid tissues of mice

International Nuclear Information System (INIS)

Privezentsev, K.V.; Sirota, N.P.; Gaziev, A.I.

1996-01-01

The effect of combined treatment of Cd and γ-irradiation on DNA damage and repair was studied in lymphoid tissues of mice using single-cell gel assay. Single i.p. injection of CdCl 2 (1 mg Cd/kg body wt), 2 h prior to irradiation resulted in increasing of DNA lesions in peripheral blood lymphocytes (PBL) when compared to non-injected animals. However, the same treatment, 48 h prior to irradiation is shown to decrease DNA damage in PBL and splenocytes in comparison with untreated mice. In thymocytes maximal protective effect of Cd was determined when mice were irradiated in 24 h after injection. The protective effect observed is due to decreasing of initial level of DNA damage in thymocytes as well as acceleration of DNA repair in PBL and splenocytes. 28 refs.; 2 figs

rhPDGF-BB promotes early healing in a rat rotator cuff repair model.

Science.gov (United States)

Kovacevic, David; Gulotta, Lawrence V; Ying, Liang; Ehteshami, John R; Deng, Xiang-Hua; Rodeo, Scott A

2015-05-01

Tendon-bone healing after rotator cuff repair occurs by fibrovascular scar tissue formation, which is weaker than a normal tendon-bone insertion site. Growth factors play a role in tissue formation and have the potential to augment soft tissue healing in the perioperative period. Our study aim was to determine if rhPDGF-BB delivery on a collagen scaffold can improve tendon-to-bone healing after supraspinatus tendon repair compared with no growth factor in rats as measured by (1) gross observations; (2) histologic analysis; and (3) biomechanical testing. Ninety-five male Sprague-Dawley rats underwent acute repair of the supraspinatus tendon. Rats were randomized into one of five groups: control (ie, repair only), scaffold only, and three different platelet-derived growth factor (PDGF) doses on the collagen scaffold. Animals were euthanized 5 days after surgery to assess cellular proliferation and angiogenesis. The remaining animals were analyzed at 4 weeks to assess repair site integrity by gross visualization, fibrocartilage formation with safranin-O staining, and collagen fiber organization with picrosirius red staining, and to determine the biomechanical properties (ie, load-to-failure testing) of the supraspinatus tendon-bone construct. The repaired supraspinatus tendon was in continuity with the bone in all animals. At 5 days, rhPDGF-BB delivery on a scaffold demonstrated a dose-dependent response in cellular proliferation and angiogenesis compared with the control and scaffold groups. At 28 days, with the numbers available, rhPDGF-BB had no effect on increasing fibrocartilage formation or improving collagen fiber maturity at the tendon-bone insertion site compared with controls. The control group had higher tensile loads to failure and stiffness (35.5 ± 8.8 N and 20.3 ± 4.5 N/mm) than all the groups receiving the scaffold, including the PDGF groups (scaffold: 27 ± 6.4 N, p = 0.021 and 13 ± 5.7 N/mm, p = 0.01; 30 µg/mL PDGF: 26.5 ± 7.5 N, p = 0.014 and 13

18.2.3 Current Concepts on Tissue Engineering for Meniscus Repair

OpenAIRE

Mandelbaum, B.; Roos, H.; Shive, M.S.; Hambly, K.; Mithoefer, K.; Della Villa, S.; Silvers, H.J.; Hambly, K.; Fontana, A.; Dalemans, W.; Celis, P.; Brittberg, M.; Marcacci, M.; Kon, E.; Delcogliano, M.

2009-01-01

Introduction Articular cartilage lesions are a common pathology of the knee joint and many patients could benefit from cartilage repair. Untreated, however, cartilage defects may lead to osteoarthritis (OA). Thus, surgical treatment options may offer a possibility for patients with cartilage defects to avoid OA or to delay the progression of OA. Therefore, cartilage repair techniques require sophisticated follow-up, if possible non-invasively. Although clinical findings are the primary criter...

Repair mechanism of retinal pigment epithelial tears in age-related macular degeneration.

Science.gov (United States)

Mukai, Ryo; Sato, Taku; Kishi, Shoji

2015-03-01

To investigate repair mechanisms of retinal pigment epithelial (RPE) tears in age-related macular degeneration. The authors retrospectively studied 10 eyes with age-related macular degeneration that developed RPE tears during follow-up or after treatment with an anti-vascular endothelial growth factor drug or photodynamic therapy combined with ranibizumab. After development of the RPE tears, all follow-ups exceeded 13 months. Spectral domain or swept-source optical coherence tomography have been used to examine consecutive retinal changes where the RPE tears developed and attempted to determine the repair mechanisms. Retinal pigment epithelial tears developed during the natural course (n = 4) after ranibizumab treatment (n = 2) and after photodynamic therapy and ranibizumab (n = 4). Subretinal fluid persisted for more than 6 months after the RPE tears developed (n = 4), with the area where the RPE was lost found to be covered with thickened proliferative tissue. In 6 eyes where the subretinal fluid was absorbed within 2 months, optical coherence tomography showed the outer retina appeared to be directly attached to Bruch membrane, and there was attenuation of the normal hyperreflective band attributable to normal RPE during follow-up. Results suggest that two repair processes may be present in the area where RPE tears developed. Persistent subretinal fluid may lead to repair with thick proliferative tissue, while the outer retina appears to attach to Bruch membrane when there is early subretinal fluid resolution after RPE tear development.

Effects of in vitro low oxygen tension preconditioning of adipose stromal cells on their in vivo chondrogenic potential: application in cartilage tissue repair.

Directory of Open Access Journals (Sweden)

Sophie Portron

Full Text Available PURPOSE: Multipotent stromal cell (MSC-based regenerative strategy has shown promise for the repair of cartilage, an avascular tissue in which cells experience hypoxia. Hypoxia is known to promote the early chondrogenic differentiation of MSC. The aim of our study was therefore to determine whether low oxygen tension could be used to enhance the regenerative potential of MSC for cartilage repair. METHODS: MSC from rabbit or human adipose stromal cells (ASC were preconditioned in vitro in control or chondrogenic (ITS and TGF-β medium and in 21 or 5% O2. Chondrogenic commitment was monitored by measuring COL2A1 and ACAN expression (real-time PCR. Preconditioned rabbit and human ASC were then incorporated into an Si-HPMC hydrogel and injected (i into rabbit articular cartilage defects for 18 weeks or (ii subcutaneously into nude mice for five weeks. The newly formed tissue was qualitatively and quantitatively evaluated by cartilage-specific immunohistological staining and scoring. The phenotype of ASC cultured in a monolayer or within Si-HPMC in control or chondrogenic medium and in 21 or 5% O2 was finally evaluated using real-time PCR. RESULTS/CONCLUSIONS: 5% O2 increased the in vitro expression of chondrogenic markers in ASC cultured in induction medium. Cells implanted within Si-HPMC hydrogel and preconditioned in chondrogenic medium formed a cartilaginous tissue, regardless of the level of oxygen. In addition, the 3D in vitro culture of ASC within Si-HPMC hydrogel was found to reinforce the pro-chondrogenic effects of the induction medium and 5% O2. These data together indicate that although 5% O2 enhances the in vitro chondrogenic differentiation of ASC, it does not enhance their in vivo chondrogenesis. These results also highlight the in vivo chondrogenic potential of ASC and their potential value in cartilage repair.

Low rate of reoperations after acute type A aortic dissection repair from The Nordic Consortium Registry

DEFF Research Database (Denmark)

Pan, Emily; Gudbjartsson, Tomas; Ahlsson, Anders

2018-01-01

Bakey classification nor the extent of proximal or distal repair predicted freedom from a later reoperation. The only independent risk factor associated with a later proximal reoperation was a history of connective tissue disease. CONCLUSIONS: Type A aortic dissection repair in low- to medium-volume centers......OBJECTIVES: To describe the relationship between the extent of primary aortic repair and the incidence of reoperations after surgery for type A aortic dissection. METHODS: A retrospective cohort of 1159 patients treated for type A aortic dissection at eight Nordic low- to medium......-sized cardiothoracic centers from 2005 to 2014. Data were gathered from patient records and national registries. Patients were separately divided into 3 groups according to the distal anastomoses technique (ascending aorta [n = 791], hemiarch [n = 247], and total arch [n = 66]), and into 2 groups for proximal repair...

Engineered Heart Repair.

Science.gov (United States)

Fujita, B; Zimmermann, W-H

2017-08-01

There is a pressing need for the development of advanced heart failure therapeutics. Current state-of-the-art is protection from neurohumoral overstimulation, which fails to address the underlying cause of heart failure, namely loss of cardiomyocytes. Implantation of stem cell-derived cardiomyocytes via tissue-engineered myocardium is being advanced to realize the remuscularization of the failing heart. Here, we discuss pharmacological challenges pertaining to the clinical translation of tissue-engineered heart repair with a focus on engineered heart muscle (EHM). © 2017 American Society for Clinical Pharmacology and Therapeutics.

Opportunities and Challenges for Repair of Macrovascular Disease using Circulating Blood-Derived Progenitor Cells

OpenAIRE

Loeken, Mary R.

2014-01-01

There are currently few solutions for diabetic vascular disease that involve repair of damaged tissues. The manuscript by Porat, et al., suggests a possible method to use a patient’s own circulating blood cells to provide progenitors to repair damaged vascular tissues.

Osteocalcin expressing cells from tendon sheaths in mice contribute to tendon repair by activating Hedgehog signaling

OpenAIRE

Wang, Yi; Zhang, Xu; Huang, Huihui; Xia, Yin; Yao, YiFei; Mak, Arthur Fuk-Tat; Yung, Patrick Shu-Hang; Chan, Kai-Ming; Wang, Li; Zhang, Chenglin; Huang, Yu; Mak, Kingston King-Lun

2017-01-01

Both extrinsic and intrinsic tissues contribute to tendon repair, but the origin and molecular functions of extrinsic tissues in tendon repair are not fully understood. Here we show that tendon sheath cells harbor stem/progenitor cell properties and contribute to tendon repair by activating Hedgehog signaling. We found that Osteocalcin (Bglap) can be used as an adult tendon-sheath-specific marker in mice. Lineage tracing experiments show that Bglap-expressing cells in adult sheath tissues pos...

Chitosan and Its Potential Use as a Scaffold for Tissue Engineering in Regenerative Medicine

Science.gov (United States)

Rodríguez-Vázquez, Martin; Vega-Ruiz, Brenda; Ramos-Zúñiga, Rodrigo; Saldaña-Koppel, Daniel Alexander; Quiñones-Olvera, Luis Fernando

2015-01-01

Tissue engineering is an important therapeutic strategy to be used in regenerative medicine in the present and in the future. Functional biomaterials research is focused on the development and improvement of scaffolding, which can be used to repair or regenerate an organ or tissue. Scaffolds are one of the crucial factors for tissue engineering. Scaffolds consisting of natural polymers have recently been developed more quickly and have gained more popularity. These include chitosan, a copolymer derived from the alkaline deacetylation of chitin. Expectations for use of these scaffolds are increasing as the knowledge regarding their chemical and biological properties expands, and new biomedical applications are investigated. Due to their different biological properties such as being biocompatible, biodegradable, and bioactive, they have given the pattern for use in tissue engineering for repair and/or regeneration of different tissues including skin, bone, cartilage, nerves, liver, and muscle. In this review, we focus on the intrinsic properties offered by chitosan and its use in tissue engineering, considering it as a promising alternative for regenerative medicine as a bioactive polymer. PMID:26504833

Stem cell death and survival in heart regeneration and repair.

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Abdelwahid, Eltyeb; Kalvelyte, Audrone; Stulpinas, Aurimas; de Carvalho, Katherine Athayde Teixeira; Guarita-Souza, Luiz Cesar; Foldes, Gabor

2016-03-01

Cardiovascular diseases are major causes of mortality and morbidity. Cardiomyocyte apoptosis disrupts cardiac function and leads to cardiac decompensation and terminal heart failure. Delineating the regulatory signaling pathways that orchestrate cell survival in the heart has significant therapeutic implications. Cardiac tissue has limited capacity to regenerate and repair. Stem cell therapy is a successful approach for repairing and regenerating ischemic cardiac tissue; however, transplanted cells display very high death percentage, a problem that affects success of tissue regeneration. Stem cells display multipotency or pluripotency and undergo self-renewal, however these events are negatively influenced by upregulation of cell death machinery that induces the significant decrease in survival and differentiation signals upon cardiovascular injury. While efforts to identify cell types and molecular pathways that promote cardiac tissue regeneration have been productive, studies that focus on blocking the extensive cell death after transplantation are limited. The control of cell death includes multiple networks rather than one crucial pathway, which underlies the challenge of identifying the interaction between various cellular and biochemical components. This review is aimed at exploiting the molecular mechanisms by which stem cells resist death signals to develop into mature and healthy cardiac cells. Specifically, we focus on a number of factors that control death and survival of stem cells upon transplantation and ultimately affect cardiac regeneration. We also discuss potential survival enhancing strategies and how they could be meaningful in the design of targeted therapies that improve cardiac function.

[Aesthetic effect of wound repair with flaps].

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Tan, Qian; Zhou, Hong-Reng; Wang, Shu-Qin; Zheng, Dong-Feng; Xu, Peng; Wu, Jie; Ge, Hua-Qiang; Lin, Yue; Yan, Xin

2012-08-01

To investigate the aesthetic effect of wound repair with flaps. One thousand nine hundred and ninety-six patients with 2082 wounds hospitalized from January 2004 to December 2011. These wounds included 503 deep burn wounds, 268 pressure sores, 392 soft tissue defects caused by trauma, 479 soft tissue defects due to resection of skin cancer and mole removal, 314 soft tissue defects caused by scar excision, and 126 other wounds. Wound area ranged from 1.5 cm x 1.0 cm to 30.0 cm x 22.0 cm. Sliding flaps, expanded flaps, pedicle flaps, and free flaps were used to repair the wounds in accordance with the principle and timing of wound repair with flaps. Five flaps showed venous congestion within 48 hours post-operation, 2 flaps of them improved after local massage. One flap survived after local heparin wet packing and venous bloodletting. One flap survived after emergency surgical embolectomy and bridging with saphenous vein graft. One flap showed partial necrosis and healed after skin grafting. The other flaps survived well. One thousand three hundred and twenty-one patients were followed up for 3 months to 2 years, and flaps of them were satisfactory in shape, color, and elasticity, similar to that of normal skin. Some patients underwent scar revision later with good results. Application of suitable flaps in wound repair will result in quick wound healing, good function recovery, and satisfactory aesthetic effect.

Repair-modification of radiodamaged genes

International Nuclear Information System (INIS)

Volpe, P.; Institute of Experimental Medicine, Rome; Eremenko, T.

1995-01-01

It is proposed that through repair-modification, the modified base 5mC may have facilitated the divergent evolution of coding (hypomethylated exon) and uncoding (hypermethylated promoter and intron) sequences in eukaryotic genes. The radioinduced repair patches appearing in regions lacking 5mC are fully reconstructed by excision-repair, whereas those appearing in regions containing 5mC are incompletely reconstructed by this conventional mechanism. Such a second class of repair patches may, however, become fully reconstructed, in the S phase, by repair-modification. In fact, while DNA polymerase β - which is a key enzyme of excision-repair - is active through the whole interphase. DNA methylase - which is responsible for post-synthetic DNA modification - is essentially active in S. Uncoupling of these two enzyme systems, outside S, might explain why in unsynchronised cells repair patches of non-replicating strands are hypomethylated when compared with specific methylation of replicating strands. In other words, excision-repair would always be able to re-establish the primary ATGC language of both damaged unmethylated and methylated regions, while repair-modification would be able to re-establish the modified ATGC(5mC) language of the damaged methylated regions, only in S, but not in G 1 or G 2 . In these two phases, when DNA methylation is inversely correlated with pre-mRNA transcription (as in the case of many tissue-specific genes), such demethylation might induce a silent transcriptional unit to become active. (Author)

Chitinase-like proteins as regulators of innate immunity and tissue repair: helpful lessons for asthma?

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Sutherland, Tara E

2018-02-19

Chitinases and chitinase-like proteins (CLPs) belong to the glycoside hydrolase family 18 of proteins. Chitinases are expressed in mammals and lower organisms, facilitate chitin degradation, and hence act as host-defence enzymes. Gene duplication and loss-of-function mutations of enzymatically active chitinases have resulted in the expression of a diverse range of CLPs across different species. CLPs are genes that are increasingly associated with inflammation and tissue remodelling not only in mammals but also across distant species. While the focus has remained on understanding the functions and expression patterns of CLPs during disease in humans, studies in mouse and lower organisms have revealed important and overlapping roles of the CLP family during physiology, host defence and pathology. This review will summarise recent insights into the regulatory functions of CLPs on innate immune pathways and discuss how these effects are not only important for host defence and tissue injury/repair after pathogen invasion, but also how they have extensive implications for pathological processes involved in diseases such as asthma. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Quantitative Methods for Measuring Repair Rates and Innate-Immune Cell Responses in Wounded Mouse Skin

Directory of Open Access Journals (Sweden)

Zhi Li

2018-02-01

Full Text Available In skin wounds, innate-immune cells clear up tissue debris and microbial contamination, and also secrete cytokines and other growth factors that impact repair process such as re-epithelialization and wound closure. After injury, there is a rapid influx and efflux of immune cells at wound sites, yet the function of each innate cell population in skin repair is still under investigation. Flow cytometry is a valuable research tool for detecting and quantifying immune cells; however, in mouse back skin, the difficulty in extracting immune cells from small area of skin due to tissue complexity has made cytometric analysis an underutilized tool. In this paper, we provide detailed methods on the digestion of lesion-specific skin without disrupting antigen expression followed by multiplex cell staining that allows for identification of seven innate-immune populations, including rare subsets such as group-3 innate lymphoid cells (ILC3s, by flow-cytometry analysis. Furthermore, when studying the functions of immune cells to tissue repair an important metric to monitor is size of the wound opening. Normal wounds close steadily albeit at non-linear rates, while slow or stalled wound closure can indicate an underlying problem with the repair process. Calliper measurements are difficult and time-consuming to obtain and can require repeated sedation of experimental animals. We provide advanced methods for measuring of wound openness; digital 3D image capture and semi-automated image processing that allows for unbiased, reliable measurements that can be taken repeatedly over time.

Mechanisms of DNA damage repair in adult stem cells and implications for cancer formation.

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Weeden, Clare E; Asselin-Labat, Marie-Liesse

2018-01-01

Maintenance of genomic integrity in tissue-specific stem cells is critical for tissue homeostasis and the prevention of deleterious diseases such as cancer. Stem cells are subject to DNA damage induced by endogenous replication mishaps or exposure to exogenous agents. The type of DNA lesion and the cell cycle stage will invoke different DNA repair mechanisms depending on the intrinsic DNA repair machinery of a cell. Inappropriate DNA repair in stem cells can lead to cell death, or to the formation and accumulation of genetic alterations that can be transmitted to daughter cells and so is linked to cancer formation. DNA mutational signatures that are associated with DNA repair deficiencies or exposure to carcinogenic agents have been described in cancer. Here we review the most recent findings on DNA repair pathways activated in epithelial tissue stem and progenitor cells and their implications for cancer mutational signatures. We discuss how deep knowledge of early molecular events leading to carcinogenesis provides insights into DNA repair mechanisms operating in tumours and how these could be exploited therapeutically. Copyright © 2017 Elsevier B.V. All rights reserved.

[Ru(bipy)3]2+ nanoparticle-incorporate dental light cure resin to promote photobiomodulation therapy for enhanced vital pulp tissue repair

Science.gov (United States)

Mosca, Rodrigo C.; Young, Nicholas; Zeituni, Carlos A.; Arany, Praveen R.

2018-02-01

The use of nanoparticle on dental light cure resin is not new, currently several compounds (nanoadditives) are used to promote better communication between the restorative material and biological tissues. The interest for this application is growing up to enhance mechanical proprieties to dental tissue cells regeneration. Bioactive nanoparticles and complex compounds with multiple functions are the major target for optimizing the restorative materials. In this work, we incorporate [Ru(bipy)3]2+ nanoparticles, that absorbs energy at 450 nm (blue-light) and emits strongly at 620 nm (red-light), in PLGA Microspheres and insert it in Dental Light Cure Resin to promote the Photobiomodulation Therapy (PBM) effects to accelerate dental pulp repair by in vitro using cytotoxicity and proliferation assay.

A two-compartment mechanochemical model of the roles of transforming growth factor β and tissue tension in dermal wound healing.

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Murphy, Kelly E; Hall, Cameron L; McCue, Scott W; Sean McElwain, D L

2011-03-07

The repair of dermal tissue is a complex process of interconnected phenomena, where cellular, chemical and mechanical aspects all play a role, both in an autocrine and in a paracrine fashion. Recent experimental results have shown that transforming growth factor -β (TGFβ) and tissue mechanics play roles in regulating cell proliferation, differentiation and the production of extracellular materials. We have developed a 1D mathematical model that considers the interaction between the cellular, chemical and mechanical phenomena, allowing the combination of TGFβ and tissue stress to inform the activation of fibroblasts to myofibroblasts. Additionally, our model incorporates the observed feature of residual stress by considering the changing zero-stress state in the formulation for effective strain. Using this model, we predict that the continued presence of TGFβ in dermal wounds will produce contractures due to the persistence of myofibroblasts; in contrast, early elimination of TGFβ significantly reduces the myofibroblast numbers resulting in an increase in wound size. Similar results were obtained by varying the rate at which fibroblasts differentiate to myofibroblasts and by changing the myofibroblast apoptotic rate. Taken together, the implication is that elevated levels of myofibroblasts is the key factor behind wounds healing with excessive contraction, suggesting that clinical strategies which aim to reduce the myofibroblast density may reduce the appearance of contractures. Copyright © 2010 Elsevier Ltd. All rights reserved.

The Application of Corals in Bone Tissue Engineering

Directory of Open Access Journals (Sweden)

Iraj Nabipour

2017-05-01

Full Text Available Natural coral exoskeleton and coralline hydroxyapatite have been used as bone replacement graft for repairing of bone defects in animal models and humans since two decades ago. These bone replacement grafts have an osteoconductive, biodegradable and biocompatible features. Currently, three lines of researches in bone tissue engineering are conducting on corals. Corals have been used for construction of bony composites, stem cells attachments, and the growth factors-scaffold-based approaches. This review have paid to the wide range of coral use in clinical experiments as a bone graft substitute and cell-scaffold-based approaches in bone tissue engineering.

Self-production of tissue factor-coagulation factor VII complex by ovarian cancer cells

OpenAIRE

Yokota, N; Koizume, S; Miyagi, E; Hirahara, F; Nakamura, Y; Kikuchi, K; Ruf, W; Sakuma, Y; Tsuchiya, E; Miyagi, Y

2009-01-01

Background: Thromboembolic events are a major complication in ovarian cancer patients. Tissue factor (TF) is frequently overexpressed in ovarian cancer tissue and correlates with intravascular thrombosis. TF binds to coagulation factor VII (fVII), changing it to its active form, fVIIa. This leads to activation of the extrinsic coagulation cascade. fVII is produced by the liver and believed to be supplied from blood plasma at the site of coagulation. However, we recently showed that ovarian ca...

Combining rhinoplasty with septal perforation repair.

Science.gov (United States)

Foda, Hossam M T; Magdy, Emad A

2006-11-01

A combined septal perforation repair and rhinoplasty was performed in 80 patients presenting with septal perforations (size 1 to 5 cm) and external nasal deformities. The external rhinoplasty approach was used for all cases and the perforation was repaired using bilateral intranasal mucosal advancement flaps with a connective tissue interposition graft in between. Complete closure of the perforation was achieved in 90% of perforations of size up to 3.5 cm and in only 70% of perforations that were larger than 3.5 cm. Cosmetically, 95% were very satisfied with their aesthetic result. The external rhinoplasty approach proved to be very helpful in the process of septal perforation repair especially in large and posteriorly located perforations and in cases where the caudal septal cartilage was previously resected. Our results show that septal perforation repair can be safely combined with rhinoplasty and that some of the routine rhinoplasty maneuvers, such as medial osteotomies and dorsal lowering, could even facilitate the process of septal perforation repair.

Growth factor effects on costal chondrocytes for tissue engineering fibrocartilage

Science.gov (United States)

Johns, D.E.; Athanasiou, K.A.

2010-01-01

Tissue engineered fibrocartilage could become a feasible option for replacing tissues like the knee meniscus or temporomandibular joint disc. This study employed five growth factors insulin-like growth factor-I, transforming growth factor-β1, epidermal growth factor, platelet-derived growth factor-BB, and basic fibroblast growth factor in a scaffoldless approach with costal chondrocytes, attempting to improve biochemical and mechanical properties of engineered constructs. Samples were quantitatively assessed for total collagen, glycosaminoglycans, collagen type I, collagen type II, cells, compressive properties, and tensile properties at two time points. Most treated constructs were worse than the no growth factor control, suggesting a detrimental effect, but the IGF treatment tended to improve the constructs. Additionally, the 6wk time point was consistently better than 3wks, with total collagen, glycosaminoglycans, and aggregate modulus doubling during this time. Further optimization of the time in culture and exogenous stimuli will be important in making a more functional replacement tissue. PMID:18597118

Comparing Biomechanical Properties, Repair Times, and Value of Common Core Flexor Tendon Repairs.

Science.gov (United States)

Chauhan, Aakash; Schimoler, Patrick; Miller, Mark C; Kharlamov, Alexander; Merrell, Gregory A; Palmer, Bradley A

2018-05-01

The aim of the study was to compare biomechanical strength, repair times, and repair values for zone II core flexor tendon repairs. A total of 75 fresh-frozen human cadaveric flexor tendons were harvested from the index through small finger and randomized into one of 5 repair groups: 4-stranded cross-stitch cruciate (4-0 polyester and 4-0 braided suture), 4-stranded double Pennington (2-0 knotless barbed suture), 4-stranded Pennington (4-0 double-stranded braided suture), and 6-stranded modified Lim-Tsai (4-0 looped braided suture). Repairs were measured in situ and their repair times were measured. Tendons were linearly loaded to failure and multiple biomechanical values were measured. The repair value was calculated based on operating room costs, repair times, and suture costs. Analysis of variance (ANOVA) and Tukey post hoc statistical analysis were used to compare repair data. The braided cruciate was the strongest repair ( P > .05) but the slowest ( P > .05), and the 4-stranded Pennington using double-stranded suture was the fastest ( P > .05) to perform. The total repair value was the highest for braided cruciate ( P > .05) compared with all other repairs. Barbed suture did not outperform any repairs in any categories. The braided cruciate was the strongest of the tested flexor tendon repairs. The 2-mm gapping and maximum load to failure for this repair approached similar historical strength of other 6- and 8-stranded repairs. In this study, suture cost was negligible in the overall repair cost and should be not a determining factor in choosing a repair.

Three-Dimensional Printing and Cell Therapy for Wound Repair.

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van Kogelenberg, Sylvia; Yue, Zhilian; Dinoro, Jeremy N; Baker, Christopher S; Wallace, Gordon G

2018-05-01

Significance: Skin tissue damage is a major challenge and a burden on healthcare systems, from burns and other trauma to diabetes and vascular disease. Although the biological complexities are relatively well understood, appropriate repair mechanisms are scarce. Three-dimensional bioprinting is a layer-based approach to regenerative medicine, whereby cells and cell-based materials can be dispensed in fine spatial arrangements to mimic native tissue. Recent Advances: Various bioprinting techniques have been employed in wound repair-based skin tissue engineering, from laser-induced forward transfer to extrusion-based methods, and with the investigation of the benefits and shortcomings of each, with emphasis on biological compatibility and cell proliferation, migration, and vitality. Critical issues: Development of appropriate biological inks and the vascularization of newly developed tissues remain a challenge within the field of skin tissue engineering. Future Directions: Progress within bioprinting requires close interactions between material scientists, tissue engineers, and clinicians. Microvascularization, integration of multiple cell types, and skin appendages will be essential for creation of complex skin tissue constructs.

Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer

Science.gov (United States)

2012-01-01

Background Cancers often arise within an area of cells (e.g. an epithelial patch) that is predisposed to the development of cancer, i.e. a "field of cancerization" or "field defect." Sporadic colon cancer is characterized by an elevated mutation rate and genomic instability. If a field defect were deficient in DNA repair, DNA damages would tend to escape repair and give rise to carcinogenic mutations. Purpose To determine whether reduced expression of DNA repair proteins Pms2, Ercc1 and Xpf (pairing partner of Ercc1) are early steps in progression to colon cancer. Results Tissue biopsies were taken during colonoscopies of 77 patients at 4 different risk levels for colon cancer, including 19 patients who had never had colonic neoplasia (who served as controls). In addition, 158 tissue samples were taken from tissues near or within colon cancers removed by resection and 16 tissue samples were taken near tubulovillous adenomas (TVAs) removed by resection. 568 triplicate tissue sections (a total of 1,704 tissue sections) from these tissue samples were evaluated by immunohistochemistry for 4 DNA repair proteins. Substantially reduced protein expression of Pms2, Ercc1 and Xpf occurred in field defects of up to 10 cm longitudinally distant from colon cancers or TVAs and within colon cancers. Expression of another DNA repair protein, Ku86, was infrequently reduced in these areas. When Pms2, Ercc1 or Xpf were reduced in protein expression, then either one or both of the other two proteins most often had reduced protein expression as well. The mean inner colon circumferences, from 32 resections, of the ascending, transverse and descending/sigmoid areas were measured as 6.6 cm, 5.8 cm and 6.3 cm, respectively. When combined with other measurements in the literature, this indicates the approximate mean number of colonic crypts in humans is 10 million. Conclusions The substantial deficiencies in protein expression of DNA repair proteins Pms2, Ercc1 and Xpf in about 1 million

Reversibly tethering growth factors to surfaces : guiding cell function at the cell-material interface

NARCIS (Netherlands)

Cabanas Danés, Jordi

2013-01-01

Development of novel methodologies for tethering growth factors (GFs) to materials is highly desired for the generation of biomaterials with improved tissue repair properties. Progress in the development of biomaterials that incorporate GFs and the in vivo performance of such biomaterials in tissue

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