Composite transcriptome assembly of RNA-seq data in a sheep model for delayed bone healing.

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Jäger, Marten; Ott, Claus-Eric; Grünhagen, Johannes; Hecht, Jochen; Schell, Hanna; Mundlos, Stefan; Duda, Georg N; Robinson, Peter N; Lienau, Jasmin

2011-03-24

The sheep is an important model organism for many types of medically relevant research, but molecular genetic experiments in the sheep have been limited by the lack of knowledge about ovine gene sequences. Prior to our study, mRNA sequences for only 1,556 partial or complete ovine genes were publicly available. Therefore, we developed a composite de novo transcriptome assembly method for next-generation sequence data to combine known ovine mRNA and EST sequences, mRNA sequences from mouse and cow, and sequences assembled de novo from short read RNA-Seq data into a composite reference transcriptome, and identified transcripts from over 12 thousand previously undescribed ovine genes. Gene expression analysis based on these data revealed substantially different expression profiles in standard versus delayed bone healing in an ovine tibial osteotomy model. Hundreds of transcripts were differentially expressed between standard and delayed healing and between the time points of the standard and delayed healing groups. We used the sheep sequences to design quantitative RT-PCR assays with which we validated the differential expression of 26 genes that had been identified by RNA-seq analysis. A number of clusters of characteristic expression profiles could be identified, some of which showed striking differences between the standard and delayed healing groups. Gene Ontology (GO) analysis showed that the differentially expressed genes were enriched in terms including extracellular matrix, cartilage development, contractile fiber, and chemokine activity. Our results provide a first atlas of gene expression profiles and differentially expressed genes in standard and delayed bone healing in a large-animal model and provide a number of clues as to the shifts in gene expression that underlie delayed bone healing. In the course of our study, we identified transcripts of 13,987 ovine genes, including 12,431 genes for which no sequence information was previously available. This

Evaluation of a Topical Herbal Agent for the Promotion of Bone Healing

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Wing-Sum Siu

2015-01-01

Full Text Available A topically used Chinese herbal paste, namely, CDNR, was designed to facilitate fracture healing which is usually not addressed in general hospital care. From our in vitro studies, CDNR significantly inhibited the release of nitric oxide from RAW264.7 cells by 51 to 77%. This indicated its anti-inflammatory effect. CDNR also promoted the growth of bone cells by stimulating the proliferation of UMR106 cells up to 18%. It also increased the biomechanical strength of the healing bone in a drill-hole defect rat model by 16.5% significantly. This result revealed its in vivo efficacy on facilitation of bone healing. Furthermore, the detection of the chemical markers of CDNR in the skin and muscle of the treatment area demonstrated its transdermal properties. However, CDNR did not affect the bone turnover markers in serum of the rats. With its anti-inflammatory and bone formation properties, CDNR is found effective in promoting bone healing.

Experimental fracture healing: evaluation using radionuclide bone imaging: concise communication

International Nuclear Information System (INIS)

Gumerman, L.W.; Fogel, S.R.; Goodman, M.A.; Hanley, E.N. Jr.; Kappakas, G.S.; Rutkowski, R.; Levine, G.

1978-01-01

Radionuclide bone imaging was performed in a rabbit model to observe the course of fracture healing and to establish criteria for distinguishing nonunion and delayed healing from normal healing. Sequential gamma-camera images (with pinhole collimator) were collected and subjected to computer analysis. Five groups were established: (a) control--immobilization; (b) control--immobilization plus periosteal stripping; (c) simple fracture--osteotomy; (d) delayed union--osteotomy plus periosteal stripping; and (e) nonunion--osteotomy, periosteal stripping and polymethyl methacrylate interposed between fracture fragments. Histographic representation of absolute count rates along rabbit tibias followed a predictable pattern in the simple-fracture and delayed-union groups. They differed only in the time of appearance of phases. The non-union group demonstrated no recognizable sequential pattern. In this experimental model, serial bone scanning the quantitative data analysis has shown potential for indicating the course of healing in fractures and for serving as a guide to treatment

Bone healing and bone substitutes.

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Costantino, Peter D; Hiltzik, David; Govindaraj, Satish; Moche, Jason

2002-02-01

With the advent of new biomaterials and surgical techniques, the reconstructive surgeon has a wider range of treatment modalities for the rehabilitation and reconstruction of craniofacial skeletal deformities than ever before. These innovative substances act as true bone graft substitutes, thereby allowing the surgeon to avoid the use of autogenous bone grafts and their associated donor site morbidity. Surgeons have long been interested in producing a composite graft that can heal faster by induction, incorporate with surrounding tissues, and be remodeled to resemble native bone. Currently, there are a host of bone graft substitutes available that vary in both their composition and properties. Craniomaxillofacial surgeons must therefore become comfortable with numerous biomaterials to best tailor the treatment for each patient individually. Ongoing investigations into the next phase of tissue engineering will continue to bring us closer to the ability to regenerate or replace bone.

Injection of demineralized bone matrix with bone marrow concentrate improves healing in unicameral bone cyst.

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Di Bella, Claudia; Dozza, Barbara; Frisoni, Tommaso; Cevolani, Luca; Donati, Davide

2010-11-01

Unicameral bone cysts are benign lesions that usually spontaneously regress with skeletal maturity; however, the high risk of pathologic fractures often justifies treatment that could reinforce a weakened bone cortex. Various treatments have been proposed but there is no consensus regarding the best procedure. We compared the healing rates and failures of two methods of cure based on multiple injections of corticosteroid or a single injection of demineralized bone matrix (DBM) in association with bone marrow concentrate (BMC). We retrospectively reviewed 184 patients who had one of the two treatments for unicameral bone cysts with cortical erosion. Clinical records were reviewed for treatment failures and radiographs for healing in all patients. The minimum followup was 12 months for the Steroids Group (mean, 48 months; range, 12-120 months) and 12 months for the DBM + BMC Group (mean, 20 months; range, 12-28 months). After one treatment we observed a lower healing rate of cysts treated with multiple injections of steroids compared with the healing after the first injection of DBM + BMC (21% versus 58%, respectively). At last followup, 38% healed with steroids and 71% with DBM + BMC. The rate of failure after one steroid injection was higher than after a single injection of BDM + BMC (63% versus 24%, respectively). We observed no difference in fracture rates after treatment between the two groups. A single injection of DBM added with autologous bone marrow concentrate appears to provide a higher healing rate with a lower number of failures compared with a single injection of steroids.

Proteomic Analysis of Gingival Tissue and Alveolar Bone during Alveolar Bone Healing*

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Yang, Hee-Young; Kwon, Joseph; Kook, Min-Suk; Kang, Seong Soo; Kim, Se Eun; Sohn, Sungoh; Jung, Seunggon; Kwon, Sang-Oh; Kim, Hyung-Seok; Lee, Jae Hyuk; Lee, Tae-Hoon

2013-01-01

Bone tissue regeneration is orchestrated by the surrounding supporting tissues and involves the build-up of osteogenic cells, which orchestrate remodeling/healing through the expression of numerous mediators and signaling molecules. Periodontal regeneration models have proven useful for studying the interaction and communication between alveolar bone and supporting soft tissue. We applied a quantitative proteomic approach to analyze and compare proteins with altered expression in gingival sof...

[Polarized microscopic observation of the collagen change in bone healing during bone lengthening].

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Zou, Pei; Li, Junhui; Li, Zhuyi

2006-01-01

To investigate the feature and regularity of the collagen change in bone healing during bone lengthening. Bone lengthening model was made in the middle segment of the rabbit tibia. Five days after the model was established, the bone was lengthened 1.5 mm per day for 14 days. The rabbits were put to death after elongation, 7, 14, 21, 30, 40, 50, 60 and 70 days after elongation. The distracted area of the bone was imbedded with paraffin. After being stained by the picric acid-sirius red staining, the slice was observed under polarized microscope. The features of the collagen change in the distracted bone were as follows: (1) In the fibrous tissue of the distracted area during lengthening period and the early stage after lengthening, there was not only collagen III but also much collagen I. (2) Collagen I , II and III were observed in the cartilage. (3) Collagen I, II and III were also observed in the pseudo-growth plate. (4) Collagen I took the dominance during lengthening period and the late stage after lengthening. New bone formation in bone lengthening is under the distracted force, so the collagen changes have different features compared with that in fracture healing. Collagen I, II and III can be identified by picric acid-sirius red staining and polarized microscope, so a new method for studying the collagen typing in bone repairing is provided.

Parathyroid hormone and bone healing

DEFF Research Database (Denmark)

Ellegaard, M; Jørgensen, N R; Schwarz, P

2010-01-01

, no pharmacological treatments are available. There is therefore an unmet need for medications that can stimulate bone healing. Parathyroid hormone (PTH) is the first bone anabolic drug approved for the treatment of osteoporosis, and intriguingly a number of animal studies suggest that PTH could be beneficial...

Simulation of peri-implant bone healing due to immediate loading in dental implant treatments.

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Chou, Hsuan-Yu; Müftü, Sinan

2013-03-15

The goal of this work was to investigate the role of immediate loading on the peri-implant bone healing in dental implant treatments. A mechano-regulatory tissue differentiation model that takes into account the stimuli through the solid and the fluid components of the healing tissue, and the diffusion of pluripotent stem cells into the healing callus was used. A two-dimensional axisymmetric model consisting of a dental implant, the healing callus tissue and the host bone tissue was constructed for the finite element analysis. Poroelastic material properties were assigned to the healing callus and the bone tissue. The effects of micro-motion, healing callus size, and implant thread design on the length of the bone-to-implant contact (BIC) and the bone volume (BV) formed in the healing callus were investigated. In general, the analysis predicted formation of a continuous layer of soft tissue along the faces of the implant which are parallel to the loading direction. This was predicted to be correlated with the high levels of distortional strain transferred through the solid component of the stimulus. It was also predicted that the external threads on the implant, redistribute the interfacial load, thus help reduce the high distortional stimulus and also help the cells to differentiate to bone tissue. In addition, the region underneath the implant apex was predicted to experience high fluid stimulus that results in the development of soft tissue. The relationship between the variables considered in this study and the outcome measures, BV and BIC, was found to be highly nonlinear. A three-way analysis of variance (ANOVA) of the results was conducted and it showed that micro-motion presents the largest hindrance to bone formation during healing. Copyright © 2013 Elsevier Ltd. All rights reserved.

Formation of blood clot on biomaterial implants influences bone healing.

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Shiu, Hoi Ting; Goss, Ben; Lutton, Cameron; Crawford, Ross; Xiao, Yin

2014-12-01

The first step in bone healing is forming a blood clot at injured bones. During bone implantation, biomaterials unavoidably come into direct contact with blood, leading to a blood clot formation on its surface prior to bone regeneration. Despite both situations being similar in forming a blood clot at the defect site, most research in bone tissue engineering virtually ignores the important role of a blood clot in supporting healing. Dental implantology has long demonstrated that the fibrin structure and cellular content of a peri-implant clot can greatly affect osteoconduction and de novo bone formation on implant surfaces. This article reviews the formation of a blood clot during bone healing in relation to the use of platelet-rich plasma (PRP) gels. It is implicated that PRP gels are dramatically altered from a normal clot in healing, resulting in conflicting effect on bone regeneration. These results indicate that the effect of clots on bone regeneration depends on how the clots are formed. Factors that influence blood clot structure and properties in relation to bone healing are also highlighted. Such knowledge is essential for developing strategies to optimally control blood clot formation, which ultimately alter the healing microenvironment of bone. Of particular interest are modification of surface chemistry of biomaterials, which displays functional groups at varied composition for the purpose of tailoring blood coagulation activation, resultant clot fibrin architecture, rigidity, susceptibility to lysis, and growth factor release. This opens new scope of in situ blood clot modification as a promising approach in accelerating and controlling bone regeneration.

Enhanced Tendon-to-Bone Healing of Chronic Rotator Cuff Tears by Bone Marrow Aspirate Concentrate in a Rabbit Model

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Liu, Xiao Ning; Yang, Cheol-Jung; Kim, Ji Eui; Du, Zhen Wu; Ren, Ming; Zhang, Wei; Zhao, Hong Yu; Kim, Kyung Ok

2018-01-01

Background To evaluate the influence of bone marrow aspirate concentrate (BMAC) on tendon-to-bone healing in a rabbit rotator cuff model and to characterize the composition of growth factors in BMAC. Methods In this in vivo study, 40 rabbits were allocated into five groups: control (C), repair + saline (RS), repair + platelet-rich plasma (PRP; RP), repair + BMAC (RB) and repair + PRP + BMAC (RPB). A tear model was created by supraspinatus tendon transection at the footprint. Six weeks after transection, the torn tendon was repaired along with BMAC or PRP administration. Six weeks after repair, shoulder samples were harvested for biomechanical and histological testing. Ten rabbits were used for processing PRP and BMAC, followed by analysis of blood cell composition and the levels of growth factors in vitro. Results The ultimate load-to-failure was significantly higher in RPB group compared to RS group (p = 0.025). BMAC-treated groups showed higher values of biomechanical properties than RS group. The histology of BMAC-treated samples showed better collagen fiber continuity and orientation than RS group. BMAC contained significantly higher levels of the several growth factors than PRP. Conclusions Locally administered BMAC enhanced tendon-to-bone healing and has potential for clinical applications. PMID:29564054

Rapid and reliable healing of critical size bone defects with genetically modified sheep muscle.

Science.gov (United States)

Liu, F; Ferreira, E; Porter, R M; Glatt, V; Schinhan, M; Shen, Z; Randolph, M A; Kirker-Head, C A; Wehling, C; Vrahas, M S; Evans, C H; Wells, J W

2015-09-21

Large segmental defects in bone fail to heal and remain a clinical problem. Muscle is highly osteogenic, and preliminary data suggest that autologous muscle tissue expressing bone morphogenetic protein-2 (BMP-2) efficiently heals critical size defects in rats. Translation into possible human clinical trials requires, inter alia, demonstration of efficacy in a large animal, such as the sheep. Scale-up is fraught with numerous biological, anatomical, mechanical and structural variables, which cannot be addressed systematically because of cost and other practical issues. For this reason, we developed a translational model enabling us to isolate the biological question of whether sheep muscle, transduced with adenovirus expressing BMP-2, could heal critical size defects in vivo. Initial experiments in athymic rats noted strong healing in only about one-third of animals because of unexpected immune responses to sheep antigens. For this reason, subsequent experiments were performed with Fischer rats under transient immunosuppression. Such experiments confirmed remarkably rapid and reliable healing of the defects in all rats, with bridging by 2 weeks and remodelling as early as 3-4 weeks, despite BMP-2 production only in nanogram quantities and persisting for only 1-3 weeks. By 8 weeks the healed defects contained well-organised new bone with advanced neo-cortication and abundant marrow. Bone mineral content and mechanical strength were close to normal values. These data demonstrate the utility of this model when adapting this technology for bone healing in sheep, as a prelude to human clinical trials.

Platelet-rich plasma for bone healing and regeneration.

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Oryan, Ahmad; Alidadi, Soodeh; Moshiri, Ali

2016-01-01

Successful healing of large bone defects (LBDs) is a complicated phenomenon because the body's natural ability often fails to effectively repair the LBDs. New modalities should be utilized to increase the quality and accelerate bone healing. Platelet concentrates in different forms can be considered an attractive option for such purpose. Platelets as a natural source of growth factors, cytokines, and other micro and macromolecules are hypothesized to improve bone healing. This review has covered important concepts regarding platelet-rich plasma (PRP) including mechanisms of action, preparation protocols and their differences, and factors affecting the PRP efficacy during bone healing. In addition, the most recent studies in different levels which evaluated the role of PRP on bone repair has been reviewed and discussed to clarify the controversies and conflicts, and to illustrate a future prospective and directions for orthopedic surgeons to overcome current limitations and difficulties. As the efficacy of PRP is dependent on various factors, the outcome of PRP therapy is variable and unpredictable in orthopedic patients. Therefore, it is still too soon to suggest PRP as the first line treatment option in complicated bone injuries such as LBDs and nonunions. However, combination of PRP with natural and synthetic biomaterials can enhance the effectiveness of PRP.

Alveolar bone healing in rats: micro-CT, immunohistochemical and molecular analysis

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Jaqueline Suemi HASSUMI

2018-06-01

Full Text Available Abstract Alveolar bone healing after upper incisor extraction in rats is a classical model of preclinical studies. The underlying morphometric, cellular and molecular mechanism, however, remains imprecise in a unique study. Objectives The aim of this study was therefore to characterize the alveolar bone healing after upper incisor extraction in rats by micro computed tomographic (Micro-CT, immunohistochemical and real-time polymerase chain reaction (RT-PCR analysis. Material and Methods Thirty animals (Rattus norvegicus, Albinus Wistar were divided into three groups after upper incisors extraction at 7, 14, and 28 days. Micro-CT was evaluated based on the morphometric parameters. Subsequently, the histological analyses and immunostaining of osteoprotegerin (OPG, receptor activator of nuclear kappa B ligand (RANKL and tartrate resistant acid phosphate (TRAP was performed. In addition, RT-PCR analyses of OPG, RANKL, the runt-related transcription factor 2 (RUNX2, osteocalcin (OC, osteopontin (OPN, osterix (OST and receptor activator of nuclear kappa B (RANK were performed to determine the expression of these proteins in the alveolar bone healing. Results Micro-CT: The morphometric parameters of bone volume and trabecular thickness progressively increased over time. Consequently, a gradual decrease in trabecular separation, trabecular space and total bone porosity was observed. Immunohistochemical: There were no differences statistically significant between the positive labeling for OPG, RANKL and TRAP in the different periods. RT-PCR: At 28 days, there was a significant increase in OPG expression, while RANKL expression and the RANKL/OPG ratio both decreased over time. Conclusion Micro-CT showed the newly formed bone had favorable morphometric characteristics of quality and quantity. Beyond the RUNX2, OC, OPN, OST, and RANK proteins expressed in the alveolar bone healing, OPG and RANKL activity showed to be essential for activation of basic

Marginal bone loss around non-submerged implants is associated with salivary microbiome during bone healing.

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Duan, Xiao-Bo; Wu, Ting-Xi; Guo, Yu-Chen; Zhou, Xue-Dong; Lei, Yi-Ling; Xu, Xin; Mo, An-Chun; Wang, Yong-Yue; Yuan, Quan

2017-06-01

Marginal bone loss during bone healing exists around non-submerged dental implants. The aim of this study was to identify the relationship between different degrees of marginal bone loss during bone healing and the salivary microbiome. One hundred patients were recruited, and marginal bone loss around their implants was measured using cone beam computed tomography during a 3-month healing period. The patients were divided into three groups according to the severity of marginal bone loss. Saliva samples were collected from all subjected and were analysed using 16S MiSeq sequencing. Although the overall structure of the microbial community was not dramatically altered, the relative abundance of several taxonomic groups noticeably changed. The abundance of species in the phyla Spirochaeta and Synergistetes increased significantly as the bone loss became more severe. Species within the genus Treponema also exhibited increased abundance, whereas Veillonella, Haemophilus and Leptotrichia exhibited reduced abundances, in groups with more bone loss. Porphyromonasgingivalis, Treponemadenticola and Streptococcus intermedius were significantly more abundant in the moderate group and/or severe group. The severity of marginal bone loss around the non-submerged implant was associated with dissimilar taxonomic compositions. An increased severity of marginal bone loss was related to increased proportions of periodontal pathogenic species. These data suggest a potential role of microbes in the progression of marginal bone loss during bone healing.

Advanced age diminishes tendon-to-bone healing in a rat model of rotator cuff repair.

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Plate, Johannes F; Brown, Philip J; Walters, Jordan; Clark, John A; Smith, Thomas L; Freehill, Michael T; Tuohy, Christopher J; Stitzel, Joel D; Mannava, Sandeep

2014-04-01

Advanced patient age is associated with recurrent tearing and failure of rotator cuff repairs clinically; however, basic science studies have not evaluated the influence of aging on tendon-to-bone healing after rotator cuff repair in an animal model. Hypothesis/ This study examined the effect of aging on tendon-to-bone healing in an established rat model of rotator cuff repair using the aged animal colony from the National Institute on Aging of the National Institutes of Health. The authors hypothesized that normal aging decreases biomechanical strength and histologic organization at the tendon-to-bone junction after acute repair. Controlled laboratory study. In 56 F344xBN rats, 28 old and 28 young (24 and 8 months of age, respectively), the supraspinatus tendon was transected and repaired. At 2 or 8 weeks after surgery, shoulder specimens underwent biomechanical testing to compare load-to-failure and load-relaxation response between age groups. Histologic sections of the tendon-to-bone interface were assessed with hematoxylin and eosin staining, and collagen fiber organization was assessed by semiquantitative analysis of picrosirius red birefringence under polarized light. Peak failure load was similar between young and old animals at 2 weeks after repair (31% vs 26% of age-matched uninjured controls, respectively; P > .05) but significantly higher in young animals compared with old animals 8 weeks after repair (86% vs 65% of age-matched uninjured controls, respectively; P repair, fibroblasts appeared more organized and uniformly aligned in young animals on hematoxylin and eosin slides compared with old animals. Collagen birefringence analysis of the tendon-to-bone junction demonstrated that young animals had increased collagen fiber organization and similar histologic structure compared with age-matched controls (53.7 ± 2.4 gray scales; P > .05). In contrast, old animals had decreased collagen fiber organization and altered structure compared with age

In vivo study of magnesium plate and screw degradation and bone fracture healing.

Science.gov (United States)

Chaya, Amy; Yoshizawa, Sayuri; Verdelis, Kostas; Myers, Nicole; Costello, Bernard J; Chou, Da-Tren; Pal, Siladitya; Maiti, Spandan; Kumta, Prashant N; Sfeir, Charles

2015-05-01

Each year, millions of Americans suffer bone fractures, often requiring internal fixation. Current devices, like plates and screws, are made with permanent metals or resorbable polymers. Permanent metals provide strength and biocompatibility, but cause long-term complications and may require removal. Resorbable polymers reduce long-term complications, but are unsuitable for many load-bearing applications. To mitigate complications, degradable magnesium (Mg) alloys are being developed for craniofacial and orthopedic applications. Their combination of strength and degradation make them ideal for bone fixation. Previously, we conducted a pilot study comparing Mg and titanium devices with a rabbit ulna fracture model. We observed Mg device degradation, with uninhibited healing. Interestingly, we observed bone formation around degrading Mg, but not titanium, devices. These results highlighted the potential for these fixation devices. To better assess their efficacy, we conducted a more thorough study assessing 99.9% Mg devices in a similar rabbit ulna fracture model. Device degradation, fracture healing, and bone formation were evaluated using microcomputed tomography, histology and biomechanical tests. We observed device degradation throughout, and calculated a corrosion rate of 0.40±0.04mm/year after 8 weeks. In addition, we observed fracture healing by 8 weeks, and maturation after 16 weeks. In accordance with our pilot study, we observed bone formation surrounding Mg devices, with complete overgrowth by 16 weeks. Bend tests revealed no difference in flexural load of healed ulnae with Mg devices compared to intact ulnae. These data suggest that Mg devices provide stabilization to facilitate healing, while degrading and stimulating new bone formation. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

CaMKK2 Inhibition in Enhancing Bone Fracture Healing

Science.gov (United States)

2016-05-01

AWARD NUMBER: W81XWH-13-1-0188 TITLE: CaMKK2 Inhibition in Enhancing Bone Fracture Healing PRINCIPAL INVESTIGATOR: Uma Sankar, Ph.D...Enhancing Bone Fracture Healing 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0188 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Uma Sankar 5d...accelerated fracture healing . We generated unilateral mid-shaft fractures using a three-point bending method (first described for use in rats by Bonnarens and

Evaluation of an injectable bioactive borate glass cement to heal bone defects in a rabbit femoral condyle model

Energy Technology Data Exchange (ETDEWEB)

Cui, Xu [Institute of Bioengineering and Information Technology Materials, Tongji University, Shanghai 200092 (China); Center for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen 518055 (China); Huang, Wenhai [Institute of Bioengineering and Information Technology Materials, Tongji University, Shanghai 200092 (China); Zhang, Yadong, E-mail: zhangyadong6@126.com [Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120 (China); Huang, Chengcheng; Yu, Zunxiong; Wang, Lei; Liu, Wenlong; Wang, Ting [Center for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen 518055 (China); Zhou, Jie; Wang, Hui; Zhou, Nai; Wang, Deping [Institute of Bioengineering and Information Technology Materials, Tongji University, Shanghai 200092 (China); Pan, Haobo, E-mail: hb.pan@siat.ac.cn [Center for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen 518055 (China); Rahaman, Mohamed N., E-mail: rahaman@mst.edu [Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120 (China); Department of Materials Science and Engineering, Missouri University of Science and Technology, Rolla, MO 65409-0340 (United States)

2017-04-01

There is a need for synthetic biomaterials to heal bone defects using minimal invasive surgery. In the present study, an injectable cement composed of bioactive borate glass particles and a chitosan bonding solution was developed and evaluated for its capacity to heal bone defects in a rabbit femoral condyle model. The injectability and setting time of the cement in vitro decreased but the compressive strength increased (8 ± 2 MPa to 31 ± 2 MPa) as the ratio of glass particles to chitosan solution increased (from 1.0 g ml{sup −1} to 2.5 g ml{sup −1}). Upon immersing the cement in phosphate-buffered saline, the glass particles reacted and converted to hydroxyapatite, imparting bioactivity to the cement. Osteoblastic MC3T3-E1 cells showed enhanced proliferation and alkaline phosphatase activity when incubated in media containing the soluble ionic product of the cement. The bioactive glass cement showed a better capacity to stimulate bone formation in rabbit femoral condyle defects at 12 weeks postimplantation when compared to a commercial calcium sulfate cement. The injectable bioactive borate glass cement developed in this study could provide a promising biomaterial to heal bone defects by minimal invasive surgery. - Highlights: • New class of injectable bone cement composed of bioactive borate glass particles and chitosan bonding phase was created. • The cement is biocompatible and bioactive, and has a much lower temperature increase during setting than PMMA cement. • The cement has a more controllable degradation rate and higher strength over a longer time than calcium sulfate cement. • The cement showed a better ability to heal bone defects than calcium sulfate over a twelve-week implantation period.

Effects of low-intensity pulsed ultrasound on new trabecular bone during bone-tendon junction healing in a rabbit model: a synchrotron radiation micro-CT study.

Directory of Open Access Journals (Sweden)

Hongbin Lu

Full Text Available This study was designed to evaluate the effects of low-intensity pulsed ultrasound on bone regeneration during the bone-tendon junction healing process and to explore the application of synchrotron radiation micro computed tomography in three dimensional visualization of the bone-tendon junction to evaluate the microarchitecture of new trabecular bone. Twenty four mature New Zealand rabbits underwent partial patellectomy to establish a bone-tendon junction injury model at the patella-patellar tendon complex. Animals were then divided into low-intensity pulsed ultrasound treatment (20 min/day, 7 times/week and placebo control groups, and were euthanized at week 8 and 16 postoperatively (n = 6 for each group and time point. The patella-patellar tendon specimens were harvested for radiographic, histological and synchrotron radiation micro computed tomography detection. The area of the newly formed bone in the ultrasound group was significantly greater than that of control group at postoperative week 8 and 16. The high resolution three dimensional visualization images of the bone-tendon junction were acquired by synchrotron radiation micro computed tomography. Low-intensity pulsed ultrasound treatment promoted dense and irregular woven bone formation at week 8 with greater bone volume fraction, number and thickness of new trabecular bone but with lower separation. At week 16, ultrasound group specimens contained mature lamellar bone with higher bone volume fraction and thicker trabeculae than that of control group; however, there was no significant difference in separation and number of the new trabecular bone. This study confirms that low-intensity pulsed ultrasound treatment is able to promote bone formation and remodeling of new trabecular bone during the bone-tendon junction healing process in a rabbit model, and the synchrotron radiation micro computed tomography could be applied for three dimensional visualization to quantitatively evaluate

Fracture healing: Quantitative three-phase bone scintigraphy as a prognostic factor

International Nuclear Information System (INIS)

Dodig, D.; Kasal, B.; Kragic-Pranic, A.; Predic, P.

2002-01-01

Aim: Careful clinical examination and conventional radiography, together with other standard methods for evaluation of bone fracture healing, are frequently inconclusive. Furthermore, it is difficult to predict the complications of healing on the basis of clinical and radiographic findings only. Bone scintigraphy plays an important role in detecting bone fractures. This method is very sensitive, but not enough specific. The aim of this work was to evaluate the role of three-phase bone scintigraphy in the healing prognosis of long bone fractures. Material and Methods: We evaluated the three elements (perfusion, blood pool and static image) of three-phase bone scintigraphy in early prognosis of the course of fracture healing in patients with fractures of femur or tibia. Three-phase bone scintigraphy was performed in 73 patients. The patients were divided into 4 groups according to X-ray and clinical examination: 1) Non operated patients with stable fracture, 2) Operated patients with unstable fracture (infection), 3) Fractures with delayed union, 4) Patients with pseudoarthrosis. Using region of interest (ROI) method we compared the activity on the site of fracture with the activity on the symmetrical place in the healthy bone. The relative indices for each group of patients and for each element of three-bone scintigraphy were calculated in order to make possible the follow up of the fracture healing and to obtain data for prognosis and evaluation of possible complications. Results: The most valuable results were obtained by quantitative analysis of perfusion data immediately after trauma and 2-3 weeks later. Our results show a high diagnostic accuracy in identifying infection by perfusion scintigrams immediately after trauma. The perfusion indices obtained immediately and after 2-3 weeks could predict delayed union after the trauma. Quantitative analysis of blood pool phase gave no data of clinical significance in distinguishing various pathologies. Conclusion: Our

Low dose PTH improves metaphyseal bone healing more when muscles are paralyzed.

Science.gov (United States)

Sandberg, Olof; Macias, Brandon R; Aspenberg, Per

2014-06-01

Stimulation of bone formation by PTH is related to mechanosensitivity. The response to PTH treatment in intact bone could therefore be blunted by unloading. We studied the effects of mechanical loading on the response to PTH treatment in bone healing. Most fractures occur in the metaphyses, therefor we used a model for metaphyseal bone injury. One hind leg of 20 male SD rats was unloaded via intramuscular botulinum toxin injections. Two weeks later, the proximal unloaded tibia had lost 78% of its trabecular contents. At this time-point, the rats received bilateral proximal tibiae screw implants. Ten of the 20 rats were given daily injections of 5 μg/kg PTH (1-34). After two weeks of healing, screw fixation was measured by pull-out, and microCT of the distal femur cancellous compartment was performed. Pull-out force provided an estimate for cancellous bone formation after trauma. PTH more than doubled the pull-out force in the unloaded limbs (from 14 to 30 N), but increased it by less than half in the loaded ones (from 30 to 44 N). In relative terms, PTH had a stronger effect on pull-out force in unloaded bone than in loaded bone (p=0.03). The results suggest that PTH treatment for stimulation of bone healing does not require simultaneous mechanical stimulation. Copyright © 2014 Elsevier Inc. All rights reserved.

Sensitivity of tissue differentiation and bone healing predictions to tissue properties

NARCIS (Netherlands)

Isaksson, H.E.; Donkelaar, van C.C.; Ito, K.

2009-01-01

Computational models are employed as tools to investigate possible mechano-regulation pathways for tissue differentiation and bone healing. However, current models do not account for the uncertainty in input parameters, and often include assumptions about parameter values that are not yet

Laser for bone healing after oral surgery: systematic review.

Science.gov (United States)

Noba, Claudio; Mello-Moura, Anna Carolina Volpi; Gimenez, Thais; Tedesco, Tamara Kerber; Moura-Netto, Cacio

2018-04-01

The purpose of this study is to perform a systematic review on the use of lasers in oral surgery for bone healing. Selection of articles was carried out by two evaluators in Pubmed and Web of Science databases for published articles and OpenGray for gray literature. Search strategy was developed based on the PICO Question "Does the use of lasers after oral surgery improve bone healing?". Eligibility criteria were: being on laser; evaluate bone healing; involve oral surgery; do not be about implant, periodontics, orthodontics, osteonecrosis or radiotherapy, nor revisions, clinical cases, etc. Data were collected from each article in a structured spreadsheet and a descriptive analysis was performed. Risk assessment of bias of the articles was carried out through the tool elaborated by the Cochrane collaboration. A total of 827 potentially relevant references were identified. No articles were found in OpenGray. Eleven articles met the eligibility criteria and were included in the systematic review. Most of studies were in vivo and in jaw, being conducted with low-power lasers which were applied immediately after the surgical procedure of extraction. Neoformation and bone density were the outcomes of choice and there was a tendency of increase in bone density, neoformation, regeneration, mineralization, or bone condensation when laser was applied. Regarding the bias risk assessment, studies were not clear in reporting most of the parameters. Low-power laser therapy seems to reduce time of bone healing in oral surgery, although there are no defined protocols and the level of evidence is still considered weak.

Mechanical Loading Improves Tendon-Bone Healing in a Rabbit Anterior Cruciate Ligament Reconstruction Model by Promoting Proliferation and Matrix Formation of Mesenchymal Stem Cells and Tendon Cells

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Fanglong Song

2017-02-01

Full Text Available Background/Aims: This study investigated the effect of mechanical stress on tendon-bone healing in a rabbit anterior cruciate ligament (ACL reconstruction model as well as cell proliferation and matrix formation in co-culture of bone-marrow mesenchymal stem cells (BMSCs and tendon cells (TCs. Methods: The effect of continuous passive motion (CPM therapy on tendon-bone healing in a rabbit ACL reconstruction model was evaluated by histological analysis, biomechanical testing and gene expressions at the tendon-bone interface. Furthermore, the effect of mechanical stretch on cell proliferation and matrix synthesis in BMSC/TC co-culture was also examined. Results: Postoperative CPM therapy significantly enhanced tendon-bone healing, as evidenced by increased amount of fibrocartilage, elevated ultimate load to failure levels, and up-regulated gene expressions of Collagen I, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin at the tendon-bone junction. In addition, BMSC/TC co-culture treated with mechanical stretch showed a higher rate of cell proliferation and enhanced expressions of Collagen I, Collagen III, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin than that of controls. Conclusion: These results demonstrated that proliferation and differentiation of local precursor cells could be enhanced by mechanical stimulation, which results in enhanced regenerative potential of BMSCs and TCs in tendon-bone healing.

The Impact of Type 2 Diabetes on Bone Fracture Healing

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Carlos Marin

2018-01-01

Full Text Available Type 2 diabetes mellitus (T2DM is a chronic metabolic disease known by the presence of elevated blood glucose levels. Nowadays, it is perceived as a worldwide epidemic, with a very high socioeconomic impact on public health. Many are the complications caused by this chronic disorder, including a negative impact on the cardiovascular system, kidneys, eyes, muscle, blood vessels, and nervous system. Recently, there has been increasing evidence suggesting that T2DM also adversely affects the skeletal system, causing detrimental bone effects such as bone quality deterioration, loss of bone strength, increased fracture risk, and impaired bone healing. Nevertheless, the precise mechanisms by which T2DM causes detrimental effects on bone tissue are still elusive and remain poorly studied. The aim of this review was to synthesize current knowledge on the different factors influencing the impairment of bone fracture healing under T2DM conditions. Here, we discuss new approaches used in recent studies to unveil the mechanisms and fill the existing gaps in the scientific understanding of the relationship between T2DM, bone tissue, and bone fracture healing.

Biomaterial delivery of morphogens to mimic the natural healing cascade in bone.

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Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

2012-09-01

Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. Copyright © 2012 Elsevier B.V. All rights reserved.

Novel bone substitute material in alveolar bone healing following tooth extraction: an experimental study in sheep.

Science.gov (United States)

Liu, Jinyi; Schmidlin, Patrick R; Philipp, Alexander; Hild, Nora; Tawse-Smith, Andrew; Duncan, Warwick

2016-07-01

Electrospun cotton wool-like nanocomposite (ECWN) is a novel synthetic bone substitute that incorporates amorphous calcium phosphate nanoparticles into a biodegradable synthetic copolymer poly(lactide-co-glycolide). The objectives of this study were to develop a tooth extraction socket model in sheep for bone graft research and to compare ECWN and bovine-derived xenograft (BX) in this model. Sixteen cross-bred female sheep were used. Bilateral mandibular premolars were extracted atraumatically. Second and third premolar sockets were filled (Latin-square allocation) with BX, ECWN or left unfilled. Resorbable collagen membranes were placed over BX and selected ECWN grafted sockets. Eight sheep per time period were sacrificed after 8 and 16 weeks. Resin-embedded undemineralised sections were analysed for descriptive histology and histomorphometric analyses. At 8 weeks, there were with no distinct differences in healing among the different sites. At 16 weeks, osseous healing followed a fine trabecular pattern in ECWN sites. Non-grafted sites showed thick trabeculae separated by large areas of fibrovascular connective tissue. In BX grafted sites, xenograft particles were surrounded by newly formed bone or fibrovascular connective tissue. There were no statistically significant differences in bone formation across the four groups. However, ECWN sites had significantly less residual graft material than BX sites at 16 weeks (P = 0.048). This first description of a tooth extraction socket model in sheep supports the utility of this model for bone graft research. The results of this study suggested that the novel material ECWN did not impede bone ingrowth into sockets and showed evidence of material resorption. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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

2008-01-01

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

Monitoring of bone healing by piezoelectric-EMI method

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Mazlina, M. H.; Sarpinah, Bibi; Tawie, Rudy; Daho, Claira Dalislone; Annuar, Ishak

2016-02-01

Smart Piezoelectric devices which have excellent piezoelectric properties have been employed for various sensor and actuators applications. The work presented here is an attempt to demonstrate the feasibility of bone healing monitoring by using piezoelectric-electromechanical impedance (EMI) method that have several advantages such as low cost, portable, light weight and simplicity in measurement. A Piezoelectric sensor (PZT) has been widely used in damage detection of various structures including concrete, pipes and bones due to their unique sensing and actuating properties. The EMI technique has emerged as a universal Structural Health Monitoring (SHM) tool suitable for almost all engineering materials and structures. The method used for this proposed study consists of put healing agent in the host structure in particular cracks bone to be monitored by PZT-needle sensor which is embedded to the host structure. The measurements were taken in the frequency range between 0.04 to 100 kHz at 1 kHz interval using AD5933 evaluation board. The signals retrieved from the AD5933 evaluation board, were quantify and analyse to obtain Root Mean Square Deviation (RMSD) percentage value. Measurements were taken every hour for 12 hours. The result from the study shows the feasibility of the piezoelectric-EMI method to effectively detect changes during bone-cracks healing process until the cracks bone is fully recovered.

Forces associated with launch into space do not impact bone fracture healing

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Childress, Paul; Brinker, Alexander; Gong, Cynthia-May S.; Harris, Jonathan; Olivos, David J.; Rytlewski, Jeffrey D.; Scofield, David C.; Choi, Sungshin Y.; Shirazi-Fard, Yasaman; McKinley, Todd O.; Chu, Tien-Min G.; Conley, Carolynn L.; Chakraborty, Nabarun; Hammamieh, Rasha; Kacena, Melissa A.

2018-02-01

Segmental bone defects (SBDs) secondary to trauma invariably result in a prolonged recovery with an extended period of limited weight bearing on the affected limb. Soldiers sustaining blast injuries and civilians sustaining high energy trauma typify such a clinical scenario. These patients frequently sustain composite injuries with SBDs in concert with extensive soft tissue damage. For soft tissue injury resolution and skeletal reconstruction a patient may experience limited weight bearing for upwards of 6 months. Many small animal investigations have evaluated interventions for SBDs. While providing foundational information regarding the treatment of bone defects, these models do not simulate limited weight bearing conditions after injury. For example, mice ambulate immediately following anesthetic recovery, and in most cases are normally ambulating within 1-3 days post-surgery. Thus, investigations that combine disuse with bone healing may better test novel bone healing strategies. To remove weight bearing, we have designed a SBD rodent healing study in microgravity (μG) on the International Space Station (ISS) for the Rodent Research-4 (RR-4) Mission, which launched February 19, 2017 on SpaceX CRS-10 (Commercial Resupply Services). In preparation for this mission, we conducted an end-to-end mission simulation consisting of surgical infliction of SBD followed by launch simulation and hindlimb unloading (HLU) studies. In brief, a 2 mm defect was created in the femur of 10 week-old C57BL6/J male mice (n = 9-10/group). Three days after surgery, 6 groups of mice were treated as follows: 1) Vivarium Control (maintained continuously in standard cages); 2) Launch Negative Control (placed in the same spaceflight-like hardware as the Launch Positive Control group but were not subjected to launch simulation conditions); 3) Launch Positive Control (placed in spaceflight-like hardware and also subjected to vibration followed by centrifugation); 4) Launch Positive

The connection between cellular mechanoregulation and tissue patterns during bone healing.

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Repp, Felix; Vetter, Andreas; Duda, Georg N; Weinkamer, Richard

2015-09-01

The formation of different tissues in the callus during secondary bone healing is at least partly influenced by mechanical stimuli. We use computer simulations to test the consequences of different hypotheses of the mechanoregulation at the cellular level on the patterns of tissues formed during healing. The computational study is based on an experiment on sheep, where after a tibial osteotomy, histological sections were harvested at different time points. In the simulations, we used a recently proposed basic phenomenological model, which allows ossification to occur either via endochondral or intramembranous ossification, but tries otherwise to employ a minimal number of simulation parameters. The model was extended to consider also the possibility of bone resorption and consequently allowing a description of the full healing progression till the restoration of the cortex. Specifically, we investigated how three changes in the mechanoregulation influence the resulting tissue patterns: (1) a time delay between stimulation of the cell and the formation of the tissue, (2) a variable mechanosensitivity of the cells, and (3) an independence of long time intervals of the soft tissue maturation from the mechanical stimulus. For all three scenarios, our simulations do not show qualitative differences in the time development of the tissue patterns. Largest differences were observed in the intermediate phases of healing in the amount and location of the cartilage. Interestingly, the course of healing was virtually unaltered in case of scenario (3) where tissue maturation proceeded independent of mechanical stimulation.

Hydroxyapatite-doped polycaprolactone nanofiber membrane improves tendon-bone interface healing for anterior cruciate ligament reconstruction.

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Han, Fei; Zhang, Peng; Sun, Yaying; Lin, Chao; Zhao, Peng; Chen, Jiwu

2015-01-01

Hamstring tendon autograft is a routine graft for anterior cruciate ligament (ACL) reconstruction. However, ways of improving the healing between the tendon and bone is often overlooked in clinical practice. This issue can be addressed by using a biomimetic scaffold. Herein, a biomimetic nanofiber membrane of polycaprolactone/nanohydroxyapatite/collagen (PCL/nHAp/Col) is fabricated that mimics the composition of native bone tissue for promoting tendon-bone healing. This membrane has good cytocompatibility, allowing for osteoblast cell adhesion and growth and bone formation. As a result, MC3T3 cells reveal a higher mineralization level in PCL/nHAp/Col membrane compared with PCL membrane alone. Further in vivo studies in ACL reconstruction in a rabbit model shows that PCL/nHAp/Col-wrapped tendon may afford superior tissue integration to nonwrapped tendon in the interface between the tendon and host bone as well as improved mechanical strength. This study shows that PCL/nHAp/Col nanofiber membrane wrapping of autologous tendon is effective for improving tendon healing with host bone in ACL reconstruction.

Enhancement of tendon–bone healing via the combination of biodegradable collagen-loaded nanofibrous membranes and a three-dimensional printed bone-anchoring bolt

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Chou YC

2016-08-01

Full Text Available Ying-Chao Chou,1,2 Wen-Lin Yeh,2 Chien-Lin Chao,1 Yung-Heng Hsu,1,2 Yi-Hsun Yu,1,2 Jan-Kan Chen,3 Shih-Jung Liu1,2 1Department of Mechanical Engineering, Chang Gung University, 2Department of Orthopedic Surgery, Chang Gung Memorial Hospital, 3Department of Physiology and Pharmacology, Chang Gung University, Taoyuan, Taiwan Abstract: A composite biodegradable polymeric model was developed to enhance tendon graft healing. This model included a biodegradable polylactide (PLA bolt as the bone anchor and a poly(D,L-lactide-co-glycolide (PLGA nanofibrous membrane embedded with collagen as a biomimic patch to promote tendon–bone interface integration. Degradation rate and compressive strength of the PLA bolt were measured after immersion in a buffer solution for 3 months. In vitro biochemical characteristics and the nanofibrous matrix were assessed using a water contact angle analyzer, pH meter, and tetrazolium reduction assay. In vivo efficacies of PLGA/collagen nanofibers and PLA bolts for tendon–bone healing were investigated on a rabbit bone tunnel model with histological and tendon pullout tests. The PLGA/collagen-blended nanofibrous membrane was a hydrophilic, stable, and biocompatible scaffold. The PLA bolt was durable for tendon–bone anchoring. Histology showed adequate biocompatibility of the PLA bolt on a medial cortex with progressive bone ingrowth and without tissue overreaction. PLGA nanofibers within the bone tunnel also decreased the tunnel enlargement phenomenon and enhanced tendon–bone integration. Composite polymers of the PLA bolt and PLGA/collagen nanofibrous membrane can effectively promote outcomes of tendon reconstruction in a rabbit model. The composite biodegradable polymeric system may be useful in humans for tendon reconstruction. Keywords: polylactide–polyglycolide nanofibers, PLGA, collagen, 3D printing, polylactide, PLA, bone-anchoring bolts, tendon healing

The impact of nicotine on bone healing and osseointegration

DEFF Research Database (Denmark)

Balatsouka, Dimitra; Gotfredsen, Klaus; Lindh, Christian H

2005-01-01

OBJECTIVES: To examine the short-term effect of nicotine on bone healing and osseointegration. MATERIAL AND METHODS: Sixteen female rabbits were divided into two groups. The test group was exposed to nicotine tartrate for 8 weeks and the control group was exposed to placebo. Nicotine or placebo...... was administered via a miniosmotic pump and plasma cotinine levels were measured weekly. The pump delivered 15 mg of nicotine/day for the animals in the test group. All rabbits had three tibial bone preparations. In the proximal and distal bone bed, implants were placed after 4 weeks (right tibia) and after 6...... and the control group. CONCLUSION: Nicotine exposure in a short period of time did not have a significant impact on bone healing or implant osseointegration in rabbits....

The effects of surgicel and bone wax hemostatic agents on bone healing: An experimental study

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Nasser Nooh

2014-01-01

Full Text Available Background: The biological effects of hemostatic agends on the physiological healing process need to be tested. The aim of this study was to assess the effects of oxidized cellulose (surgicel and bone wax on bone healing in goats′ feet. Materials and Methods: Three congruent circular bone defects were created on the lateral aspects of the right and left metacarpal bones of ten goats. One defect was left unfilled and acted as a control; the remaining two defects were filled with bone wax and surgicel respectively. The 10 animals were divided into two groups of 5 animals each, to be sacrificed at the 3rd and 5th week postoperatively. Histological analysis assessing quality of bone formed and micro-computed tomography (MCT measuring the quantities of bone volume (BV and bone density (BD were performed. The results of MCT analysis pertaining to BV and BD were statistically analyzed using two-way analysis of variance (ANOVA and posthoc least significant difference tests. Results: Histological analysis at 3 weeks showed granulation tissue with new bone formation in the control defects, active bone formation only at the borders for surgicel filled defects and fibrous encapsulation with foreign body reaction in the bone wax filled defects. At 5 weeks, the control and surgicel filled defects showed greater bone formation; however the control defects had the greatest amount of new bone. Bone wax filled defects showed very little bone formation. The two-way ANOVA for MCT results showed significant differences for BV and BD between the different hemostatic agents during the two examination periods. Conclusion: Surgicel has superiority over bone wax in terms of osseous healing. Bone wax significantly hinders osteogenesis and induces inflammation.

Clinical factors affecting pathological fracture and healing of unicameral bone cysts.

Science.gov (United States)

Urakawa, Hiroshi; Tsukushi, Satoshi; Hosono, Kozo; Sugiura, Hideshi; Yamada, Kenji; Yamada, Yoshihisa; Kozawa, Eiji; Arai, Eisuke; Futamura, Naohisa; Ishiguro, Naoki; Nishida, Yoshihiro

2014-05-17

Unicameral bone cyst (UBC) is the most common benign lytic bone lesion seen in children. The aim of this study is to investigate clinical factors affecting pathological fracture and healing of UBC. We retrospectively reviewed 155 UBC patients who consulted Nagoya musculoskeletal oncology group hospitals in Japan. Sixty of the 155 patients had pathological fracture at presentation. Of 141 patients with follow-up periods exceeding 6 months, 77 were followed conservatively and 64 treated by surgery. The fracture risk was significantly higher in the humerus than other bones. In multivariate analysis, ballooning of bone, cyst in long bone, male sex, thin cortical thickness and multilocular cyst were significant adverse prognostic factors for pathological fractures at presentation. The healing rates were 30% and 83% with observation and surgery, respectively. Multivariate analysis revealed that fracture at presentation and history of biopsy were good prognostic factors for healing of UBC in patients under observation. The present results suggest that mechanical disruption of UBC such as fracture and biopsy promotes healing, and thus watchful waiting is indicated in these patients, whereas patients with poor prognostic factors for fractures should be considered for surgery.

The effects of low-intensity pulsed ultrasound on tendon-bone healing in a transosseous-equivalent sheep rotator cuff model.

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Lovric, Vedran; Ledger, Michael; Goldberg, Jerome; Harper, Wade; Bertollo, Nicky; Pelletier, Matthew H; Oliver, Rema A; Yu, Yan; Walsh, William R

2013-02-01

The purpose of this study was to examine the effects Low-intensity Pulsed Ultrasound has on initial tendon-bone healing in a clinically relevant extra-articular transosseous-equivalent ovine rotator cuff model. Eight skeletally mature wethers, randomly allocated to either control group (n = 4) or treatment group (n = 4), underwent rotator cuff surgery following injury to the infraspinatus tendon. All animals were killed 28 days post surgery to allow examination of early effects of Low-intensity Pulsed Ultrasound treatment. General improvement in histological appearance of tendon-bone integration was noted in the treatment group. Newly formed woven bone with increased osteoblast activity along the bone surface was evident. A continuum was observed between the tendon and bone in an interdigitated fashion with Sharpey's fibres noted in the treatment group. Low-intensity Pulsed Ultrasound treatment also increased bone mineral density at the tendon-bone interface (p < 0.01), while immunohistochemistry results revealed an increase in the protein expression patterns of VEGF (p = 0.038), RUNX2 (p = 0.02) and Smad4 (p = 0.05). The results of this study indicate that Low-intensity Pulsed Ultrasound may aid in the initial phase of tendon-bone healing process in patients who have undergone rotator cuff repair. This treatment may also be beneficial following other types of reconstructive surgeries involving the tendon-bone interface.

Vitamin E and the Healing of Bone Fracture: The Current State of Evidence

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Boekhtiar Borhanuddin

2012-01-01

Full Text Available Background. The effect of vitamin E on health-related conditions has been extensively researched, with varied results. However, to date, there was no published review of the effect of vitamin E on bone fracture healing. Purpose. This paper systematically audited past studies of the effect of vitamin E on bone fracture healing. Methods. Related articles were identified from Medline, CINAHL, and Scopus databases. Screenings were performed based on the criteria that the study must be an original study that investigated the independent effect of vitamin E on bone fracture healing. Data were extracted using standardised forms, followed by evaluation of quality of reporting using ARRIVE Guidelines, plus recalculation procedure for the effect size and statistical power of the results. Results. Six animal studies fulfilled the selection criteria. The study methods were heterogeneous with mediocre reporting quality and focused on the antioxidant-related mechanism of vitamin E. The metasynthesis showed α-tocopherol may have a significant effect on bone formation during the normal bone remodeling phase of secondary bone healing. Conclusion. In general, the effect of vitamin E on bone fracture healing remained inconclusive due to the small number of heterogeneous and mediocre studies included in this paper.

Impaired bone healing at tooth extraction sites in CD24-deficient mice: A pilot study.

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Avivi-Arber, Limor; Avivi, Doran; Perez, Marilena; Arber, Nadir; Shapira, Shiran

2018-01-01

To use a micro-computed tomography (micro-CT) to quantify bone healing at maxillary first molar extraction sites, and test the hypothesis that bone healing is impaired in CD24-knockout mice as compared with wild-type C57BL/6J mice. Under ketamine-xylazine general anaesthesia, mice had either extraction of the right maxillary first molar tooth or sham operation. Mice were sacrificed 1 (n = 12/group), 2 (n = 6/group) or 4 (n = 6/group) weeks postoperatively. The right maxillae was disected. Micro-CT was used to quantify differences in bone microstructural features at extrction sites, between CD24-knockout mice and wild-type mice. CD24-Knockout mice displayed impaired bone healing at extraction sites that was manifested as decreased trabecular bone density, and decreased number and thickness of trabeculae. This pilot study suggests that CD24 plays an important role in extraction socket bone healing and may be used as a novel biomarker of bone quality and potential therapeutic target to improve bone healing and density following alveolar bone injury.

Bone compositional study during healing of subcritical calvarial defects in rats by Raman spectroscopy

Science.gov (United States)

Ahmed, Rafay; Wing Lun Law, Alan; Cheung, Tsz Wing; Lau, Condon

2017-07-01

Subcritical calvarial defects are important to study bone regeneration during healing. In this study 1mm calvarial defects were created using trephine in the parietal bones of Sprague-Dawley rats (n=7) that served as in vivo defects. Subjects were sacrificed after 7 days and the additional defects were created on the harvested skull with the same method to serve as control defects. Raman spectroscopy is established to investigate mineral/matrix ratio, carbonate/phosphate ratio and crystallinity of three different surfaces; in vivo defects, control defects and normal surface. Results show 21% and 23% decrease in mineral/matrix after 7 days of healing from surface to in vivo and control to in vivo defects, respectively. Carbonate to phosphate ratio was found to be increased by 39% while crystallinity decreased by 26% in both surface to in vivo and control to in vivo defects. This model allows to study the regenerated bone without mechanically perturbing healing surface.

Bone graft healing in alveolar osteoplasty in patients with unilateral lip, alveolar process, and palate clefts.

Science.gov (United States)

Rychlik, Dariusz; Wójcicki, Piotr

2012-01-01

Secondary osteoplasty by means of autogenic spongy bone grafting is the most common procedure used in the reconstruction of the continuity of the maxillary alveolar process. The aim of the study was to analyze retrospectively the effect of certain factors on the course of the bone graft healing process in patients with unilateral complete clefts of the lip, alveolar process, and palate. The investigations involved 62 children aged 8 to 14 years (mean age, 11 years) with unilateral complete cleft of the lip, alveolar process, and palate operated on at the Clinic of Plastic Surgery in Polanica Zdrój from November 2007 to April 2009. All the procedures consisted in the reconstruction of the maxillary alveolar process by means of autogenic spongy bone grafting from the iliac bone. The analysis was performed on the basis of computed tomography scans presenting maxillary alveolar processes in the horizontal cross-sectional planes performed on the second or third postoperative day and after 6 months. They were used as the basis for the measurement of the volume and density (condensation) of the bone graft, the surface of its adhesion to the maxillary alveolar bone, and the volume and density of the healed bone. The following correlation coefficients were determined: between the adhesion surface of the bone to the alveolar bone and the volume of the healed bone, between the adhesion surface of the bone to the alveolar bone and the density of the healed bone, and between the density of the graft and the volume of the healed bone. Increasing the surface of the graft adhesion to the bone ridges of the alveolar cleft contributes to increased volume of the healed bone and slows down the increase in its density (on 6-month follow-up). Crushing of the bone graft increases its resorption and reduces volume of the healed bone.

Reaming debris as a novel source of autologous bone to enhance healing of bone defects

NARCIS (Netherlands)

Bakker, A.D.; Kroeze, R.J.; Korstjens, C.; de Kleine, R.H.; Frolke, J.P.M.; Klein-Nulend, J.

2011-01-01

Reaming debris is formed when bone defects are stabilized with an intramedullary nail, and contains viable osteoblast-like cells and growth factors, and might thus act as a natural osteoinductive scaffold. The advantage of using reaming debris over stem cells or autologous bone for healing bone

Reaming debris as a novel source of autologous bone to enhance healing of bone defects

NARCIS (Netherlands)

Bakker, Astrid D.; Kroeze, Robert Jan; Korstjens, Clara; de Kleine, Ruben H.; Frolke, Jan Paul M.; Klein-Nulend, Jenneke

Reaming debris is formed when bone defects are stabilized with an intramedullary nail, and contains viable osteoblast-like cells and growth factors, and might thus act as a natural osteoinductive scaffold. The advantage of using reaming debris over stem cells or autologous bone for healing bone

Bone marrow-derived mesenchymal stem cells influence early tendon-healing in a rabbit achilles tendon model.

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Chong, Alphonsus K S; Ang, Abel D; Goh, James C H; Hui, James H P; Lim, Aymeric Y T; Lee, Eng Hin; Lim, Beng Hai

2007-01-01

A repaired tendon needs to be protected for weeks until it has accrued enough strength to handle physiological loads. Tissue-engineering techniques have shown promise in the treatment of tendon and ligament defects. The present study tested the hypothesis that bone marrow-derived mesenchymal stem cells can accelerate tendon-healing after primary repair of a tendon injury in a rabbit model. Fifty-seven New Zealand White rabbits were used as the experimental animals, and seven others were used as the source of bone marrow-derived mesenchymal stem cells. The injury model was a sharp complete transection through the midsubstance of the Achilles tendon. The transected tendon was immediately repaired with use of a modified Kessler suture and a running epitendinous suture. Both limbs were used, and each side was randomized to receive either bone marrow-derived mesenchymal stem cells in a fibrin carrier or fibrin carrier alone (control). Postoperatively, the rabbits were not immobilized. Specimens were harvested at one, three, six, and twelve weeks for analysis, which included evaluation of gross morphology (sixty-two specimens), cell tracing (twelve specimens), histological assessment (forty specimens), immunohistochemistry studies (thirty specimens), morphometric analysis (forty specimens), and mechanical testing (sixty-two specimens). There were no differences between the two groups with regard to the gross morphology of the tendons. The fibrin had degraded by three weeks. Cell tracing showed that labeled bone marrow-derived mesenchymal stem cells remained viable and present in the intratendinous region for at least six weeks, becoming more diffuse at later time-periods. At three weeks, collagen fibers appeared more organized and there were better morphometric nuclear parameters in the treatment group (p tendon repair can improve histological and biomechanical parameters in the early stages of tendon-healing.

Pulsed electromagnetic field therapy improves tendon-to-bone healing in a rat rotator cuff repair model.

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Tucker, Jennica J; Cirone, James M; Morris, Tyler R; Nuss, Courtney A; Huegel, Julianne; Waldorff, Erik I; Zhang, Nianli; Ryaby, James T; Soslowsky, Louis J

2017-04-01

Rotator cuff tears are common musculoskeletal injuries often requiring surgical intervention with high failure rates. Currently, pulsed electromagnetic fields (PEMFs) are used for treatment of long-bone fracture and lumbar and cervical spine fusion surgery. Clinical studies examining the effects of PEMF on soft tissue healing show promising results. Therefore, we investigated the role of PEMF on rotator cuff healing using a rat rotator cuff repair model. We hypothesized that PEMF exposure following rotator cuff repair would improve tendon mechanical properties, tissue morphology, and alter in vivo joint function. Seventy adult male Sprague-Dawley rats were assigned to three groups: bilateral repair with PEMF (n = 30), bilateral repair followed by cage activity (n = 30), and uninjured control with cage activity (n = 10). Rats in the surgical groups were sacrificed at 4, 8, and 16 weeks. Control group was sacrificed at 8 weeks. Passive joint mechanics and gait analysis were assessed over time. Biomechanical analysis and μCT was performed on left shoulders; histological analysis on right shoulders. Results indicate no differences in passive joint mechanics and ambulation. At 4 weeks the PEMF group had decreased cross-sectional area and increased modulus and maximum stress. At 8 weeks the PEMF group had increased modulus and more rounded cells in the midsubstance. At 16 weeks the PEMF group had improved bone quality. Therefore, results indicate that PEMF improves early tendon healing and does not alter joint function in a rat rotator cuff repair model. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:902-909, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

The roles of cellular and molecular components of a hematoma at early stage of bone healing.

Science.gov (United States)

Shiu, Hoi Ting; Leung, Ping Chung; Ko, Chun Hay

2018-04-01

Bone healing is a complex repair process that commences with the formation of a blood clot at the injured bone, termed hematoma. It has evidenced that a lack of a stable hematoma causes delayed bone healing or non-union. The hematoma at the injured bone constitutes the early healing microenvironment. It appears to dictate healing pathways that ends in a regenerative bone. However, the hematoma is often clinically removed from the damaged site. Conversely, blood-derived products have been used in bone tissue engineering for treating critical sized defects, including fibrin gels and platelet-rich plasma. A second generation of platelet concentrate that is based on leukocyte and fibrin content has also been developed and introduced in market. Conflicting effect of these products in bone repair are reported. We propose that the bone healing response becomes dysregulated if the blood response and subsequent formation and properties of a hematoma are altered. This review focuses on the central structural, cellular, and molecular components of a fracture hematoma, with a major emphasis on their roles in regulating bone healing mechanism, and their interactions with mesenchymal stem cells. New angles towards a better understanding of these factors and relevant mechanisms involved at the beginning of bone healing may help to clarify limited or adverse effects of blood-derived products on bone repair. We emphasize that the recreation of an early hematoma niche with critical compositions might emerge as a viable therapeutic strategy for enhanced skeletal tissue engineering. Copyright © 2017 John Wiley & Sons, Ltd.

Scintigraphic control of bone-fracture healing under ultrasonic stimulation: An animal experimental study

International Nuclear Information System (INIS)

Klug, W.; Franke, W.G.; Knoch, H.G.

1986-01-01

In a model of closed lower-leg fracture in rabbits and of secondary bone-fracture healing, scintigraphic control until biological healing was performed. Biological fracture healing was assumed for a region of interest (ROI)-activity ratio close to 1.0. After application of sup(99m)Tc-HEDP, 151 examinations were performed. ROI activity increased significantly until day 14 p.i. and reached the maximum value (Q=6.44) on day 14 postfracture. Sixty-one lower leg fractures were treated by ultrasound from days 14-28 postfractures. These stimulated fractures were biologically healed on day 168 postfracture. The fractures that were not treated by ultrasound could not be detected by scanning after day 203 postfracture. (orig.)

[Influence of implants prepared by selective laser melting on early bone healing].

Science.gov (United States)

Liu, J Y; Chen, F; Ge, Y J; Wei, L; Pan, S X; Feng, H L

2018-02-18

To evaluate the influence of the rough surface of dental implants prepared by selective laser melting (SLM) on early bone healing around titanium implants. A total of sixteen titanium implants were involved in our research, of which eight implants were prepared by SLM (TIXOS Cylindrical, Leader-Novaxa, Milan, Italy; 3.3 mm×10 mm, internal hex) and the other eight were sandblasted, large-grit and acid-etched (SLA) implants (IMPLUS Cylindrical, Leader-Novaxa, Milan, Italy; 3.3 mm×10 mm, internal hex). All of the dental implants were inserted into the healed extraction sockets of the mandible of two adult male Beagle dogs. Half of the dental implants were designed to be healed beneath the mucosa and the other half were intended to be healed transgingivally and were immediately loaded by acrylic resin bridge restoration. Three types of tetracycline fluorescent labels, namely calcein blue, alizarin complexone and calcein, were administered into the veins of the Beagle dogs 2, 4, and 8 weeks after implant placement respectively for fluorescent evaluation of newly formed bone peri-implant. Both Beagle dogs were euthanized 12 weeks after implant insertion and the mandible block specimens containing the titanium implants and surrounding bone and soft tissue of each dog were carefully sectioned and dissected. A total of 16 hard tissue slices were obtained and stained with toluidine blue for microscopic examination and histomorphometric measurements. Histological observation was made for each slice under light microscope and laser scanning confocal microscope (LSCM). Comparison on new bone formation around titanium implants of each group was made and mineral apposition rate (MAR) was calculated for each group. Dental implants prepared by selective laser melting had achieved satisfying osseointegration to surrounding bone tissue after the healing period of 12 weeks. Newly formed bone tissue was observed creeping on the highly porous surface of the SLM implant and growing

Healing of extraction sockets filled with BoneCeramic® prior to implant placement: preliminary histological findings.

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De Coster, Peter; Browaeys, Hilde; De Bruyn, Hugo

2011-03-01

Various grafting materials have been designed to minimize edentulous ridge volume loss following tooth extraction by encouraging new bone formation in healing sockets. BoneCeramic® is a composite of hydroxyapatite and bèta-tricalcium phosphate with pores of 100-500 microns. The aim of this study was to evaluate bone regeneration in healing sockets substituted with BoneCeramic® prior to implant procedures. Fifteen extraction sockets were substituted with BoneCeramic® and 14 sockets were left to heal naturally in 10 patients (mean age 59.6 years). Biopsies were collected only from the implant recipient sites during surgery after healing periods ranging from 6-74 weeks (mean 22). In total, 24 biopsies were available; 10 from substituted and 14 from naturally healed sites. In one site, the implant was not placed intentionally and, in four substituted sites, implant placement had to be postponed due to inappropriate healing, hence from five sites biopsies were not available. Histological sections were examined by transmitted light microscope. At the time of implant surgery, bone at substituted sites was softer than in controls, compromising initial implant stability. New bone formation at substituted sites was consistently poorer than in controls, presenting predominantly loose connective tissue and less woven bone. The use of BoneCeramic® as a grafting material in fresh extraction sockets appears to interfere with normal healing processes of the alveolar bone. On the basis of the present preliminary findings, its indication as a material for bone augmentation, when implant placement is considered within 6-38 weeks after extraction, should be revised. © 2009, Copyright the Authors. Journal Compilation © 2011, Wiley Periodicals, Inc.

Influence of bioactive material coating of Ti dental implant surfaces on early healing and osseointegration of bone

International Nuclear Information System (INIS)

Yeo, In-Sung; Min, Seung-Ki; An, Young-Bai

2010-01-01

The dental implant surface type is one of many factors that determine the long-term clinical success of implant restoration. The implant surface consists of bioinert titanium oxide, but recently coatings with bioactive calcium phosphate ceramics have often been used on Ti implant surfaces. Bio-active surfaces are known to significantly improve the healing time of the human bone around the inserted dental implant. In this study, we characterized two types of coated implant surfaces by scanning electron microscopy, energy dispersive spectrometry, and surface roughness testing. The effect of surface modification on early bone healing was then tested by using the rabbit tibia model to measure bone-to-implant contact ratios and removal torque values. These modified surfaces showed different characteristics in terms of surface topography, chemical composition, and surface roughness. However, no significant differences were found in the bone-to-implant contact and the resistance to removal torque between these surfaces. Both the coated implants may induce similar favorable early bone responses in terms of the early functioning and healing of dental implants even though they differed in their surface characteristics.

Effect of Ankaferd Blood Stopper on Early Bone Tissue Healing in ...

African Journals Online (AJOL)

Keywords: Ankaferd blood stopper, Wound healing, Mineralized bone tissue, Inflammatory cell infiltration ... protein network formation with blood cells covers the primary and .... bone repair and regeneration, antibiotics and antimicrobial ...

Hyaluronic Acid Accelerates Tendon-to-Bone Healing After Rotator Cuff Repair.

Science.gov (United States)

Honda, Hirokazu; Gotoh, Masafumi; Kanazawa, Tomonoshin; Ohzono, Hiroki; Nakamura, Hidehiro; Ohta, Keisuke; Nakamura, Kei-Ichiro; Fukuda, Kanji; Teramura, Takeshi; Hashimoto, Takashi; Shichijo, Shigeki; Shiba, Naoto

2017-12-01

There is growing evidence that the subacromial injection of hyaluronic acid (HA) is effective for pain relief in rotator cuff tears; however, its effect on tendon-to-bone healing remains unknown. To examine the effect of HA on the chondrogenesis of mesenchymal stem cells (MSCs) in vitro and on tendon-to-bone healing in a rotator cuff repair model. Controlled laboratory study. Bilateral complete tears of the infraspinatus tendon were made in rabbits and subsequently repaired. Before closure, 1 mL HA was applied to the repaired site, and phosphate-buffered saline was used in the opposite side as a control. Biomechanical, histological, and immunohistochemical analyses were performed at 4, 8, and 12 weeks after surgery. After euthanizing each animal, the bone marrow was isolated from the femoral bone in the same rabbits. Then, MSCs were cultured in media for chondrogenic differentiation, and the chondral pellet production and cartilage-related gene expression levels in the cells were examined at various concentrations of HA. At 4 and 8 weeks after surgery, ultimate load-to-failure was significantly greater in the HA group than in the control group (45.61 ± 9.0 N vs 32.42 ± 9.4 N at 4 weeks, 90.7 ± 16.0 N vs 66.97 ± 10.0 N at 8 weeks; both P .05). Linear stiffness was not significant throughout the time point evaluation. The chondroid formation area at the tendon-bone interface stained by safranin O (control vs HA group) was 0.33% ± 0.7% versus 13.5% ± 12.3% at 4 weeks after surgery ( P repaired site stained by PicroSirius Red (control vs HA group) was 16.2 ± 10.6 versus 43.5 ± 21.3 at 4 weeks after surgery ( P .05), and 1.8% ± 4.0% versus 5.4% ± 4.2% at 12 weeks after surgery ( P > .05). Compared with the control group, HA significantly increased the volume of cartilaginous pellet produced by MSCs (0.0016 ± 0.0015 mm 3 at 0 mg/mL of HA, 0.0041 ± 0.0023 mm 3 at 1.0 mg/mL, and 0.0041 ± 0.0018 mm 3 at 4.0 mg/mL), with increased mRNA expression (relative ratio

Smoking and Bone Healing - A Risky Surgical Combination

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... Risky Surgical Combination A A A | Print | Share Smoking and Bone Healing – A Risky Surgical Combination Imagine ... saying that they'd prefer patients to quit smoking. There hasn't been a great deal of ...

Present status and future potential of enhancing bone healing using nanotechnology.

Science.gov (United States)

Stylios, George; Wan, Taoyu; Giannoudis, Peter

2007-03-01

An overview of the current state of tissue engineering material systems used in bone healing is presented. A variety of fabrication processes have been developed that have resulted in porous implant substrates that can address unresolved clinical problems. The merits of these biomaterial systems are evaluated in the context of the mechanical properties and biomedical performances most suitable for bone healing. An optimal scaffold for bone tissue engineering applications should be biocompatible and act as a 3D template for in vitro and in vivo bone growth; in addition, its degradation products should be non-toxic and easily excreted by the body. To achieve these features, scaffolds must consist of an interconnected porous network of micro- and nanoscale to allow extensive body fluid transport through the pores, which will trigger bone ingrowth, cell migration, tissue ingrowth, and eventually vascularization.

The accuracy of the imaging reformation of cone beam computed tomography for the assessment of bone defect healing

International Nuclear Information System (INIS)

Kang, Ho Duk; Kim, Gyu Tae; Choi, Yong Suk; Hwang, Eui Hwan

2007-01-01

To evaluate the accuracy of the imaging reformation of cone beam computed tomography for the assessment of bone defect healing in rat model. Sprague-Dawely strain rats weighing about 350 gms were selected. Then critical size bone defects were done at parietal bone with implantation of collagen sponge. The rats were divided into seven groups of 3 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 6 weeks, and 8 weeks. The healing of surgical defect was assessed by multiplanar reconstruction (MPR) images and three-dimensional (3-D) images of cone beam computed tomography, compared with soft X-ray radiograph and histopathologic examination. MPR images and 3-D images showed similar reformation of the healing amount at 3 days, 1 week, 2 weeks, and 8 weeks, however, lower reformation at 3 weeks, 4 weeks, and 6 weeks. According to imaging-based methodologies, MPR images revealed similar reformation of the healing mount than 3-D images compare with soft X-ray image. Among the four threshold values for 3-D images, 400-500 HU revealed similar reformation of the healing amount. Histopathologic examination confirmed the newly formed trabeculation correspond with imaging-based mythologies. MPR images revealed higher accuracy of the imaging reformation of cone beam computed tomography and cone beam computed tomography is a clinically useful diagnostic tool for the assessment of bone defect healing

Bone modelling at fresh extraction sockets: immediate implant placement versus spontaneous healing: an experimental study in the beagle dog.

Science.gov (United States)

Vignoletti, Fabio; Discepoli, Nicola; Müller, Anna; de Sanctis, Massimo; Muñoz, Fernando; Sanz, Mariano

2012-01-01

The purpose of this investigation is to describe histologically the undisturbed healing of fresh extraction sockets when compared to immediate implant placement. In eight beagle dogs, after extraction of the 3P3 and 4P4, implants were inserted into the distal sockets of the premolars, while the mesial sockets were left to heal spontaneously. Each animal provided four socket sites (control) and four implant sites (test). After 6 weeks, animals were sacrificed and tissue blocks were dissected, prepared for ground sectioning. The relative vertical buccal bone resorption in relation to the lingual bone was similar in both test and control groups. At immediate implant sites, however, the absolute buccal bone loss observed was 2.32 (SD 0.36) mm, what may indicate that while an apical shift of both the buccal and lingual bone crest occurred at the implant sites, this may not happen in naturally healing sockets. The results from this investigation showed that after tooth extraction the buccal socket wall underwent bone resorption at both test and control sites. This resorption appeared to be more pronounced at the implant sites, although the limitations of the histological evaluation method utilized preclude a definite conclusion. © 2011 John Wiley & Sons A/S.

Use of Radiographic Densitometry to Predict the Bone Healing Index in Distraction Osteogenesis

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A Saw

2008-04-01

Full Text Available Bone lengthening with distraction osteogenesis involves prolonged application of an external fixator frame. Qualitative and quantitative evaluation of callus has been described using various imaging modalities but there is no simple reliable and readily available method. This study aims to investigate the use of a densitometer to analyze plain radiographic images and correlate them with the rate of new bone formation as represented by the bone healing index. A total of 34 bone lengthening procedures in 29 patients were retrospectively reviewed. We used an X-Rite 301 densitometer to measure densities of new callus on plain radiographs taken at 4 and 8 weeks after surgery. Patients aged below 16y had significantly lower BHIs indicating faster bone healing and shorter duration of treatment. The ratio of radiographic densities between centre and edge of the new bone measured from plain radiographs taken at 8 weeks correlated positively with the eventual BHI of the patient. This method provides a simple and easy way to predict the rate of bone healing at an early stage of treatment and may also allow remedial action to be taken for those with poor progress in bone formation.

Chitosan nanofiber scaffold improves bone healing via stimulating trabecular bone production due to upregulation of the Runx2/osteocalcin/alkaline phosphatase signaling pathway

Science.gov (United States)

Ho, Ming-Hua; Yao, Chih-Jung; Liao, Mei-Hsiu; Lin, Pei-I; Liu, Shing-Hwa; Chen, Ruei-Ming

2015-01-01

Osteoblasts play critical roles in bone formation. Our previous study showed that chitosan nanofibers can stimulate osteoblast proliferation and maturation. This translational study used an animal model of bone defects to evaluate the effects of chitosan nanofiber scaffolds on bone healing and the possible mechanisms. In this study, we produced uniform chitosan nanofibers with fiber diameters of approximately 200 nm. A bone defect was surgically created in the proximal femurs of male C57LB/6 mice, and then the left femur was implanted with chitosan nanofiber scaffolds for 21 days and compared with the right femur, which served as a control. Histological analyses revealed that implantation of chitosan nanofiber scaffolds did not lead to hepatotoxicity or nephrotoxicity. Instead, imaging analyses by X-ray transmission and microcomputed tomography showed that implantation of chitosan nanofiber scaffolds improved bone healing compared with the control group. In parallel, microcomputed tomography and bone histomorphometric assays further demonstrated augmentation of the production of new trabecular bone in the chitosan nanofiber-treated group. Furthermore, implantation of chitosan nanofiber scaffolds led to a significant increase in the trabecular bone thickness but a reduction in the trabecular parameter factor. As to the mechanisms, analysis by confocal microscopy showed that implantation of chitosan nanofiber scaffolds increased levels of Runt-related transcription factor 2 (Runx2), a key transcription factor that regulates osteogenesis, in the bone defect sites. Successively, amounts of alkaline phosphatase and osteocalcin, two typical biomarkers that can simulate bone maturation, were augmented following implantation of chitosan nanofiber scaffolds. Taken together, this translational study showed a beneficial effect of chitosan nanofiber scaffolds on bone healing through stimulating trabecular bone production due to upregulation of Runx2-mediated alkaline

New treatment of periodontal diseases by using NF-kappaB decoy oligodeoxynucleotides via prevention of bone resorption and promotion of wound healing.

Science.gov (United States)

Shimizu, Hideo; Nakagami, Hironori; Morita, Shosuke; Tsukamoto, Ikuyo; Osako, Mariana Kiomy; Nakagami, Futoshi; Shimosato, Takashi; Minobe, Noriko; Morishita, Ryuichi

2009-09-01

Nuclear factor-kappa B (NF-kappaB) is involved in osteoclast differentiation and activation. Thus, the blockade of the NF-kappaB pathway might be a novel therapeutic strategy for treating bone metabolic diseases. Periodontitis is subgingival inflammation caused by bacterial infection; this disease also is thought to be a chronic focal point responsible for systemic diseases. In this study, NF-kappaB decoy oligodeoxynucleotides (ODNs) were topically applied for experimental periodontitis in a debris-accumulation model and wound healing in a bone-defect model of beagle dogs to investigate the effect of decoy ODN on bone metabolism. Application of NF-kappaB decoy ODN significantly reduced interleukin-6 activity in crevicular fluid and improved alveolar bone loss in the analysis of dental radiographs and DEXA. Direct measurement of exposed root that lost alveolar bone support revealed that NF-kappaB decoy treatment dramatically protected bone from loss. In a bone-defect model, NF-kappaB decoy ODN promoted the healing process as compared with control scrambled decoy in micro-CT analysis. Overall, inhibition of NF-kappaB by decoy strategy prevented the progression of bone loss in periodontitis and promoted the wound healing in bone defects through the inhibition of osteoclastic bone resorption. Targeting of NF-kappaB might be a potential therapy in various bone metabolic diseases.

Strategies for delivering bone morphogenetic protein for bone healing

Energy Technology Data Exchange (ETDEWEB)

Begam, Howa [School of Bioscience and Engineering, Jadavpur University, Kolkata 700032 (India); Nandi, Samit Kumar, E-mail: samitnandi1967@gmail.com [Department of Veterinary Surgery, Radiology West Bengal University of Animal and Fishery Sciences, Kolkata 700037 (India); Kundu, Biswanath, E-mail: biswa_kundu@rediffmail.com [Bioceramics and Coating Division, CSIR-Central Glass and Ceramic Research Institute, Kolkata 700032 (India); Chanda, Abhijit [Department of Mechanical Engineering, Jadavpur University, Kolkata 700032 (India)

2017-01-01

Bone morphogenetic proteins (BMPs) are the most significant growth factors that belong to the Transforming Growth Factor Beta (TGF-β) super-family. Though more than twenty members of this family have been identified so far in humans, Food and Drug Administration (FDA) approved two growth factors: BMP-2 and BMP-7 for treatments of spinal fusion and long-bone fractures with collagen carriers. Currently BMPs are clinically used in spinal fusion, oral and maxillofacial surgery and also in the repair of long bone defects. The efficiency of BMPs depends a lot on the selection of suitable carriers. At present, different types of carrier materials are used: natural and synthetic polymers, calcium phosphate and ceramic-polymer composite materials. Number of research articles has been published on the minute intricacies of the loading process and release kinetics of BMPs. Despite the significant evidence of its potential for bone healing demonstrated in animal models, future clinical investigations are needed to define dose, scaffold and route of administration. The efficacy and application of BMPs in various levels with a proper carrier and dose is yet to be established. The present article collates various aspects of success and limitation and identifies the prospects and challenges associated with the use of BMPs in orthopaedic surgery. - Highlights: • Currently BMPs are clinically used in spinal fusion, oral and maxillofacial surgery and also in repair of long bone defects. • Different types of carrier materials are used: natural, synthetic polymers, calcium phosphate and ceramic-polymer composite • Efficacy and application of BMPs in various levels with proper carrier and dose is yet to be established • Number of research articles has been published on minute intricacies of loading process and release kinetics of BMPs • Present article collates success, limitation and identifies prospects, challenges for use of BMPs in orthopaedic surgery.

Effect of synthetic cell-binding peptide on the healing of cortical segmental bone defects

International Nuclear Information System (INIS)

Cakmak, G.; Bolukbasi, S.; Simsek, A.; Senkoylu, A.; Erdem, O.; Yilmaz, G.

2006-01-01

To determine the effect of inorganic bone matric/Pepgen P-15 (ABM/P-15) on the healing of a critical sized segmental defect in a rat radius using a radiological and histological grading system. We carried out this study at the Research Laboratories, Gazi University School of Medicine in 2004. Critical sized segmental defects were created in the radius of 36 Wistar rats. Thirteen defects were filled with ABM/P-15 Flow (gel form), 12 defects were filled with ABM/P-15, and 11 defects were used as a control group. The rats were sacrified at the tenth week, and healing of the defects was evaluated radiographically and histologically. The usage of ABM/P-15 and ABM/P-15 Flow were demonstrated to improve healing of segmental bone defects compared with the control group. Statistical evaluation showed that there were significant differences between control sites, and the sites treated with P-15 and P-15 Flow (p=0.011). The highest radiological and histological grades were achieved by P-15. Segmental cortical bone defects may be treated with ABM/P-15 instead of bone allografts, and autografts. According to the radiological and histological parameters measured in this study, the implantation of ABM/P-15 resulted in optimum healing of the segmental cortical bone defects. Pepgen P-15 has a positive effect on bone healing, without any immunogenic features and disease transmission risk. Therefore, ABM/P-15 can also be used for orthopedic surgery. (author)

Bone Healing in Extraction Sockets Covered With Collagen Membrane Alone or Associated With Porcine-Derived Bone Graft: a Comparative Histological and Histomorphometric Analysis.

Science.gov (United States)

Guarnieri, Renzo; Testarelli, Luca; Stefanelli, Luigi; De Angelis, Francesca; Mencio, Francesca; Pompa, Giorgio; Di Carlo, Stefano

2017-01-01

The present paper reports data of a randomized study aimed to analyse and compare the histologic and histomorphometric aspects of bone healing in extraction sites covered with collagen membrane alone or associated with porcine-derived bone graft. Thirty patients, with single extraction sockets without severe bone wall defects in the premolar/molar region, were included. Ten extraction sockets were grafted with porcine-derived bone and covered with collagen membrane (group 1), 10 sites were covered with collagen membrane alone (group 2), and 10 sites healed spontaneously (group 3). After 4 months of healing, 26 (8 in group 1, 9 in group 2, and 9 in group 3) bone core specimens were harvested for histologic evaluation, then dental implants were placed. Sites in the group 1 and in the group 2 showed similar histologic and histomorphometric results without significantly differences in the percentage of vital bone (57.43% [SD 4.8] vs. 60.01% [SD 3.2]), and non-mineralized connective tissue 22.99% (SD 5.3) vs. 18.53% (SD 6.2). In group 1 a 16.57% (SD 3.8) of residual material was found. Results showed that the use of collagen membrane alone or associated to porcine-derived bone improves the healing bone process compared to that of extraction sites spontaneously healed. Moreover, histomorphometric data related to bone quality, indicated that extraction sites without severe walls defects and with a vestibular bone thickness > 1.5 mm, treated with a low resorbtion rate collagen membrane alone, do not need more than 4 months for dental implant insertion.

Radiographic healing and remodelling of cortical and cancellous bone grafts after rigid plate fixation

International Nuclear Information System (INIS)

Waris, P.; Karaharju, E.; Slaetis, P.; Paavolainen, P.

1980-01-01

Cortical and cancellous interposition grafts, with rigid plate fixation, in the tibiofibular bones of 130 rabbits were followed radiographically for one year. The cancellous grafts healed earlier, but by 12 weeks both graft types had been incorporated, the distal host-graft interface being the last to heal. Progressive cancellous transformation in both the graft and host bone led to an increased over-all bone diameter, a widened medullary canal and a thinned porotic wall. (Auth.)

Bone healing around nanocrystalline hydroxyapatite, deproteinized bovine bone mineral, biphasic calcium phosphate, and autogenous bone in mandibular bone defects

DEFF Research Database (Denmark)

Broggini, Nina; Bosshardt, Dieter D; Jensen, Simon S

2015-01-01

The individual healing profile of a given bone substitute with respect to osteogenic potential and substitution rate must be considered when selecting adjunctive grafting materials for bone regeneration procedures. In this study, standardized mandibular defects in minipigs were filled...... with nanocrystalline hydroxyapatite (HA-SiO), deproteinized bovine bone mineral (DBBM), biphasic calcium phosphate (BCP) with a 60/40% HA/β-TCP (BCP 60/40) ratio, or particulate autogenous bone (A) for histological and histomorphometric analysis. At 2 weeks, percent filler amongst the test groups (DBBM (35.65%), HA......-SiO (34.47%), followed by BCP 60/40 (23.64%)) was significantly higher than the more rapidly substituted autogenous bone (17.1%). Autogenous bone yielded significantly more new bone (21.81%) over all test groups (4.91%-7.74%) and significantly more osteoid (5.53%) than BCP 60/40 (3%) and DBBM (2...

An experimental setup to evaluate innovative therapy options for the enhancement of bone healing using BMP as a benchmark – a pilot study

Directory of Open Access Journals (Sweden)

B Preininger

2012-04-01

Full Text Available Critical or delayed bone healing in rat osteotomy (OT models is mostly achieved through large defects or instability. We aimed to design a rat OT model for impaired bone healing based on age, gender and parity. The outcome should be controllable through variations of the haematoma in the OT including a bone morphogenetic protein (BMP 2 guided positive control.Using external fixation to stabilise femoral a 2 mm double OT in 12 month old, female Sprague Dawley rats after a minimum of 3 litters healing was characterised following in situ haematoma formation (ISH-group, transplantation of a BMP charged autologous blood clot (BMP-group and the artificial blood clot only (ABC-group into the OT-gap. In vivo micro-computer tomography (µCT scans were performed after 2, 4 and 6 weeks. After 6 weeks specimens underwent histological analyses.In µCT examinations and histological analyses no bony bridging was observed in all but one animal in the ISH-group. In the BMP group complete bridging was achieved in all animals. The ABC-group showed less mineralised tissue formation and smaller bridging scores during the course of healing than the ISH-group.In this pilot study we introduce a model for impaired bone healing taking the major biological risk factors into account. We could show that the in situ fracture haematoma is essential for bone regeneration. Using BMP as a positive control the presented experimental setup can serve to evaluate innovative therapeutical concepts in long bone application.

Monitoring of Postoperative Bone Healing Using Smart Trauma-Fixation Device With Integrated Self-Powered Piezo-Floating-Gate Sensors.

Science.gov (United States)

Borchani, Wassim; Aono, Kenji; Lajnef, Nizar; Chakrabartty, Shantanu

2016-07-01

Achieving better surgical outcomes in cases of traumatic bone fractures requires postoperative monitoring of changes in the growth and mechanical properties of the tissue and bones during the healing process. While current in-vivo imaging techniques can provide a snapshot of the extent of bone growth, it is unable to provide a history of the healing process, which is important if any corrective surgery is required. Monitoring the time evolution of in-vivo mechanical loads using existing technology is a challenge due to the need for continuous power while maintaining patient mobility and comfort. This paper investigates the feasibility of self-powered monitoring of the bone-healing process using our previously reported piezo-floating-gate (PFG) sensors. The sensors are directly integrated with a fixation device and operate by harvesting energy from microscale strain variations in the fixation structure. We show that the sensors can record and store the statistics of the strain evolution during the healing process for offline retrieval and analysis. Additionally, we present measurement results using a biomechanical phantom comprising of a femur fracture fixation plate; bone healing is emulated by inserting different materials, with gradually increasing elastic moduli, inside a fracture gap. The PFG sensor can effectively sense, compute, and record continuously evolving statistics of mechanical loading over a typical healing period of a bone, and the statistics could be used to differentiate between different bone-healing conditions. The proposed sensor presents a reliable objective technique to assess bone-healing progress and help decide on the removal time of the fixation device.

Physiological role of growth factors and bone morphogenetic proteins in osteogenesis and bone fracture healing: а review

Directory of Open Access Journals (Sweden)

S. Sagalovsky

2015-01-01

Full Text Available The repair of large bone defects remains a major clinical orthopedic challenge. Bone regeneration and fracture healing is a complex physiological mechanisms regulated by a large number of biologically active molecules. Multiple factors regulate this cascade of molecular events, which affects different stages in the osteoblast and chondroblast lineage during such processes as migration, proliferation, chemotaxis, differentiation, inhibition, and extracellular protein synthesis. A recent review has focused on the mechanisms by which growth and differentiation factors regulate the fracture healing process. Rapid progress in skeletal cellular and molecular biology has led to identification of many signaling molecules associated with formation of skeletal tissues, including a large family of growth factors (transforming growth factor-β and bone morphogenetic proteins, fibroblast growth factor, insulin-like growth factor, vascular endothelial growth factor, platelet-derived growth factor, cytokines and interleukins. There is increasing evidence indicating that they are critical regulators of cellular proliferation, differentiation, extracellular matrix biosynthesis and bone mineralization. A clear understanding of cellular and molecular pathways involved in fracture healing is not only critical for improvement of fracture treatments, but it may also enhance further our knowledge of mechanisms involved in skeletal growth and repair, as well as mechanisms of aging. This suggests that, in the future, they may play a major role in the treatment of bone disease and fracture repair.

The mechanical heterogeneity of the hard callus influences local tissue strains during bone healing: a finite element study based on sheep experiments.

Science.gov (United States)

Vetter, A; Liu, Y; Witt, F; Manjubala, I; Sander, O; Epari, D R; Fratzl, P; Duda, G N; Weinkamer, R

2011-02-03

During secondary fracture healing, various tissue types including new bone are formed. The local mechanical strains play an important role in tissue proliferation and differentiation. To further our mechanobiological understanding of fracture healing, a precise assessment of local strains is mandatory. Until now, static analyses using Finite Elements (FE) have assumed homogenous material properties. With the recent quantification of both the spatial tissue patterns (Vetter et al., 2010) and the development of elastic modulus of newly formed bone during healing (Manjubala et al., 2009), it is now possible to incorporate this heterogeneity. Therefore, the aim of this study is to investigate the effect of this heterogeneity on the strain patterns at six successive healing stages. The input data of the present work stemmed from a comprehensive cross-sectional study of sheep with a tibial osteotomy (Epari et al., 2006). In our FE model, each element containing bone was described by a bulk elastic modulus, which depended on both the local area fraction and the local elastic modulus of the bone material. The obtained strains were compared with the results of hypothetical FE models assuming homogeneous material properties. The differences in the spatial distributions of the strains between the heterogeneous and homogeneous FE models were interpreted using a current mechanobiological theory (Isakson et al., 2006). This interpretation showed that considering the heterogeneity of the hard callus is most important at the intermediate stages of healing, when cartilage transforms to bone via endochondral ossification. Copyright © 2010 Elsevier Ltd. All rights reserved.

A mechano-biological model of multi-tissue evolution in bone

Science.gov (United States)

Frame, Jamie; Rohan, Pierre-Yves; Corté, Laurent; Allena, Rachele

2017-12-01

Successfully simulating tissue evolution in bone is of significant importance in predicting various biological processes such as bone remodeling, fracture healing and osseointegration of implants. Each of these processes involves in different ways the permanent or transient formation of different tissue types, namely bone, cartilage and fibrous tissues. The tissue evolution in specific circumstances such as bone remodeling and fracturing healing is currently able to be modeled. Nevertheless, it remains challenging to predict which tissue types and organization can develop without any a priori assumptions. In particular, the role of mechano-biological coupling in this selective tissue evolution has not been clearly elucidated. In this work, a multi-tissue model has been created which simultaneously describes the evolution of bone, cartilage and fibrous tissues. The coupling of the biological and mechanical factors involved in tissue formation has been modeled by defining two different tissue states: an immature state corresponding to the early stages of tissue growth and representing cell clusters in a weakly neo-formed Extra Cellular Matrix (ECM), and a mature state corresponding to well-formed connective tissues. This has allowed for the cellular processes of migration, proliferation and apoptosis to be described simultaneously with the changing ECM properties through strain driven diffusion, growth, maturation and resorption terms. A series of finite element simulations were carried out on idealized cantilever bending geometries. Starting from a tissue composition replicating a mid-diaphysis section of a long bone, a steady-state tissue formation was reached over a statically loaded period of 10,000 h (60 weeks). The results demonstrated that bone formation occurred in regions which are optimally physiologically strained. In two additional 1000 h bending simulations both cartilaginous and fibrous tissues were shown to form under specific geometrical and loading

Evolution of bone biomechanical properties at the micrometer scale around titanium implant as a function of healing time

International Nuclear Information System (INIS)

Vayron, Romain; Mathieu, Vincent; Haiat, Guillaume; Matsukawa, Mami; Tsubota, Ryo; Barthel, Etienne

2014-01-01

The characterization of the biomechanical properties of newly formed bone tissue around implants is important to understand the osseointegration process. The objective of this study is to investigate the evolution of elastic properties of newly formed bone tissue as a function of healing time. To do so, nanoindentation and micro-Brillouin scattering techniques are coupled following a multimodality approach using histological analysis. Coin-shaped implants were placed in vivo at a distance of 200 µm from the cortical bone surface, leading to an initially empty cavity. Two rabbits were sacrificed after 7 and 13 weeks of healing time. The histological analyses allow us to distinguish mature and newly formed bone tissue. The bone mechanical properties were measured in mature and newly formed bone tissue. Analysis of variance and Tukey–Kramer tests reveals a significant effect of healing time on the indentation modulus and ultrasonic velocities of bone tissue. The results show that bone mass density increases by 12.2% (2.2% respectively) between newly formed bone at 7 weeks (13 weeks respectively) and mature bone. The dependence of bone properties on healing time may be explained by the evolution of bone microstructure and mineralization. (paper)

Comparison of xenogenic bone bioimplant and calcium phosphate granules on experimental femoral bone defect healing in rabbits

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GH Mousavi

2012-05-01

Full Text Available Rebuilding and renovation of lost bone whether because of physiologic or pathologic factors was one of the surgeons’ motivations from the past. Osteogenesis of decalcified bone induced by growth factors contained in it. This study is to assay probability effect of decalcified bone and calcium phosphate granules on osteogenesis which is made in experimental flaw and it is as a laboratory pattern in rabbit femur.This experimental study is made on 15 male rabbits. Animals were divided randomly into 3 groups (control and treatments.After induction of general anesthesia, 2 holes in size of 2 mm in diameter was made using a dental bit in femur width to medullary channel. After surgery, the control group left untreated and decalcified bones was placed in group 2 and calcium phosphate granules were placed in group 3. Histopathological and histomorphometrical studies for evaluation of bone healing were carried out in experimental rats, which were euthanized after 45 days of the experiment using hematoxylin-eosin (H&E staining method.In control group, defect seemed to be filled with woven bone and bone marrow spaces and in spite of a poor osteogenic activity. In calcium phosphate group, young bone trabeculas increased in number and bone trabeculas more organized. Histomorphometric results, observed that calcium phosphate granules has significant effect on bone healing than decalcified and control groups.

Collagenases and gelatinases in bone healing. The focus on mandibular fractures

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Kurzepa Jacek

2014-06-01

Full Text Available Due to high amount of collagen fibres in the structure of bone, the enzymes capable of collagen digestion play a key role in bone remodelling. Matrix metalloproteinases (MMPs, prevailing extracellular endopeptideses, can digest extracellularly located proteins, e.g. collagen, proteoglycans, elastin or fibronectin. Among MMPs, collagenases (MMP-1, MMP-8 and MMP-13 and gelatinases (MMP-2 and MMP-9 can cleave collagen particles to forms that are able to undergo further steps of catabolism intracellularly. In addition, activity of the gelatinases (as an activation of proinflammatory cytokines facilitates spreading inflammation that is necessary during the first stage of bone healing. Further studies related to the role of various MMPs in mandibular fractures should precisely explain their function in the bone healing and evaluate the influence of MMPs inhibitors on that process. This review provides the basic information about two groups among MMPs family, collagenases and gelatinases, and their role in repairing processes after mandibular fractures.

Bone compaction enhances implant fixation in a canine gap model

DEFF Research Database (Denmark)

Kold, Søren; Rahbek, Ole; Toft, Marianne

2005-01-01

A new bone preparation technique, compaction, has increased fixation of implants inserted with exact-fit or press-fit to bone. Furthermore, a demonstrated spring-back effect of compacted bone might be of potential value in reducing the initial gaps that often exist between clinical inserted...... implants and bone. However, it is unknown whether the compression and breakage of trabeculae during the compaction procedure results in impaired gap-healing of compacted bone. Therefore, we compared compaction with conventional drilling in a canine gap model. Grit-blasted titanium implants (diameter 6 mm...... that the beneficial effect of reduced gap size, as compacted bone springs back, is not eliminated by an impaired gap-healing of compacted bone....

Ultrasound stimulation on bone healing. The optimization of stimulation time

International Nuclear Information System (INIS)

Rosim, R.C.; Paulin, J.B.P.; Goncalves, R.P.

1990-01-01

Previous works in ultrasonic simulation of bone healing dealt with parameters optimization. Albertin (1983) studied the stimulation time and found forty minutes as ideal. However, this stimulation time was the largest one employed and remained some doubt about the most appropriated value. 30, 40, 50 and 60 minutes of stimulation time were selected, while others parameters were held constant with: pulse width in 200 μs, repetition rate in 1000 pulses per second and amplitude in 30 V. Partial incomplete transverse osteotomies were done in the middle third of radio in the right forearm of rabbits. Twenty four animals divided in four subgroups, with 6 animals each were stimulated. The daily stimulation time for each subgroup was 30, 40, 50 and minutes respectively, during 15 consecutive days. The stimulation procedure started 24 hours after surgery. After the stimulation period, radiological, histological and morphometric evaluations were done and greater bone healing was found for the 50 minutes stimulation subgroup, in them new bone was also prominent. (author)

The clinical study of the early soft tissue healing and marginal bone resorption after non-submerged implants

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Xu Anchen; Yang Desheng; Hu Bei; Leng Bin; Zhang Li

2009-01-01

Objective: To compare the amount of early marginal bone resorption in the first three months after non-submerged implants and to explore the relationship between the amount of early marginal bone resorption and the soft tissue healing in the first month. Method: ITI with non-submerged implants were implanted in 33 patients. Digital panoramic radiographs were taken during the operation, one month and three months later. The amount of marginal bone resorption was measured in the first, second and the third month after implant operation. The soft tissue healing was observed after 10 days. Results: There was significant difference (P<0.01) in the amount of early marginal bone resorption between one month and three months later. The early marginal bone resorption in the first month after implantation kept correlation with the soft tissue healing on 10th day(r=0.794, P<0.01). Conclusion: The amount of early marginal bone resorption in the first month exceeds that in the second and the third months after implant operation, and the soft tissue healing affects the amount of early marginal bone resorption in the first month. Biological seal is the critical factor influencing the early marginal bone resorption. (authors)

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

Expression of bone morphogenic protein 2/4, transforming growth factor-β1, and bone matrix protein expression in healing area between vascular tibia grafts and irradiated bone-experimental model of osteonecrosis

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Schultze-Mosgau, Stefan; Lehner, Bernhard; Roedel, Franz; Wehrhan, Falk; Amann, Kerstin; Kopp, Juergen; Thorwarth, Michael; Nkenke, Emeka; Grabenbauer, Gerhard

2005-01-01

Purpose: For the surgical treatment of osteoradionecrosis after multimodal therapy of head-and-neck cancers, free vascular bone grafts are used to reconstruct osseous structures in the previously irradiated graft bed. Reduced, or even absent osseous healing in the transition area between the vascular graft and the irradiated graft bed represents a clinical problem. Inflammatory changes and fibrosis lead to delayed healing, triggered by bone morphogentic protein 2/4 (BMP2/4) and transforming growth factor (TGF)-β 1 . Given the well-known fibrosis-inducing activity of TGF-β 1 , an osteoinductive effect has been reported for BMP2/4. However, the influence of irradiation (RT) on this cytokine expression remains elusive. Therefore, the aim of the present in vivo study was to analyze the expression of BMP2/4, TGF-β 1 , collagen I, and osteocalcin in the transition area between the bone graft and the graft bed after RT. Methods and materials: Twenty Wistar rats (male, weight 300-500 g) were used in this study. A free vascular tibia graft was removed in all rats and maintained pedicled in the groin region. Ten rats underwent RT with 5 x 10 Gy to the right tibia, the remainder served as controls. After 4 weeks, the previously removed tibia grafts were regrafted into the irradiated (Group 1) and nonirradiated (Group 2) graft beds. The interval between RT and grafting was 4 weeks. After a 4-week osseous healing period, the bone grafts were removed, and the transition area between the nonirradiated graft and the irradiated osseous graft bed was examined histomorphometrically (National Institutes of Health imaging program) and immunohistochemically (avidin-biotin-peroxidase complex) for the expression of BMP2/4, TGF-β 1 , collagen I, and osteocalcin. Results: Absent or incomplete osseous healing of the graft was found in 9 of 10 rats after RT with 50 Gy and in 1 of 10 of the rats with nonirradiated osseous grafts. Histomorphometrically, the proportion of osseous healing in

Longitudinal analysis of osteogenic and angiogenic signaling factors in healing models mimicking atrophic and hypertrophic non-unions in rats.

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Susann Minkwitz

Full Text Available Impaired bone healing can have devastating consequences for the patient. Clinically relevant animal models are necessary to understand the pathology of impaired bone healing. In this study, two impaired healing models, a hypertrophic and an atrophic non-union, were compared to physiological bone healing in rats. The aim was to provide detailed information about differences in gene expression, vascularization and histology during the healing process. The change from a closed fracture (healing control group to an open osteotomy (hypertrophy group led to prolonged healing with reduced mineralized bridging after 42 days. RT-PCR data revealed higher gene expression of most tested osteogenic and angiogenic factors in the hypertrophy group at day 14. After 42 days a significant reduction of gene expression was seen for Bmp4 and Bambi in this group. The inhibition of angiogenesis by Fumagillin (atrophy group decreased the formation of new blood vessels and led to a non-healing situation with diminished chondrogenesis. RT-PCR results showed an attempt towards overcoming the early perturbance by significant up regulation of the angiogenic regulators Vegfa, Angiopoietin 2 and Fgf1 at day 7 and a further continuous increase of Fgf1, -2 and Angiopoietin 2 over time. However µCT angiograms showed incomplete recovery after 42 days. Furthermore, lower expression values were detected for the Bmps at day 14 and 21. The Bmp antagonists Dan and Twsg1 tended to be higher expressed in the atrophy group at day 42. In conclusion, the investigated animal models are suitable models to mimic human fracture healing complications and can be used for longitudinal studies. Analyzing osteogenic and angiogenic signaling patterns, clear changes in expression were identified between these three healing models, revealing the importance of a coordinated interplay of different factors to allow successful bone healing.

Oxytocin promotes bone formation during the alveolar healing process in old acyclic female rats.

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Colli, Vilma Clemi; Okamoto, Roberta; Spritzer, Poli Mara; Dornelles, Rita Cássia Menegati

2012-09-01

OT was reported to be a direct regulator of bone mass in young rodents, and this anabolic effect on bone is a peripheral action of OT. The goal of this study was to investigate the peripheral action of oxytocin (OT) in the alveolar healing process in old female rats. Females Wistar rats (24-month-old) in permanent diestrus phase, received two ip (12h apart) injections of saline (NaCl 0.15M - control group) or OT (45μg/rat - treated group). Seven days later, the right maxillary incisor was extracted and analyses were performed up to 28 days of the alveolar healing process (35 days after saline or OT administration). Calcium and phosphorus plasma concentrations did not differ between the groups. The plasma biochemical bone formations markers, alkaline phosphatase (ALP) and osteocalcin were significantly higher in the treated group. Histomorphometric analyses confirmed bone formation as the treated group presented the highest mean value of post-extraction bone formation. Tartrate-resistant acid phosphatase (TRAP) was significantly reduced in the treated group indicating an anti-resorptive effect of OT. Immunohistochemistry reactions performed in order to identify the presence of osteocalcin and TRAP in the bone cells of the dental socket confirmed these outcomes. OT was found to promote bone formation and to inhibit bone resorption in old acyclic female rats during the alveolar healing process. Published by Elsevier Ltd.

Locally delivered ethyl-2,5-dihydroxybenzoate using 3D printed bone implant for promotion of bone regeneration in a osteoporotic animal model

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B-J Kwon

2018-01-01

Full Text Available Osteoporosis is a disease characterized by low bone mass, most commonly caused by an increase in bone resorption that is not matched by sufficient bone formation. The most common complications of postmenopausal osteoporosis are bone-related defects and fractures. Fracture healing is a multifactorial bone regeneration process, influenced by both biological and mechanical factors related to age, osteoporosis and stability of the osteosynthesis. During the treatment of bone defects in osteoporotic conditions, imbalanced bone remodeling is the leading cause for implant failure. To overcome these problems, ethyl-2,5-dihydroxybenzoate (E-2,5-DHB, a drug that promotes bone formation and inhibits bone resorption, was used. E-2,5-DHB-incorporating titanium (Ti implants using poly(lactic-co-glycolic acid (PLGA coating for local delivery of E-2,5-DHB were developed and the effects on bone healing of femoral defects were evaluated in an osteoporotic model. The release of E-2,5-DHB resulted in decreased bone resorption and increased bone formation around the implant. Thus, it was confirmed that, in the osteoporotic model, bone healing was increased and implant fixation was enhanced. These results suggested that E-2,5-DHB-coated Ti implants have great potential as an ultimate local drug delivery system for bone tissue scaffolds.

Vibration acceleration promotes bone formation in rodent models.

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Ryohei Uchida

Full Text Available All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF mouse model and a rib fracture healing (RFH rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model or nine days (RFH model. All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT. In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model had significantly greater wet weight and were significantly larger (macroscopically and radiographically than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group, but

Histometric study of alveolar bone healing in rats treated with the nonsteroidal anti-inflammatory drug nimesulide.

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Teófilo, Juliana Mazzonetto; Giovanini, Gabriela Salgueiro; Fracon, Ricardo Nogueira; Lamano, Teresa

2011-04-01

There is extensive experimental and clinical evidence in the orthopedic area that prolonged use of nonselective (inhibitor of both cyclooxygenases 1 and 2) nonsteroidal anti-inflammatory drugs can hinder long bone fracture healing, spinal fusion rate, and new bone formation around implants. The purpose of the present study was to investigate whether nimesulide (Nimesulida, Medley S.A., Campinas, SP, Brazil), a preferential cyclooxygenase-2 inhibitor, can hinder alveolar bone healing, in rats. Treated rats received oral doses (5 mg/kg/rat/day) of nimesulide from the day of tooth extraction until euthanasia 2 weeks later and control rats received tap water (n = 5 per group). The volume of neoformed bone inside the alveolar socket was estimated in semiserial longitudinal histological sections by a differential point-counting method, and the significance of the difference between groups was analyzed by Student t test (P alveolar bone healing in rats.

Inflammatory Microenvironment Persists After Bone Healing in Intra-articular Ankle Fractures.

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Adams, Samuel B; Leimer, Elizabeth M; Setton, Lori A; Bell, Richard D; Easley, Mark E; Huebner, Janet L; Stabler, Thomas V; Kraus, Virginia B; Olson, Steven A; Nettles, Dana L

2017-05-01

Post-traumatic osteoarthritis (PTOA) is responsible for the majority of cases of ankle arthritis. While acute and end-stage intra-articular inflammation has previously been described, the state of the joint between fracture healing and end-stage PTOA remains undefined. This study characterized synovial fluid (SF) composition of ankles after bone healing of an intra-articular fracture to identify factors that may contribute to the development of PTOA. Of an original 21 patients whose SF was characterized acutely following intra-articular ankle fractures, 7 returned for planned hardware (syndesmotic screw) removal after bone healing (approximately 6 months) and consented to a second bilateral SF collection. SF concentrations of 15 cytokines and matrix metalloproteinases (MMPs) and 2 markers each of cartilage catabolism (CTXII and glycosaminoglycan) and hemarthrosis (biliverdin and bilirubin) were compared for previously fractured and contralateral, uninjured ankles from the same patient. Analysis was also performed to determine the effect of the number of fracture lines and involvement of soft tissue on SF composition. Interleukin (IL)-6, IL-8, MMP-1, MMP-2, and MMP-3 were significantly elevated in the SF from healed ankles compared to matched contralateral uninjured ankles at approximately 6 months after fracture. There were no differences in markers of cartilage catabolism or hemarthrosis. Only IL-1α was affected by the number of fracture lines while differences were not detected for other analytes or with respect to the involvment of soft tissue. Sustained intra-articular inflammation, even after complete bone healing, was suggested by elevations of pro-inflammatory cytokines (IL-6 and IL-8). In addition, elevated concentrations of MMPs were also noted and were consistent with a persistent inflammatory environment. This study suggests new evidence of persistent intra-articular inflammation after intra-articular ankle fracture healing and suggests potential

Effect of the Interposition of Calcium Phosphate Materials on Tendon-Bone Healing During Repair of Chronic Rotator Cuff Tear.

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Zhao, Song; Peng, Lingjie; Xie, Guoming; Li, Dingfeng; Zhao, Jinzhong; Ning, Congqin

2014-08-01

The current nature of tendon-bone healing after rotator cuff (RC) repair is still the formation of granulation tissue at the tendon-bone interface rather than the formation of fibrocartilage, which is the crucial structure in native tendon insertion and can be observed after knee ligament reconstruction. The interposition of calcium phosphate materials has been found to be able to enhance tendon-bone healing in knee ligament reconstruction. However, whether the interposition of these kinds of materials can enhance tendon-bone healing or even change the current nature of tendon-bone healing after RC repair still needs to be explored. The interposition of calcium phosphate materials during RC repair would enhance tendon-bone healing or change its current nature of granulation tissue formation into a more favorable process. Controlled laboratory study. A total of 144 male Sprague-Dawley rats underwent unilateral detachment of the supraspinatus tendon, followed by delayed repair after 3 weeks. The animals were allocated into 1 of 3 groups: (1) repair alone, (2) repair with Ca5(PO4)2SiO4 (CPS) bioceramic interposition, or (3) repair with hydroxyapatite (HA) bioceramic interposition at the tendon-bone interface. Animals were sacrificed at 2, 4, or 8 weeks postoperatively, and microcomputed tomography (micro-CT) was used to quantify the new bone formation at the repair site. New fibrocartilage formation and collagen organization at the tendon-bone interface was evaluated by histomorphometric analysis. Biomechanical testing of the supraspinatus tendon-bone complex was performed. Statistical analysis was performed using 1-way analysis of variance. Significance was set at P repair, CPS bioceramic significantly increased the area of fibrocartilage at the tendon-bone interface compared with the control and HA groups. Moreover, CPS and HA bioceramics had significantly improved collagen organization. Biomechanical tests indicated that the CPS and HA groups have greater ultimate

Protein growth factors loaded highly porous chitosan scaffold: A comparison of bone healing properties

International Nuclear Information System (INIS)

Nandi, Samit K.; Kundu, Biswanath; Basu, Debabrata

2013-01-01

Present study aimed to investigate and compare effectiveness of porous chitosan alone and in combination with insulin like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in bone healing. Highly porous (85 ± 2%) with wide distribution of macroporous (70–900 μm) chitosan scaffolds were fabricated as bone substitutes by employing a simple liquid hardening method using 2% (w/v) chitosan suspension. IGF-1 and BMP-2 were infiltrated using vacuum infiltration with freeze drying method. Adsorption efficiency was found to be 87 ± 2 and 90 ± 2% for BMP-2 and IGF-1 respectively. After thorough material characterization (pore details, FTIR and SEM), samples were used for subsequent in vivo animal trial. Eighteen rabbit models were used to evaluate and compare control (chitosan) (group A), chitosan with IGF-1 (group B) and chitosan with BMP-2 (group C) in the repair of critical size bone defect in tibia. Radiologically, there was evidence of radiodensity in defect area from 60th day (initiated on 30th day) in groups B and C as compared to group A and attaining nearly bony density in most of the part at day 90. Histological results depicted well developed osteoblastic proliferation around haversian canal along with proliferating fibroblast, vascularization and reticular network which was more pronounced in group B followed by groups C and A. Fluorochrome labeling and SEM studies in all groups showed similar outcome. Hence, porous chitosan alone and in combination with growth factors (GFs) can be successfully used for bone defect healing with slight advantage of IGF-1 in chitosan samples. - Highlights: ► Fabrication and characterization of porous chitosan with or without IGF-1 and BMP-2 ► Highly porous growth factor loaded chitosan studied in animal subjects for 3 months ► Parameters studied: histopathology, radiology and fluorochrome labeling ► IGF-1 loaded porous chitosan found to be very effective for bone defect healing

Protein growth factors loaded highly porous chitosan scaffold: A comparison of bone healing properties

Energy Technology Data Exchange (ETDEWEB)

Nandi, Samit K., E-mail: samitnandi1967@gmail.com [Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences, Kolkata (India); Kundu, Biswanath, E-mail: biswa_kundu@rediffmail.com [Bioceramics and Coating Division, CSIR—Central Glass and Ceramic Research Institute, Kolkata (India); Basu, Debabrata [Bioceramics and Coating Division, CSIR—Central Glass and Ceramic Research Institute, Kolkata (India)

2013-04-01

Present study aimed to investigate and compare effectiveness of porous chitosan alone and in combination with insulin like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in bone healing. Highly porous (85 ± 2%) with wide distribution of macroporous (70–900 μm) chitosan scaffolds were fabricated as bone substitutes by employing a simple liquid hardening method using 2% (w/v) chitosan suspension. IGF-1 and BMP-2 were infiltrated using vacuum infiltration with freeze drying method. Adsorption efficiency was found to be 87 ± 2 and 90 ± 2% for BMP-2 and IGF-1 respectively. After thorough material characterization (pore details, FTIR and SEM), samples were used for subsequent in vivo animal trial. Eighteen rabbit models were used to evaluate and compare control (chitosan) (group A), chitosan with IGF-1 (group B) and chitosan with BMP-2 (group C) in the repair of critical size bone defect in tibia. Radiologically, there was evidence of radiodensity in defect area from 60th day (initiated on 30th day) in groups B and C as compared to group A and attaining nearly bony density in most of the part at day 90. Histological results depicted well developed osteoblastic proliferation around haversian canal along with proliferating fibroblast, vascularization and reticular network which was more pronounced in group B followed by groups C and A. Fluorochrome labeling and SEM studies in all groups showed similar outcome. Hence, porous chitosan alone and in combination with growth factors (GFs) can be successfully used for bone defect healing with slight advantage of IGF-1 in chitosan samples. - Highlights: ► Fabrication and characterization of porous chitosan with or without IGF-1 and BMP-2 ► Highly porous growth factor loaded chitosan studied in animal subjects for 3 months ► Parameters studied: histopathology, radiology and fluorochrome labeling ► IGF-1 loaded porous chitosan found to be very effective for bone defect healing.

Can platelet-rich plasma (PRP) improve bone healing? A comparison between the theory and experimental outcomes.

Science.gov (United States)

Malhotra, Angad; Pelletier, Matthew H; Yu, Yan; Walsh, William R

2013-02-01

The increased concentration of platelets within platelet-rich plasma (PRP) provides a vehicle to deliver supra-physiologic concentrations of growth factors to an injury site, possibly accelerating or otherwise improving connective tissue regeneration. This potential benefit has led to the application of PRP in several applications; however, inconsistent results have limited widespread adoption in bone healing. This review provides a core understanding of the bone healing mechanisms, and corresponds this to the factors present in PRP. In addition, the current state of the art of PRP preparation, the key aspects that may influence its effectiveness, and treatment outcomes as they relate specifically to bone defect healing are presented. Although PRP does have a sound scientific basis, its use for bone healing appears only beneficial when used in combination with osteoconductive scaffolds; however, neither allograft nor autograft appear to be appropriate carriers. Aggressive processing techniques and very high concentrations of PRP may not improve healing outcomes. Moreover, many other variables exist in PRP preparation and use that influence its efficacy; the effect of these variables should be understood when considering PRP use. This review includes the essentials of what has been established, what is currently missing in the literature, and recommendations for future directions.

Histologic Evaluation of Critical Size Defect Healing With Natural and Synthetic Bone Grafts in the Pigeon ( Columba livia ) Ulna.

Science.gov (United States)

Tunio, Ahmed; Jalila, Abu; Goh, Yong Meng; Shameha-Intan; Shanthi, Ganabadi

2015-06-01

Fracture and bone segment loss are major clinical problems in birds. Achieving bone formation and clinical union in a fracture case is important for the survival of the bird. To evaluate the efficacy of bone grafts for defect healing in birds, 2 different bone grafts were investigated in the healing of a bone defect in 24 healthy pigeons ( Columba livia ). In each bird, a 1-cm critical size defect (CSD) was created in the left ulna, and the fracture was stabilized with external skeletal fixation (ESF). A graft of hydroxyapatite (HA) alone (n = 12 birds) or demineralized bone matrix (DBM) combined with HA (n = 12 birds) was implanted in the CSD. The CSD healing was evaluated at 3 endpoints: 3, 6, and 12 weeks after surgery. Four birds were euthanatized at each endpoint from each treatment group, and bone graft healing in the ulna CSD was evaluated by histologic examination. The CSD and graft implants were evaluated for quality of union, cortex development, and bone graft incorporation. Results showed no graft rejection in any bird, and all birds had connective tissue formation in the defect because of the bone graft application. These results suggest that bone defect healing can be achieved by a combination of osteoinductive and osteoconductive bone graft materials for clinical union and new bone regeneration in birds. The combination of DBM and HA resulted in a better quality bone graft (P < .05) than did HA alone, but there was no significant differences in cortex development or bone graft incorporation at 3, 6, or 12 weeks. From the results of this study, we conclude that HA bone grafts, alone or in combination with DBM, with external skeletal fixation is suitable and safe for bone defect and fracture treatment in pigeons.

Effect of platelet-rich plasma combined with demineralised bone matrix on bone healing in rabbit ulnar defects.

Science.gov (United States)

Galanis, Vasilios; Fiska, Alice; Kapetanakis, Stylianos; Kazakos, Konstantinos; Demetriou, Thespis

2017-09-01

This study evaluates the effect of autologous platelet-rich plasma (PRP) combined with xenogeneic demineralised bone matrix (DBM) on bone healing of critical-size ulnar defects (2-2.5 times the ulnar diameter) in New Zealand White rabbits. Critical-size defects were created unilaterally in the ulna of 36 rabbits, while keeping the contralateral limb intact. They were divided into three groups. In Group A, the defect was filled with autologous PRP and in Group B, with autologous PRP combined with DBM; in Group C, the defect remained empty. The rabbits were euthanised 12 weeks postoperatively. Radiological, biomechanical and histological assessments were carried out and statistical analysis of the results was performed. Group B had significantly higher radiological and histological scores than Groups A and C. Defects in Group B showed significant new bone formation, whereas there was minimal or no new bone formation in Groups A and C. Only specimens in Group B showed macroscopic bone union. Biomechanical evaluation of the treated and intact contralateral limbs in Group B showed significant differences. In this study, statistically significant enhancement of bone healing was found in critical-size defects treated with PRP and DBM, as shown by radiological findings, gross assessment, and biomechanical and histopathological results. Defects in the two other groups remained unbridged. Therefore, PRP was effective only when it was used in combination with a bone graft. Copyright: © Singapore Medical Association

Immunolocalization of Myostatin (GDF-8) Following Musculoskeletal Injury and the Effects of Exogenous Myostatin on Muscle and Bone Healing

OpenAIRE

Elkasrawy, Moataz; Immel, David; Wen, Xuejun; Liu, Xiaoyan; Liang, Li-Fang; Hamrick, Mark W.

2012-01-01

The time course and cellular localization of myostatin expression following musculoskeletal injury are not well understood; therefore, the authors evaluated the temporal and spatial localization of myostatin during muscle and bone repair following deep penetrant injury in a mouse model. They then used hydrogel delivery of exogenous myostatin in the same injury model to determine the effects of myostatin exposure on muscle and bone healing. Results showed that a “pool” of intense myostatin sta...

Use of Radiographic Densitometry to Predict the Bone Healing Index in Distraction Osteogenesis

OpenAIRE

A Saw; S Manimaran; S Faizal; AM Bulgiba

2008-01-01

Bone lengthening with distraction osteogenesis involves prolonged application of an external fixator frame. Qualitative and quantitative evaluation of callus has been described using various imaging modalities but there is no simple reliable and readily available method. This study aims to investigate the use of a densitometer to analyze plain radiographic images and correlate them with the rate of new bone formation as represented by the bone healing index. A total of 34 bone lengthening pro...

Comparison in bone turnover markers during early healing of femoral neck fracture and trochanteric fracture in elderly patients

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Shota Ikegami

2009-10-01

Full Text Available Healing of fractures is different for each bone and bone turnover markers may reflect the fracture healing process. The purpose of this study was to determine the characteristic changes in bone turnover markers during the fracture healing process. The subjects were consecutive patients with femoral neck or trochanteric fracture who underwent surgery and achieved bone union. There were a total of 39 patients, including 33 women and 6 men. There were 18 patients (16 women and 2 men with femoral neck fracture and 21 patients (17 women and 4 men with trochanteric fracture. Serum bone-specific alkaline phosphatase (BAP was measured as a bone formation marker. Urine and serum levels of N-terminal telopeptide of type I collagen (NTX, as well as urine levels of C-terminal telopeptide of type I collagen (CTX and deoxypyridinoline (DPD, were measured as markers of bone resorption. All bone turnover markers showed similar changes in patients with either type of fracture, but significantly higher levels of both bone formation and resorption markers were observed in trochanteric fracture patients than in neck fracture patients. BAP showed similar levels at one week after surgery and then increased. Bone resorption markers were increased after surgery in patients with either fracture. The markers reached their peak values at three weeks (BAP and urinary NTX, five weeks (serum NTX and DPD, and 2-3 weeks (CTX after surgery. The increase in bone turnover markers after hip fracture surgery and the subsequent decrease may reflect increased bone formation and remodeling during the healing process. Both fractures had a similar bone turnover marker profile, but the extent of the changes differed between femoral neck and trochanteric fractures.

Comparison in bone turnover markers during early healing of femoral neck fracture and trochanteric fracture in elderly patients.

Science.gov (United States)

Ikegami, Shota; Kamimura, Mikio; Nakagawa, Hiroyuki; Takahara, Kenji; Hashidate, Hiroyuki; Uchiyama, Shigeharu; Kato, Hiroyuki

2009-10-10

Healing of fractures is different for each bone and bone turnover markers may reflect the fracture healing process. The purpose of this study was to determine the characteristic changes in bone turnover markers during the fracture healing process. The subjects were consecutive patients with femoral neck or trochanteric fracture who underwent surgery and achieved bone union. There were a total of 39 patients, including 33 women and 6 men. There were 18 patients (16 women and 2 men) with femoral neck fracture and 21 patients (17 women and 4 men) with trochanteric fracture. Serum bone-specific alkaline phosphatase (BAP) was measured as a bone formation marker. Urine and serum levels of N-terminal telopeptide of type I collagen (NTX), as well as urine levels of C-terminal telopeptide of type I collagen (CTX) and deoxypyridinoline (DPD), were measured as markers of bone resorption. All bone turnover markers showed similar changes in patients with either type of fracture, but significantly higher levels of both bone formation and resorption markers were observed in trochanteric fracture patients than in neck fracture patients. BAP showed similar levels at one week after surgery and then increased. Bone resorption markers were increased after surgery in patients with either fracture. The markers reached their peak values at three weeks (BAP and urinary NTX), five weeks (serum NTX and DPD), and 2-3 weeks (CTX) after surgery. The increase in bone turnover markers after hip fracture surgery and the subsequent decrease may reflect increased bone formation and remodeling during the healing process. Both fractures had a similar bone turnover marker profile, but the extent of the changes differed between femoral neck and trochanteric fractures.

The effects of photobiomodulation on healing of bone defects in streptozotocin induced diabetic rats

Science.gov (United States)

Martinez Costa Lino, Maíra D.; Bastos de Carvalho, Fabíola; Ferreira Moraes, Michel; Augusto Cardoso, José; Pinheiro, Antônio L. B.; Maria Pedreira Ramalho, Luciana

2011-03-01

Previous studies have shown positive effects of Low level laser therapy (LLLT) on the repair of bone defects, but there are only a few that associates bone healing in the presence of a metabolic disorder as Diabetes Melitus and LLLT. The aim of this study was to assess histologically the effect of LLLT (AsGaAl), 780nm, 70mW, CW, Ø~0.4mm, 16J/cm2 per session) on the repair of surgical defects created in the femur of diabetic and non-diabetic Wistar Albinus rats. Surgical bone defects were created in 60 animals divided into four groups of 15 animals each: Group C (non-diabetic - control); Group CL (non-diabetic + LLLT); Group CD (diabetic); Group CDL (diabetic + LLLT). The animals on the irradiated group received 16 J/cm2 per session divided into four points around the defect, being the first irradiation immediately after surgery and repeated every 48h for 14 days. The animals were killed 15, 21 and 30 days after surgery. The results of the present investigation showed histological evidence of improved amount of collagen fibers at early stages of the bone healing (15 days) and increased amount of well organized bone trabeculae at the end of the experimental period (30 days) on irradiated animals, (diabetic and non-diabetic) compared to non irradiated ones. It is concluded that LLLT has a positive biomodulative effect on the healing process of bone defects, even when diabetes mellitus was present.

Effect of Platelet-Rich Plasma and Bioactive Glass Powder for the Improvement of Rotator Cuff Tendon-to-Bone Healing in a Rabbit Model

Directory of Open Access Journals (Sweden)

Yang Wu

2014-11-01

Full Text Available To test the hypothesis that a platelet-rich plasma (PRP plus bioactive glass (BG mixture could shorten the tendon-bone healing process in rotator cuff tendon repair, thirty mature male New Zealand white rabbits were randomly divided into three groups, Control, PRP, and PRP + BG. All groups underwent a surgical procedure to establish a rotator cuff tendon healing model. Mechanical examinations and histological assays were taken to verify the adhesion of the tendon-bone. Real-time PCR was adopted to analyze Bone Morphogenetic Protein-2 (BMP-2. The maximum load-to-failure value in mechanical examinations was significantly higher in the PRP + BG group than that in the control group after six weeks (Control 38.73 ± 8.58, PRP 54.49 ± 8.72, PRP + BG 79.15 ± 7.62, p < 0.001, but it was not significantly different at 12 weeks (PRP 74.27 ± 7.74, PRP + BG 82.57 ± 6.63, p = 0.145. In histological assays, H&E (hematoxylin-eosin staining showed that the interface between the tendon-bone integration was much sturdier in the PRP + BG group compared to the other two groups at each time point, and more ordered arranged tendon fibers can be seen at 12 weeks. At six weeks, the mRNA expression levels of BMP-2 in the PRP + BG group were higher than those in the other groups (PRP + BG 0.65 ± 0.11, PRP 2.284 ± 0.07, Control 0.12 ± 0.05, p < 0.05. However, there was no significant difference in the mRNA expression levels of BMP-2 among the three groups at 12 weeks (p = 0.922, 0.067, 0.056. BMP-2 levels in PRP and PRP+BG groups were significantly lower at 12 weeks compared to six weeks (p = 0.006, <0.001.We found that the PRP + BG mixture could enhance tendon-bone healing in rotator cuff tendon repair.

Does longstanding nicotine exposure impair bone healing and osseointegration? An experimental study in rabbits

DEFF Research Database (Denmark)

Gotfredsen, Klaus; Lindh, Christian H; Berglundh, Tord

2009-01-01

OBJECTIVES: The aim of this study was to analyze the effect of longstanding nicotine exposure on bone healing and osseointegration of titanium implants. MATERIALS AND METHODS: 20 female rabbits received either nicotine (n = 10) or saline (n = 10) administered subcutaneously via mini-osmotic pumps...... for 32 weeks. The pump delivered 6 microg/kg/min of nicotine for the animals in the test group. Blood samples were collected and plasma cotinine levels were measured monthly. Six months after the commencement of nicotine or saline administration three osteotomy preparations, one in right, femoral condyle...... increase in RMT between 2 and 4 weeks within each group. The histomorphometric analysis of bone-to-implant contact and bone density in the bone defects revealed no differences between the test and the control group after 2 or 4 weeks of healing. CONCLUSION: Longstanding (6 months) nicotine exposure did...

Peri-implant soft tissue and marginal bone adaptation on implant with non-matching healing abutments: micro-CT analysis.

Science.gov (United States)

Finelle, Gary; Papadimitriou, Dimitrios E V; Souza, André B; Katebi, Negin; Gallucci, German O; Araújo, Mauricio G

2015-04-01

To assess (i) the outcome of changing the horizontal-offset dimension on the peri-implant soft tissues and the crestal bone and (ii) the effect of different healing abutments (flared vs. straight) on the marginal peri-implant soft tissues and crestal bone. Two-piece dental implants diameters of 3.5 and 4.5 mm were placed at least 1 mm subcrestal in five beagle dogs. Three different investigational groups: (i) 3.5-mm-diameter implant with narrow healing abutment (3.5N), (ii) 4.5-mm-diameter implant with narrow healing abutment (4.5N), and (iii) 3.5-mm-diameter implant with wide healing abutment (3.5W), were assessed. After 4 months of healing, the vertical distance from the marginal crestal bone (MB) to the implant shoulder (IS); the vertical distance from the IS to the first bone-to-implant contact; and the horizontal distance of bone ingrowth on the implant platform were measured with a high-resolution micro-CT (Xradia MicroXCT-200 system). Implants with a narrow healing caps showed an interproximal MB located between 0 and 1 mm above the implant shoulder, while the 3.5W group exhibits a mean value -0.50 mm. As all implants in group 3.5N presented a fBIC located at the level of the IS. For the 4.5N group, the mean fBIC-IS distance was -0.52 mm apically to the IS. For the 3.5WC group, the mean fBIC-IS distance was -1.42 mm. Horizontal bone apposition was only observed for the 3.5N group and the 4.5N group. The dimension of the horizontal offset would play a minimal role in reducing bone remodeling, whereas the configuration of the transmucosal component would directly influence marginal bone remodeling. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A study of the bone healing kinetics of plateau versus screw root design titanium dental implants.

LENUS (Irish Health Repository)

Leonard, Gary

2009-03-01

This study was designed to compare the bone healing process around plateau root from (PRF) and screw root from (SRF) titanium dental implants over the immediate 12 week healing period post implant placement.

Dietary arginine silicate inositol complex increased bone healing: histologic and histomorphometric study

Directory of Open Access Journals (Sweden)

Yaman F

2016-06-01

Full Text Available Ferhan Yaman,1 Izzet Acikan,1 Serkan Dundar,2 Sercan Simsek,3 Mehmet Gul,4 İbrahim Hanifi Ozercan,3 James Komorowski,5 Kazim Sahin6 1Department of Oral-Maxillofacial Surgery, Faculty of Dentistry, Dicle University, Diyarbakir, Turkey; 2Department of Periodontology, Faculty of Dentistry, Firat University, Elazig, Turkey; 3Department of Pathology, Faculty of Medicine, Firat University, Elazig, Turkey; 4Department of Periodontology, Faculty of Dentistry, Dicle University, Diyarbakir, Turkey; 5Nutrition 21, LLC, Purchase, NY, USA; 6Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey Background: Arginine silicate inositol complex (ASI; arginine 49.5%, silicon 8.2%, and inositol 25% is a novel material that is a bioavailable source of silicon and arginine. ASI offers potential benefits for vascular and bone health. Objective: The aim of this study was to evaluate the potential effects of ASI complex on bone healing of critical-sized defects in rats. Methods: The rats were randomly assigned to two groups of 21 rats each. The control group was fed a standard diet for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The ASI group was fed a diet containing 1.81 g/kg of ASI for 12 weeks; after the first 8 weeks, a calvarial critical-sized defect was created, and the rats were sacrificed 7, 14, and 28 days later. The calvarial bones of all the rats were then harvested for evaluation. Results: Osteoblasts and osteoclasts were detected at higher levels in the ASI group compared with the control group at days 7, 14, and 28 of the calvarial defect (P<0.05. New bone formation was detected at higher levels in the ASI group compared with the controls at day 28 (P<0.05. However, new bone formation was not detected at days 7 and 14 in both the groups (P>0.05. Conclusion: ASI supplementation significantly improved bone tissue

Use of a strontium-enriched calcium phosphate cement in accelerating the healing of soft-tissue tendon graft within the bone tunnel in a rabbit model of anterior cruciate ligament reconstruction.

Science.gov (United States)

Kuang, G M; Yau, W P; Lu, W W; Chiu, K Y

2013-07-01

We investigated whether strontium-enriched calcium phosphate cement (Sr-CPC)-treated soft-tissue tendon graft results in accelerated healing within the bone tunnel in reconstruction of the anterior cruciate ligament (ACL). A total of 30 single-bundle ACL reconstructions using tendo Achillis allograft were performed in 15 rabbits. The graft on the tested limb was treated with Sr-CPC, whereas that on the contralateral limb was untreated and served as a control. At timepoints three, six, nine, 12 and 24 weeks after surgery, three animals were killed for histological examination. At six weeks, the graft-bone interface in the control group was filled in with fibrovascular tissue. However, the gap in the Sr-CPC group had already been completely filled in with new bone, and there was evidence of the early formation of Sharpey fibres. At 24 weeks, remodelling into a normal ACL-bone-like insertion was found in the Sr-CPC group. Coating of Sr-CPC on soft tissue tendon allograft leads to accelerated graft healing within the bone tunnel in a rabbit model of ACL reconstruction using Achilles tendon allograft.

Mimicking Bone Healing Process to Self Repair Concrete Structure Novel Approach Using Porous Network Concrete

NARCIS (Netherlands)

Sangadji, S.; Schlangen, H.E.J.G.

2013-01-01

To repair concrete cracks in difficult or dangerous conditions such as underground structures or hazardous liquid containers, self healing mechanism is a promising alternative method. This research aims to imitate the bone self healing process by putting porous concrete internally in the concrete

Effect of platelet-rich plasma on tendon-to-bone healing after rotator cuff repair in rats: an in vivo experimental study.

Science.gov (United States)

Hapa, Onur; Cakıcı, Hüsamettin; Kükner, Aysel; Aygün, Hayati; Sarkalan, Nazlı; Baysal, Gökhan

2012-01-01

The purpose of this experimental study was to analyze the effects of local autologous platelet-rich plasma (PRP) injection on tendon-to-bone healing in a rotator cuff repair model in rats. Rotator cuff injury was created in 68 left shoulders of rats. PRP was obtained from the blood of an additional 15 rats. The 68 rats were divided into 4 groups with 17 rats in each group; PRP group (Week 2), control group (Week 2), PRP group (Week 4), and control group (Week 4). Platelet-rich plasma or saline was injected to the repair area intraoperatively. Rats were sacrificed 2 and 4 weeks after the surgery. Histological analysis using a semiquantitative scoring was performed on 7 rats per group. Tendon integrity and increases in vascularity and inflammatory cells and the degree of new bone formation were evaluated and compared between the groups. The remaining tendons (n=10) were mechanically tested. Degree of inflammation and vascularity were less in the study group at both time intervals (protator cuff tendon-to-bone healing and enhance initial tendon-to-bone healing remodeling. This may represent a clinically important improvement in rotator cuff repair.

Potential Therapeutic Use of Relaxin in Healing Cranial Bone Defects

Science.gov (United States)

2016-08-01

attributes that are likely to benefit bone fracture healing, and it has an excellent safety profile in humans. In brief, to test the hypothesis we use a... euthanasia approximately 3 months later, the percent GFP+ chimerism was 71 + 8%. Not unexpectedly, some mice showed a decline in chimerism over time

[Analysis of the results of bone healing in femurs lengthened by the gradual distraction method in children and adolescents].

Science.gov (United States)

Jochymek, J; Skvaril, J; Ondrus, S

2009-10-01

Treatment of leg length inequality via lengthening of the shorter extremity is an infrequent orthopedic procedure due to the requirement of special distraction devices and possible serious complications. Essential qualitative changes in operative technique development are associated with the name of G. A. Ilizarov, who paved the way for the autoregenerate gradual distraction method in the 1950s. In the years 1990 through 2007 a total of 67 patients underwent femur lengthening via gradual distraction using various types of external fixators at the Department of Pediatric Surgery, Orthopedics, and Traumatology, Faculty Hospital in Brno. The quality of bone healing was monitored and a number of parameters followed and statistically evaluated using regularly scheduled X-ray examinations. In 13 cases we had to remove the external fixator following the distraction phase, perform an osteosynthesis via a splint and fill the distraction gap via spongioplasty. The bone healing was satisfactory in the remaining 54 patients and the lengthened bone required no other fixation method. The analysis showed statistically significant deceleration in bone healing following distraction in female patients over 12 years of age, and in boys over 14 years of age. Lack of periosteal callus five weeks after surgery always signified serious problems in further healing. Severe complications were recorded in 11 cases during the distraction phase, and in 12 cases after the removal of the distraction apparatus. Our results fully correspond with the data and experience of others cited authors. In addition our study showed deceleration in bone healing in girls over 12 years and in boys over 14 years of age and serious problem in healing when is lack of periostal callus five weeks after surgery. The aim of this report was to present the results of our study of distraction gap bone healing using the gradual lengthening approach. Key words: leg lengthening, gradual distraction, external fixation, leg

Relationship between blood flow and radiostrontium uptake in the healing bone fracture

International Nuclear Information System (INIS)

Schuemichen, C.; Mundriziewski, L.; Tischler, E.; Hoffmann, G.

1979-01-01

The healing of a diaphyseal tibia fracture was followed in the rat. Callus formation, blood flow and Sr-85 uptake were assessed by a ratio comparison of the fractured to the contralateral side. No correlation was found between blood flow and Sr-85 deposition in the callus and the adjacent bone of the same extremity. It is concluded that the deposition of a radiopharmaceutical in bone is primarily related to the presence of calcifiable organic bone matrix and only secondarily to the bone formation rate and to variations in the local blood flow. (orig.) 891 MG/orig. 892 MBE [de

Biological methods to enhance bone healing and fracture repair.

Science.gov (United States)

Verdonk, René; Goubau, Yannick; Almqvist, Fredrik K; Verdonk, Peter

2015-04-01

This article looks into normal physiological fracture healing with special emphasis on the diamond concept. A precise definition of nonunion of long bones is described. Most often inadequate fixation (too rigid or too loose) is the reason for nonunion in long bone fractures. Because a critical bone defect cannot be bridged, it may lead directly or indirectly (lack of fixation) to nonunion. Individual inadequate local biological characteristics are also often found to be the cause; poor soft tissue coverage as well as a lack of periosteum and muscle or fascia or skin defects can lead to compromised vascularity in situ. Systemic factors are now much more recognized, e.g., smoking, diabetes, and cachexia, as well as the limited impact of some medications, e.g., nonsteroidal anti-inflammatory drugs and steroids. Today's mode of treatment for nonunion is approached in this article, and suggestions for appropriate treatment of long bone nonunion is presented. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Alveolar bone healing process in spontaneously hypertensive rats (SHR). A radiographic densitometry study.

Science.gov (United States)

Manrique, Natalia; Pereira, Cassiano Costa Silva; Garcia, Lourdes Maria Gonzáles; Micaroni, Samuel; Carvalho, Antonio Augusto Ferreira de; Perri, Sílvia Helena Venturoli; Okamoto, Roberta; Sumida, Doris Hissako; Antoniali, Cristina

2012-01-01

Hypertension is one of the most important public health problems worldwide. If undiagnosed or untreated, this pathology represents a systemic risk factor and offers unfavorable conditions for dental treatments, especially those requiring bone healing. The purpose of this study was to demonstrate, by analysis of bone mineral density (BMD), that the alveolar bone healing process is altered in spontaneously hypertensive rats (SHRs). Wistar rats and SHRs were submitted to extraction of the upper right incisor and were euthanized 7, 14, 21, 28 and 42 days after surgery. Right maxillae were collected, radiographed and analyzed using Digora software. BMD was expressed as minimum (min), middle (med) and maximum (max) in the medium (MT) and apical (AT) thirds of the dental alveolus. The results were compared across days and groups. Wistar showed difference in med and max BMD in the MT between 7 and 28 and also between 14 and 28 days. The AT exhibited significant difference in med and min BMD between 7 and 28 days, as well as difference in min BMD between 28 and 42 days. SHRs showed lower med BMD in the MT at 28 days when compared to 21 and 42 days. Differences were observed across groups in med and min BMD at day 28 in the MT and AT; and in max BMD at 14, 21 and 42 days in the MT. These results suggest that the alveolar bone healing process is delayed in SHRs comparing with Wistar rats.

The effects of odontogenic and nonodontogenic tissues on bone healing in Guinea pig mandible

International Nuclear Information System (INIS)

Kim, So Jung; Hwang, Eui Hwan; Lee, Sang Rae; Hong, Jung Pyo

1996-01-01

This study was for comparing healing patterns and effects between with odontogenic and nonodontogenic tissues on the defected mandible. Experimental bone defects that measured 3 mm in diameter were created on the mandibular body of guinea pig by removal of bone with the use of trephine burs and bone defects were grafted with Biogran (Orthovita Co., U.S. A.) and covered with Dura Mata (Pfrimmer-Viggo GmbH Co., Germany). Guinea pigs were serially terminated by fours on the 3 days, the 1 week, the 2 weeks, the 3 weeks, the 4 weeks, and the 5 weeks after experiment, and the mandibular body was removed and fixed with 10% neutral formalin. They were decalcified and embedded in paraffin as using the usual methods. The specimen sectioned and stained with hematoxylin and eosin and toluidine blue. They were observed with a light microscope and a polarizing microscope. The obtained results were as follows: 1. Defected bone was healed fast from the odontogenic tissues in early stage of the experiment. 2. The arrangement of the bone matrix was relatively regular in the bone from the nonodontogenic tissues, but irregular in the bone from the odotogenic tissues. 3. Compact bone has started to be absorbed and changed to the pattern of matrix bone tissue from 3 weeks after experiment.

Below the Callus Surface: Applying Paleohistological Techniques to Understand the Biology of Bone Healing in Skeletonized Human Remains.

Science.gov (United States)

Assis, Sandra; Keenleyside, Anne

2016-01-01

Bone trauma is a common occurrence in human skeletal remains. Macroscopic and imaging scrutiny is the approach most currently used to analyze and describe trauma. Nevertheless, this line of inquiry may not be sufficient to accurately identify the type of traumatic lesion and the associated degree of bone healing. To test the usefulness of histology in the examination of bone healing biology, we used an integrative approach that combines gross inspection and microscopy. Six bone samples belonging to 5 adult individuals with signs of bone trauma were collected from the Human Identified Skeletal Collection from the Museu Bocage (Lisbon, Portugal). Previous to sampling, the lesions were described according to their location, morphology, and healing status. After sampling, the bone specimens were prepared for plane light and polarized light analysis. The histological analysis was pivotal: (1) to differentiate between types of traumatic lesions; (2) to ascertain the posttraumatic interval, and (3) to diagnose other associated pathological conditions. The outer surface of a bone lesion may not give a complete picture of the biology of the tissue's response. Accordingly, microscopic analysis is essential to differentiate, characterize, and classify trauma signs. © 2016 S. Karger AG, Basel.

The effect of layer-by-layer chitosan-hyaluronic acid coating on graft-to-bone healing of a poly(ethylene terephthalate) artificial ligament.

Science.gov (United States)

Li, Hong; Ge, Yunsheng; Zhang, Pengyun; Wu, Lingxiang; Chen, Shiyi

2012-01-01

Surface coating with an organic layer-by-layer self-assembled template of chitosan and hyaluronic acid on a poly(ethylene terephthalate) (PET) artificial ligament was designed for the promotion and enhancement of graft-to-bone healing after artificial ligament implantation in a bone tunnel. The results of in vitro culturing of MC3T3-E1 mouse osteoblastic cells supported the hypothesis that the layer-by-layer coating of chitosan and hyaluronic acid could promote the cell compatibility of grafts and could promote osteoblast proliferation. A rabbit extra-articular tendon-to-bone healing model was used to evaluate the effect of this kind of surface-modified stainless artificial ligament in vivo. The final results proved that this organic compound coating could significantly promote and enhance new bone formation at the graft-bone interface histologically and, correspondingly, the experimental group with coating had significantly higher biomechanical properties compared with controls at 8 weeks (P < 0.05).

Preliminary study on the effect of parenteral naloxone, alone and in association with calcium gluconate, on bone healing in an ovine "drill hole" model system

Directory of Open Access Journals (Sweden)

Langhoff Jens D

2007-05-01

Full Text Available Abstract Background Several diseases affect bone healing and physiology. Many drugs that are commonly used in orthopaedics as "analgesics" or anti-inflammatory agents impair bone healing. Stressful conditions are associated with decreased serum osteocalcin concentration. High endorphin levels alter calcium metabolism, blocking the membrane channels by which calcium normally enters cells. The consequent decrease of intracellular calcium impairs the activities of calcium-related enzymes. Naloxone is a pure opioid antagonist. Morphine-induced osteocalcin inhibition was abolished when osteoblasts were incubated with naloxone. Naloxone restored the altered cellular and tissue physiology by removing β-endorphins from specific receptors. However, this is only possible if the circulating Ca concentration is adequate. The aim of the present study was to evaluate the efficacy of parenteral naloxone administration in inducing fast mineralization and callus remodelling in a group of sheep with a standardised bone lesion. Methods Twenty ewes were randomly assigned to 4 treatment groups. Group A acted as control, group B received a solution of calcium gluconate, group C a solution of naloxone, and group D a solution of calcium gluconate and naloxone. A transverse hole was drilled in the left metacarpus, including both cortices, then parenteral treatment was administered intramuscularly, daily for four weeks. Healing was evaluated by weekly radiographic examination for eight weeks. For quantitative evaluation, the ratio of the radiographic bone density between the drill area and the adjacent cortical bone was calculated. After eight weeks the sheep were slaughtered and a sample of bone was collected for histopathology Results Group D showed a higher radiographic ratio than the other groups. Sheep not treated with naloxone showed a persistently lower ratio in the lateral than the medial cortex (P Conclusion A low-dose parenteral regimen of naloxone enhances

Ultrasound to stimulate mandibular bone defect healing : A placebo-controlled single-blind study in rats

NARCIS (Netherlands)

Schortinghuis, J; Ruben, JL; Raghoebar, GM; Stegenga, B

Purpose: Because of the limitations of the body to heal large maxillofacial bone defects, an attempt was made to stimulate mandibular defect healing with low intensity pulsed ultrasound in rats. This ultrasound consists of a 1.5-MHz pressure wave administered in pulses of 200 musec, with an average

Tendon Reattachment to Bone in an Ovine Tendon Defect Model of Retraction Using Allogenic and Xenogenic Demineralised Bone Matrix Incorporated with Mesenchymal Stem Cells.

Directory of Open Access Journals (Sweden)

Tanujan Thangarajah

Full Text Available Tendon-bone healing following rotator cuff repairs is mainly impaired by poor tissue quality. Demineralised bone matrix promotes healing of the tendon-bone interface but its role in the treatment of tendon tears with retraction has not been investigated. We hypothesized that cortical demineralised bone matrix used with minimally manipulated mesenchymal stem cells will result in improved function and restoration of the tendon-bone interface with no difference between xenogenic and allogenic scaffolds.In an ovine model, the patellar tendon was detached from the tibial tuberosity and a complete distal tendon transverse defect measuring 1 cm was created. Suture anchors were used to reattach the tendon and xenogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5, or allogenic demineralised bone matrix + minimally manipulated mesenchymal stem cells (n = 5 were used to bridge the defect. Graft incorporation into the tendon and its effect on regeneration of the enthesis was assessed using histomorphometry. Force plate analysis was used to assess functional recovery.Compared to the xenograft, the allograft was associated with significantly higher functional weight bearing at 6 (P = 0.047, 9 (P = 0.028, and 12 weeks (P = 0.009. In the allogenic group this was accompanied by greater remodeling of the demineralised bone matrix into tendon-like tissue in the region of the defect (p = 0.015, and a more direct type of enthesis characterized by significantly more fibrocartilage (p = 0.039. No failures of tendon-bone healing were noted in either group.Demineralised bone matrix used with minimally manipulated mesenchymal stem cells promotes healing of the tendon-bone interface in an ovine model of acute tendon retraction, with superior mechanical and histological results associated with use of an allograft.

The effect of methotrexate on the bone healing of mandibular condylar process fracture: an experimental study in rats.

Science.gov (United States)

Cavalcanti, Samantha Cristine Santos X B; Corrêa, Luciana; Mello, Suzana Beatriz Veríssimo; Luz, João Gualberto C

2014-10-01

Methotrexate (MTX) is an anti-metabolite used in rheumatology and oncology. High doses are indicated for oncological treatment, whereas low doses are indicated for chronic inflammatory diseases. This study evaluated the effect of two MTX treatment schedules on the bone healing of the temporomandibular joint fracture in rats. Seventy-five adult male Wistar rats were used to generate an experimental unilateral medially rotated condylar fracture model that allows an evaluation of bone healing and the articular structures. The animals were subdivided into three groups that each received one of the following treatments intraperitoneally: saline (1 mL/week), low-dose MTX (3 mg/kg/week) and high-dose MTX (30 mg/kg). The histological study comprised fracture site and temporomandibular joint evaluations and bone neoformation was evaluated by histomorphometric analysis. A biochemical parameter of bone formation was also assessed. When compared with saline, high-dose MTX delayed bone fracture repairs. In this latter group, after 90 days, the histological analysis revealed atrophy of the fibrocartilage and the presence of fibrous tissue in the joint space. The histomorphometric analysis revealed diminished bone neoformation. The alkaline phosphatase levels also decreased after MTX treatment. It was concluded that high-dose MTX impaired mandibular condyle repair and induced degenerative articular changes. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

A histological and micro-CT investigation in to the effect of NGF and EGF on the periodontal, alveolar bone, root and pulpal healing of replanted molars in a rat model - a pilot study.

Science.gov (United States)

Furfaro, Francesco; Ang, Estabelle S M; Lareu, Ricky R; Murray, Kevin; Goonewardene, Mithran

2014-01-06

This study aims to investigate, utilising micro-computed tomography (micro-CT) and histology, whether the topical application of nerve growth factor (NGF) and/or epidermal growth factor (EGF) can enhance periodontal, alveolar bone, root and pulpal tissue regeneration while minimising the risk of pulpal necrosis, root resorption and ankylosis of replanted molars in a rat model. Twelve four-week-old male Sprague-Dawley rats were divided into four groups: sham, collagen, EGF and NGF. The maxillary right first molar was elevated and replanted with or without a collagen membrane impregnated with either the growth factors EGF or NGF, or a saline solution. Four weeks after replantation, the animals were sacrificed and the posterior maxilla was assessed using histological and micro-CT analysis. The maxillary left first molar served as the control for the corresponding right first molar. Micro-CT analysis revealed a tendency for all replanted molars to have reduced root length, root volume, alveolar bone height and inter-radicular alveolar bone volume. It appears that the use of the collagen membrane had a negative effect while no positive effect was noted with the incorporation of EGF or NGF. Histologically, the incorporation of the collagen membrane was found to negatively affect pulpal, root, periodontal and alveolar bone healing with pulpal inflammation and hard tissue formation, extensive root resorption and alveolar bone fragmentation. The incorporation of EGF and NGF did not improve root, periodontal or alveolar bone healing. However, EGF was found to improve pulp vascularisation while NGF-improved pulpal architecture and cell organisation, although not to the level of the control group. Results indicate a possible benefit on pulpal vascularisation and pulpal cell organisation following the incorporation of EGF and NGF, respectively, into the alveolar socket of replanted molars in the rat model. No potential benefit of EGF and NGF was detected in periodontal or root

Effect of bone marrow and low power lasers on fracture healing with destruction of both periosteum and endosteum in rabbits

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M. G. Thanoon

2010-01-01

Full Text Available Ten mature rabbits of local breed were used in this study; weighing between 1.5 to 1.75 kg and aged about 1–2 years. These animals were divided into two equal groups; in group A destruction of both periosteum and endosteum was done one centimeter from each side of mid-shaft femoral bone fracture, then sufficient amount of autogenously bone marrow was injected directly at the fracture site after immobilization by intramedullary pin. In group B a similar procedure was achieved as in group A, but in additional to that He-Ne infrared laser therapy was used for several sessions. The result of radiological findings indicated that, the fracture healing occurred within group B at fifteen weeks, whereas in group A the healing occurred at eighteen weeks after operation. The implantation of autologous bone marrow enhanced the fracture healing, whereas using of combinations of autologous bone marrow and He-Ne infrared laser therapy hastened the healing.

A technique to evaluate bone healing in non-human primates using sequential sub(99m)Tc-methylene diphosphonate scintigraphy

International Nuclear Information System (INIS)

Dormehl, I.C.

1982-01-01

The assessment of bone healing through sequential nuclear medical scintigraphy requires a method of consistent localization of the exact fracture area in each consecutive image as the study progresses. This is difficult when there is surrounding bone activity as in the early stages of trauma, and also if complications should set in. The image profile feature, available from most nuclear medical computer software, facilitates this procedure considerably, as is indicated in the present report on bone healing in baboons. Together with roentgenology and histology a sup(99m)Tc-MDP study was in this way successfully done on the healing of long bone fractures experimentally induced in non-human primates. Different surgical implants were used. The results indicated that sup(99m)Tc-MDP accurately reflects the physiological activity in bone. The time-activity curves obtained are presently being studied together with extensive histology, bearing possible clinical application in mind. (orig.) [de

Thrombospondin-2 Influences the Proportion of Cartilage and Bone During Fracture Healing

OpenAIRE

Taylor, Douglas K; Meganck, Jeffrey A; Terkhorn, Shawn; Rajani, Rajiv; Naik, Amish; O'Keefe, Regis J; Goldstein, Steven A; Hankenson, Kurt D

2009-01-01

Thrombospondin-2 (TSP2) is a matricellular protein with increased expression during growth and regeneration. TSP2-null mice show accelerated dermal wound healing and enhanced bone formation. We hypothesized that bone regeneration would be enhanced in the absence of TSP2. Closed, semistabilized transverse fractures were created in the tibias of wildtype (WT) and TSP2-null mice. The fractures were examined 5, 10, and 20 days after fracture using ?CT, histology, immunohistochemistry, quantitativ...

Mate tea (Ilex paraguariensis) improves bone formation in the alveolar socket healing after tooth extraction in rats.

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Brasilino, Matheus da Silva; Stringhetta-Garcia, Camila Tami; Pereira, Camila Scacco; Pereira, Ariana Aparecida Ferreira; Stringhetta, Karina; Leopoldino, Andréia Machado; Crivelini, Marcelo Macedo; Ervolino, Edilson; Dornelles, Rita Cássia Menegati; de Melo Stevanato Nakamune, Ana Cláudia; Chaves-Neto, Antonio Hernandes

2018-04-01

The objective of this study was to investigate the effects of mate tea (MT) [Ilex paraguariensis] on alveolar socket healing after tooth extraction. Sixteen male rats were divided into MT and control groups. MT was administered by intragastric gavage at a dose of 20 mg/kg/day for 28 days before and 28 days after right maxillary incisor extraction. The control group received an equal volume of water. Histopathological and histometric analysis of the neoformed bone area and osteocyte density were performed, as well as immunohistochemical analysis of osteocalcin (OCN), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), tartrate-resistant acid phosphatase (TRAP), and manganese superoxide dismutase (MnSOD) in the alveolar socket. Calcium, phosphorus, alkaline phosphatase (ALP) activity, total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured in plasma, whereas TRAP activity was determined in serum. Histometry evidenced an increase in bone area (P alveolar socket healing on day 28 after tooth extraction. Regular MT ingestion improves the antioxidant defenses and bone formation, which is beneficial for alveolar socket bone healing after tooth extraction.

Effect of Simvastatin collagen graft on wound healing of defective bone

International Nuclear Information System (INIS)

Kang, Jun Ho; Kim, Gyu Tae; Choi, Yong Suk; Lee, Hyeon Woo; Hwang, Eui Hwan

2008-01-01

To observe and evaluate the effects of Simvastatin-induced osteogenesis on the wound healing of defective bone. 64 defective bones were created in the parietal bone of 32 New Zealand White rabbits. The defects were grafted with collagen matrix carriers mixed with Simvastatin solution in the experimental group of 16 rabbits and with collagen matrix carriers mixed with water in the controlled group. The rabbits were terminated at an interval of 3, 5, 7, and 9 days, 2, 4, 6, and 8 weeks after the formation of defective bone. The wound healing was evaluated by soft X-ray radiography. The tissues within defective bones were evaluated through the analysis of flow cytometry for the manifestation of Runx2 and Osteocalcin, and observed histopathologically by using H-E stain and Masson's trichrome stain. Results : 1. In the experimental group, flow cytometry revealed more manifestation of Runx2 at 5, 7, and 9 days and Osteocalcin at 2 weeks than in the controlled groups, but there was few difference in comparison with the controlled group. 2. In the experimental group, flow cytometry revealed considerably more cells and erythrocytes at 5, 7, and 9 days in comparison with the controlled group. 3. In the experimental group, soft x-ray radiography revealed the extended formation of trabeculation at 2, 4, 6, and 8 weeks. 4. Histopathological features of the experimental group showed more fibroblasts and newly formed vessels at 5 and 7 days, and the formation of osteoid tissues at 9 days, and the newly formed trabeculations at 4 and 6 weeks. As the induced osteogenesis by Simvastatin, there was few contrast of the manifestation between Runx2 and Osteocalcin based on the differentiation of osteoblasts. But it was considered that the more formation of cells and erythrocytes depending on newly formed vessels in the experimental group obviously had an effect on the bone regeneration.

Conservative treatment for pediatric lumbar spondylolysis to achieve bone healing using a hard brace: what type and how long?: Clinical article.

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Sairyo, Koichi; Sakai, Toshinori; Yasui, Natsuo; Dezawa, Akira

2012-06-01

Various kinds of trunk braces have been used to achieve bone healing in cases of pediatric lumbar spondylolysis. However, the optimal brace for achieving bone healing is unclear. The purpose of the present study was to determine in what types of spondylolysis bone healing can be achieved and how long it takes. In this prospective study, 63 pars interarticularis defects (spondylolysis) among 37 patients who were younger than 18 years (mean 13.5 ± 2.7 years) were treated using a hard brace. The youngest patient was 8 years old. Based on the results of CT scanning, the lyses were classified into 3 categories: early, progressive, and terminal defects. Progressive defects were further divided into 2 types according to STIR MRI findings: those with high signal intensity at the adjacent pedicle and those with low signal intensity (that is, a normal appearance). A hard brace, such as a molded plastic thoracolumbosacral orthosis, was used to immobilize the trunk. Approximately every 3 months, CT scanning was performed to evaluate bone healing until approximately 6 months. The union rates were 94%, 64%, 27%, and 0% for the early, progressive with high signal intensity, progressive with low signal intensity, and terminal defects, respectively. It was noted that no terminal defect was healed using conservative treatment. The mean time to healing among the defects that showed bone healing was 3.2, 5.4, and 5.7 months for the early, progressive with high signal intensity, and progressive with low signal intensity groups, respectively. Patients with early-stage defects are the best candidates for conservative treatment with a hard brace because more than 90% of such cases can be healed in 3 months.

Treatment with paracetamol, ketorolac or etoricoxib did not hinder alveolar bone healing: a histometric study in rats

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Ricardo Nogueira Fracon

2010-12-01

Full Text Available Prostaglandins control osteoblastic and osteoclastic function under physiological or pathological conditions and are important modulators of the bone healing process. The non-steroidal anti-inflammatory drugs (NSAIDs inhibit cyclooxygenase (COX activity and consequently prostaglandins synthesis. Experimental and clinical evidence has indicated a risk for reparative bone formation related to the use of non-selective (COX-1 and COX-2 and COX-2 selective NSAIDs. Ketorolac is a non-selective NSAID which, at low doses, has a preferential COX-1 inhibitory effect and etoricoxib is a new selective COX-2 inhibitor. Although literature data have suggested that ketorolac can interfere negatively with long bone fracture healing, there seems to be no study associating etoricoxib with reparative bone formation. Paracetamol/acetaminophen, one of the first choices for pain control in clinical dentistry, has been considered a weak anti-inflammatory drug, although supposedly capable of inhibiting COX-2 activity in inflammatory sites. OBJECTIVE: The purpose of the present study was to investigate whether paracetamol, ketorolac and etoricoxib can hinder alveolar bone formation, taking the filling of rat extraction socket with newly formed bone as experimental model. MATERIAL AND METHODS: The degree of new bone formation inside the alveolar socket was estimated two weeks after tooth extraction by a differential point-counting method, using an optical microscopy with a digital camera for image capture and histometry software. Differences between groups were analyzed by ANOVA after confirming a normal distribution of sample data. RESULTS AND CONCLUSIONS: Histometric results confirmed that none of the tested drugs had a detrimental effect in the volume fraction of bone trabeculae formed inside the alveolar socket.

Effects of combined hydroxyapatite and human platelet rich plasma on bone healing in rabbit model: radiological, macroscopical, hidtopathological and biomechanical evaluation.

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Oryan, A; Meimandi Parizi, A; Shafiei-Sarvestani, Z; Bigham, A S

2012-12-01

Hydroxyapatite is an osteoconductive material used as a bone graft extender and exhibits excellent biocompatibility with soft tissues such as skin, muscle and gums, making it an ideal candidate for orthopedic and dental implants or components of implants. Synthetic hydroxyapatite has been widely used in repair of hard tissues, and common uses include bone repair, bone augmentation, as well as coating of implants or acting as fillers in bone or teeth. On the other hand, human platelet rich plasma (hPRP) has been used as a source of osteoinductive factor. A combination of hPRP and hydroxyapatite is expected to create a composite with both osteoconductive and osteoinductive properties. This study examined the effect of a combination of hydroxyapatite and hPRP on osteogenesis in vivo, using rabbit model bone healing. A critical size defect of 10 mm long was created in the radial diaphysis of 36 rabbit and either supplied with hydroxyapatite-human PRP or hydroxyapatite or was left empty (control group). Radiographs of each forelimb were taken postoperatively on 1st day and then at the 2nd, 4th, 6th and 8th weeks post injury to evaluate bone formation, union and remodeling of the defect. The operated radiuses of half of the animals in each group were removed on 56th postoperative day and were grossly and histopathologically evaluated. In addition, biomechanical test was conducted on the operated and normal forearms of the other half of the animals of each group. This study demonstrated that hydroxyapatite-humanPRP, could promote bone regeneration in critical size defects with a high regenerative capacity. The results of the present study demonstrated that hydroxyapatite-hPRP could be an attractive alternative for reconstruction of the major diaphyseal defects of the long bones in animal models.

Enhanced Healing of Segmental Bone Defects by Modulation of the Mechanical Environment

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2013-10-01

Employment opportunities received based upon experience/ training supported by this award Partly based upon her research during the completion of...School, Coventry CV4 7AL, United Kingdom References 1. Stevenson S. Enhancement of fracture healing with autogenous and allogeneic bone grafts. Clin

Dual delivery of rhPDGF-BB and bone marrow mesenchymal stromal cells expressing the BMP2 gene enhance bone formation in a critical-sized defect model.

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Park, Shin-Young; Kim, Kyoung-Hwa; Shin, Seung-Yun; Koo, Ki-Tae; Lee, Yong-Moo; Seol, Yang-Jo

2013-11-01

Bone tissue healing is a dynamic, orchestrated process that relies on multiple growth factors and cell types. Platelet-derived growth factor-BB (PDGF-BB) is released from platelets at wound sites and induces cellular migration and proliferation necessary for bone regeneration in the early healing process. Bone morphogenetic protein-2 (BMP-2), the most potent osteogenic differentiation inducer, directs new bone formation at the sites of bone defects. This study evaluated a combinatorial treatment protocol of PDGF-BB and BMP-2 on bone healing in a critical-sized defect model. To mimic the bone tissue healing process, a dual delivery approach was designed to deliver the rhPDGF-BB protein transiently during the early healing phase, whereas BMP-2 was supplied by rat bone marrow stromal cells (BMSCs) transfected with an adenoviral vector containing the BMP2 gene (AdBMP2) for prolonged release throughout the healing process. In in vitro experiments, the dual delivery of rhPDGF-BB and BMP2 significantly enhanced cell proliferation. However, the osteogenic differentiation of BMSCs was significantly suppressed even though the amount of BMP-2 secreted by the AdBMP2-transfected BMSCs was not significantly affected by the rhPDGF-BB treatment. In addition, dual delivery inhibited the mRNA expression of BMP receptor type II and Noggin in BMSCs. In in vivo experiments, critical-sized calvarial defects in rats showed enhanced bone regeneration by dual delivery of autologous AdBMP2-transfected BMSCs and rhPDGF-BB in both the amount of new bone formed and the bone mineral density. These enhancements in bone regeneration were greater than those observed in the group treated with AdBMP2-transfected BMSCs alone. In conclusion, the dual delivery of rhPDGF-BB and AdBMP2-transfected BMSCs improved the quality of the regenerated bone, possibly due to the modulation of PDGF-BB on BMP-2-induced osteogenesis.

Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration.

Science.gov (United States)

Albanese, Antonino; Licata, Maria E; Polizzi, Bianca; Campisi, Giuseppina

2013-06-13

Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed

Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration

Science.gov (United States)

2013-01-01

Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed

Human amniotic membrane, best healing accelerator, and the choice of bone induction for vestibuloplasty technique (an animal study

Directory of Open Access Journals (Sweden)

Ahad Khoshzaban

2010-12-01

Full Text Available Mohammad H Samandari1, Shahriar Adibi2, Ahad Khoshzaban3, Sara Aghazadeh5, Parviz Dihimi4, Siamak S Torbaghan6, Saeed H Keshel5, Zohreh Shahabi71Department of Oral and Maxillofacial Surgery, Dentistry Faculty, 2Dental Research of Torabinejad Research Centre, 3Iranian Tissue Bank Research and Preparation Centre, Imam Khomeini Hospital Complex, 4Department of Oral and Maxillofacial Pathology, Dentistry Faculty, Isfahan University of Medical Sciences, Isfahan, Iran; 5Stem Cells Preparation Unit, Eye Research Center, Farabi Hospital, 6Department of Pathology, Imam Khomeini Medical Centre, 7BMT Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, IranObjective: To investigate the effects of amniotic membrane (AM in bone induction and wound healing after vestibuloplasty surgery on animal samples while receptacle proteins such as growth factors were considered as accelerators for wound healing and bone induction after these operations.Material and methods: Ten adult dogs (5 females, 5 males; race, Iranian mixed; weight, 44 pounds were included, which underwent surgery for transplantation on mandible and maxillary. AM was used for promoting bone induction and healing.Results: The tissue samples were obtained after 2, 8, and 12 weeks for histology survey. No significant differences were observed between male and female or left and right jaws. AM decreased fibrinoleukocytic exudates and inflammation in the experimental group, had significant effects on bone formation, considerably improves wound healing, and gives rise to bone induction (P < 0.0001.Conclusions: Our study findings indicate that the AM is a suitable cover for different injuries and acellular AM has the potential for rapid improvement and bone induction. The AM contains collagen, laminin, and fibronectin, which provide an appropriate substrate for bone induction. This substrate promoted bone induction and might contribute to induction of the progenitor cells and/or stem

Time kinetics of bone defect healing in response to BMP-2 and GDF-5 characterised by in vivo biomechanics

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D Wulsten

2011-02-01

Full Text Available This study reports that treatment of osseous defects with different growth factors initiates distinct rates of repair. We developed a new method for monitoring the progression of repair, based upon measuring the in vivo mechanical properties of healing bone. Two different members of the bone morphogenetic protein (BMP family were chosen to initiate defect healing: BMP-2 to induce osteogenesis, and growth-and-differentiation factor (GDF-5 to induce chondrogenesis. To evaluate bone healing, BMPs were implanted into stabilised 5 mm bone defects in rat femurs and compared to controls. During the first two weeks, in vivo biomechanical measurements showed similar values regardless of the treatment used. However, 2 weeks after surgery, the rhBMP-2 group had a substantial increase in stiffness, which was supported by the imaging modalities. Although the rhGDF-5 group showed comparable mechanical properties at 6 weeks as the rhBMP-2 group, the temporal development of regenerating tissues appeared different with rhGDF-5, resulting in a smaller callus and delayed tissue mineralisation. Moreover, histology showed the presence of cartilage in the rhGDF-5 group whereas the rhBMP-2 group had no cartilaginous tissue.Therefore, this study shows that rhBMP-2 and rhGDF-5 treated defects, under the same conditions, use distinct rates of bone healing as shown by the tissue mechanical properties. Furthermore, results showed that in vivo biomechanical method is capable of detecting differences in healing rate by means of change in callus stiffness due to tissue mineralisation.

Impact of different synthetic bone fillers on healing of extraction sockets: an experimental study in dogs.

Science.gov (United States)

Hong, Ji-Youn; Lee, Jung-Seok; Pang, Eun-Kyoung; Jung, Ui-Won; Choi, Seong-Ho; Kim, Chong-Kwan

2014-02-01

The objective of this study was to elucidate the socket healing process and biodegradation of incorporating synthetic bone fillers followed by grafting of the fresh extraction socket. Third premolars in four quadrants of eight beagle dogs were extracted and randomly treated with either one of hydroxyapatite (HA), biphasic calcium phosphate (BCP), β-tricalcium phosphate (β-TCP), or no graft (C). Histologic observations and histomorphometric analysis at three zones (apical, middle, and coronal) of the socket were performed. Socket area (S) and the proportions of newly formed bone (%NB), residual biomaterials (%RB), and fibrovascular connective tissue (%FCT) at 2, 4, and 8 weeks were measured. The numbers of osteoclast-like multinucleated cells (No.OC) were also determined at the three zones. %NB was significantly higher in control group compared with the grafted groups at all healing periods. %NB of HA and BCP increased with time, whereas %RB showed different patterns that decreased in BCP, unlike the minimal change observed in HA. %NB of β-TCP showed smallest portion compared with other grafted groups at 2 and 4 weeks, however, significantly increased at 8 weeks. %RB of β-TCP was less than HA and BCP at all healing periods. Numbers of multinucleated cells were greater in BCP and β-TCP, followed by HA and smallest in control group. Within the limit of this study, bone formation of the extraction socket was delayed in the sockets grafted with synthetic bone fillers and showed different healing process according to the biodegradation patterns. © 2012 John Wiley & Sons A/S.

Influence of Piezosurgery on Bone Healing around Titanium Implants: A Histological Study in Rats.

Science.gov (United States)

Sirolli, Marcelo; Mafra, Carlos Eduardo Secco; Santos, Rodrigo Albuquerque Basílio Dos; Saraiva, Luciana; Holzhausen, Marinella; César, João Batista

2016-01-01

The aim of this study was to evaluate histomorphometrically the influence of two techniques of dental implant site preparation on bone healing around titanium implants. Fifteen male Wistar rats (±300 g) were used in the study. Each tibia was randomly assigned to receive the implant site preparation either with a conventional drilling technique (control - DRILL group) or with a piezoelectric device (PIEZO group). The animals were sacrificed after 30 days and then the following histomorphometric parameters were evaluated (percentage) separately for cortical and cancellous regions: proportion of mineralized tissue (PMT) adjacent to implant threads (500 μm adjacent); bone area within the threads (BA) and bone-implant contact (BIC). The results demonstrated that there were no statistically significant differences between both groups for cancellous BIC (p>0.05) and cortical PMT (p>0.05). On the other hand, a higher percentage of BA was observed in the PIEZO group in the cortical (71.50±6.91 and 78.28±4.38 for DRILL and PIEZO groups, respectively; ppiezosurgery also showed higher PMT values in the cancellous zone (9.35±5.54 and 18.72±13.21 for DRILL and PIEZO groups, respectively; ppiezosurgery was beneficial to bone healing rates in the cancellous bone region, while the drill technique produced better results in the cortical bone.

No effect of Osteoset, a bone graft substitute, on bone healing in humans: a prospective randomized double-blind study

DEFF Research Database (Denmark)

Petruskevicius, Juozas; Nielsen, Mette Strange; Kaalund, Søren

2002-01-01

We studied the effects of a newly marketed bone substitute, Osteoset, on bone healing in a tibial defect in humans. 20 patients undergoing an ACL (anterior cruciate ligament) reconstruction with bone-patella tendon-bone graft were block-randomized into 2 groups of 10 each. In the treatment group......, the tibial defect was filled manually with Osteoset pellets, in the control group the defect was left empty. CTs of the defect were taken on the first day after the operation, 6 weeks, 3 and 6 months postoperatively. We found about the same amount of bone in the defect in the Osteoset and control groups...... after 6 weeks, 3, and 6 months. In the control group, but not in the Osteoset group, the bone volume increased from 6 weeks to 3 months. The Osteoset pellets were almost resorbed after 6 weeks....

Local administration of a hedgehog agonist accelerates fracture healing in a mouse model

International Nuclear Information System (INIS)

Kashiwagi, Miki; Hojo, Hironori; Kitaura, Yoshiaki; Maeda, Yujiro; Aini, Hailati; Takato, Tsuyoshi; Chung, Ung-il; Ohba, Shinsuke

2016-01-01

Bone fracture healing is processed through multiple biological stages including the transition from cartilaginous callus to bony callus formation. Because of its specific, temporal and indispensable functions demonstrated by mouse genetic studies, Hedgehog (Hh) signaling is one of the most potent signaling pathways involved in these processes, but the effect of Hh-signaling activation by small compounds on the repair process had not yet been addressed. Here we examined therapeutic effects of local and one shot-administration of the Hh agonist known as smoothened agonist (SAG) on bone fracture healing in a mouse model. A quantitative analysis with three-dimensional micro-computed tomography showed that SAG administration increased the size of both the cartilaginous callus and bony callus at 14 days after the surgery. A histological analysis showed that SAG administration increased the number of cells expressing a proliferation marker and a chondrocyte marker in cartilaginous callus as well as the cells expressing an osteoblast marker in bony callus. These results indicate that the SAG administration resulted in an enhancement of callus formation during bone fracture healing, which is at least in part mediated by an increase in chondrocyte proliferation in cartilaginous callus and the promotion of bone formation in bony callus. Therapeutic strategies with a SAG-mediated protocol may thus be useful for the treatment of bone fractures. - Highlights: • Local administration of a Hh agonist accelerates callus formation. • The Hh agonist administration promotes chondrocyte proliferation in the soft callus. • The Hh agonist administration increases osteoblast formation in the hard callus.

Impaired Fracture Healing after Hemorrhagic Shock

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Philipp Lichte

2015-01-01

Full Text Available Impaired fracture healing can occur in severely injured patients with hemorrhagic shock due to decreased soft tissue perfusion after trauma. We investigated the effects of fracture healing in a standardized pressure controlled hemorrhagic shock model in mice, to test the hypothesis that bleeding is relevant in the bone healing response. Male C57/BL6 mice were subjected to a closed femoral shaft fracture stabilized by intramedullary nailing. One group was additionally subjected to pressure controlled hemorrhagic shock (HS, mean arterial pressure (MAP of 35 mmHg for 90 minutes. Serum cytokines (IL-6, KC, MCP-1, and TNF-α were analyzed 6 hours after shock. Fracture healing was assessed 21 days after fracture. Hemorrhagic shock is associated with a significant increase in serum inflammatory cytokines in the early phase. Histologic analysis demonstrated a significantly decreased number of osteoclasts, a decrease in bone quality, and more cartilage islands after hemorrhagic shock. μCT analysis showed a trend towards decreased bone tissue mineral density in the HS group. Mechanical testing revealed no difference in tensile failure. Our results suggest a delay in fracture healing after hemorrhagic shock. This may be due to significantly diminished osteoclast recruitment. The exact mechanisms should be studied further, particularly during earlier stages of fracture healing.

FLUOXETINE INHIBITS OSTEOBLAST DIFFERENTIATION & MINERALIZATION IN FRACTURE HEALING

Science.gov (United States)

Bradaschia-Correa, Vivian; Josephson, Anne M; Mehta, Devan; Mizrahi, Matthew; Neibart, Shane S; Liu, Chao; Kennedy, Oran; Castillo, Alesha B; Egol, Kenneth A; Leucht, Philipp

2016-01-01

Chronic use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression has been linked to osteoporosis. In this study, we investigated the effect of chronic SSRI use on fracture healing in two murine models of bone regeneration. First, we performed a comprehensive analysis of endochondral bone healing in a femur fracture model. C57/BL6 mice treated with fluoxetine, the most commonly prescribed SSRI, developed a normal cartilaginous soft-callus at 14 days after fracture and demonstrated a significantly smaller and biomechanically weaker bony hard-callus at 28 days. In order to further dissect the mechanism that resulted in a smaller bony regenerate, we used an intramembranous model of bone healing and revealed that fluoxetine treatment resulted in a significantly smaller bony callus at 7 and 14 days postinjury. In order to test whether the smaller bony regenerate following fluoxetine treatment was caused by an inhibition of osteogenic differentiation and/or mineralization, we employed in vitro experiments, which established that fluoxetine treatment decreases osteogenic differentiation and mineralization and that this effect is serotonin-independent. Finally, in a translational approach, we tested whether cessation of the medication would result in restoration of the regenerative potential. However, histologic and µCT analysis revealed non-union formation in these animals with fibrous tissue interposition within the callus. In conclusion, fluoxetine exerts a direct, inhibitory effect on osteoblast differentiation and mineralization, shown in two disparate murine models of bone repair. Discontinuation of the drug did not result in restoration of the healing potential, but rather led to complete arrest of the repair process. Besides the well-established effect of SSRIs on bone homeostasis, our study provides strong evidence that fluoxetine use negatively impacts fracture healing. PMID:27869327

Extracorporeal shockwave enhanced regeneration of fibrocartilage in a delayed tendon-bone insertion repair model.

Science.gov (United States)

Chow, Dick Ho Kiu; Suen, Pui Kit; Huang, Le; Cheung, Wing-Hoi; Leung, Kwok-Sui; Ng, Chun; Shi, San Qiang; Wong, Margaret Wan Nar; Qin, Ling

2014-04-01

Fibrous tissue is often formed in delayed healing of tendon bone insertion (TBI) instead of fibrocartilage. Extracorporeal shockwave (ESW) provides mechanical cues and upregulates expression of fibrocartilage-related makers and cytokines. We hypothesized that ESW would accelerate fibrocartilage regeneration at the healing interface in a delayed TBI healing model. Partial patellectomy with shielding at the TBI interface was performed on 32 female New Zealand White Rabbits for establishing this delayed TBI healing model. The rabbits were separated into the control and ESW group for evaluations at postoperative week 8 and 12. Shielding was removed at week 4 and a single ESW treatment was applied at week 6. Fibrocartilage regeneration was evaluated histomorphologically and immunohistochemically. Vickers hardness of the TBI matrix was measured by micro-indentation. ESW group showed higher fibrocartilage area, thickness, and proteoglycan deposition than the control in week 8 and 12. ESW increased expression of SOX9 and collagen II significantly in week 8 and 12, respectively. ESW group showed a gradual transition of hardness from bone to fibrocartilage to tendon, and had a higher Vickers hardness than the control group at week 12. In conclusion, ESW enhanced fibrocartilage regeneration at the healing interface in a delayed TBI healing model. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Enhancement of Tendon–Bone Healing for Anterior Cruciate Ligament (ACL Reconstruction Using Bone Marrow-Derived Mesenchymal Stem Cells Infected with BMP-2

Directory of Open Access Journals (Sweden)

Shiyi Chen

2012-10-01

Full Text Available At present, due to the growing attention focused on the issue of tendon–bone healing, we carried out an animal study of the use of genetic intervention combined with cell transplantation for the promotion of this process. Here, the efficacy of bone marrow stromal cells infected with bone morphogenetic protein-2 (BMP-2 on tendon–bone healing was determined. A eukaryotic expression vector containing the BMP-2 gene was constructed and bone marrow-derived mesenchymal stem cells (bMSCs were infected with a lentivirus. Next, we examined the viability of the infected cells and the mRNA and protein levels of BMP-2-infected bMSCs. Gastrocnemius tendons, gastrocnemius tendons wrapped by bMSCs infected with the control virus (bMSCs+Lv-Control, and gastrocnemius tendons wrapped by bMSCs infected with the recombinant BMP-2 virus (bMSCs+Lv-BMP-2 were used to reconstruct the anterior cruciate ligament (ACL in New Zealand white rabbits. Specimens from each group were harvested four and eight weeks postoperatively and evaluated using biomechanical and histological methods. The bMSCs were infected with the lentivirus at an efficiency close to 100%. The BMP-2 mRNA and protein levels in bMSCs were significantly increased after lentiviral infection. The bMSCs and BMP-2-infected bMSCs on the gastrocnemius tendon improved the biomechanical properties of the graft in the bone tunnel; specifically, bMSCs infected with BMP-2 had a positive effect on tendon–bone healing. In the four-week and eight-week groups, bMSCs+Lv-BMP-2 group exhibited significantly higher maximum loads of 29.3 ± 7.4 N and 45.5 ± 11.9 N, respectively, compared with the control group (19.9 ± 6.4 N and 21.9 ± 4.9 N (P = 0.041 and P = 0.001, respectively. In the eight-week groups, the stiffness of the bMSCs+Lv-BMP-2 group (32.5 ± 7.3 was significantly higher than that of the bMSCs+Lv-Control group (22.8 ± 7.4 or control groups (12.4 ± 6.0 (p = 0.036 and 0.001, respectively. Based on the

Knockdown of SVCT2 impairs in-vitro cell attachment, migration and wound healing in bone marrow stromal cells

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Rajnikumar Sangani

2014-03-01

Full Text Available Bone marrow stromal cell (BMSC adhesion and migration are fundamental to a number of pathophysiologic processes, including fracture and wound healing. Vitamin C is beneficial for bone formation, fracture repair and wound healing. However, the role of the vitamin C transporter in BMSC adhesion, migration and wound healing is not known. In this study, we knocked-down the sodium-dependent vitamin C transporter, SVCT2, the only known transporter of vitamin C in BMSCs, and performed cell adhesion, migration, in-vitro scratch wound healing and F-actin re-arrangement studies. We also investigated the role of oxidative stress on the above processes. Our results demonstrate that both oxidative stress and down-regulation of SVCT2 decreased cell attachment and spreading. A trans-well cell migration assay showed that vitamin C helped in BMSC migration and that knockdown of SVCT2 decreased cell migration. In the in-vitro scratch wound healing studies, we established that oxidative stress dose-dependently impairs wound healing. Furthermore, the supplementation of vitamin C significantly rescued the BMSCs from oxidative stress and increased wound closing. The knockdown of SVCT2 in BMSCs strikingly decreased wound healing, and supplementing with vitamin C failed to rescue cells efficiently. The knockdown of SVCT2 and induction of oxidative stress in cells produced an alteration in cytoskeletal dynamics. Signaling studies showed that oxidative stress phosphorylated members of the MAP kinase family (p38 and that vitamin C inhibited their phosphorylation. Taken together, these results indicate that both the SVCT2 transporter and oxidative stress play a vital role in BMSC attachment, migration and cytoskeletal re-arrangement. BMSC-based cell therapy and modulation of SVCT2 could lead to a novel therapeutic approach that enhances bone remodeling, fracture repair and wound healing in chronic disease conditions.

Estrogen receptor α- (ERα), but not ERβ-signaling, is crucially involved in mechanostimulation of bone fracture healing by whole-body vibration.

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Haffner-Luntzer, Melanie; Kovtun, Anna; Lackner, Ina; Mödinger, Yvonne; Hacker, Steffen; Liedert, Astrid; Tuckermann, Jan; Ignatius, Anita

2018-05-01

Mechanostimulation by low-magnitude high frequency vibration (LMHFV) has been shown to provoke anabolic effects on the intact skeleton in both mice and humans. However, experimental studies revealed that, during bone fracture healing, the effect of whole-body vibration is profoundly influenced by the estrogen status. LMHFV significantly improved fracture healing in ovariectomized (OVX) mice being estrogen deficient, whereas bone regeneration was significantly reduced in non-OVX, estrogen-competent mice. Furthermore, estrogen receptors α (ERα) and β (ERβ) were differentially expressed in the fracture callus after whole-body vibration, depending on the estrogen status. Based on these data, we hypothesized that ERs may mediate vibration-induced effects on fracture healing. To prove this hypothesis, we investigated the effects of LMHFV on bone healing in mice lacking ERα or ERβ. To study the influence of the ER ligand estrogen, both non-OVX and OVX mice were used. All mice received a femur osteotomy stabilized by an external fixator. Half of the mice were sham-operated or subjected to OVX 4 weeks before osteotomy. Half of each group received LMHFV with 0.3 g and 45 Hz for 20 min per day, 5 days per week. After 21 days, fracture healing was evaluated by biomechanical testing, μCT analysis, histomorphometry and immunohistochemistry. Absence of ERα or ERβ did not affect fracture healing in sham-treated mice. Wildtype (WT) and ERβ-knockout mice similarly displayed impaired bone regeneration after OVX, whereas ERα-knockout mice did not. Confirming previous data, in WT mice, LMHFV negatively affected bone repair in non-OVX mice, whereas OVX-induced compromised healing was significantly improved by vibration. In contrast, vibrated ERα-knockout mice did not display significant differences in fracture healing compared to non-vibrated animals, both in non-OVX and OVX mice. Fracture healing in ERβ-knockout mice was similarly affected by LMHFV as in WT

Fracture healing using degradable magnesium fixation plates and screws.

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Chaya, Amy; Yoshizawa, Sayuri; Verdelis, Kostas; Noorani, Sabrina; Costello, Bernard J; Sfeir, Charles

2015-02-01

Internal bone fixation devices made with permanent metals are associated with numerous long-term complications and may require removal. We hypothesized that fixation devices made with degradable magnesium alloys could provide an ideal combination of strength and degradation, facilitating fracture fixation and healing while eliminating the need for implant removal surgery. Fixation plates and screws were machined from 99.9% pure magnesium and compared with titanium devices in a rabbit ulnar fracture model. Magnesium device degradation and the effect on fracture healing and bone formation were assessed after 4 weeks. Fracture healing with magnesium device fixation was compared with that of titanium devices using qualitative histologic analysis and quantitative histomorphometry. Micro-computed tomography showed device degradation after 4 weeks in vivo. In addition, 2-dimensional micro-computed tomography slices and histologic staining showed that magnesium degradation did not inhibit fracture healing or bone formation. Histomorphology showed no difference in bone-bridging fractures fixed with magnesium and titanium devices. Interestingly, abundant new bone was formed around magnesium devices, suggesting a connection between magnesium degradation and bone formation. Our results show potential for magnesium fixation devices in a loaded fracture environment. Furthermore, these results suggest that magnesium fixation devices may enhance fracture healing by encouraging localized new bone formation. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Effect of Simvastatin collagen graft on wound healing of defective bone

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Kang, Jun Ho; Kim, Gyu Tae [Department of Oral and Maxillofacial Radiology, School of Dentistry, Kyung Hee University, Seoul (Korea, Republic of); Choi, Yong Suk; Lee, Hyeon Woo; Hwang, Eui Hwan [Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul (Korea, Republic of)

2008-09-15

To observe and evaluate the effects of Simvastatin-induced osteogenesis on the wound healing of defective bone. 64 defective bones were created in the parietal bone of 32 New Zealand White rabbits. The defects were grafted with collagen matrix carriers mixed with Simvastatin solution in the experimental group of 16 rabbits and with collagen matrix carriers mixed with water in the controlled group. The rabbits were terminated at an interval of 3, 5, 7, and 9 days, 2, 4, 6, and 8 weeks after the formation of defective bone. The wound healing was evaluated by soft X-ray radiography. The tissues within defective bones were evaluated through the analysis of flow cytometry for the manifestation of Runx2 and Osteocalcin, and observed histopathologically by using H-E stain and Masson's trichrome stain. Results : 1. In the experimental group, flow cytometry revealed more manifestation of Runx2 at 5, 7, and 9 days and Osteocalcin at 2 weeks than in the controlled groups, but there was few difference in comparison with the controlled group. 2. In the experimental group, flow cytometry revealed considerably more cells and erythrocytes at 5, 7, and 9 days in comparison with the controlled group. 3. In the experimental group, soft x-ray radiography revealed the extended formation of trabeculation at 2, 4, 6, and 8 weeks. 4. Histopathological features of the experimental group showed more fibroblasts and newly formed vessels at 5 and 7 days, and the formation of osteoid tissues at 9 days, and the newly formed trabeculations at 4 and 6 weeks. As the induced osteogenesis by Simvastatin, there was few contrast of the manifestation between Runx2 and Osteocalcin based on the differentiation of osteoblasts. But it was considered that the more formation of cells and erythrocytes depending on newly formed vessels in the experimental group obviously had an effect on the bone regeneration.

Inferior tendon graft to bone tunnel healing at the tibia compared to that at the femur after anterior cruciate ligament reconstruction

International Nuclear Information System (INIS)

Lui, P.P.Y.; Ho, G.; Shum, W.T.; Lee, Y.W.; Ho, P.Y.; Lo, W.N.; Lo, C.K.

2010-01-01

Tunnel widening after anterior cruciate ligament (ACL) reconstruction (ACLR) is commonly reported without a clear understanding of the mechanism. This study aimed to quantify the spatiotemporal change of the newly formed bone mass, bone tunnel diameter, and area along both bone tunnels using micro-computed tomography (μCT) and correlated the result with histology. ACLR was performed in 24 rabbits. At baseline and weeks 2, 6, and 12, the juxta-articular, middle, and exit segments of both tunnels were harvested for μCT and histological evaluation. μCT and histology revealed significant bone tunnel and graft-bone tunnel healing, respectively, only at week 6 after reconstruction. Despite this, the mean tunnel diameter and area remained relatively unchanged with time. The newly formed bone mass [new bone volume/total bone volume (BV/TV) ratio] and its bone mineral density (BMD) were both higher, whereas the mean tunnel diameter and area were significantly smaller at the femoral tunnel compared to those at the tibial tunnel at weeks 6 and 12 and at week 12, respectively. These were consistent with histological findings, which showed inferior graft remodeling and integration at the tibial tunnel at weeks 6 and 12. The BV/TV increased, whereas the mean tunnel diameter and area decreased toward the exit segment of both tunnels. However, whereas better histological healing occurred at the femoral exit segment, poorer graft remodeling and Sharpey's fiber formation occurred at the tibial exit segment. Poor healing was observed during the initial 6 weeks, particularly that of the tibia, after ACLR. Bone resorption was rapid during healing, resulting in unchanged tunnel diameter and area with time. (author)

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

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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

Differential fracture healing resulting from fixation stiffness variability. A mouse model

International Nuclear Information System (INIS)

Gardner, M.J.; Putnam, S.M.; Wong, A.; Streubel, P.N.; Kotiya, A.; Silva, M.J.

2011-01-01

The mechanisms underlying the interaction between the local mechanical environment and fracture healing are not known. We developed a mouse femoral fracture model with implants of different stiffness, and hypothesized that differential fracture healing would result. Femoral shaft fractures were created in 70 mice, and were treated with an intramedullary nail made of either tungsten (Young's modulus=410 GPa) or aluminium (Young's modulus=70 GPa). Mice were then sacrificed at 2 or 5 weeks. Fracture calluses were analyzed using standard microCT, histological, and biomechanical methods. At 2 weeks, callus volume was significantly greater in the aluminium group than in the tungsten group (61.2 vs. 40.5 mm 3 , p=0.016), yet bone volume within the calluses was no different between the groups (13.2 vs. 12.3 mm 3 ). Calluses from the tungsten group were stiffer on mechanical testing (18.7 vs. 9.7 N/mm, p=0.01). The percent cartilage in the callus was 31.6% in the aluminium group and 22.9% in the tungsten group (p=0.40). At 5 weeks, there were no differences between any of the healed femora. In this study, fracture implants of different stiffness led to different fracture healing in this mouse fracture model. Fractures treated with a stiffer implant had more advanced healing at 2 weeks, but still healed by callus formation. Although this concept has been well documented previously, this particular model could be a valuable research tool to study the healing consequences of altered fixation stiffness, which may provide insight into the pathogenesis and ideal treatment of fractures and non-unions. (author)

Investigation of a pre-clinical mandibular bone notch defect model in miniature pigs: clinical computed tomography, micro-computed tomography, and histological evaluation.

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Carlisle, Patricia L; Guda, Teja; Silliman, David T; Lien, Wen; Hale, Robert G; Brown Baer, Pamela R

2016-02-01

To validate a critical-size mandibular bone defect model in miniature pigs. Bilateral notch defects were produced in the mandible of dentally mature miniature pigs. The right mandibular defect remained untreated while the left defect received an autograft. Bone healing was evaluated by computed tomography (CT) at 4 and 16 weeks, and by micro-CT and non-decalcified histology at 16 weeks. In both the untreated and autograft treated groups, mineralized tissue volume was reduced significantly at 4 weeks post-surgery, but was comparable to the pre-surgery levels after 16 weeks. After 16 weeks, CT analysis indicated that significantly greater bone was regenerated in the autograft treated defect than in the untreated defect (P=0.013). Regardless of the treatment, the cortical bone was superior to the defect remodeled over 16 weeks to compensate for the notch defect. The presence of considerable bone healing in both treated and untreated groups suggests that this model is inadequate as a critical-size defect. Despite healing and adaptation, the original bone geometry and quality of the pre-injured mandible was not obtained. On the other hand, this model is justified for evaluating accelerated healing and mitigating the bone remodeling response, which are both important considerations for dental implant restorations.

Evaluation of healing potential of autogenous, macroscopic fat deposited or fat free, omental graft in experimental radius bone defect in rabbit: Radiological study

International Nuclear Information System (INIS)

Masouleh, M.N.; Haghdoost, I.S.; Heydari, G.A.C.; Raissi, A.; Mohitmafi, S.

2011-01-01

This study was designed for evaluation of the difference between the ability of greater omentum graft with or without macroscopic fat deposition in acceleration of bone healing process. Adult female New Zealand white rabbits (n=15) were randomly divided into three equal groups. In groups A and B, the drilled hole on the left radius was filled by the omentum without and with macroscopic fat deposition, respectively while drilled hole on the right radius left intact for consideration as control. In group C, the drilled hole on the left and right radius was filled by the omentum sample with and without macroscopic fat deposition, respectively. Experimental bone defects on the radiuses were secured by the pieces of greater omentum, with or without macroscopic fat deposition, which obtained as an autogenous graft from each rabbit in accompany with control samples. Standardized serial radiography for evaluation of bone healing was performed and the difference in bone healing process in three groups of study was determined. According to the obtained data, the radius bones which filled by omentum without macroscopic fat deposition showed faster healing process than the radius bones which filled by omentum with macroscopic fat deposition (P<0.05). (author)

Effects of Recombinant Human Bone Morphogenetic Protein-2 on Vertical Bone Augmentation in a Canine Model.

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Hsu, Yung-Ting; Al-Hezaimi, Khalid; Galindo-Moreno, Pablo; O'Valle, Francisco; Al-Rasheed, Abdulaziz; Wang, Hom-Lay

2017-09-01

Vertical bone augmentation (VBA) remains unpredictable and challenging for most clinicians. This study aims to compare hard tissue outcomes of VBA, with and without recombinant human bone morphogenetic protein (rhBMP)-2, under space-making titanium mesh in a canine model. Eleven male beagle dogs were used in the study. Experimental ridge defects were created to form atrophic ridges. VBA was performed via guided bone regeneration using titanium mesh and allografts. In experimental hemimandibles, rhBMP-2/absorbable collagen sponge was well mixed with allografts prior to procedures, whereas a control buffer was applied within controls. Dogs were euthanized after a 4-month healing period. Clinical and radiographic examinations were performed to assess ridge dimensional changes. In addition, specimens were used for microcomputed tomography (micro-CT) assessment and histologic analysis. Membrane exposure was found on five of 11 (45.5%) rhBMP-2-treated sites, whereas it was found on nine of 11 (81.8%) non-rhBMP-2-treated sites. Within 4 months of healing, rhBMP-2-treated sites showed better radiographic bone density, greater defect fill, and significantly more bone gain in ridge height (P 0.05). Under light microscope, predominant lamellar patterns were found in the specimen obtained from rhBMP-2 sites. With inherent limitations of the canine model and the concern of such a demanding surgical technique, current findings suggest that the presence of rhBMP-2 in a composite graft allows an increase of vertical gain, with formation of ectopic bone over the titanium mesh in comparison with non-rhBMP-2 sites.

Ozone Treatment of Alveolar Bone in the Cape Chacma Baboon Does Not Enhance Healing Following Trauma

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Kotze, Marthinus; Bütow, Kürt-W; Olorunju, Steve A.; Kotze, Harry F.

2013-01-01

In the international literature, the role of Ozone (O3) in the advancement in alveolar bone healing in the absence of bone pathology was not tested before. The purpose of this study was to evaluate alveolar bone regeneration after a bone defect was created and treated with a single topical administration of O3. Alveolar bone defects were created on five healthy chacma baboons. One side of the maxilla and mandible was topically treated with a single treatment of an O3/O2 mixture (3,5–4 % O3), ...

Chitosan porous 3D scaffolds embedded with resolvin D1 to improve in vivo bone healing.

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Vasconcelos, Daniela P; Costa, Madalena; Neves, Nuno; Teixeira, José H; Vasconcelos, Daniel M; Santos, Susana G; Águas, Artur P; Barbosa, Mário A; Barbosa, Judite N

2018-06-01

The aim of this study was to investigate the effect chitosan (Ch) porous 3D scaffolds embedded with resolvin D1 (RvD1), an endogenous pro-resolving lipid mediator, on bone tissue healing. These scaffolds previous developed by us have demonstrated to have immunomodulatory properties namely in the modulation of the macrophage inflammatory phenotypic profile in an in vivo model of inflammation. Herein, results obtained in an in vivo rat femoral defect model demonstrated that two months after Ch + RvD1 scaffolds implantation, an increase in new bone formation, in bone trabecular thickness, and in collagen type I and Coll I/Coll III ratio were observed. These results suggest that Ch scaffolds embedded with RvD1 were able to lead to the formation of new bone with improvement of trabecular thickness. This study shows that the presence of RvD1 in the acute phase of the inflammatory response to the implanted biomaterial had a positive role in the subsequent bone tissue repair, thus demonstrating the importance of innovative approaches for the control of immune responses to biomedical implants in the design of advanced strategies for regenerative medicine. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1626-1633, 2018. © 2018 Wiley Periodicals, Inc.

Influence of Healing Period Upon Bone Turn Over on Maxillary Sinus Floor Augmentation Grafted Solely with Deproteinized Bovine Bone Mineral: A Prospective Human Histological and Clinical Trial.

Science.gov (United States)

Wang, Feng; Zhou, Wenjie; Monje, Alberto; Huang, Wei; Wang, Yueping; Wu, Yiqun

2017-04-01

To investigate the influence of maturation timing upon histological, histomorphometric and clinical outcomes when deproteinized bovine bone mineral (DBBM) was used as a sole biomaterial for staged maxillary sinus floor augmentation (MSFA). Patients with a posterior edentulous maxillary situation and a vertical bone height ≤ 4 mm were included in this study. A staged MSFA was carried out. After MSFA with DBBM as a sole grafting material, biopsy cores were harvested with simultaneous implant placement followed by a healing period of 5, 8, and 11 months, respectively. Micro-CT, histologic and histomorphometric analyses were performed. Forty-one patients were enrolled and 38 bone core biopsies were harvested. Significantly greater BV/TV was observed between 5- and 8-month healing from micro-CT analysis. Histomorphometric analyses showed the ratio of mineralized newly formed bone increased slightly from 5 to 11 months; however, no statistically significant difference was reached (p = .409). Residual bone substitute decreased from 37.3 ± 5.04% to 20.6 ± 7.45%, achieving a statistical significant difference from of 5 up to 11 months (p < .01). Moreover, no implant failure, biological or technical complication occurred after 12-month follow-up of functional loading. DBBM utilized as sole grafting material in staged MSFA demonstrated to be clinically effective regardless of the healing period. Histomorphometrical and micro-CT assessments revealed that at later stages of healing (8 and 11 months) there is a higher proportion of newly-bone formation compared to earlier stages (5 months). Moreover, the longer the maturation period, the substantially lesser remaining biomaterial could be expected. Even though, these facts did not seem to negatively impact on the implant prognosis 1-year after loading. © 2016 Wiley Periodicals, Inc.

A Passive and Wireless Sensor for Bone Plate Strain Monitoring.

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Tan, Yisong; Hu, Jiale; Ren, Limin; Zhu, Jianhua; Yang, Jiaqi; Liu, Di

2017-11-16

This paper reports on a sensor for monitoring bone plate strain in real time. The detected bone plate strain could be used for judging the healing state of fractures in patients. The sensor consists of a magnetoelastic material, which can be wirelessly connected and passively embedded. In order to verify the effectiveness of the sensor, a tibia-bone plate-screw (TBS) model was established using the finite element analysis method. A variation of the bone plate strain was obtained via this model. A goat hindquarter tibia was selected as the bone fracture model in the experiment. The tibia was fixed on a high precision load platform and an external force was applied. Bone plate strain variation during the bone fracture healing process was acquired with sensing coils. Simulation results indicated that bone plate strain decreases as the bone gradually heals, which is consistent with the finite element analysis results. This validated the soundness of the sensor reported here. This sensor has wireless connections, no in vivo battery requirement, and long-term embedding. These results can be used not only for clinical practices of bone fracture healing, but also for bone fracture treatment and rehabilitation equipment design.

Study of healing process and prognosis of medial femoral neck fracture evaluated by bone scintigraphy

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Suzuki, K [Yokohama City Univ. (Japan). Faculty of Medicine

1981-02-01

As to healing process and prognosis of femoral neck fracture, radionuclide bone scintigraphy using sup(99m)Tc phosphorus compound was performed and the following results were obtained. 1. In cases of osteosynthesis, scintigraphical study showed a certain serial pattern until fracture was uneventfully healed. 2. On the other hand, in cases with non-union or late segmental collapse of the head, scintigraphy revealed defect at superolateral or central area in the head. This finding could be already noted prior to roentgenographical evaluation. 3. In the study of radionuclide uptake count on the femoral head of resected specimen, the higher value was observed in the area along medial fracture edge to medial margin of the head. Histological study showed feature of increased new bone formation at the area of higher radionuclide uptake. Vascular supply through the bone marrow of the neck and superior retinacular artery was thought to play an important role for the new bone formation. 4. From the aforementioned results, sup(99m)Tc phosphorus compound scintigraphy was considered as one of the quite useful methods for early diagnosis of complications after femoral neck fracture.

Dynamics of bone healing after osteotomy with piezosurgery or conventional drilling - histomorphometrical, immunohistochemical, and molecular analysis.

Science.gov (United States)

Esteves, Jônatas Caldeira; Marcantonio, Elcio; de Souza Faloni, Ana Paula; Rocha, Fernanda Regina Godoy; Marcantonio, Rosemary Adriana; Wilk, Katarzyna; Intini, Giuseppe

2013-09-23

Piezosurgery is an osteotomy system used in medical and dental surgery. Many studies have proven clinical advantages of piezosurgery in terms of quality of cut, maneuverability, ease of use, and safety. However, few investigations have tested its superiority over the traditional osteotomy systems in terms of dynamics of bone healing. Therefore, the aim of this study was to evaluate the dynamics of bone healing after osteotomies with piezosurgery and to compare them with those associated to traditional bone drilling. One hundred and ten rats were divided into two groups with 55 animals each. The animals were anesthetized and the tibiae were surgically exposed to create defects 2 mm in diameter by using piezosurgery (Piezo group) and conventional drilling (Drill group). Animals were sacrificed at 3, 7, 14, 30 and 60 days post-surgery. Bone samples were collected and processed for histological, histomorphometrical, immunohistochemical, and molecular analysis. The histological analysis was performed at all time points (n = 8) whereas the histomorphometrical analysis was performed at 7, 14, 30 and 60 days post-surgery (n = 8). The immunolabeling was performed to detect Vascular Endothelial Growth Factor (VEGF), Caspase-3 (CAS-3), Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL), and Osteocalcin (OC) at 3, 7, and 14 days (n = 3). For the molecular analysis, animals were sacrificed at 3, 7 and 14 days, total RNA was collected, and quantification of the expression of 21 genes related to BMP signaling, Wnt signaling, inflammation, osteogenenic and apoptotic pathways was performed by qRT-PCR (n = 5). Histologically and histomorphometrically, bone healing was similar in both groups with the exception of a slightly higher amount of newly formed bone observed at 30 days after piezosurgery (p piezosurgery are comparable to those observed with conventional drilling.

Effect of microthreads on coronal bone healing of narrow-diameter implants with reverse-tapered design in beagle dogs.

Science.gov (United States)

Chang, Yun-Young; Kim, Su-Hwan; Park, Keun-Oh; Yun, Jeong-Ho

2017-12-01

The objective of this study was to investigate the effect of microthreads on the coronal bone healing of narrow-diameter implants with reverse-tapered design. A total of 52 implants were classified into two groups according to presence or absence of coronal microthreads, the reverse-tapered narrow-diameter implant (RTN) group, and the reverse-tapered narrow-diameter implant with microthreads (RTNM) group. The implants were installed in split-mouth design in the edentulous mandible of six dogs. Three animals were sacrificed at 4 weeks and three at 8 weeks. Resonance frequency analysis, bone measurement using microcomputed tomography (micro-CT), removal torque test, and histometric analysis were performed. No significant differences in implant stability quotient value were observed between the groups at baseline, 4 weeks, or 8 weeks. Bone measurement using micro-CT showed that bone-implant contact volume (BICV) and bone-implant contact volume ratio (BICVR) in the coronal part of RTNM were statistically higher than those in RTN at 4 and 8 weeks. Histometric analysis showed statistically higher bone-implant contact length (BICL) in the coronal part of RTNM than in RTN at 4 weeks; however, bone-implant contact ratio (BICR) was not significantly different between the groups. At 8 weeks, the BICL and BICR did not differ significantly between the groups. Removal torque test showed no significant differences between the groups at 4 and 8 weeks. The microthreads might facilitate more coronal bone-implant contact due to increased surface areas at an early healing phase; however, they did not significantly affect coronal bone healing at 8 weeks. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Potential Effect of Leukocyte-Platelet-Rich Fibrin in Bone Healing of Skull Base: A Pilot Study

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Felipe Fredes

2017-01-01

Full Text Available Background. Reconstruction of surgical defects following cranial base surgery is challenging. Others have demonstrated that leukocyte-platelet-rich fibrin (L-PRF stimulates tissue healing and bone regeneration. However, these studies have addressed mostly maxillofacial surgical wounds. Objective. The objective of this study was to assess the possible adjuvant role of L-PRF in inducing neoossification of the surgical bone defect in anterior skull base surgery. Methods. We identified patients who had undergone an endoscopic endonasal surgery of the anterior skull base in which L-PRF membranes were used for the reconstruction of the bone defect and who were followed up with postoperative CT scans. CT findings were then correlated with baseline scans and with the CT scans of a patient who had undergone imaging and histologic analysis after maxillofacial surgery in which L-PRF was used and in which we demonstrated bone formation. Results. Five patients fulfilled the inclusion criteria. In four patients, the CT scan demonstrated closure of the bony defect by neoosteogenesis; however, the bone appeared less dense than the surrounding normal bone. A comparison with the control patient yielded similar radiological features. Conclusion. This case series suggests that L-PRF may induce bone healing and regeneration at the surgical site defect. Multi-institutional studies with a larger series of patients are required to confirm this possibility.

The application of sequential sup(99m)Tc-methylene diphosphonate scintigraphy to evaluate bone healing in non human primates

International Nuclear Information System (INIS)

Dormehl, I.C.; Mennen, U.; Goosen, D.J.

1982-01-01

The study was performed to devise and assess a sensitive non-invasive method for investigated the healing process of long bones in non-human primates. A specific clinical application in mind is the early detection of non-healing or delayed healing of fractures in the aged. Important for accurate evaluation is the consistency of the localisation of the fracture site and the region of healthy bone from each scintiscan for the entire study. The present report concerns a technique which seems to be successful for this purpose, and is found useful towards the clinical application. Four adult chacma baboons (Papio ursinus) were used in the experiment. All four animals were clinically and radiographically normal. They were housed indoors in environmentally controlled rooms for the duration of the experiment and they were fed a balanced commercial diet with water freely available. Eight forearms, i.e. a total of 16 radius and ulna bones were osteotomized with a Gigli saw to create simple standard and controlled fractures

Inhibition of GSK-3β Rescues the Impairments in Bone Formation and Mechanical Properties Associated with Fracture Healing in Osteoblast Selective Connexin 43 Deficient Mice

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Loiselle, Alayna E.; Lloyd, Shane A. J.; Paul, Emmanuel M.; Lewis, Gregory S.; Donahue, Henry J.

2013-01-01

Connexin 43 (Cx43) is the most abundant gap junction protein in bone and is required for osteoblastic differentiation and bone homeostasis. During fracture healing, Cx43 is abundantly expressed in osteoblasts and osteocytes, while Cx43 deficiency impairs bone formation and healing. In the present study we selectively deleted Cx43 in the osteoblastic lineage from immature osteoblasts through osteocytes and tested the hypothesis that Cx43 deficiency results in delayed osteoblastic differentiation and impaired restoration of biomechanical properties due to attenuated β-catenin expression relative to wild type littermates. Here we show that Cx43 deficiency results in alterations in the mineralization and remodeling phases of healing. In Cx43 deficient fractures the mineralization phase is marked by delayed expression of osteogenic genes. Additionally, the decrease in the RankL/ Opg ratio, osteoclast number and osteoclast size suggest decreased osteoclast bone resorption and remodeling. These changes in healing result in functional deficits as shown by a decrease in ultimate torque at failure. Consistent with these impairments in healing, β-catenin expression is attenuated in Cx43 deficient fractures at 14 and 21 days, while Sclerostin (Sost) expression, a negative regulator of bone formation is increased in Cx43cKO fractures at 21 days, as is GSK-3β, a key component of the β-catenin proteasomal degradation complex. Furthermore, we show that alterations in healing in Cx43 deficient fractures can be rescued by inhibiting GSK-3β activity using Lithium Chloride (LiCl). Treatment of Cx43 deficient mice with LiCl restores both normal bone formation and mechanical properties relative to LiCl treated WT fractures. This study suggests that Cx43 is a potential therapeutic target to enhance fracture healing and identifies a previously unknown role for Cx43 in regulating β-catenin expression and thus bone formation during fracture repair. PMID:24260576

Bone marrow mesenchymal stem cells accelerate the hyperglycemic refractory wound healing by inhibiting an excessive inflammatory response.

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Nan, Wenbin; Xu, Zhihao; Chen, Zhibin; Yuan, Xin; Lin, Juntang; Feng, Huigen; Lian, Jie; Chen, Hongli

2017-05-01

The aim of the present study was to evaluate the healing effect of bone marrow-derived mesenchymal stem cells administered to hyperglycemia model mice with skin wounds, and to explore the underlying mechanism contributing to their effects in promoting refractory wound healing. A full‑thickness skin wound mouse model was established, and refers to a wound of the skin and subcutaneous tissue. The mice were randomly divided into three groups: Blank control group, hyperglycemic group and a hyperglycemic group treated with stem cells. Wound healing was monitored and the wound‑healing rate was determined at 3, 6, 9, and 12 days following trauma. The structure of the organization of new skin tissue was observed by hematoxylin and eosin staining, and expression levels of the inflammatory cytokines interleukin (IL)‑6 and tumor necrosis factor (TNF)‑α were determined from 1 to 6 days following trauma. The wound healing of the hyperglycemic group was slower than that of the blank group, and the hyperglycemic mice treated with stem cells presented faster healing than the hyperglycemia group. The horny layer and granular layer of the skin were thinner and incomplete in the new skin tissue of the hyperglycemic group, whereas the new skin wound tissue basal layer was flat and demonstrated better fusion with the wound edge in the other two groups. The expression of inflammatory cytokines (IL‑6 and TNF‑α) was significantly increased in all three groups, with continuously higher expression in the hyperglycemic group and decreased expression in the other two groups over time. Hyperglycemia refractory wounds are likely related to the excessive expression of inflammatory cytokines surrounding the wound area. Stem cells may be able to alleviate the excessive inflammatory reaction in the wound tissue of hyperglycemic mice, so as to promote wound healing.

Icariin Promotes Tendon-Bone Healing during Repair of Rotator Cuff Tears: A Biomechanical and Histological Study.

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Ye, Chenyi; Zhang, Wei; Wang, Shengdong; Jiang, Shuai; Yu, Yuanbin; Chen, Erman; Xue, Deting; Chen, Jianzhong; He, Rongxin

2016-10-25

To investigate whether the systematic administration of icariin (ICA) promotes tendon-bone healing after rotator cuff reconstruction in vivo, a total of 64 male Sprague Dawley rats were used in a rotator cuff injury model and underwent rotator cuff reconstruction (bone tunnel suture fixation). Rats from the ICA group ( n = 32) were gavage-fed daily with ICA at 0.125 mg/g, while rats in the control group ( n = 32) received saline only. Micro-computed tomography, biomechanical tests, serum ELISA (calcium; Ca, alkaline phosphatase; AP, osteocalcin; OCN) and histological examinations (Safranin O and Fast Green staining, type I, II and III collagen (Col1, Col2, and Col3), CD31, and vascular endothelial growth factor (VEGF)) were analyzed two and four weeks after surgery. In the ICA group, the serum levels of AP and OCN were higher than in the control group. More Col1-, Col2-, CD31-, and VEGF-positive cells, together with a greater degree of osteogenesis, were detected in the ICA group compared with the control group. During mechanical testing, the ICA group showed a significantly higher ultimate failure load than the control group at both two and four weeks. Our results indicate that the systematic administration of ICA could promote angiogenesis and tendon-bone healing after rotator cuff reconstruction, with superior mechanical strength compared with the controls. Treatment for rotator cuff injury using systematically-administered ICA could be a promising strategy.

Type 2 Diabetes and Metformin Influence on Fracture Healing in an Experimental Rat Model.

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La Fontaine, Javier; Chen, Chris; Hunt, Nathan; Jude, Edward; Lavery, Lawrence

2016-01-01

Persons with diabetes have a greater incidence of fractures compared with persons without diabetes. However, very little published information is available concerning the deleterious effect of late-stage diabetes on osseous structure and bone healing. The purpose of the present study was to evaluate the role of diabetes on fracture healing in a rat femur repair model. Thirty-six lean and diabetic Zucker rats were subdivided into 3 groups: (1) 12 lean rats as the control group; (2) 12 diabetic rats without blood glucose control (DM group); and (3) 12 diabetic rats treated with 300 mg/kg metformin to reduce the blood glucose levels (DM + Met group). Radiographs were taken every week to determine the incidence of bone repair and delayed union. All the rats were killed at 6 weeks after surgery. In both the sham-operated and the fractured and repaired femurs, significant decreases in the fracture-load/weight and marginal decreases in the fracture-load between the lean and DM groups were found. Metformin treatment significantly reduced the blood glucose and body weight 12 days postoperatively. Furthermore, a decrease in the fracture-load and fracture-load/weight in the repaired femurs was found in the DM + Met group. Diabetes impairs bone fracture healing. Metformin treatment reduces the blood glucose and body weight but had an adverse effect on fracture repair in diabetic rats. Further investigations are needed to reveal the mechanisms responsible for the effects of type 2 diabetes mellitus on bone and bone quality and the effect of medications such as metformin might have in diabetic bone in the presence of neuropathy and vascular disease. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

Cola beverage consumption delays alveolar bone healing: a histometric study in rats

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Juliana Mazzonetto Teófilo

2010-06-01

Full Text Available Epidemiological studies have suggested that cola beverage consumption may affect bone metabolism and increase bone fracture risk. Experimental evidence linking cola beverage consumption to deleterious effects on bone is lacking. Herein, we investigated whether cola beverage consumption from weaning to early puberty delays the rate of reparative bone formation inside the socket of an extracted tooth in rats. Twenty male Wistar rats received cola beverage (cola group or tap water (control group ad libitum from the age of 23 days until tooth extraction at 42 days and euthanasia 2 and 3 weeks later. The neoformed bone volume inside the alveolar socket was estimated in semi-serial longitudinal sections using a quantitative differential point-counting method. Histological examination suggested a decrease in the osteogenic process within the tooth sockets of rats from both cola groups, which had thinner and sparser new bone trabeculae. Histometric data confirmed that alveolar bone healing was significantly delayed in cola-fed rats at three weeks after tooth extraction (ANOVA, p = 0.0006, followed by Tukey's test, p < 0.01. Although the results of studies in rats cannot be extrapolated directly to human clinical dentistry, the present study provides evidence that cola beverage consumption negatively affect maxillary bone formation.

Effects of Bone Marrow Mesenchymal Stem Cells-Conditioned Medium on Tibial Partial Osteotomy Model of Fracture Healing in Hypothyroidism Rats

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Sefati, Niloofar; Norouzian, Mohsen; Abbaszadeh, Hojjat-Allah; Abdollahifar, Mohammad-Amin; Amini, Abdollah; Bagheri, Mohammad; Aryan, Arefeh; Fadaei Fathabady, Fatemeh

2018-03-01

Hypothyroidism is associated with dysfunction of the bone turnover with reduced osteoblastic bone formation and osteoclastic bone resorption. Mesenchyme stem cells (MSCs) secrete various factors and cytokines that may stimulate bone regeneration. The aim of this study was to determine the effects of MSCs-conditioned medium (CM) in hypothyroidism male rats after inducing bone defect. : In this study, 24 male rats were randomly assigned to three groups: (I) hypothyroidism+bone defect (HYPO), (II) hypothyroidism+bone defect+CM (HYPO+CM), and (III) no hypothyroidism+bone defect (control). Four weeks after surgery, the right tibia was removed, and immediately, biomechanical and histological examinations were performed. The results showed a significant reduction in bending stiffness (32.64±3.99), maximum force (14.63±1.89), high stress load (7.59±2.31), and energy absorption (12.68±2.12) at the osteotomy site in hypothyroidism rats in comparison to the control and hypothyroidism+condition medium groups (P<0.05). There was also a significant decrease in the trabecular bone volume (3.86±3.88) and the number of osteocytes (5800±859.8) at the osteotomy site in hypothyroidism rats compared to the control and hypothyroidism+condition medium groups (P<0.01 and P<0.02, respectively). The present study suggests that the use of the CM can improve the fracture regeneration and accelerates bone healing at the osteotomy site in hypothyroidism rats.

Improvement of Bone Healing by Neutralization of microRNA-335-5p, but not by Neutralization of microRNA-92A in Bone Marrow Mononuclear Cells Transplanted into a Large Femur Defect of the Rat.

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Janko, Maren; Dietz, Konstantin; Rachor, Julia; Sahm, Julian; Schroder, Katrin; Schaible, Alexander; Nau, Christoph; Seebach, Caroline; Marzi, Ingo; Henrich, Dirk

2018-04-23

Transplanted bone marrow mononuclear cells (BMC) support the healing of large bone defects. Neutralization of microRNA (MiR) that negatively affects key processes of the reparative response in BMC might help to further improve the beneficial effect of transplanted BMC in bone healing. Hence, the aim of this study was to evaluate if the neutralization of MiR-92A (vascularization) and MiR-335-5p (osteogenic differentiation) in BMC using specific antiMiRs leads to a further improvement of the BMC-supported therapy of large bone defects. BMC transiently transfected with antiMiR- 92A, antiMiR-335, antiMiR-92A, and antiMiR-355 or control antiMiR were seeded on β-TCP (beta-tricalcium phosphate) and placed in a femoral large bone defect (5 mm) in Sprague-Dawley rats. Ultimate load as well as osseous integration of the β-TCP-scaffolds were significantly improved in the antiMiR-335 group compared to the control group after 8 weeks, whereas neutralization of antiMiR-92A lead to an improvement of early vascularization after 1 week, but not to enhanced bone healing after 8 weeks. We demonstrated that the targeted inhibition of MiRs in transplanted BMC is a new approach that enhances BMC-supported bone healing.

Dynamics of bone healing after osteotomy with piezosurgery or conventional drilling – histomorphometrical, immunohistochemical, and molecular analysis

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2013-01-01

Background Piezosurgery is an osteotomy system used in medical and dental surgery. Many studies have proven clinical advantages of piezosurgery in terms of quality of cut, maneuverability, ease of use, and safety. However, few investigations have tested its superiority over the traditional osteotomy systems in terms of dynamics of bone healing. Therefore, the aim of this study was to evaluate the dynamics of bone healing after osteotomies with piezosurgery and to compare them with those associated to traditional bone drilling. Methods One hundred and ten rats were divided into two groups with 55 animals each. The animals were anesthetized and the tibiae were surgically exposed to create defects 2 mm in diameter by using piezosurgery (Piezo group) and conventional drilling (Drill group). Animals were sacrificed at 3, 7, 14, 30 and 60 days post-surgery. Bone samples were collected and processed for histological, histomorphometrical, immunohistochemical, and molecular analysis. The histological analysis was performed at all time points (n = 8) whereas the histomorphometrical analysis was performed at 7, 14, 30 and 60 days post-surgery (n = 8). The immunolabeling was performed to detect Vascular Endothelial Growth Factor (VEGF), Caspase-3 (CAS-3), Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL), and Osteocalcin (OC) at 3, 7, and 14 days (n = 3). For the molecular analysis, animals were sacrificed at 3, 7 and 14 days, total RNA was collected, and quantification of the expression of 21 genes related to BMP signaling, Wnt signaling, inflammation, osteogenenic and apoptotic pathways was performed by qRT-PCR (n = 5). Results Histologically and histomorphometrically, bone healing was similar in both groups with the exception of a slightly higher amount of newly formed bone observed at 30 days after piezosurgery (p piezosurgery are comparable to those observed with conventional drilling. PMID:24053147

Identification of genes differentially regulated in rat alveolar bone wound healing by subtractive hybridization.

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Ohira, T; Myokai, F; Shiomi, N; Yamashiro, K; Yamamoto, T; Murayama, Y; Arai, H; Nishimura, F; Takashiba, S

2004-07-01

Periodontal healing requires the participation of regulatory molecules, cells, and scaffold or matrix. Here, we hypothesized that a certain set of genes is expressed in alveolar bone wound healing. Reciprocal subtraction gave 400 clones from the injured alveolar bone of Wistar rats. Identification of 34 genes and analysis of their expression in injured tissue revealed several clusters of unique gene regulation patterns, including the up-regulation at 1 wk of cytochrome c oxidase regulating electron transfer and energy metabolism, presumably occurring at the site of inflammation; up-regulation at 2.5 wks of pro-alpha-2 type I collagen involving the formation of a connective tissue structure; and up-regulation at 1 and 2 wks and down-regulation at 2.5 and 4 wks of ubiquitin carboxyl-terminal hydrolase l3 involving cell cycle, DNA repair, and stress response. The differential expression of genes may be associated with the processes of inflammation, wound contraction, and formation of a connective tissue structure.

VEGF and BFGF Expression and Histological Characteristics of the Bone-Tendon Junction during Acute Injury Healing

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Lin Wang

2014-03-01

Full Text Available Bone-tendon junction (BTJ injuries are common and may be caused by acute trauma and delayed healing during exercise or work. To understand the nature of the healing process of BTJ injuries would help to prevent injuries and improve treatment. Thirty-three mature female rabbit hindlimbs were assigned to normal control (CON, n = 7 and injury groups (n = 26. The acute injury was established by administering one 7 plum-blossom needle puncture. Specimens were harvested post injury at 1, 2, 4, and 8 weeks (ND1W, n = 6; ND2W, n = 6; ND4W, n = 7; and ND8W, n = 7. The injury existed in all of the injury groups. Compared with the CON group, all of the animals in the injury group showed poor cell profiles, an unclear or undetectable tide mark, a proteoglycan area and profile changes; the BTJ cell density diminished significantly in the ND1W (p 0.05. The basic fibroblast growth factor (bFGF expression in the CON group was significantly less than in the ND1W group (p 0.05. The bFGF and VEGF expression levels indicated that the healing process stopped at 8 weeks post injury or was not activated, although the injury had not healed by histological examination. A repeatable animal model of BTJ acute injury was established in this study, and the results described the BTJ acute injury healing difficult concerned with the repairing stop.

Osteoporosis influences the middle and late periods of fracture healing in a rat osteoporotic model

Institute of Scientific and Technical Information of China (English)

WANG Jian-wei; LI Wei; XU Shao-wen; YANG Di-sheng; WANG Yun; LIN Min; ZHAO Guang-feng

2005-01-01

Objective: To evaluate the influence of osteoporosis on the middle and late periods of fracture healing process through observing the histomorphological changes, bone mineral density and biomechanical properties in ovariectomized rats. Methods: Eighty-four female SD rats of 4 months old were randomly divided into osteoporosis group and sham operation group, 42 in each. Rats in osteoporosis group were performed ovariectomy operation while those in sham operation group were given sham operation. A midshaft tibia fracture model was established 10 weeks after ovariectomy. Tibias were harvested 2, 4, 6, 12, 18 weeks after fracture for bone mineral density, histomorphological and biomechanical evaluation. Results: Compared with the sham operation group, callus bone mineral density was 12.8%, 18.0%, 17.0% lower in osteoporosis group 6, 12, 18 weeks after fracture, respectively (P<0.05); callus failure load was 24.3%, 31.5%, 26.6%, 28.8% lower in osteoporosis group, and callus failure stress was 23.9%, 33.6%, 19.1%, 24.9% lower in osteoporosis group 4, 6, 12, 18 weeks after fracture, respectively (P<0.05). In osteoporosis group, endochondral bone formation was delayed, more osteoclast cells could be seen around the trabecula, and the new bone trabecula arranged loosely and irregularly. Conclusions: Osteoporosis influences the middle and late periods of fracture healing in the rat osteoporotic model. The impairment is considered to be the result of combined effects of prolonged endochondral calcification, high activated osteoclast cell and the deceleration of the increase in bone mineral density.

Locally administrated perindopril improves healing in an ovariectomized rat tibial osteotomy model.

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Xiong Zhao

Full Text Available Angiotensin-converting enzyme inhibitors are widely prescribed to regulate blood pressure. High doses of orally administered perindopril have previously been shown to improve fracture healing in a mouse femur fracture model. In this study, perindopril was administered directly to the fracture area with the goal of stimulating fracture repair. Three months after being ovariectomized (OVX, tibial fractures were produced in Sprague-Dawley rats and subsequently stabilized with intramedullary wires. Perindopril (0.4 mg/kg/day was injected locally at the fractured site for a treatment period of 7 days. Vehicle reagent was used as a control. Callus quality was evaluated at 2 and 4 weeks post-fracture. Compared with the vehicle group, perindopril treatment significantly increased bone formation, increased biomechanical strength, and improved microstructural parameters of the callus. Newly woven bone was arranged more tightly and regularly at 4 weeks post-fracture. The ultimate load increased by 66.1 and 76.9% (p<0.01, and the bone volume over total volume (BV/TV increased by 29.9% and 24.3% (p<0.01 at 2 and 4 weeks post-fracture, respectively. These findings suggest that local treatment with perindopril could promote fracture healing in ovariectomized rats.

Improved Achilles tendon healing by early mechanical loading in a rabbit model.

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Wang, Jihong; Jiang, Dianming; Wen, Shuzheng; Jing, Shangfei; Fan, Dongsheng; Hao, Zengtao; Han, Chaoqian

2015-01-01

To investigate the structure and the attachment strength of a healing tendon-bone interface and the role of mechanical loading in tendon healing. Sixty rabbits underwent unilateral detachment and repair of the Achilles tendon. Thirty animals were immobilized (Group A), and the others wereallowed loadingimmediately postoperatively (Group B). Animals were sacrificed at 4 weeks and evaluated for histological and biomechanical testing. Statistical analysis was performed with an independent t test with significance set at P = 0.05. The ultimate stress was greater in group B (4.598 ± 1.321 N/mm(2)) compared with the control group (3.388 ± 0.994 N/mm(2)) (P tendon-to-bone interface with a larger area of chondrocytes was found in group B (P tendon-to-bone interface.

In Vivo Study of Ligament-Bone Healing after Anterior Cruciate Ligament Reconstruction Using Autologous Tendons with Mesenchymal Stem Cells Affinity Peptide Conjugated Electrospun Nanofibrous Scaffold

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Jingxian Zhu

2013-01-01

Full Text Available Electrospinning nanofibrous scaffold was commonly used in tissue regeneration recently. Nanofibers with specific topological characteristics were reported to be able to induce osteogenic differentiation of MSCs. In this in vivo study, autologous tendon grafts with lattice-like nanofibrous scaffold wrapping at two ends of autologous tendon were used to promote early stage of ligament-bone healing after rabbit ACL reconstruction. To utilize native MSCs from bone marrow, an MSCs specific affinity peptide E7 was conjugated to nanofibrous meshes. After 3 months, H-E assessment and specific staining of collagen type I, II, and III showed direct ligament-bone insertion with typical four zones (bone, calcified fibrocartilage, fibrocartilage, and ligament in bioactive scaffold reconstruction group. Diameters of bone tunnel were smaller in nanofibrous scaffold conjugated E7 peptide group than those in control group. The failure load of substitution complex also indicated a stronger ligament-bone insertion healing using bioactive scaffold. In conclusion, lattice-like nanofibrous scaffold with specific MSCs affinity peptide has great potential in promoting early stage of ligament-bone healing after ACL reconstruction.

Bone healing response in cyclically loaded implants: Comparing zero, one, and two loading sessions per day.

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de Barros E Lima Bueno, Renan; Dias, Ana Paula; Ponce, Katia J; Wazen, Rima; Brunski, John B; Nanci, Antonio

2018-05-31

When bone implants are loaded, they are inevitably subjected to displacement relative to bone. Such micromotion generates stress/strain states at the interface that can cause beneficial or detrimental sequels. The objective of this study is to better understand the mechanobiology of bone healing at the tissue-implant interface during repeated loading. Machined screw shaped Ti implants were placed in rat tibiae in a hole slightly bigger than the implant diameter. Implants were held stable by a specially-designed bone plate that permits controlled loading. Three loading regimens were applied, (a) zero loading, (b) one daily loading session of 60 cycles with an axial force of 1.5 N/cycle for 7 days, and (c) two such daily sessions with the same axial force also for 7 days. Finite element analysis was used to characterize the mechanobiological conditions produced by the loading sessions. After 7 days, the implants with surrounding interfacial tissue were harvested and processed for histological, histomorphometric and DNA microarray analyses. Histomorphometric analyses revealed that the group subjected to repeated loading sessions exhibited a significant decrease in bone-implant contact and increase in bone-implant distance, as compared to unloaded implants and those subjected to only one loading session. Gene expression profiles differed during osseointegration between all groups mainly with respect to inflammatory and unidentified gene categories. The results indicate that increasing the daily cyclic loading of implants induces deleterious changes in the bone healing response, most likely due to the accumulation of tissue damage and associated inflammatory reaction at the bone-implant interface. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Ceramic-polylactide composite material used in a model of healing of osseous defects in rabbits.

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Myciński, Paweł; Zarzecka, Joanna; Skórska-Stania, Agnieszka; Jelonek, Agnieszka; Okoń, Krzysztof; Wróbel, Maria

The growing demand for various kinds of bone regeneration material has in turn increased the desire to find materials with optimal physical, chemical, and biological properties. The objective of the present study was to identify the proportions of ceramic and polylactide components in a bone substitute material prepared in collaboration with the Crystal Chemistry of Drugs Team of the Faculty of Chemistry at the Jagiellonian University, which would be optimal for bone regeneration processes. Another goal was to provide a histological analysis of the influence of a ceramic-polylactide composite on the healing of osseous defects in rabbits. The study was performed on laboratory animals (18 New Zealand White rabbits). The following study groups were formed: - group A (study group, 9 animals) - in this group we performed a histological analysis of healing with a ceramic-polylactide composite based on an 80/20 mix of hydroxyapatite and polylactide; - group B (study group, 9 animals) - in this group we performed a histological analysis of healing with a ceramic-polylactide composite with a reduced amount of hydroxyapatite compared to the previous group, i.e. in a ratio of 61/39; - group K (control, 18 animals) - the control group comprised self-healing, standardised osseous defects prepared in the calvarial bone of the rabbits on the contralateral side. In the assessment of histological samples, we were also able to eliminate individual influences that might have led to differentiation in wound healing. The material used in the histological analysis took the form of rabbit bone tissue samples, containing both defects, with margins of around 0.5 cm, taken 1, 3, and 6 months after the experiment. The osseous defects from groups A and B filled with ceramic-polylactide material healed with less inflammatory infiltration than was the case with control group K. They were also characterised by faster regression, and no resorption or osteonecrosis, which allowed for better

Effect of healing time on bone-implant contact of orthodontic micro-implants: a histologic study.

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Ramazanzadeh, Barat Ali; Fatemi, Kazem; Dehghani, Mahboobe; Mohtasham, Nooshin; Jahanbin, Arezoo; Sadeghian, Hamed

2014-01-01

Objectives. This study aimed to evaluate the effect of immediate and delayed loading of orthodontic micro-implants on bone-implant contact. Materials and Methods. Sixty four micro-implants were implanted in dog's jaw bone. The micro-implants were divided into loaded and unloaded (control) groups. The control group had two subgroups: four and eight weeks being implanted. The loaded group had two subgroups of immediate loading and delayed (after four weeks healing) loading. Loaded samples were subjected to 200g load for four weeks. After sacrificing the animals micro-implants and surrounding tissues were observed histologically. Bone-implant contact ratios (BIC) were calculated and different groups' results were compared by three-way ANOVA. Results. Mean survival rate was 96.7% in general. Survival rates were 96.7%, 94.4% and 100% for control, immediate and delayed loaded groups, respectively. BIC values were not significantly different in loaded and control groups, immediate and delayed loading groups, and pressure and tension sides. Mandibular micro-implants had significantly higher BIC than maxillary ones in immediate loading, 4-weeks control, and 8-weeks control groups (P = 0.021, P = 0.009, P = 0.003, resp.). Conclusion Immediate or delayed loading of micro-implants in dog did not cause significant difference in Bone-implant contact which could be concluded that healing time had not significant effect on micro-implant stability.

Atelocollagen Enhances the Healing of Rotator Cuff Tendon in Rabbit Model.

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Suh, Dong-Sam; Lee, Jun-Keun; Yoo, Ji-Chul; Woo, Sang-Hun; Kim, Ga-Ram; Kim, Ju-Won; Choi, Nam-Yong; Kim, Yongdeok; Song, Hyun-Seok

2017-07-01

Failure of rotator cuff healing is a common complication despite the rapid development of surgical repair techniques for the torn rotator cuff. To verify the effect of atelocollagen on tendon-to-bone healing in the rabbit supraspinatus tendon compared with conventional cuff repair. Controlled laboratory study. A tear of the supraspinatus tendon was created and repaired in 46 New Zealand White rabbits. They were then randomly allocated into 2 groups (23 rabbits per group; 15 for histological and 8 for biomechanical test). In the experimental group, patch-type atelocollagen was implanted between bone and tendon during repair; in the control group, the torn tendon was repaired without atelocollagen. Each opposite shoulder served as a sham (tendon was exposed only). Histological evaluation was performed at 4, 8, and 12 weeks. Biomechanical tensile strength was tested 12 weeks after surgery. Histological evaluation scores of the experimental group (4.0 ± 1.0) were significantly superior to those of the control group (7.7 ± 2.7) at 12 weeks ( P = .005). The load to failure was significantly higher in the experimental group (51.4 ± 3.9 N) than in the control group (36.4 ± 5.9 N) ( P = .001). Histological and biomechanical studies demonstrated better results in the experimental group using atelocollagen in a rabbit model of the supraspinatus tendon tear. Atelocollagen patch could be used in the cuff repair site to enhance healing.

A study of radiological features of healing in long bone fractures among infants less than a year

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Warner, Christopher; Miller, Angie; Weinman, Jason; Fadell, Michael [Children' s Hospital Colorado, Department of Radiology, Aurora, CO (United States); Maguire, Sabine; Trefan, Laszlo [Cardiff University, Institute of Primary Care and Child Health, Cardiff (United Kingdom)

2017-03-15

To create a timetable for dating long bone fractures in infants aged less than 1 year using previously defined radiographic signs of fracture healing. A retrospective cross-sectional time series of long bone fractures in infants aged less than 1 year was conducted from 2006 to 2013. After exclusion criteria were applied 59 digital image series were available for review from 40 infants. Utilizing published criteria for dating fractures, the presence or absence of four pre-defined features of healing was scored: periosteal reaction, callus, bridging, and remodeling. Three radiologists independently scored radiographs with a 3-point scale, marking each feature as present, absent, or equivocal. The times in days when features were first seen, peaked (feature agreed present in >40% of images), and last seen were noted. Statistical analysis using free marginal kappa was conducted. The level of agreement among the three radiologists was high (0.64-0.85). The sequence in which the features were seen was: periosteal reaction range 7-130 (present in the majority of cases between 9 and 49 days); callus range 9-130 (present in the majority of cases between days 9-26); bridging range 15-130 (seen in the majority of cases between 15 and 67 days); remodeling range 51-247 days. This study provides a timetable of radiological features of long bone healing among young infants for the first time. Dating of incomplete long bone fractures is challenging, beyond the presence of periosteal reaction, but a consistent sequence of changes is present in complete fractures. (orig.)

Rapid biomimetic mineralization of collagen fibrils and combining with human umbilical cord mesenchymal stem cells for bone defects healing

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Ye, Bihua; Luo, Xueshi; Li, Zhiwen [Department of Material Science and Engineering, Engineering Research Center of Artificial Organs and Materials, Jinan University, Guangzhou 510632 (China); Zhuang, Caiping [Department of Anesthesiology, Huizhou Central People' s Hospital, Huizhou 516001 (China); Li, Lihua, E-mail: tlihuali@jnu.edu.cn [Department of Material Science and Engineering, Engineering Research Center of Artificial Organs and Materials, Jinan University, Guangzhou 510632 (China); Lu, Lu; Ding, Shan; Tian, Jinhuan [Department of Material Science and Engineering, Engineering Research Center of Artificial Organs and Materials, Jinan University, Guangzhou 510632 (China); Zhou, Changren, E-mail: tcrz9@jnu.edu.cn [Department of Material Science and Engineering, Engineering Research Center of Artificial Organs and Materials, Jinan University, Guangzhou 510632 (China)

2016-11-01

Collagen biomineralization is regulated by complicated interactions between the collagen matrix and non-collagenous extracellular proteins. Here, the use of sodium tripolyphosphate to simulate the templating functional motif of the C-terminal fragment of non-collagenous proteins is reported, and a low molecular weight polyacrylic acid served as a sequestration agent to stabilize amorphous calcium phosphate into nanoprecursors. Self-assembled collagen fibrils served as a fixed template for achieving rapid biomimetic mineralization in vitro. Results demonstrated that, during the mineralization process, intrafibrillar and extrafibrillar hydroxyapatite mineral with collagen fibrils formed and did so via bottom-up nanoparticle assembly based on the non-classical crystallization approach in the presence of these dual biomimetic functional analogues. In vitro human umbilical cord mesenchymal stem cell (hUCMSC) culture found that the mineralized scaffolds have a better cytocompatibility in terms of cell viability, adhesion, proliferation, and differentiation into osteoblasts. A rabbit femoral condyle defect model was established to confirm the ability of the n-HA/collagen scaffolds to facilitate bone regeneration and repair. The images of gross anatomy, MRI, CT and histomorphology taken 6 and 12 weeks after surgery showed that the biomimetic mineralized collagen scaffolds with hUCMSCs can promote the healing speed of bone defects in vivo, and both of the scaffolds groups performing better than the bone defect control group. As new bone tissue formed, the scaffolds degraded and were gradually absorbed. All these results demonstrated that both of the scaffolds and cells have better histocompatibility. - Highlights: • A rapid and facile biomimetic mineralization approach is proposed. • Intrafibrillar and extrafibrillar mineralization of collagen fibrils was achieved. • HA/COL scaffolds promote hUCMSCs adhesion, proliferation, and differentiation. • Feasibility of h

Rapid biomimetic mineralization of collagen fibrils and combining with human umbilical cord mesenchymal stem cells for bone defects healing

International Nuclear Information System (INIS)

Ye, Bihua; Luo, Xueshi; Li, Zhiwen; Zhuang, Caiping; Li, Lihua; Lu, Lu; Ding, Shan; Tian, Jinhuan; Zhou, Changren

2016-01-01

Collagen biomineralization is regulated by complicated interactions between the collagen matrix and non-collagenous extracellular proteins. Here, the use of sodium tripolyphosphate to simulate the templating functional motif of the C-terminal fragment of non-collagenous proteins is reported, and a low molecular weight polyacrylic acid served as a sequestration agent to stabilize amorphous calcium phosphate into nanoprecursors. Self-assembled collagen fibrils served as a fixed template for achieving rapid biomimetic mineralization in vitro. Results demonstrated that, during the mineralization process, intrafibrillar and extrafibrillar hydroxyapatite mineral with collagen fibrils formed and did so via bottom-up nanoparticle assembly based on the non-classical crystallization approach in the presence of these dual biomimetic functional analogues. In vitro human umbilical cord mesenchymal stem cell (hUCMSC) culture found that the mineralized scaffolds have a better cytocompatibility in terms of cell viability, adhesion, proliferation, and differentiation into osteoblasts. A rabbit femoral condyle defect model was established to confirm the ability of the n-HA/collagen scaffolds to facilitate bone regeneration and repair. The images of gross anatomy, MRI, CT and histomorphology taken 6 and 12 weeks after surgery showed that the biomimetic mineralized collagen scaffolds with hUCMSCs can promote the healing speed of bone defects in vivo, and both of the scaffolds groups performing better than the bone defect control group. As new bone tissue formed, the scaffolds degraded and were gradually absorbed. All these results demonstrated that both of the scaffolds and cells have better histocompatibility. - Highlights: • A rapid and facile biomimetic mineralization approach is proposed. • Intrafibrillar and extrafibrillar mineralization of collagen fibrils was achieved. • HA/COL scaffolds promote hUCMSCs adhesion, proliferation, and differentiation. • Feasibility of h

The Healing Effect of Conditioned Media and Bone Marrow-Derived Stem Cells in Laryngotracheal Stenosis: A Comparison in Experimental Dog Model.

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Iravani, Kamyar; Sobhanmanesh, Arash; Ashraf, Mohammad Javad; Hashemi, Seyed Basir; Mehrabani, Davood; Zare, Shahrokh

2017-05-01

Differences in causes, severities, areas of stenosis, and the association with swallowing and phonation of larynx and trachea can result into Laryngotracheal stenosis (LTS).This study evaluated the healing effect of bone marrow stem cells (BMSCs) in experimentally induced LTS dog model. Seven dogs were enrolled. BMSCs were isolated from proximal humerus and shoulder of a dog and cultured in media containing alpha minimal essential medium, fetal bovine serum, penicillin and streptomycin, and L-glutamine. BMSCs were characterized morphologically, by RT-PCR, and osteogenic induction. Karyotyping was undertaken for chromosomal stability. Mechanical trauma to laryngeal mucosa was identically conducted by Tru-cut punch forceps in right and left vocal folds. Two milliliter of conditioned media or BMSCs (2×10 6 ) were injected in the right site of the tissue and the left side was considered as control after LTS induction. The larynx was visualized 2, 4 and 6 weeks after treatment. Six weeks post-treatment, the larynges were evaluated histologically. BMSCs were adhered to culture flasks, spindle shape and positive for mesenchymal marker and negative for hematopoietic markers. Osteogenic induction was verified by Alizarin red staining. Karyotype was normal. A complete epithelialization and minimal chronic inflammatory cell infiltration were noted in submucosa of both left (control) and right (cases) vocal folds. The healing effect of conditioned media and BMSCs in comparison to the control group was more prominent. As thickness of fibrosis in cases were less than control group, conditioned media and BMSCs were shown to be good choices in healing of LTS.

Parathyroid Hormone (1-34 Might Not Improve Early Bone Healing after Sinus Augmentation in Healthy Rabbits

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Jisun Huh

2017-01-01

Full Text Available Purpose. This study evaluated the effect of administering intermittent parathyroid hormone [PTH (1-34, henceforth PTH] on the early-stage bone healing of maxillary sinus augmentation in healthy rabbits. Materials and Methods. Bovine bone mineral was grafted on the sinuses of 20 female New Zealand white rabbits. The animals were randomly divided into two groups, PTH (n=10 or saline (n=10, in which either PTH or saline was injected subcutaneously 5 days a week for 2 weeks. Half of the animals in each group were killed at 2 weeks postoperatively and the other half were killed at 4 weeks postoperatively. The dosage of PTH was 10 μg/kg/day. Radiographic and histomorphometric analyses were performed. Result. The new bone area (NBA did not differ significantly between the PTH and saline groups. The NBA in the PTH group in the total augmented area and in the demarcated window, center, and Schneiderian membrane regions increased significantly from 2 to 4 weeks. The number of osteoclasts decreased significantly from 2 to 4 weeks in both groups, with no difference between the two groups. Conclusion. Intermittent PTH might not stimulate new bone formation in healthy rabbits during the first 4 weeks of healing.

Polyhedral microcrystals encapsulating bone morphogenetic protein 2 improve healing in the alveolar ridge.

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Matsumoto, Goichi; Ueda, Takayo; Sugita, Yoshihiko; Kubo, Katsutoshi; Mizoguchi, Megumi; Kotani, Eiji; Oda, Naoki; Kawamata, Shin; Segami, Natsuki; Mori, Hajime

2015-08-01

Atelocollagen sponges incorporating polyhedra encapsulating bone morphogenetic protein 2 (BMP-2) were implanted into lateral bone defects in the mandible. Half of the bone defects on the left side were treated with atelocollagen sponges containing 1.8 × 10(7) BMP-2 polyhedra, and half were treated with sponges containing 3.6 × 10(6) BMP-2 polyhedra. As controls, we treated the right-side bone defects in each animal with an atelocollagen sponge containing 5 µg of recombinant human BMP-2 (rhBMP-2) or 1.8 × 10(7) empty polyhedral. After a healing period of six months, whole mandibles were removed for micro-computed tomography (CT) and histological analyses. Micro-CT images showed that more bone had formed at all experimental sites than at control sites. However, the density of the new bone was not significantly higher at sites with an atelocollagen sponge containing BMP-2 polyhedra than at sites with an atelocollagen sponge containing rhBMP-2 or empty polyhedra. Histological examination confirmed that the BMP-2 polyhedra almost entirely replaced the atelocollagen sponges and connected the original bone with the regenerated bone. These results show that the BMP-2 delivery system facilitates the regeneration of new bone in the mandibular alveolar bone ridge and has an advance in the technology of bone regeneration for implant site development. © The Author(s) 2015.

Functional Attachment of Soft Tissues to Bone: Development, Healing, and Tissue Engineering

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Lu, Helen H.; Thomopoulos, Stavros

2014-01-01

Connective tissues such as tendons or ligaments attach to bone across a multitissue interface with spatial gradients in composition, structure, and mechanical properties. These gradients minimize stress concentrations and mediate load transfer between the soft and hard tissues. Given the high incidence of tendon and ligament injuries and the lack of integrative solutions for their repair, interface regeneration remains a significant clinical challenge. This review begins with a description of the developmental processes and the resultant structure-function relationships that translate into the functional grading necessary for stress transfer between soft tissue and bone. It then discusses the interface healing response, with a focus on the influence of mechanical loading and the role of cell-cell interactions. The review continues with a description of current efforts in interface tissue engineering, highlighting key strategies for the regeneration of the soft tissue–to-bone interface, and concludes with a summary of challenges and future directions. PMID:23642244

Immunolocalization of Myostatin (GDF-8) Following Musculoskeletal Injury and the Effects of Exogenous Myostatin on Muscle and Bone Healing

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Elkasrawy, Moataz; Immel, David; Wen, Xuejun; Liu, Xiaoyan; Liang, Li-Fang

2012-01-01

The time course and cellular localization of myostatin expression following musculoskeletal injury are not well understood; therefore, the authors evaluated the temporal and spatial localization of myostatin during muscle and bone repair following deep penetrant injury in a mouse model. They then used hydrogel delivery of exogenous myostatin in the same injury model to determine the effects of myostatin exposure on muscle and bone healing. Results showed that a “pool” of intense myostatin staining was observed among injured skeletal muscle fibers 12–24 hr postsurgery and that myostatin was also expressed in the soft callus chondrocytes 4 days following osteotomy. Hydrogel delivery of 10 or 100 µg/ml recombinant myostatin decreased fracture callus cartilage area relative to total callus area in a dose-dependent manner by 41% and 80% (pMyostatin treatment also decreased fracture callus total bone volume by 30.6% and 38.8% (pmyostatin yielding the greatest decrease in callus bone volume. Finally, exogenous myostatin treatment caused a significant dose-dependent increase in fibrous tissue formation in skeletal muscle. Together, these findings suggest that early pharmacological inhibition of myostatin is likely to improve the regenerative potential of both muscle and bone following deep penetrant musculoskeletal injury. PMID:22205678

Comparing the effects of chlorhexidine and persica on alveolar bone healing following tooth extraction in rats, a randomised controlled trial.

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Dorri, Mojtaba; Shahrabi, Shokufeh; Navabazam, Alireza

2012-02-01

Chlorhexidine is broadly prescribed by clinicians for treating extraction socket wounds; however, studies have reported adverse effects for chlorhexidine. Persica, a herbal antibacterial agent, could be an alternative for chlorhexidine. The aim of this randomised controlled trial was to investigate the effects of persica and chlorhexidine on alveolar bone healing following tooth extraction in rats. Eighteen Wistar rats were randomly allocated to three study groups: 0.2% chlorhexidine, 10% persica and controls (tap water). The rats were mouth-rinsed for 14 days. On day 8, the mandibular right first molars of all the rats were extracted. On day 21, the rats were euthanized and histological slides of their extraction sockets were prepared. The amount of new bone formation and the number of inflammatory cells in the extraction socket for each rat were recorded. Data were analysed using linear regression and Mann-Whitney tests. There was no significant difference between the control group and the intervention groups in terms of new bone formation and inflammatory cell count. The mean new bone formation was significantly higher in the persica group than in the chlorhexidine group. There was a significant association between new bone formation and inflammatory cell count in the entire sample. In conclusion, there were no significant differences between rinsing with tap water and rinsing with 0.2% chlorhexidine and 10% persica in enhancing extraction socket wound healing in rats. Extraction socket wound healing in rats was better enhanced with 10% persica than 0.2% chlorhexidine.

Assessment of regeneration of bone in the extracted third molar sockets augmented using xenograft (CollaPlugTN Zimmer in comparison with the normal healing on the contralateral side

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Murugan Ranganathan

2017-01-01

Full Text Available Introduction: Alveolar bone resorption is a significant clinical problem. Bone loss in third molar region following extraction or surgical removal not only leads to periodontal problems in second molar region but also it may lead to some serious problems like increased incidence of angle fractures. In order to reduce the risks following third molar surgery, the socket should be augmented with bone grafts. In recent days guided tissue regeneration is the most accepted and successful technique followed many authors and its efficacy has been proved. Materials and Methods: Based upon our clinical experience, the use of bio absorbable collagen wound dressing such as CollaPlugTN has achieved quick healing and more primary wound coverage. Amongst the graft materials collagen is preferable due to its high biocompatibility and hemostatic ability. This study was done to assess the regeneration of bone in the extracted third molar sockets using xenograft (CollaPlugTN-Zimmer which was compared with the normal healing on the contra lateral side. The assessment was done to analyze post-operative healing complications and to compare the bone density formed between control site and implant site radiologically. Conclusion: On this basis of this study, the use of collaplugTN appears to be beneficial to the patient in postoperative wound healing and also for better bone formation. The use of this material was advantageous because of its simplicity of application cost effectiveness and availability. There is enhanced wound healing and early bone formation.

Assessment of Regeneration of Bone in the Extracted Third Molar Sockets Augmented Using Xenograft (CollaPlugTN Zimmer) in Comparison with the Normal Healing on the Contralateral Side.

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Ranganathan, Murugan; Balaji, M; Krishnaraj, R; Narayanan, Vivek; Thangavelu, Annamalai

2017-11-01

Alveolar bone resorption is a significant clinical problem. Bone loss in third molar region following extraction or surgical removal not only leads to periodontal problems in second molar region but also it may lead to some serious problems like increased incidence of angle fractures. In order to reduce the risks following third molar surgery, the socket should be augmented with bone grafts. In recent days guided tissue regeneration is the most accepted and successful technique followed many authors and its efficacy has been proved. Based upon our clinical experience, the use of bio absorbable collagen wound dressing such as CollaPlug TN has achieved quick healing and more primary wound coverage. Amongst the graft materials collagen is preferable due to its high biocompatibility and hemostatic ability. This study was done to assess the regeneration of bone in the extracted third molar sockets using xenograft (CollaPlug TN -Zimmer) which was compared with the normal healing on the contra lateral side. The assessment was done to analyze post-operative healing complications and to compare the bone density formed between control site and implant site radiologically. On this basis of this study, the use of collaplugTN appears to be beneficial to the patient in postoperative wound healing and also for better bone formation. The use of this material was advantageous because of its simplicity of application cost effectiveness and availability. There is enhanced wound healing and early bone formation.

Biology and augmentation of tendon-bone insertion repair

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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.

Broken Bones (For Parents)

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... Safe Videos for Educators Search English Español Broken Bones KidsHealth / For Parents / Broken Bones What's in this ... bone fragments in place. When Will a Broken Bone Heal? Fractures heal at different rates, depending upon ...

Alveolar socket healing: what can we learn?

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Araújo, Mauricio G; Silva, Cléverson O; Misawa, Mônica; Sukekava, Flavia

2015-06-01

Tooth extraction induces a series of complex and integrated local changes within the investing hard and soft tissues. These local alterations arise in order to close the socket wound and to restore tissue homeostasis, and are referred to as '"socket healing". The aims of the present report were twofold: first, to describe the socket-healing process; and, second, to discuss what can be learned from the temporal sequence of healing events, in order to improve treatment outcomes. The socket-healing process may be divided into three sequential, and frequently overlapping, phases: inflammatory; proliferative; and modeling/remodeling. Several clinical and experimental studies have demonstrated that the socket-healing process promotes up to 50% reduction of the original ridge width, greater bone resorption at the buccal aspect than at the lingual/palatal counterpart and a larger amount of alveolar bone reduction in the molar region. In conclusion, tooth extraction, once a simple and straightforward surgical procedure, should be performed in the knowledge that ridge reduction will follow and that further clinical steps should be considered to compensate for this, when considering future options for tooth replacement. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Three-Dimensional Bio-Printed Scaffold Sleeves With Mesenchymal Stem Cells for Enhancement of Tendon-to-Bone Healing in Anterior Cruciate Ligament Reconstruction Using Soft-Tissue Tendon Graft.

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Park, Sin Hyung; Choi, Yeong-Jin; Moon, Sang Won; Lee, Byung Hoon; Shim, Jin-Hyung; Cho, Dong-Woo; Wang, Joon Ho

2018-01-01

To investigate the efficacy of the insertion of 3-dimensional (3D) bio-printed scaffold sleeves seeded with mesenchymal stem cells (MSCs) to enhance osteointegration between the tendon and tunnel bone in anterior cruciate ligament (ACL) reconstruction in a rabbit model. Scaffold sleeves were fabricated by 3D bio-printing. Before ACL reconstruction, MSCs were seeded into the scaffold sleeves. ACL reconstruction with hamstring tendon was performed on both legs of 15 adult rabbits (aged 12 weeks). We implanted 15 bone tunnels with scaffold sleeves with MSCs and implanted another 15 bone tunnels with scaffold sleeves without MSCs before passing the graft. The specimens were harvested at 4, 8, and 12 weeks. H&E staining, immunohistochemical staining of type II collagen, and micro-computed tomography of the tunnel cross-sectional area were evaluated. Histologic assessment was conducted with a histologic scoring system. In the histologic assessment, a smooth bone-to-tendon transition through broad fibrocartilage formation was identified in the treatment group, and the interface zone showed abundant type II collagen production on immunohistochemical staining. Bone-tendon healing histologic scores were significantly higher in the treatment group than in the control group at all time points. Micro-computed tomography at 12 weeks showed smaller tibial (control, 9.4 ± 0.9 mm 2 ; treatment, 5.8 ± 2.9 mm 2 ; P = .044) and femoral (control, 9.6 ± 2.9 mm 2 ; treatment, 6.0 ± 1.0 mm 2 ; P = .03) bone-tunnel areas in the treated group than in the control group. The 3D bio-printed scaffold sleeve with MSCs exhibited excellent results in osteointegration enhancement between the tendon and tunnel bone in ACL reconstruction in a rabbit model. If secure biological healing between the tendon graft and tunnel bone can be induced in the early postoperative period, earlier, more successful rehabilitation may be facilitated. Three-dimensional bio-printed scaffold sleeves with

Do bisphosphonates inhibit direct fracture healing?: A laboratory investigation using an animal model.

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Savaridas, T; Wallace, R J; Salter, D M; Simpson, A H R W

2013-09-01

Fracture repair occurs by two broad mechanisms: direct healing, and indirect healing with callus formation. The effects of bisphosphonates on fracture repair have been assessed only in models of indirect fracture healing. A rodent model of rigid compression plate fixation of a standardised tibial osteotomy was used. Ten skeletally mature Sprague-Dawley rats received daily subcutaneous injections of 1 µg/kg ibandronate (IBAN) and ten control rats received saline (control). Three weeks later a tibial osteotomy was rigidly fixed with compression plating. Six weeks later the animals were killed. Fracture repair was assessed with mechanical testing, radiographs and histology. The mean stress at failure in a four-point bending test was significantly lower in the IBAN group compared with controls (8.69 Nmm(-2) (sd 7.63) vs 24.65 Nmm(-2) (sd 6.15); p = 0.017). On contact radiographs of the extricated tibiae the mean bone density assessment at the osteotomy site was lower in the IBAN group than in controls (3.7 mmAl (sd 0.75) vs 4.6 mmAl (sd 0.57); p = 0.01). In addition, histological analysis revealed progression to fracture union in the controls but impaired fracture healing in the IBAN group, with predominantly cartilage-like and undifferentiated mesenchymal tissue (p = 0.007). Bisphosphonate treatment in a therapeutic dose, as used for risk reduction in fragility fractures, had an inhibitory effect on direct fracture healing. We propose that bisphosphonate therapy not be commenced until after the fracture has united if the fracture has been rigidly fixed and is undergoing direct osteonal healing.

A 5-year comparison of marginal bone level following immediate loading of single-tooth implants placed in healed alveolar ridges and extraction sockets in the maxilla.

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Berberi, Antoine N; Sabbagh, Joseph M; Aboushelib, Moustafa N; Noujeim, Ziad F; Salameh, Ziad A

2014-01-01

The aim of present investigation was to evaluate marginal bone level after 5-year follow-up of implants placed in healed ridges and fresh extraction sockets in maxilla with immediate loading protocol. Thirty-six patients in need of a single-tooth replacement in the anterior maxilla received 42 Astra Tech implants (Astra Tech Implant system™, Dentsply Implants, Mölndal, Sweden). Implants were placed either in healed ridges (group I) or immediately into fresh extraction sockets (group II). Implants were restored and placed into functional loading immediately by using a prefabricated abutment. Marginal bone level relative to the implant reference point was recorded at implant placement, crown cementation, 12, 36, and 60 months following loading using intra-oral radiographs. Measurements were made on the mesial and distal sides of each implant. Overall, two implants were lost from the group II, before final crown cementation: they were excluded from the study. The mean change in marginal bone loss (MBL) after implant placement was 0.26 ± 0.161 mm for 1 year, and 0.26 ± 0.171 mm for 3 years, and 0.21 ± 0.185 mm for 5 years in extraction sockets and was 0.26 ± 0.176 mm for 1 year and 0.21 ± 0.175 mm for 3 years, and 0.19 ± 0.172 mm for 5 years in healed ridges group. Significant reduction of marginal bone was more pronounced in implants inserted in healed ridges (P sockets (P sockets or healed ridges were similar. Functional loading technique by using prefabricated abutment placed during the surgery time seems to maintain marginal bone around implant in both healed and fresh extraction sites.

Evaluation of the effect of platelet rich plasma (PRP) on enhancement of bone healing in diaphyseal bone defects by radiography and computed tomography

International Nuclear Information System (INIS)

Özak, Ahmet; Yardimci, Cenk; Nİsbet, Özlem H.; Bayrak, İlkay Koray; Nİsbet, Cevat

2010-01-01

The effect of platelet-rich plasma (PRP) with autogenous cancellous bone graft on enhancement of bone healing in diaphyseal bone defects was evaluated. A 4-mm defect was created in the middiaphysis of the tibias of 20 rabbits. Rabbits were divided into two groups of ten animals each: only autogenous cancellous graft, PRP and autogenous cancellous graft. In animals of group 1, only autogenous cancellous grafts, and to those in group 2, PRP and autogenous cancellous grafts, were applied to the defect. Radiographical and computed tomography (CT) views were taken and evaluated on postoperative days 0, 15, 30, 60, and 90. According to the bone formation, union, and remodeling scores, group 1 had better scores than group 2 on days 30, 60, and 90. The density was significantly increased on day 60 than on days 0, 15, and 30 in group 1. In conclusion, it was evaluated that PRP could not enhance the bone regeneration in diaphyseal defects when used with autogenous cancellous bone graft

Augmentation of bone defect healing using a new biocomposite scaffold: an in vivo study in sheep.

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van der Pol, U; Mathieu, L; Zeiter, S; Bourban, P-E; Zambelli, P-Y; Pearce, S G; Bouré, L P; Pioletti, D P

2010-09-01

Previous studies support resorbable biocomposites made of poly(L-lactic acid) (PLA) and beta-tricalcium phosphate (TCP) produced by supercritical gas foaming as a suitable scaffold for tissue engineering. The present study was undertaken to demonstrate the biocompatibility and osteoconductive properties of such a scaffold in a large animal cancellous bone model. The biocomposite (PLA/TCP) was compared with a currently used beta-TCP bone substitute (ChronOS, Dr. Robert Mathys Foundation), representing a positive control, and empty defects, representing a negative control. Ten defects were created in sheep cancellous bone, three in the distal femur and two in the proximal tibia of each hind limb, with diameters of 5 mm and depths of 15 mm. New bone in-growth (osteoconductivity) and biocompatibility were evaluated using microcomputed tomography and histology at 2, 4 and 12 months after surgery. The in vivo study was validated by the positive control (good bone formation with ChronOS) and the negative control (no healing with the empty defect). A major finding of this study was incorporation of the biocomposite in bone after 12 months. Bone in-growth was observed in the biocomposite scaffold, including its central part. Despite initial fibrous tissue formation observed at 2 and 4 months, but not at 12 months, this initial fibrous tissue does not preclude long-term application of the biocomposite, as demonstrated by its osteointegration after 12 months, as well as the absence of chronic or long-term inflammation at this time point. 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Periodontal and endodontic pathology delays extraction socket healing in a canine model

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2017-01-01

Purpose The aim of the present exploratory study was to evaluate extraction socket healing at sites with a history of periodontal and endodontic pathology. Methods The mandibular 4th premolar teeth in 5 adult beagle dogs served as experimental units. Periodontal and endodontic lesions were induced in 1 premolar site in each animal using wire ligatures and pulpal exposure over 3 months (diseased sites). The contralateral premolar sites served as healthy controls. The mandibular 4th premolar teeth were then extracted with minimal trauma, followed by careful wound debridement. The animals were sacrificed at days 1, 7, 30, 60, and 90 post-extraction for analysis, and the healing patterns at the healthy and diseased extraction sites were compared using radiography, scanning electron microscopy, histology, and histometry. Results During the first 7 days of healing, a significant presence of inflammatory granulation tissue was noted at the diseased sites (day 1), along with a slightly accelerated rate of fibrin clot resolution on day 7. On day 30, the diseased extraction sites showed a greater percentage of persistent fibrous connective tissue, and an absence of bone marrow formation. In contrast, healthy sites showed initial signs of bone marrow formation on day 30, and subsequently a significantly greater proportion of mature bone marrow formation on both days 60 and 90. Radiographs exhibited sclerotic changes adjoining apical endodontic lesions, with scanning electron microscopy showing collapsed Volkmann canals protruding from these regions in the diseased sites. Furthermore, periodontal ligament fibers exhibited a parallel orientation to the alveolar walls of the diseased sites, in contrast to a perpendicular arrangement in the healthy sites. Conclusions Within the limitations of this study, it appears that a history of periodontal and endodontic pathology may critically affect bone formation and maturation, leading to delayed and compromised extraction socket

Does footprint preparation influence tendon-to-bone healing after rotator cuff repair in an animal model?

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Ficklscherer, Andreas; Loitsch, Thomas; Serr, Michaela; Gülecyüz, Mehmet F; Niethammer, Thomas R; Müller, Hans-Helge; Milz, Stefan; Pietschmann, Matthias F; Müller, Peter E

2014-02-01

The aim of this study was to investigate the influence of footprint spongialization and radiofrequency ablation on rotator cuff repair outcomes compared with an untreated group in a rat model. We randomly assigned 189 Sprague-Dawley rats to either a spongialization, radiofrequency ablation, or untreated group. After separation of the supraspinatus tendon from the greater tubercle, the footprint was prepared by removing the cortical bone with a burr (spongialization), was prepared by ablating soft tissue with a radiofrequency ablation device, or was left unaltered (untreated). Biomechanical testing (after 7 weeks, n = 165) and histologic analysis after 1 and 7 weeks (n = 24) followed reinsertion. The mean load to failure was 17.51 ± 4.46 N/mm(2) in the spongialization group, 15.56 ± 4.85 N/mm(2) in the radiofrequency ablation group, and 19.21 ± 5.19 N/mm(2) in the untreated group. A significant difference was found between the spongialization and radiofrequency ablation groups (P = .0409), as well as between the untreated and radiofrequency ablation groups (P = .0014). There was no significant difference between the spongialization and untreated groups (P = .2456). The mean area of fibrocartilage transition, characterized by the presence of type II collagen, was larger after 1 and 7 weeks in the spongialization group (0.57 ± 0.1 mm(2) and 0.58 ± 0.1 mm(2), respectively) and untreated group (0.51 ± 0.1 mm(2) and 0.51 ± 0.2 mm(2), respectively) than in the radiofrequency ablation group (0.11 ± 0.1 mm(2) and 0.4 ± 0.1 mm(2), respectively) with P rotator cuff repair may influence tendon-to-bone healing. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Effect of Poloxamer 407 as a carrier vehicle on rotator cuff healing in a rat model

OpenAIRE

Kim, Soung-Yon; Chae, Soo-Won; Lee, Juneyoung

2014-01-01

Background In vivo studies showing the effects of biologic healing-promoting factors on tendon-to-bone healing after rotator cuff repair have focused only on biologic healing-promoting factors and have not taken into consideration the effect of the carrier vehicle. Moreover, most studies have evaluated the healing process using different carrier vehicles, each of which may have specific effects on tendon healing. This may explain the large variability seen in outcomes in research studies. In ...

Influence of low-level laser therapy on the healing of human bone maxillofacial defects: A systematic review.

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Santinoni, Carolina Dos Santos; Oliveira, Hiskell Francine Fernandes; Batista, Victor Eduardo de Souza; Lemos, Cleidiel Aparecido Araujo; Verri, Fellippo Ramos

2017-04-01

This systematic review evaluates the effectiveness of low-level laser therapy (LLLT) to enhance maxillofacial area bone repair. A comprehensive search of studies published up to February 2017 and listed in PubMed/MEDLINE, Scopus, and Cochrane Library databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The 15 selected studies evaluated a total of 374 patients (mean age, 28.5years) who were treated with LLLT. Gallium-arsenide (GaAs) and gallium aluminium arsenide (GaAlAs) were the most commonly used devices, and LLLT parameters varied greatly. Wavelengths varied from 500 to 1000nm. Tooth extraction, distraction osteogenesis, maxillary expansion, periodontal defects, orthodontic movement and maxillary cystic defects were evaluated. From the 15 selected studies, six evaluated bone repair (primary outcomes). Of these, four studies showed improvement in bone formation after using LLLT, two demonstrated improved results for only one follow up period, and one showed no additional benefits. The other 9 studies evaluated secondary parameters related to healing (secondary outcomes) in the maxillofacial area after applying LLLT, including anti-inflammatory, analgesic, and healing accelerator effects, and quality of life related to oral health. There were no adverse or negative effects of LLLT reported. Within the limitation of this review, a possible improvement in bone density can be found when LLLT is applied postoperatively in maxillofacial bony defects. LLLT also seems to promote anti-inflammatory and analgesic effects and accelerate healing, as well as enhance quality of life related to oral health. However, LLLT use protocols need to be standardized before more specific conclusions can be drawn about this subject. Copyright © 2017 Elsevier B.V. All rights reserved.

THE EFFECTS OF AN EARLY RETURN TO TRAINING ON THE BONE-TENDON JUNCTION POST-ACUTE MICRO-INJURY HEALING

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Lin Wang

2012-06-01

Full Text Available Bone-tendon junction (BTJ overuse injuries are common athletic and occupational problems. BTJ injuries may sometimes be caused by resuming training too early after injury. To study the effects of post-injury resuming training within 48 hours on the acute injury healing process, as it is often the case for athletes. Twelve mature female rabbits were assigned to one of the following groups: acute injury (AI, n = 6, post-injury early return to training (PIERT, n = 6 and normal control (CON, n = 6. Tissue specimens were harvested at week 4. The radiological and histological characteristics of the AI and PIERT groups were compared among the groups. The trabecular thickness of the PIERT group was significantly different from those of the AI and CON group. A histological evaluation revealed poor collagen fibre alignment, extensive scar tissue and lowered cell density in the AI and PIERT groups compared with the CON group, but no significant differences were observed between the AI group and the PIERT group. The fibrocartilage zone and proteoglycan area in the PIERT group were significantly different from those in AI group. No differences were observed in the Total VOI volume (TV, Object volume (OBV, Percent object volume (BV/TV and trabecular number (Tb.N among the AI, PIERT and CON groups. In conclusion, a repeatable animal model of bone-tendon junction acute micro-damage by puncture was established. Resuming training in 48 hours did not significantly deteriorate the BTJ injury healing, but improved bone remodelling and increased fibrocartilage zone thickness

In vitro migration and proliferation ("wound healing") potential of mesenchymal stromal cells generated from human CD271(+) bone marrow mononuclear cells.

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Latifi-Pupovci, Hatixhe; Kuçi, Zyrafete; Wehner, Sibylle; Bönig, Halvard; Lieberz, Ralf; Klingebiel, Thomas; Bader, Peter; Kuçi, Selim

2015-09-25

Emerging evidence indicates that mesenchymal stromal cells (MSCs) isolated from different tissue sources may be used in vivo as tissue restorative agents. To date, there is no evidence, however, on migration and proliferation ("wound healing") potential of different subsets of MSCs. The main goal of this study was therefore to compare the in vitro "wound healing" capacity of MSCs generated from positively selected CD271(+) bone marrow mononuclear cells (CD271-MSCs) and MSCs generated by plastic adherence (PA-MSCs). The in vitro model of wound healing (CytoSelect™ 24-Well Wound Healing Assay) was used in order to compare the migration and proliferation potential of CD271-MSCs and PA-MSCs of passage 2 and 4 cultured in presence or absence of growth factors or cytokines. CD271-MSCs of both passages when compared to PA-MSCs demonstrated a significantly higher potential to close the wound 12 and 24 h after initiation of the wound healing assay (P MSCs of second passage was significantly improved after stimulation with FGF-2 (P MSCs of P4 12 h after the treatment (P MSCs of both passages with growth factors or cytokines did not affect their migratory potential. Our in vitro data provide the first evidence that CD271-MSCs are significantly more potent in "wound healing" than their counterparts PA-MSCs.

Application of osteomucoperiosteal flap in large unicystic ameloblastoma to promote early bone healing: An alternative to primary bone grafting

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Gagan Khare

2011-01-01

Full Text Available Background: The unicystic variety of ameloblastoma is reported to be significantly less prone to recurrence in young patients than its conventional counterpart, and therefore can be treated conservatively. This paper describes a technique of using an osteoperiosteal flap to allow complete enucleation of a unicystic ameloblastoma. The technique maintains the continuity of the mandible and restores full thickness as well as strength of the mandible to promote early healing. It also maintains blood supply and proper facial contour so that esthetics is unimpaired. Materials and Methods: We describe two cases of unicystic ameloblastoma in which we used an osteoperiosteal flap. This flap was then infractured at the lower border to obliterate the dead space. Results: The sequential radiographs demonstrate early incorporation of the graft and complete filling of the defect by 3 months. At 5 years of follow-up in our first case, complete healing of bone was observed. Conclusions: We believe that these procedures can be the treatment of choice in such cases, especially with larger lesions, as these rapidly restore the patient′s facial contour to normal as well as reduce the healing time.

Assessment of polycaprolacton (PCL) nanocomposite scaffold compared with hydroxyapatite (HA) on healing of segmental femur bone defect in rabbits.

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Eftekhari, Hadi; Jahandideh, Alireza; Asghari, Ahmad; Akbarzadeh, Abolfazl; Hesaraki, Saeed

2017-08-01

Segmental bone loss due to trauma, infection, and tumor resection and even non-union results in the vast demand for replacement and restoration of the function of the lost bone. The objective of this study is to utilize novel inorganic-organic nanocomposites for biomedical applications. Biodegradable implants have shown great promise for the repair of bone defects and have been commonly used as bone substitutes, which traditionally would be treated using metallic implants. In this study, 45 mature male New Zealand white rabbits 6-8 months and weighting 3-3.5 kg were examined. Rabbits were divided into three groups. Surgical procedures were done after an intramuscular injection of Ketamine 10% (ketamine hydrochloride, 50 mg/kg), Rompun 5% (xylazine, 5 mg/kg). Then an approximately 6 mm diameter - 5 mm cylinder bone defect was created in the femur of one of the hind limbs. After inducing the surgical wound, all rabbits were colored and randomly divided into three experimental groups of nine animals each: Group 1 received medical pure nanocomposite polycaprolactone (PCL) granules, Group 2 received hydroxyapatite and Group 3 was a control group with no treatment. Histopathological evaluation was performed on days 15, 30 and 45 after surgery. On day 45 after surgery, the quantity of newly formed lamellar bone in the healing site in PCL group was better than onward compared with HA and control groups. Finally, nanocomposite PCL granules exhibited a reproducible bone-healing potential.

Evaluation of Osteoconductive and Osteogenic Potential of a Dentin-Based Bone Substitute Using a Calvarial Defect Model

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Ibrahim Hussain

2012-01-01

Full Text Available The aim of this study was to assess the osteoconductive and osteogenic properties of processed bovine dentin using a robust rabbit calvarial defect model. In total, 16 New Zealand White rabbits were operated to create three circular defects in the calvaria. One defect was left unfilled, one filled with collected autogenous bone, and the third defect was filled with the dentin-based bone substitute. Following surgery and after a healing period of either 1 or 6 weeks, a CT scan was obtained. Following sacrificing, the tissues were processed for histological examination. The CT data showed the density in the area grafted with the dentin-based material was higher than the surrounding bone and the areas grafted with autologous bone after 1 week and 6 weeks of healing. The area left unfilled remained an empty defect after 1 week and 6 weeks. Histological examination of the defects filled with the dentin product after 6 weeks showed soft tissue encapsulation around the dentin particles. It can be concluded that the rabbit calvarial model used in this study is a robust model for the assessment of bone materials. Bovine dentin is a biostable material; however, it may not be suitable for repairing large 4-wall defects.

Sequential healing of open extraction sockets. An experimental study in monkeys.

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Scala, Alessandro; Lang, Niklaus P; Schweikert, Michael T; de Oliveira, José Américo; Rangel-Garcia, Idelmo; Botticelli, Daniele

2014-03-01

To describe the sequential healing of open extraction sockets at which no attempts to obtain a primary closure of the coronal access to the alveolus have been made. The third mandibular premolar was extracted bilaterally in 12 monkeys, and no sutures were applied to close the wound. The healing after 4, 10, 20, 30, 90 and 180 days was morphometrically studied. After 4 days of healing, a blood clot mainly occupied the extraction sockets, with the presence of an inflammatory cells' infiltrate. A void was confined in the central zones of the coronal and middle regions, in continuity with the entrance of the alveoli. At 10 days, the alveolus was occupied by a provisional matrix, with new bone formation lining the socket bony walls. At 20 days, the amount of woven bone was sensibly increasing. At 30 days, the alveolar socket was mainly occupied by mineralized immature bone at different stages of healing. At 90 and 180 days, the amount of mineralized bone decreased and substituted by trabecular bone and bone marrow. Bundle bone decreased from 95.5% at 4 days to 7.6% at 180 days, of the whole length of the inner alveolar surface. Modeling processes start from the lateral and apical walls of the alveolus, leading to the closure of the socket with newly formed bone within a month from extraction. Remodeling processes will follow the previous stages, resulting in trabecular and bone marrow formation and in a corticalization of the socket access. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Using Hydroxyapatite-Gelatin Scaffold Seeded with Bone Marrow Stromal Cells as a Bone Graft in Animal Model

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Mahsoumeh Behruzi

2016-11-01

Full Text Available Background: Nowadays, composite scaffolds with some desired characteristics have a numerous applications in hard tissue engineering. In present study, the role of composite hydroxyapatite - gelatin was examined in both alone and coated by Bone Marrow Stromal Stem Cells (BMSCs conditions in the process of healing bone defects, reduction of time repair and the immune response of body by laboratory studies (in vitro and in vivo on the skull of adult rats as well. Materials and Methods: In present study, nano-hydroxyapatite powder and gelatin were used to provide nano-hydroxyapatite-gelatin scaffold, BMSCs were isolated by Flushing method. Fifteen adult male Wistar rats weighing 250-200 g were used. Studing groups included bone defect with hydroxyapatite-gelatin scaffold, bone defect with hydroxyapatite-gelatin with BMSCs and bone defects without scaffolding as a controlwhich were examined after a week and a month after surgery. MTT assay was used in order to evaluation of biocompatibility of scaffolds. To confirm the healing progress trend and the presence of inflammatory cells we used hematoxylin-eosin and we used Masson's trichrome staining in order to study of synthesis of collagen fibers. Results: The results of MTT showed that the scaffold has no toxic effects on stromal cells. The first signs of ossification in hydroxyapatite-gelatin with BMSCs cells group, appeared in the first week. However, in the fourth week, ossification was completed and the scaffold remaining was found as embedded islands in the spongy bone tissue. The greatest number of lymphocytes was observed in the experimental group after one week of planting scaffold. Conclusion: it seems that Hydroxyapatite-gelatin scaffold coated with BMSCs cells has a potential role in the healing process of bone and it can be suitable as a therapeutic strategy to repair extensive bone lesions.

Influence of bone marrow on osseointegration in long bones: an experimental study in sheep.

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Morelli, Fabrizio; Lang, Niklaus P; Bengazi, Franco; Baffone, Davide; Vila Morales, C Dadonim; Botticelli, Daniele

2015-03-01

To evaluate the influence of yellow bone marrow on osseointegration of titanium oral implants using a long bone model. The two tibiae of eight sheep were used as experimental sites. Two osteotomies for implant installation were prepared in each tibia. At the control sites, no further treatments were performed while, at the test sites, bone marrow was removed from the osteotomy site with a curette to an extent that exceeded the implant dimensions. As a result, the apical portion of the implants at the control sites was in contact with bone marrow while, at the test sites, it was in contact with the blood clot. After 2 months, the same procedures were performed in the contralateral side. After another month, the animal was sacrificed. Ground sections were obtained for histological analysis. After 1 month of healing, no differences between test and control sites were found in the apical extension of osseointegration and the percentage of new bone-to-implant contact. However, after 3 months of healing, a higher percentage of new bone-to-implant contact was found at the test compared to the control sites in the marrow compartment. The apical extension of osseointegration, however, was similar to that found at the 1-month healing period both for test and control sites. Osseointegration appeared to be favored by the presence of a blood clot when compared to the presence of yellow fatty bone marrow. Moreover, the contact with cortical bone appeared to be a prerequisite for the osseointegration process in the long bone model. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The effects of Zinc supplementation on serum zinc, alkaline phosphatase activity and fracture healing of bones

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Sadighi, A.; Moradi, A.; Roshan, Marjan M.; Ostadrahimi, A.

2009-01-01

Objective was to determine the effect of zinc supplementation on callus information, serum zinc and alkaline phosphatase activity in humans. This randomized, double-blind, placebo controlled clinical trial was conducted on 60 patients with traumatic bone fracture referred to Shohada Hospital of Tabriz, Iran from August to December 2007. Subjects were randomly divided into 2 groups: cases (n=30), receiving one capsule of zinc sulfate consists of 50 mg zinc each day and the controls (n=30), receiving placebo for 60 days. Individual and clinical information was determined by a questionnaire: nutritional intake by 3 days food records at the beginning and the end of trial. Serum zinc and alkaline phosphatase was measured by atomic absorption spectroscopy and by enzymatic method. Callus information during fracture healing was evaluated by radiography of the bone. There was no significant difference in physical activity, gender, age, type of fractures and nutrient intake, between the 2 groups. The administration of zinc caused a significant elevation of serum zinc and alkaline phosphatase activity. Assessment of bone x-rays showed a significant progress in callus formation in cases compared to the controls. This study shows that zinc supplementation can stimulate fracture healing, however, it needs further study. (author)

The influence of root surface distance to alveolar bone and periodontal ligament on periodontal wound healing.

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Montevecchi, Marco; Parrilli, Annapaola; Fini, Milena; Gatto, Maria Rosaria; Muttini, Aurelio; Checchi, Luigi

2016-10-01

The purpose of this animal study was to perform a 3-dimensional micro-computed tomography (micro-CT) analysis in order to investigate the influence of root surface distance to the alveolar bone and the periodontal ligament on periodontal wound healing after a guided tissue regeneration (GTR) procedure. Three adult Sus scrofa domesticus specimens were used. The study sample included 6 teeth, corresponding to 2 third mandibular incisors from each animal. After coronectomy, a circumferential bone defect was created in each tooth by means of calibrated piezoelectric inserts. The experimental defects had depths of 3 mm, 5 mm, 7 mm, 9 mm, and 11 mm, with a constant width of 2 mm. One tooth with no defect was used as a control. The defects were covered with a bioresorbable membrane and protected with a flap. After 6 months, the animals were euthanised and tissue blocks were harvested and preserved for micro-CT analysis. New alveolar bone was consistently present in all experimental defects. Signs of root resorption were observed in all samples, with the extent of resorption directly correlated to the vertical extent of the defect; the medial third of the root was the most commonly affected area. Signs of ankylosis were recorded in the defects that were 3 mm and 7 mm in depth. Density and other indicators of bone quality decreased with increasing defect depth. After a GTR procedure, the periodontal ligament and the alveolar bone appeared to compete in periodontal wound healing. Moreover, the observed decrease in bone quality indicators suggests that intrabony defects beyond a critical size cannot be regenerated. This finding may be relevant for the clinical application of periodontal regeneration, since it implies that GTR has a dimensional limit.

Short-term effects of teriparatide versus placebo on bone biomarkers, structure, and fracture healing in women with lower-extremity stress fractures: A pilot study.

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Almirol, Ellen A; Chi, Lisa Y; Khurana, Bharti; Hurwitz, Shelley; Bluman, Eric M; Chiodo, Christopher; Matzkin, Elizabeth; Baima, Jennifer; LeBoff, Meryl S

2016-09-01

In this pilot, placebo-controlled study, we evaluated whether brief administration of teriparatide (TPTD) in premenopausal women with lower-extremity stress fractures would increase markers of bone formation in advance of bone resorption, improve bone structure, and hasten fracture healing according to magnetic resonance imaging (MRI). Premenopausal women with acute lower-extremity stress fractures were randomized to injection of TPTD 20-µg subcutaneous (s.c.) (n = 6) or placebo s.c. (n = 7) for 8 weeks. Biomarkers for bone formation N-terminal propeptide of type I procollagen (P1NP) and osteocalcin (OC) and resorption collagen type-1 cross-linked C-telopeptide (CTX) and collagen type 1 cross-linked N-telopeptide (NTX) were measured at baseline, 4 and 8 weeks. The area between the percent change of P1NP and CTX over study duration is defined as the anabolic window. To assess structural changes, peripheral quantitative computed topography (pQCT) was measured at baseline, 8 and 12 weeks at the unaffected tibia and distal radius. The MRI of the affected bone assessed stress fracture healing at baseline and 8 weeks. After 8 weeks of treatment, bone biomarkers P1NP and OC increased more in the TPTD- versus placebo-treated group (both p ≤ 0.01), resulting in a marked anabolic window (p ≤ 0.05). Results from pQCT demonstrated that TPTD-treated women showed a larger cortical area and thickness compared to placebo at the weight bearing tibial site, while placebo-treated women had a greater total tibia and cortical density. No changes at the radial sites were observed between groups. According to MRI, 83.3% of the TPTD- and 57.1% of the placebo-treated group had improved or healed stress fractures (p = 0.18). In this randomized, pilot study, brief administration of TPTD showed anabolic effects that TPTD may help hasten fracture healing in premenopausal women with lower-extremity stress fractures. Larger prospective studies are warranted to determine

Evaluation of Bone Healing After Osteotomies Prepared With Er:YAG Laser in Contact and Noncontact Modes and Piezosurgery--An Animal Study.

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Gabrić, Dragana; Blašković, Marko; Gjorgijevska, Elizabeta; Mladenov, Mitko; Tašič, Blaž; Jurič, Ivona Bago; Ban, Ticijana

2016-01-01

To analyze the healing of bone tissue treated with Er:YAG laser contact and noncontact modes of and piezosurgery in a rat model using triangular laser profilometry. Twenty-four 10-week-old adult male Wistar rats were used in the study. Three osteotomies on the medial part of tibia were performed in each animal, 1 in the right tibia and 2 in the left tibia. The osteotomies were performed with a piezoelectric device set at maximal power and the Er:YAG laser in contact mode (power, 7.5 W; pulse energy, 375 mJ; repetition rate, 20 Hz; MSP mode) and noncontact mode (power, 7.5 W; pulse energy, 750 mJ; repetition rate, 10 Hz; QSP mode) with a novel type of circular, digitally controlled handpiece (x-Runner). After surgery, 6 animals were immediately euthanized (group 1), and the others were euthanized after 1 week (group 2, n = 6), 2 weeks (group 3, n = 6), and 3 weeks (group 4, n = 6). Bone healing after osteotomy was analyzed using a 3-dimensional laser scanning technique (ie, laser triangulation profilometry). The volume reduction rates are similar for all 3 techniques (0.2 to 0.25 mm(3) per week). Greater volume reduction of 0.25 mm3 per week was observed for the Er:YAG laser in noncontact mode (x-Runner). After 3 weeks, almost complete healing of the prepared osteotomy was observed. Within the limitations of this study, the osteotomies performed by the Er:YAG laser in digitally controlled noncontact mode healed the fastest. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Assessment of bone healing ability of calcium phosphate cements loaded with platelet lysate in rat calvarial defects.

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Babo, Pedro S; Carvalho, Pedro P; Santo, Vítor E; Faria, Susana; Gomes, Manuela E; Reis, Rui L

2016-11-01

Injectable calcium phosphate cements have been used as a valid alternative to autologous bone grafts for bone augmentation with the additional advantage of enabling minimally invasive implantation procedures and for perfectly fitting the tissue defect. Nevertheless, they have low biodegradability and lack adequate biochemical signaling to promote bone healing and remodeling. In previous in vitro studies, we observed that the incorporation of platelet lysate directly into the cement paste or loaded in hyaluronic acid microspheres allowed to modulate the cement degradation and the in vitro expression of osteogenic markers in seeded human adipose derived stem cells. The present study aimed at investigating the possible effect of this system in new bone formation when implanted in calvarial bilateral defects in rats. Different formulations were assessed, namely plain calcium phosphate cements, calcium phosphate cements loaded with human platelet lysate, hybrid injectable formulations composed of the calcium phosphate cement incorporating hyaluronin acid non-loaded microparticles (20% hyaluronin acid) or with particles loaded with platelet lysate. The degradability and new bone regrowth were evaluated in terms of mineral volume in the defect, measured by micro-computed tomography and histomorphometric analysis upon 4, 8 and 12 weeks of implantation. We observed that the incorporation of hyaluronin acid microspheres induced an overly rapid cement degradation, impairing the osteoconductive properties of the cement composites. Moreover, the incorporation of platelet lysate induced higher bone healing than the materials without platelet lysate, up to four weeks after surgery. Nevertheless, this effect was not found to be significant when compared to the one observed in the sham-treated group. © The Author(s) 2016.

A 5-year comparison of marginal bone level following immediate loading of single-tooth implants placed in healed alveolar ridges and extraction sockets in the maxilla

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Berberi, Antoine N.; Sabbagh, Joseph M.; Aboushelib, Moustafa N.; Noujeim, Ziad F.; Salameh, Ziad A.

2014-01-01

Purpose: The aim of present investigation was to evaluate marginal bone level after 5-year follow-up of implants placed in healed ridges and fresh extraction sockets in maxilla with immediate loading protocol. Materials and Methods: Thirty-six patients in need of a single-tooth replacement in the anterior maxilla received 42 Astra Tech implants (Astra Tech Implant system™, Dentsply Implants, Mölndal, Sweden). Implants were placed either in healed ridges (group I) or immediately into fresh extraction sockets (group II). Implants were restored and placed into functional loading immediately by using a prefabricated abutment. Marginal bone level relative to the implant reference point was recorded at implant placement, crown cementation, 12, 36, and 60 months following loading using intra-oral radiographs. Measurements were made on the mesial and distal sides of each implant. Results: Overall, two implants were lost from the group II, before final crown cementation: they were excluded from the study. The mean change in marginal bone loss (MBL) after implant placement was 0.26 ± 0.161 mm for 1 year, and 0.26 ± 0.171 mm for 3 years, and 0.21 ± 0.185 mm for 5 years in extraction sockets and was 0.26 ± 0.176 mm for 1 year and 0.21 ± 0.175 mm for 3 years, and 0.19 ± 0.172 mm for 5 years in healed ridges group. Significant reduction of marginal bone was more pronounced in implants inserted in healed ridges (P prefabricated abutment placed during the surgery time seems to maintain marginal bone around implant in both healed and fresh extraction sites. PMID:24550840

Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34.

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Yongxin Ren

Full Text Available Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH.Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/- mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/- mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/- mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/- mice compared to vehicle-treated wild-type and Pth(-/- mice.Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.

Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34).

Science.gov (United States)

Ren, Yongxin; Liu, Bo; Feng, Yuxu; Shu, Lei; Cao, Xiaojian; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

2011-01-01

Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s) whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH. Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/-)) mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg) for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/-) mice compared to vehicle-treated wild-type and Pth(-/-) mice. Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.

Comparison of ossification of demineralized bone, hydroxyapatite, Gelfoam, and bone wax in cranial defect repair.

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Papay, F A; Morales, L; Ahmed, O F; Neth, D; Reger, S; Zins, J

1996-09-01

Demineralized bone allografts in the repair of calvarial defects are compared with other common bone fillers. This study uses a video-digitizing radiographic analysis of calvarial defect ossification to determine calcification of bone defects and its relation to postoperative clinical examination and regional controls. The postoperative clinical results at 3 months demonstrated that bony healing was greatest in bur holes filled with demineralized bone and hydroxyapatite. Radiographic analysis demonstrated calcification of demineralized bone-filled defects compared to bone wax- and Gelfoam-filled regions. Hydroxyapatite granules are radiographically dense, thus not allowing accurate measurement of true bone healing. The results suggest that demineralized bone and hydroxyapatite provide better structural support via bone healing to defined calvarial defects than do Gelfoam and bone wax.

Three-dimensional graphene foams loaded with bone marrow derived mesenchymal stem cells promote skin wound healing with reduced scarring

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Li, Zhonghua [Department of Burn and Plastic Surgery, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China); Department of Burn and Plastic Surgery, The Fourth People' s Hospital Of Jinan, Jinan 250031 (China); Wang, Haiqin [Department of Obstetrics and Gynecology, The Fifth People' s Hospital Of Jinan, Jinan 250022 (China); Yang, Bo; Sun, Yukai [Department of Burn and Plastic Surgery, The Fourth People' s Hospital Of Jinan, Jinan 250031 (China); Huo, Ran, E-mail: rhuo12@163.com [Department of Burn and Plastic Surgery, Provincial Hospital Affiliated to Shandong University, Jinan 250021 (China)

2015-12-01

The regeneration of functional skin remains elusive, due to poor engraftment, deficient vascularization, and excessive scar formation. Aiming to overcome these issues, the present study proposed the combination of a three-dimensional graphene foam (GF) scaffold loaded with bone marrow derived mesenchymal stem cells (MSCs) to improve skin wound healing. The GFs demonstrated good biocompatibility and promoted the growth and proliferation of MSCs. Meanwhile, the GFs loaded with MSCs obviously facilitated wound closure in animal model. The dermis formed in the presence of the GF structure loaded with MSCs was thicker and possessed a more complex structure at day 14 post-surgery. The transplanted MSCs correlated with upregulation of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which may lead to neo-vascularization. Additionally, an anti-scarring effect was observed in the presence of the 3D-GF scaffold and MSCs, as evidenced by a downregulation of transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) together with an increase of TGF-β3. Altogether, the GF scaffold could guide the wound healing process with reduced scarring, and the MSCs were crucial to enhance vascularization and provided a better quality neo-skin. The GF scaffold loaded with MSCs possesses necessary bioactive cues to improve wound healing with reduced scarring, which may be of great clinical significance for skin wound healing. - Highlights: • The GFs promoted the growth and proliferation of MSCs. • The GFs loaded with MSCs obviously facilitated wound closure in the animal model. • An anti-scarring effect was observed in the presence of 3D-GF scaffold and MSCs. • The GF scaffold loaded with MSCs has great effect on skin wound healing.

Three-dimensional graphene foams loaded with bone marrow derived mesenchymal stem cells promote skin wound healing with reduced scarring

International Nuclear Information System (INIS)

Li, Zhonghua; Wang, Haiqin; Yang, Bo; Sun, Yukai; Huo, Ran

2015-01-01

The regeneration of functional skin remains elusive, due to poor engraftment, deficient vascularization, and excessive scar formation. Aiming to overcome these issues, the present study proposed the combination of a three-dimensional graphene foam (GF) scaffold loaded with bone marrow derived mesenchymal stem cells (MSCs) to improve skin wound healing. The GFs demonstrated good biocompatibility and promoted the growth and proliferation of MSCs. Meanwhile, the GFs loaded with MSCs obviously facilitated wound closure in animal model. The dermis formed in the presence of the GF structure loaded with MSCs was thicker and possessed a more complex structure at day 14 post-surgery. The transplanted MSCs correlated with upregulation of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which may lead to neo-vascularization. Additionally, an anti-scarring effect was observed in the presence of the 3D-GF scaffold and MSCs, as evidenced by a downregulation of transforming growth factor-beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) together with an increase of TGF-β3. Altogether, the GF scaffold could guide the wound healing process with reduced scarring, and the MSCs were crucial to enhance vascularization and provided a better quality neo-skin. The GF scaffold loaded with MSCs possesses necessary bioactive cues to improve wound healing with reduced scarring, which may be of great clinical significance for skin wound healing. - Highlights: • The GFs promoted the growth and proliferation of MSCs. • The GFs loaded with MSCs obviously facilitated wound closure in the animal model. • An anti-scarring effect was observed in the presence of 3D-GF scaffold and MSCs. • The GF scaffold loaded with MSCs has great effect on skin wound healing

Modeling of anisotropic wound healing

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Valero, C.; Javierre, E.; García-Aznar, J. M.; Gómez-Benito, M. J.; Menzel, A.

2015-06-01

Biological soft tissues exhibit non-linear complex properties, the quantification of which presents a challenge. Nevertheless, these properties, such as skin anisotropy, highly influence different processes that occur in soft tissues, for instance wound healing, and thus its correct identification and quantification is crucial to understand them. Experimental and computational works are required in order to find the most precise model to replicate the tissues' properties. In this work, we present a wound healing model focused on the proliferative stage that includes angiogenesis and wound contraction in three dimensions and which relies on the accurate representation of the mechanical behavior of the skin. Thus, an anisotropic hyperelastic model has been considered to analyze the effect of collagen fibers on the healing evolution of an ellipsoidal wound. The implemented model accounts for the contribution of the ground matrix and two mechanically equivalent families of fibers. Simulation results show the evolution of the cellular and chemical species in the wound and the wound volume evolution. Moreover, the local strain directions depend on the relative wound orientation with respect to the fibers.

Experimental study on healing process of rat mandibular bone fracture examined by radiological procedures

International Nuclear Information System (INIS)

Iuchi, Yukio; Furumoto, Keiichi

1994-01-01

The healing process of rat mandibular fractures was stereoscopically observed daily, using plain roentgenography in the lateral-oblique and tooth axis directions and bone scintigraphy using 99m-Tc-methylene diphosphoric acid (Tc-99m-MDP). The findings were compared with microradiograms of regional polished specimens. X-ray findings included the following. Up to 3 days after bone fracture, the fracture mesiodistally showed distinct radiolucency, with sharp and irregular fracture stump. Radiopacity of the fracture site gradually increased 7 days or later, and bone trabecular formation by callus and stump bridging started to occur at 14 days. Findings similar to those in the control group were observed 49 days or later. The inside was difficult to differentiate, irrespective of the observation time. Bone scans in the mesiodistal and buccolingual planes revealed tracer uptake in the areas of mandibular and soft tissue damage one day after bone fracture. Tracer uptake began to be seen in the fracture site 3 days later, and became marked at 14 days. Then Tc-99m DMP began to be localized and returned to the findings similar to those at 49 days. Bone scanning tended to show wider areas earlier than roentgenography. Microradiographic mesiodistal examination revealed distinct radiopacy of the fracture line for 3 days after bone fracture. Seven days later, bone resorption cavity occurred in the cortical bone around the fracture stump, along with neogenesis of callus. Neogenesis and calcification began to occur gradually, and 14 days later, the fracture osteoremodeling of the internal bone trabeculae was observed. Bone trabecular formation within the bone, however, occurred later. (N.K.)

Healing of osteotomy sites applying either piezosurgery or two conventional saw blades: a pilot study in rabbits.

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Ma, Li; Stübinger, Stefan; Liu, Xi Ling; Schneider, Urs A; Lang, Niklaus P

2013-08-01

The purpose of this study was to compare bone healing of experimental osteotomies applying either piezosurgery or two different oscillating saw blades in a rabbit model. The 16 rabbits were randomly assigned into four groups to comply with observation periods of one, two, three and five weeks. In all animals, four osteotomy lines were performed on the left and right nasal bone using a conventional saw blade, a novel saw blade and piezosurgery. All three osteotomy techniques revealed an advanced gap healing starting after one week. The most pronounced new bone formation took place between two and three weeks, whereby piezoelectric surgery revealed a tendency to faster bone formation and remodelling. Yet, there were no significant differences between the three modalities. The use of a novel as well as the piezoelectric bone-cutting instrument revealed advanced bone healing with a favourable surgical performance compared to a traditional saw.

The Effect of Low Molecular Weight Heparins on Fracture Healing.

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Kapetanakis, Stylianos; Nastoulis, Evangelos; Demesticha, Theano; Demetriou, Thespis

2015-01-01

Venous Thromboembolism is a serious complication in the trauma patient. The most commonly studied and used anticoagulant treatment in prophylaxis of thrombosis is heparin. The prolonged use of unfractionated heparin has been connected with increased incidence of osteoporotic fractures. Low molecular-weight-heparins (LMWHs) have been the golden rule in antithrombotic therapy during the previous two decades as a way to overcome the major drawbacks of unfractioned heparin. However there are few studies reporting the effects of LMWHs on bone repair after fractures. This review presents the studies about the effects of LMWHs on bone biology (bone cells and bone metabolism) and underlying the mechanisms by which LMWHs may impair fracture healing process. The authors' research based on literature concluded that there are no facts and statistics for the role of LMWHs on fracture healing process in humans and the main body of evidence of their role comes from in vitro and animal studies. Further large clinical studies designed to compare different types of LMWHs, in different dosages and in different patient or animal models are needed for exploring the effects of LMWHs on fracture healing process.

Alveolar wound healing after implantation with a pool of commercially available bovine bone morphogenetic proteins (BMPs): a histometric study in rats.

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Calixto, Romeu Felipe Elias; Teófilo, Juliana Mazzonetto; Brentegani, Luiz Guilherme; Lamano-Carvalho, Teresa Lúcia

2007-01-01

The capacity of a commercially available pool of bovine bone morphogenetic proteins (BMPs) to stimulate osteogenesis in the rat alveolar healing was investigated by histometric analysis. Male rats were anesthetized and had their upper incisor extracted. A pool of purified bovine BMPs adsorbed to microgranular resorbable hydroxyapatite was agglutinated with bovine collagen and saline before implantation into the alveolar socket. The implanted and control rats (n=30 per group) were sacrificed 1 to 9 weeks postoperatively, the hemi-maxillae were decalcified, processed for paraffin embedding and semi-serial longitudinal sections were obtained and stained with hematoxylin and eosin. The volume fraction of alveolar healing components was estimated by a differential point-counting method in histologic images. The results showed that in both, control and implanted rats, the alveolar healing followed the histologic pattern usually described in the literature. Quantitative data confirmed that the BMPs mixture did not stimulate new bone formation in the alveolar socket of implanted rats. These results suggest that the pool of BMPs adsorbed to hydroxyapatite and agglutinated with bovine collagen did not warrant incorporation of the osteoinductive proteins to a slow-absorption system that would allow a BMPs release rate compatible to that of new bone formation, and thus more adequate to osteoinduction.

Healing of Large Segmental Bone Defect after Implantation of Autogenous Cancellous Bone Graft in Comparison to Hydroxyapatite and 0.5% Collagen Scaffold Combined with Mesenchymal Stem Cells

Czech Academy of Sciences Publication Activity Database

Nečas, A.; Proks, P.; Urbanová, L.; Srnec, R.; Stehlík, L.; Crha, M.; Raušer, P.; Plánka, L.; Janovec, J.; Dvořák, M.; Amler, Evžen; Vojtová, L.; Jančář, J.

2010-01-01

Roč. 79, č. 4 (2010), s. 607-612 ISSN 0001-7213 R&D Projects: GA MŠk 2B06130 Institutional support: RVO:68378041 Keywords : fracture fixation * bone healing * comminuted fracture Subject RIV: FI - Traumatology, Orthopedics Impact factor: 0.534, year: 2010

Maxillary Bone Regeneration Based on Nanoreservoirs Functionalized ε-Polycaprolactone Biomembranes in a Mouse Model of Jaw Bone Lesion

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Marion Strub

2018-01-01

Full Text Available Current approaches of regenerative therapies constitute strategies for bone tissue reparation and engineering, especially in the context of genetical diseases with skeletal defects. Bone regeneration using electrospun nanofibers’ implant has the following objectives: bone neoformation induction with rapid healing, reduced postoperative complications, and improvement of bone tissue quality. In vivo implantation of polycaprolactone (PCL biomembrane functionalized with BMP-2/Ibuprofen in mouse maxillary defects was followed by bone neoformation kinetics evaluation using microcomputed tomography. Wild-Type (WT and Tabby (Ta mice were used to compare effects on a normal phenotype and on a mutant model of ectodermal dysplasia (ED. After 21 days, no effect on bone neoformation was observed in Ta treated lesion (4% neoformation compared to 13% in the control lesion. Between the 21st and the 30th days, the use of biomembrane functionalized with BMP-2/Ibuprofen in maxillary bone lesions allowed a significant increase in bone neoformation peaks (resp., +8% in mutant Ta and +13% in WT. Histological analyses revealed a neoformed bone with regular trabecular structure, areas of mineralized bone inside the membrane, and an improved neovascularization in the treated lesion with bifunctionalized membrane. In conclusion, PCL functionalized biomembrane promoted bone neoformation, this effect being modulated by the Ta bone phenotype responsible for an alteration of bone response.

Zmpste24-/- mouse model for senescent wound healing research.

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Butala, Parag; Szpalski, Caroline; Soares, Marc; Davidson, Edward H; Knobel, Denis; Warren, Stephen M

2012-12-01

The graying of our population has motivated the authors to better understand age-related impairments in wound healing. To increase research throughput, the authors hypothesized that the Hutchinson-Gilford progeria syndrome Zmpste24-deficient (Zmpste24(-/-)) mouse could serve as a model of senescent wound healing. Using a stented excisional wound closure model, the authors tested this hypothesis on 8-week-old male Zmpste24(-/-) mice (n = 25) and age-matched male C57BL/6J wild-type mice (n = 25). Wounds were measured photogrammetrically and harvested for immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction, and circulating vasculogenic progenitor cells were measured by flow cytometry. Zmpste24(-/-) mice had a significant delay in wound closure compared with wild-type mice during the proliferative/vasculogenic phase. Zmpste24(-/-) wounds had decreased proliferation, increased 8-hydroxy-2'-deoxyguanosine levels, increased proapoptotic signaling (i.e., p53, PUMA, BAX), decreased antiapoptotic signaling (i.e., Bcl-2), and increased DNA fragmentation. These changes correlated with decreased local vasculogenic growth factor expression, decreased mobilization of bone marrow-derived vasculogenic progenitor cells, and decreased new blood vessel formation. Age-related impairments in wound closure are multifactorial. The authors' data suggest that the Hutchinson-Gilford progeria syndrome Zmpste24(-/-) progeroid syndrome shares mechanistic overlap with normal aging and therefore might provide a uniquely informative model with which to study age-associated impairments in wound closure.

Does Periosteal Graft Combined With Platelet-Rich Plasma Enhance the Healing of Bone Defect?

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Türkseven, Arzu; Özçelik, Derya; Çaliş, Mert; Celik, Hakan Hamdi; Yilmaz, Fahri; Önbaş, Ömer; Vatansever, Alper; Toplu, Gaye

2018-02-12

This study investigated the effect of periosteal graft + platelet-rich plasma (PRP) combination on facial bone defect healing. Five-millimeter critical sized defects in zygomatic arches of 12 adult New Zealand rabbits were created. Rabbits were randomly divided into 3 groups: First group (control group): bone defects of left zygomatic arches of 6 rabbits were wrapped with a silicone tube. Second group (periosteal graft group): bone defects of left zygomatic arches of 6 rabbits were wrapped with periosteal graft. Third group (experimental group): bone defects of right zygomatic arches of 12 rabbits were wrapped with periosteal graft-PRP combination. New bone formation was evaluated at 8th and 16th weeks. One rabbit was sacrificed at 8th week. Remaining 11 rabbits were imaged with 3-dimensional computed tomography (CT) at 16th week; then, zygomatic arches were removed for micro-CT and histologic examinations. Three-dimensional CT analysis at 16th week revealed no significant difference between groups regarding new bone formation (P = 0.232). Micro-CT analysis of new regenerated bone at 16th week displayed significant differences between groups 1 and 3 regarding mean bone volume (BV, mm) (P = 0.028) and mean bone mineral density (BMD, mm) (P = 0.001). There was no difference between groups 2 and 3 or between groups 1 and 2, regarding BV or BMD. Histological Bone Regeneration Scorings at 16th week displayed significant difference between groups (P = 0.015). Negative correlation between 3-dimensional CT and histologic results (r = 0.120); positive correlations between BV/BMD values in micro-CT and histologic results (r = 0.524 and r = 0.456) were found. By enhancing bone formation capacity of periosteal grafts, periosteal graft-PRP combination provided bone formation having more volume and density comparing with silicone tube application.

Radiographic evaluation of fracture healing after rigid plate fixation

International Nuclear Information System (INIS)

Paavolainen, P.; Karaharju, E.; Slaetis, P.; Waris, P.

1981-01-01

Experimental osteotomies were made in 35 rabbit tibio-fibular bones and fixed with rigid stainless steel osteosynthesis plates (DCP/ASIF). The radiographic and histopathologic appearances in the healing osteotomies and adjacent bone were analysed at intervals from 3 up to 24 weeks postoperatively. Radiologically the osteotomy had closed at 9 weeks and microscopically this could be confirmed as longitudinal orientation of the cutter heads across the osteotomy gap with longitudinal orientation of the bone structure. The healing of the osteotomy was accompanied by gross structural changes in the adjacent cortical bone with loss of intracortical and subendosteal osteons, cementing lines and intermediate tissue between the osteons. This was characterized by decreasing attenuation of the cortical bone after healing of the osteotomy and should clinically be regarded as an indication for removal of the implant. (Auth.)

Effect of abutment height on interproximal implant bone level in the early healing: A randomized clinical trial.

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Blanco, Juan; Pico, Alexandre; Caneiro, Leticia; Nóvoa, Lourdes; Batalla, Pilar; Martín-Lancharro, Pablo

2018-01-01

The aim of this randomized clinical trial was to compare the effect on the interproximal implant bone loss (IBL) of two different heights (1 and 3 mm) of definitive abutments placed at bone level implants with a platform switched design. Twenty-two patients received forty-four implants (6.5-10 mm length and 3.5-4 mm diameter) to replace at least two adjacent missing teeth, one bridge set to each patient-two implants per bridge. Patients were randomly allocated, and two different abutment heights, 1 and 3 mm using only one abutment height per bridge, were used. Clinical and radiological measurements were performed at 3 and 6 months after surgery. Interproximal bone level changes were compared between treatment groups. The association between IBL and categorical variables (history of periodontitis, smoking, implant location, implant diameter, implant length, insertion torque, width of keratinized mucosa, bone density, gingival biotype and antagonist) was also performed. At 3 months, implants with a 1-mm abutment had significantly greater IBL (0.83 ± 0.19 mm) compared to implants with a 3-mm abutment (0.14 ± 0.08 mm). At 6 months, a greater IBL was observed at implants with 1-mm abutments compared to implants with 3-mm abutments (0.91 ± 0.19 vs. 0.11 ± 0.09 mm). The analysis of the relation between patient characteristics and clinical variables with IBL revealed no significant differences at any moment except for smoking. Abutment height is an important factor to maintain interproximal implant bone level in early healing. Short abutments led to a greater interproximal bone loss in comparison with long abutments after 6 months. Other variables except smoking showed no relation with interproximal bone loss in early healing. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acceleration of bone union after structural bone grafts with a collagen-binding basic fibroblast growth factor anchored-collagen sheet for critical-size bone defects

International Nuclear Information System (INIS)

Ueno, Masaki; Uchida, Kentaro; Saito, Wataru; Inoue, Gen; Takahira, Naonobu; Takaso, Masashi; Matsushita, Osamu; Yogoro, Mizuki; Nishi, Nozomu; Ogura, Takayuki; Hattori, Shunji; Tanaka, Keisuke

2014-01-01

Bone allografts are commonly used for the repair of critical-size bone defects. However, the loss of cellular activity in processed grafts markedly reduces their healing potential compared with autografts. To overcome this obstacle, we developed a healing system for critical-size bone defects that consists of overlaying an implanted bone graft with a collagen sheet (CS) loaded with basic fibroblast growth factor (bFGF) fused to the collagen-binding domain derived from a Clostridium histolyticum collagenase (CB-bFGF). In a murine femoral defect model, defect sites treated with CS/CB-bFGF had a significantly larger callus volume than those treated with CS/native bFGF. In addition, treatment with CS/CB-bFGF resulted in the rapid formation of a hard callus bridge and a larger total callus volume at the host–graft junction than treatment with CS/bFGF. Our results suggest that the combined use of CS and CB-bFGF helps accelerate the union of allogenic bone grafts. (paper)

Radiographic evaluation of using Persian Gulf coral powder effect on bone healing defects in rabbits

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Mehdi Marjani

2011-11-01

Full Text Available Background: ‍Considering the fact that research on the marine products and creatures, in particular coral, has started just in the past decade and more attentions are focused on the benefits of this material, it has been decided to utilize the coral native to Persian Gulf as oral powder to heal tibia bone defect in rabbit. Methods: In this experimental study 18 New Zealander rabbits weighing 2.5-3 kg were categorized randomly in 3 groups (control, oral calcium powder and oral coral powder group of 6 rabbits. For inducing the defect, the first 3rd part of tibial bone was blunt dissected. A whole with the depth of 0.6-0.8 mm and diameter of 4 mm was produced in all 3 groups in the same style. The Calcium group was treated daily with 1150 mg calcium powder, coral group received 1220 mg of coral powder and control group were kept under standard condition. Course of treatment was 2 months and on days 0,10,20,30,40,50,63 the animals were evaluated for healing criteria such as filling the defects, density, external callus formation and intercortical callus. Results: Radiologic parameters indicates that filling defect, density, external and inter cortical callus and absorption for animals receiving coral is better than that of control and calcium group (P<0/05. Conclusion: In conclusion, by oral administration of Persian Gulf coral powder results increasing the rate of bone formation. Finally for human use, these results must be evaluated more in clinical studies.

Effect of calcium citrate on bone integration in a rabbit femur defect model.

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Zhang, Wei; Wang, Wei; Chen, Qing-Yu; Lin, Zhong-Qin; Cheng, Shao-Wen; Kou, Dong-Quan; Ying, Xiao-Zhou; Shen, Yue; Cheng, Xiao-Jie; Nie, Peng-Fei; Li, Xiu-Cui; Rompis, Ferdinand An; Huang, Hang; Zhang, Hua; Mu, Zhong-Lin; Peng, Lei

2012-04-01

To explore effect of calcium citrate on bone integration in a rabbit femur defect model, and to compare the bone formation with different sizes by radiological and histological study. Twenty-four male Japanese white rabbits were randomly divided into three groups (Group A, B, C) in this study. Under anesthesia, defects of four sizes (1.2, 1.5, 2.0 and 2.5 mm) were created in each of the rabbits. Commercially pure calcium citrate powder was placed inside the medullary compartment of the femur (Experimental), while in the contralateral femur (Control) nothing was implanted. The defects were analyzed using radiography and histological analysis by using Imagepro-Plus 6.0 software after animal was sacrificed at 4th(Group A), 6th(Group B) and 8th(Group C) weeks postoperatively. Four samples were analyzed for each size of defect and each healing period. The histological and the radiologic evaluation were performed after sacrification of all rabbits on postoperative 4th and 6th weeks, It showed significant difference between the experimental group and the control group when these defects were less than or equal to 2.0 mm. No statistical difference was observed when these defects were larger than 2.0 mm at all healing periods except at the 4th week. Calcium citrate affects the early periods of bone defects healing mechanism in Japanese white rabbits positively, especially when the defect is not too large. We suggest further studies on calcium citrate to determine the effects of various dosages, administration ways and the experimental time on the bone defects. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Early Loading of Fluoridated Implants Placed in Fresh Extraction Sockets and Healed Bone: A 3- to 5-Year Clinical and Radiographic Follow-Up Study of 39 Consecutive Patients.

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Oxby, Gert; Oxby, Fredrik; Oxby, Johan; Saltvik, Tomas; Nilsson, Peter

2015-10-01

Immediate placement of implants in extraction sockets for early loading is an attractive treatment modality due to reduced treatment time. However, the outcome of fluoridated implants in this situation with regard to bone levels and health of soft tissues is not well documented. To evaluate the outcome of early loading of OsseoSpeed(™) dental implants placed into fresh extraction sockets and healed bone in consecutive patients treated in a private clinic. A total of 182 OsseoSpeed(™) implants (Astra Tech Implant System, DENTSPLY Implants, Mölndal, Sweden), 72 in immediate extraction sockets and 110 in healed sites, were placed in 39 consecutive patients. The implants were loaded with permanent restorations within 60 days (average 31 days). Clinical and radiographic follow-up examinations were performed annually for at least 3 years (mean 55 months). An aesthetic index was used to evaluate the soft tissues adjacent to the prosthetic restorations. No implant was lost during the observation period, giving a survival rate of 100%. Bone level changes during the observation period were minimal, with a mean marginal bone loss of 0.3 ± 0.9 mm around the delayed implants and a mean marginal bone gain of 0.3 ± 1.4 mm around the immediate implants (p = .0036). The frequency distribution of bone level revealed that 85% of implants placed in fresh extraction sockets and 84% of implants in healed bone did not show any loss of bone level during follow-up (p = NS). Soft tissue complications were observed at two immediate implant sites in one patient. The remaining 180 implants received the highest aesthetic score. Moreover, no signs of peri-implant purulent infection or aggressive bone loss were found during the follow-up period. Early loading of fluoridated implants with permanent constructions appears to be a viable therapy for implants placed immediately in extraction sites and in healed bone. © 2014 Wiley Periodicals, Inc.

[Bone remodeling and modeling/mini-modeling.

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Hasegawa, Tomoka; Amizuka, Norio

Modeling, adapting structures to loading by changing bone size and shapes, often takes place in bone of the fetal and developmental stages, while bone remodeling-replacement of old bone into new bone-is predominant in the adult stage. Modeling can be divided into macro-modeling(macroscopic modeling)and mini-modeling(microscopic modeling). In the cellular process of mini-modeling, unlike bone remodeling, bone lining cells, i.e., resting flattened osteoblasts covering bone surfaces will become active form of osteoblasts, and then, deposit new bone onto the old bone without mediating osteoclastic bone resorption. Among the drugs for osteoporotic treatment, eldecalcitol(a vitamin D3 analog)and teriparatide(human PTH[1-34])could show mini-modeling based bone formation. Histologically, mature, active form of osteoblasts are localized on the new bone induced by mini-modeling, however, only a few cell layer of preosteoblasts are formed over the newly-formed bone, and accordingly, few osteoclasts are present in the region of mini-modeling. In this review, histological characteristics of bone remodeling and modeling including mini-modeling will be introduced.

Anatomic and histological study of the rabbit mandible as an experimental model for wound healing and surgical therapies.

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Campillo, V-E; Langonnet, S; Pierrefeu, A; Chaux-Bodard, A-G

2014-10-01

The rabbit is one of the most widely used models for studying bone remodeling or dental implant osseointegration but very few data are available about the rabbit's mandible. The aim of this work was to describe the anatomy of the rabbit mandible and to estimate the available bone volume for experimental studies. First, with a dissection, the morphology of the mandible was described and the mental foramen, the position of the main salivary glands and muscular insertions were located. Then, by X-ray imaging, the position of the inferior alveolar canal, the dental root courses and volume and bone density were described. Finally, with frontal sections of the mandible body, the rabbit's dental and alveolar bone histological structure were assessed. Thus, the relevance of the rabbit mandible as an experimental model for wound healing or surgical therapies was discussed. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Application of a novel bone osteotomy plate leads to reduction in heat-induced bone tissue necrosis in sheep.

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Bekić, Marijo; Davila, Slavko; Hrskanović, Mato; Bekić, Marijana; Seiwerth, Sven; Erdeljić, Viktorija; Capak, Darko; Butković, Vladimir

2008-12-01

Previous studies have shown substantial effect thermal damage can have on new bone formation following osteotomy. In this study we evaluated the extent of thermal damage which occurs in four different methods of osteotomy and the effects it can have on bone healing. We further wanted to test whether a special osteotomy plate we constructed can lead to diminished heat generation during osteotomy and enhanced bone healing. The four methods evaluated included osteotomy performed by chisel, a newly constructed osteotomy plate, Gigly and oscillating saw. Twelve adult sheep underwent osteotomy performed on both tibiae. Bone fragments were stabilized using a fixation plate. Callus size was assessed using standard radiographs. Densitometry and histological evaluation were performed at 8 weeks following osteotomy. Temperature measurements were performed both in vivo during the operation, and ex vivo on explanted tibiae. The defects healed without complications and showed typical course of secondary fracture healing with callus ingrowth into the osteotomy gap. Radiographic examination of bone healing showed a tendency towards more callus formation in bones osteotomized using Gigly and oscillating saw, but this difference lacked significance. Use of Gigly and oscillating saw elicited much higher temperatures at the bone cortex surface, which subsequently lead to slightly impaired bone healing according to histological analysis. BMD was equal among all bones. In conclusion, the time required for complete healing of the defect differed depended greatly on the instruments used. The newly constructed osteotomy plate showed best results based on histological findings of capillary and osteoblast density.

Dynamic locking screw improves fixation strength in osteoporotic bone: an in vitro study on an artificial bone model.

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Pohlemann, Tim; Gueorguiev, Boyko; Agarwal, Yash; Wahl, Dieter; Sprecher, Christoph; Schwieger, Karsten; Lenz, Mark

2015-04-01

The novel dynamic locking screw (DLS) was developed to improve bone healing with locked-plate osteosynthesis by equalising construct stiffness at both cortices. Due to a theoretical damping effect, this modulated stiffness could be beneficial for fracture fixation in osteoporotic bone. Therefore, the mechanical behaviour of the DLS at the screw-bone interface was investigated in an artificial osteoporotic bone model and compared with conventional locking screws (LHS). Osteoporotic surrogate bones were plated with either a DLS or a LHS construct consisting of two screws and cyclically axially loaded (8,500 cycles, amplitude 420 N, increase 2 mN/cycle). Construct stiffness, relative movement, axial screw migration, proximal (P) and distal (D) screw pullout force and loosening at the bone interface were determined and statistically evaluated. DLS constructs exhibited a higher screw pullout force of P 85 N [standard deviation (SD) 21] and D 93 N (SD 12) compared with LHS (P 62 N, SD 28, p = 0.1; D 57 N, SD 25, p LHS (p = 0.01). DLS constructs showed significantly lower axial construct stiffness (403 N/mm, SD 21, p LHS (529 N/mm, SD 27; 0.8 mm, SD 0.04). Based on the model data, the DLS principle might also improve in vivo plate fixation in osteoporotic bone, providing enhanced residual holding strength and reducing screw cutout. The influence of pin-sleeve abutment still needs to be investigated.

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 ...

Bone regeneration by implantation of adipose-derived stromal cells expressing BMP-2

International Nuclear Information System (INIS)

Li Huiwu; Dai Kerong; Tang Tingting; Zhang Xiaoling; Yan Mengning; Lou Jueren

2007-01-01

In this study, we reported that the adipose-derived stromal cells (ADSCs) genetically modified by bone morphogenetic protein 2 (BMP-2) healed critical-sized canine ulnar bone defects. First, the osteogenic and adipogenic differentiation potential of the ADSCs derived from canine adipose tissue were demonstrated. And then the cells were modified by the BMP-2 gene and the expression and bone-induction ability of BMP-2 were identified. Finally, the cells modified by BMP-2 gene were applied to a β-tricalcium phosphate (TCP) carrier and implanted into ulnar bone defects in the canine model. After 16 weeks, radiographic, histological, and histomorphometry analysis showed that ADSCs modified by BMP-2 gene produced a significant increase of newly formed bone area and healed or partly healed all of the bone defects. We conclude that ADSCs modified by the BMP-2 gene can enhance the repair of critical-sized bone defects in large animals

Porous decellularized tissue engineered hypertrophic cartilage as a scaffold for large bone defect healing.

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Cunniffe, Gráinne M; Vinardell, Tatiana; Murphy, J Mary; Thompson, Emmet M; Matsiko, Amos; O'Brien, Fergal J; Kelly, Daniel J

2015-09-01

Clinical translation of tissue engineered therapeutics is hampered by the significant logistical and regulatory challenges associated with such products, prompting increased interest in the use of decellularized extracellular matrix (ECM) to enhance endogenous regeneration. Most bones develop and heal by endochondral ossification, the replacement of a hypertrophic cartilaginous intermediary with bone. The hypothesis of this study is that a porous scaffold derived from decellularized tissue engineered hypertrophic cartilage will retain the necessary signals to instruct host cells to accelerate endogenous bone regeneration. Cartilage tissue (CT) and hypertrophic cartilage tissue (HT) were engineered using human bone marrow derived mesenchymal stem cells, decellularized and the remaining ECM was freeze-dried to generate porous scaffolds. When implanted subcutaneously in nude mice, only the decellularized HT-derived scaffolds were found to induce vascularization and de novo mineral accumulation. Furthermore, when implanted into critically-sized femoral defects, full bridging was observed in half of the defects treated with HT scaffolds, while no evidence of such bridging was found in empty controls. Host cells which had migrated throughout the scaffold were capable of producing new bone tissue, in contrast to fibrous tissue formation within empty controls. These results demonstrate the capacity of decellularized engineered tissues as 'off-the-shelf' implants to promote tissue regeneration. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Marginal Bone Remodeling around healing Abutment vs Final Abutment Placement at Second Stage Implant Surgery: A 12-month Randomized Clinical Trial.

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Nader, Nabih; Aboulhosn, Maissa; Berberi, Antoine; Manal, Cordahi; Younes, Ronald

2016-01-01

The periimplant bone level has been used as one of the criteria to assess the success of dental implants. It has been documented that the bone supporting two-piece implants undergoes resorption first following the second-stage surgery and later on further to abutment connection and delivery of the final prosthesis. The aim of this multicentric randomized clinical trial was to evaluate the crestal bone resorption around internal connection dental implants using a new surgical protocol that aims to respect the biological distance, relying on the benefit of a friction fit connection abutment (test group) compared with implants receiving conventional healing abutments at second-stage surgery (control group). A total of partially edentulous patients were consecutively treated at two private clinics, with two adjacent two-stage implants. Three months after the first surgery, one of the implants was randomly allocated to the control group and was uncovered using a healing abutment, while the other implant received a standard final abutment and was seated and tightened to 30 Ncm. At each step of the prosthetic try-in, the abutment in the test group was removed and then retightened to 30 Ncm. Horizontal bone changes were assessed using periapical radiographs immediately after implant placement and at 3 (second-stage surgery), 6, 9 and 12 months follow-up examinations. At 12 months follow-up, no implant failure was reported in both groups. In the control group, the mean periimplant bone resorption was 0.249 ± 0.362 at M3, 0.773 ± 0.413 at M6, 0.904 ± 0.36 at M9 and 1.047 ± 0.395 at M12. The test group revealed a statistically significant lower marginal bone loss of 20.88% at M3 (0.197 ± 0.262), 22.25% at M6 (0.601 ± 0.386), 24.23% at M9 (0.685 ± 0.341) and 19.2% at M9 (0.846 ± 0.454). The results revealed that bone loss increased over time, with the greatest change in bone loss occurring between 3 and 6 months. Alveolar bone loss was significantly greater in the

The science of ultrasound therapy for fracture healing

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Della Rocca Gregory

2009-01-01

Full Text Available Fracture healing involves a complex interplay of cellular processes, culminating in bridging of a fracture gap with bone. Fracture healing can be compromised by numerous exogenous and endogenous patient factors, and intense research is currently going on to identify modalities that can increase the likelihood of successful healing. Low-intensity pulsed ultrasound (LIPUS has been proposed as a modality that may have a benefit for increasing reliable fracture healing as well as perhaps increasing the rate of fracture healing. We conducted a review to establish basic scince evidence of therapeutic role of lipus in fracture healing. An electronic search without language restrictions was accomplished of three databases (PubMed, Embase, Cinahl for ultrasound-related research in osteocyte and chondrocyte cell culture and in animal fracture models, published from inception of the databases through December, 2008. Studies deemed to be most relevant were included in this review. Multiple in vitro and animal in vivo studies were identified. An extensive body of literature exists which delineates the mechanism of action for ultrasound on cellular and tissue signaling systems that may be related to fracture healing. Research on LIPUS in animal fracture models has demonstrated promising results for acceleration of fracture healing and for promotion of fracture healing in compromised tissue beds. A large body of cellular and animal research exists which reveals that LIPUS may be beneficial for accelerating normal fracture healing or for promoting fracture healing in compromised tissue beds. Further investigation of the effects of LIPUS in human fracture healing is warranted for this promising new therapy.

Histomorphometric evaluation of the effect of systemic and topical ozone on alveolar bone healing following tooth extraction in rats.

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Erdemci, F; Gunaydin, Y; Sencimen, M; Bassorgun, I; Ozler, M; Oter, S; Gulses, A; Gunal, A; Sezgin, S; Bayar, G R; Dogan, N; Gider, I K

2014-06-01

The aim of this study was to investigate the effects of systemic and topical ozone applications on alveolar bone healing following tooth extraction. One hundred and twelve male Wistar rats were divided into eight groups of 14 rats each; seven groups were experimental (A-G) and one formed the control group (K). The experimental groups were further divided into two sub-groups, with seven rats in each - sacrificed on days 14 and 28 (subgroups 1 and 2). The maxillary right central incisors were extracted under general anaesthesia following the administration of local anaesthesia. After sacrifice, semi-serial histological sections were prepared, and mineralized and trabecular bone and osteoid and osteoblast surfaces were measured. Measurements of the trabecular bone showed statistically higher values in the groups treated with systemic ozone (D(2): 50.01 ± 2.12; E(2): 49.03 ± 3.03; F(2): 48.76 ± 2.61; G(2): 50.24 ± 3.37) than in the groups that underwent topical ozone administration (A(2): 46.01 ± 3.07; B(2): 46.79 ± 3.09; C(2): 47.07 ± 2.12; P = 0.030 (G(2)-A(2), G(2)-B(2), G(2)-C(2))). Within the limitations of the current study, it may be concluded that postoperative long-term systemic ozone application can accelerate alveolar bone healing following extraction. However, additional studies are required to clarify the effects of the different ozone applications on new bone formation. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Effect of antiresorptive drugs in the alveolar bone healing. A histometric and immunohistochemical study in ovariectomized rats.

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Ramalho-Ferreira, Gabriel; Faverani, Leonardo Perez; Momesso, Gustavo Antonio Correa; Luvizuto, Eloá Rodrigues; de Oliveira Puttini, Igor; Okamoto, Roberta

2017-06-01

The aim of this study is to evaluate the alendronate and raloxifene influence in the alveolar healing process of osteoporotic rats. Sixty-four female rats were divided in four groups: sham rats (SHAM), ovariectomized rats and no medical treatment (OVX NT), ovariectomized rats and submitted to alendronate treatment (OVX ALE), and ovariectomized and submitted to raloxifene treatment (OVX RAL). The histomorphometrical and immunohistochemical analysis was performed. The quantitative data were analyzed through Kruskal-Wallis and Dunn tests (α = 0.05). In the longest period, SHAM and OVX RAL groups showed the better bone formation responses (P alveolar healing process in osteoporotic rats, but not enough to achieve the histometrical and protein expression values that were observed in the SHAM group. Alendronate is largely used as a potent antiresorptive agent. Otherwise, considering the undesirable effects in relation to the alveolar healing, other antiosteoporosis medications should be studied. Raloxifene seems to be a good candidate once its action mechanism involves the activation of osteoblasts.

Wound healing in animal models: review article

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Fariba Jaffary

2017-10-01

Full Text Available Wound healing and reduction of its recovery time is one of the most important issues in medicine. Wound is defined as disruption of anatomy and function of normal skin. This injury could be the result of physical elements such as  surgical incision, hit or pressure cut of the skin and gunshot wound. Chemical or caustic burn is another category of wound causes that can be induced by acid or base contact irritation. Healing is a process of cellular and extracellular matrix interactions that occur in the damaged tissue. Wound healing consists of several stages including hemostasis, inflammatory phase, proliferative phase and new tissue formation which reconstructs by new collagen formation. Wounds are divided into acute and chronic types based on their healing time. Acute wounds have sudden onset and in normal individuals usually have healing process of less than 4 weeks without any residual side effects. In contrast, chronic wounds have gradual onset. Their inflammatory phase is prolonged and the healing process is stopped due to some background factors like diabetes, ischemia or local pressure. If the healing process lasts more than 4 weeks it will be classified as chronic wound. Despite major advances in the treatment of wounds, still finding effective modalities for healing wounds in the shortest possible time with the fewest side effects is a current challenge. In this review different phases of wound healing and clinical types of wound such as venous leg ulcer, diabetic foot ulcer and pressure ulcer are discussed. Also acute wound models (i.e burn wounds or incisional wound and chronic wound models (such as venous leg ulcers, diabetic foot ulcer, pressure ulcers or bedsore in laboratory animals are presented. This summary can be considered as a preliminary step to facilitate designing of more targeted and applied research in this area.

Recombinant human bone morphogenetic protein-2 in the treatment of bone fractures

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Neil Ghodadra

2008-09-01

Full Text Available Neil Ghodadra, Kern SinghDepartment of Orthopedic Surgery, Rush University Medical Center, Chicago, Illinois, USAAbstract: Over one million fractures occur per year in the US and are associated with impaired healing increasing patient morbidity, stress, and economic costs. Despite improvements in surgical technique, internal fixation, and understanding of biologics, fracture healing is delayed or impaired in up to 4% of all fractures. Complications due to impaired fracture healing present therapeutic challenges to the orthopedic surgeon and often lead to chronic functional and psychological disability for the patient. As a result, it has become clinically desirable to augment mechanical fixation with biologic strategies in order to accelerate osteogenesis and promote successful arthrodesis. The discovery of bone morphogenic protein (BMP has been pivotal in understanding the biology of fracture healing and has been a source of intense clinical research as an adjunct to fracture treatment. Multiple in vitro and in vivo studies in animals have elucidated the complex biologic interactions between BMPs and cellular receptors and have convincingly demonstrated rhBMP-2 to be a safe, effective treatment option to enhance bone healing. Multiple clinical trials in trauma surgery have provided level 1 evidence for the use of rhBMP-2 as a safe and effective treatment of fractures. Human clinical trials have provided further insight into BMP-2 dosage, time course, carriers, and efficacy in fracture healing of tibial defects. These promising results have provided hope that a new biologic field of technology has emerged as a useful adjunct in the treatment of skeletal injuries and conditions.Keywords: bone morphogenic protein-2, bone fracture, bone healing

Experimental Evaluation of the Effectiveness of Demineralized Bone Matrix and Collagenated Heterologous Bone Grafts Used Alone or in Combination with Platelet-Rich Fibrin on Bone Healing in Sinus Floor Augmentation.

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Peker, Elif; Karaca, Inci Rana; Yildirim, Benay

2016-01-01

The aim of this study was an experimental evaluation of the effectiveness of demineralized bone matrix (DBM) and collagenated heterologous bone graft (CHBG) used alone or in combination with platelet-rich fibrin on bone healing in sinus floor augmentation procedures. In this study, 36 New Zealand rabbits were used. The bilateral sinus elevation was performed, and 72 defects were obtained. The rabbit maxillary sinuses were divided into four groups according to the augmentation biomaterials obtained: demineralized bone matrix (Grafton DBM Putty, Osteotech; DBM group), DBM combined with platelet-rich fibrin (PRF; DBM + PRF group), collagenated heterologous bone graft (CHBG; Apatos Mix, OsteoBiol, Tecnoss; CHBG group), CHBG combined with PRF (CHBG + PRF group). All groups were sacrificed at 2, 4, and 8 weeks after surgery for histologic, histomorphometric, and immunohistochemical analyses. The inflammatory reaction was moderate to intense at the second week in all groups and declined from 2 to 8 weeks. New bone formation was started at the second week and increased from 2 to 8 weeks in all groups. There was no significant difference in bone formation between the experimental groups that used PRF mixed graft material and control groups that used only graft material. The percentage of new bone formation showed a significant difference in DBM groups and DBM + PRF groups compared with other groups. There were osteoclasts around all the bone graft materials used, but the percentage of residual graft particles was significantly higher in CHBG groups and CHBG + PRF groups at the eighth week. There is no beneficial effect of the application of PRF in combination with demineralized bone matrix or collagenated heterologous bone graft on bone formation in sinus floor augmentation. The results of this study showed that both collagenated heterologous bone graft and demineralized bone matrix have osteoconductive properties, but demineralized bone matrix showed more bone formation

Effects of platelet-rich fibrin on healing of intra-bony defects treated with anorganic bovine bone mineral.

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Sezgin, Yasemin; Uraz, Ahu; Taner, I Levent; Çulhaoğlu, Rana

2017-01-26

Anorganic bovine bone mineral (ABBM) is extensively used in the treatment of intra-bony defects. Platelet-rich fibrin (PRF) is a new-generation platelet concentrate with a simplified technique. Although certain studies have reported the use of PRF in the treatment of intra-bony defects, to date, none of them have evaluated its additive effects with ABBM. Therefore, a randomised, split-mouth clinical trial was conducted to compare healing of intra-bony defects treated with an ABBM-PRF combination with healing of those treated with ABBM alone. By using a split-mouth design, 15 paired intra-bony defects were randomly treated with either ABBM alone (control group) or ABBM-PRF combination (test group). Following clinical parameters and radiographical measurements were recorded at baseline and 6 months after treatment: plaque index (PI), gingival index (GI), probing depth (PD), gingival recession (GR), clinical attachment level (CAL), vertical bone loss, depth of defect and defect angle. Preoperative clinical and radiographical measurements were similar for the test and control groups. Statistically significant reductions in GI, PD, CAL, vertical bone loss, depth of intra-bony defect and widening of defect angle were detected after treatment in both groups. With respect to inter-group analysis, gain in CAL was significantly greater in the test group than in the control group, whereas no inter-group differences were observed in any other parameter. The results of this study indicate that both therapies are effective in the treatment of intra-bony defects.

A 5- Year Comparison of Marginal Bone Level Following Immediate Loading of Single-Tooth Implants Placed in Healed Alveolar Ridges and Extraction Sockets in the Maxilla.

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Antoine Nicolas Berberi

2014-01-01

Full Text Available AbstractPurpose: The aim of present investigation was to evaluate marginal bone level after 5-year follow-up of implants placed in healed ridges and fresh extraction sockets in maxilla with immediate loading protocol.Materials and Methods: Thirty-six patients in need of a single tooth replacement in the anterior maxilla received 42 Astra Tech implants (Astra Tech Implant system™, Dentsply Implants, Mölndal, Sweden. Implants were placed in healed ridges (group I or immediately into extraction sockets (group II. Implants were restored and placed into functional loading immediately by using a prefabricated abutment. Marginal bone level relative to the implant reference point was recorded at implant placement, crown cementation, 12, 36 and 60 months following loading using intra-oral radiographs. Measurements were made on the mesial and distal sides of each implantResults: Overall, two implants were lost from the group II, before final crown cementation: they were excluded from the study and all remaining implants osseointegrated successfully after 5 years of functional loading. The mean change in marginal bone loss after implant placement was 0.267±0.161 for one year, and 0.265±0.171 for three years and 0.213±0.185 for five years in extraction sockets and was 0.266±0.176 for one year and 0.219±0.175 for three years and 0.194±0.172 for five years in healed ridges group. Significant reduction of marginal bone loss was more pronounced in implants inserted in healed ridges (P

Studies on focal alveolar bone healing with technetium (Tc)-99m labeled methylene diphosphonate and gold-collimated cadmium telluride probe

International Nuclear Information System (INIS)

Tsuchimochi, M.; Hosain, F.; Engelke, W.; Zeichner, S.J.; Ruttimann, U.E.; Webber, R.L.

1991-01-01

The benefit of using a collimator for a miniaturized cadmium telluride probe was evaluated by monitoring the bone-healing processes for 13 weeks after the induction of small iatrogenic alveolar bone lesions in one side of the mandible in beagles. Technetium (Tc)-99m labeled methylene diphosphonate (200 to 300 MBq, 5.1 to 8.1 mCi, in a solution of 0.5 to 1 ml, intravenously) was used as a bone-seeking radiopharmaceutical. The radioactivity over the bone lesion (L) and the contralateral normal site (C) in the mandible were measured between 1.5 and 2 hours after injection of the tracer, and the activity ratio L/C served as an index of relative bone uptake. A study of six dogs revealed that the healing response to a hemispheric bone defect of 2 mm diameter in the cortical bone could not be detected by an uncollimated probe, and in a repeated study in two dogs the use of a gold collimator (5 mm in diameter, 5 mm in length) did not increase the L/C ratio significantly. A second study in six dogs with 5 mm lesions showed that although systematic trends in the time courses of the L/C ratio obtained both with and without the collimator could be demonstrated, the L/C ratio of collimated versus uncollimated measurements was significantly (p less than 0.005) increased. In three of the latter six dogs, abscesses developed after 9 weeks, leading to a second increase (p less than 0.05) of the L/C ratio with collimation compared with the noninflammation group; without collimation no significant (p greater than 0.15) difference between the two groups could be demonstrated

Role of Osteal Macrophages in Bone Metabolism

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Sun Wook Cho

2015-03-01

Full Text Available Macrophages have been shown to have pleiotropic functions in various pathophysiologies, especially in terms of anti-inflammatory and regenerative activity. Recently, the novel functions of bone marrow resident macrophages (called osteal macrophages were intensively studied in bone development, remodeling and tissue repair processes. This review discusses the current evidence for a role of osteal macrophages in bone modeling, remodeling, and fracture healing processes.

Determining the Role of Sost and Sostdc1 During Fracture Healing

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Yee, Cristal Sook Ngei [Univ. of California, Merced, CA (United States)

2016-01-01

The bone is a dynamic organ, often changing throughout the course of the human lifespan with its continuous remodeling, laying down new bone and resorbing old bone. With age, the bone becomes increasingly porous and mechanically unstable, leading to the development of osteoporosis in some individuals. Elderly patients with osteoporosis are at an increased risk of fracturing their bones which contributes to a higher mortality rate. Recent studies have revealed that type 1 diabetic mellitus (T1DM) patients also have an osteoporotic bone phenotype and impaired fracture healing, independent of age. Currently, there is a lack of available treatments that can improve impaired healing and directly enhance bone formation. Therefore, there is a great need for developing new therapies that can not only aid type 1 diabetic patients with osteoporosis to improve bone phenotype, but that could also aid patients with difficult or impaired fracture healing. In this thesis, I will be discussing the role of Wnt signaling and Sclerostin, a Wnt antagonist that negatively regulates bone formation, in the content of fracture repair.

The use of 18F-fluoride and 18F-FDG PET scans to assess fracture healing in a rat femur model

International Nuclear Information System (INIS)

Hsu, W.K.; Feeley, B.T.; Krenek, L.; Stout, D.B.; Chatziioannou, A.F.; Lieberman, J.R.

2007-01-01

Currently available diagnostic techniques can be unreliable in the diagnosis of delayed fracture healing in certain clinical situations, which can lead to increased complication rates and costs to the health care system. This study sought to determine the utility of positron emission tomography (PET) scanning with 18 F-fluoride ion, which localizes in regions of high osteoblastic activity, and 18 F-fluorodeoxyglucose (FDG), an indicator of cellular glucose metabolism, in assessing bone healing in a rat femur fracture model. Fractures were created in the femurs of immunocompetent rats. Animals in group I had a fracture produced via a manual three-point bending technique. Group II animals underwent a femoral osteotomy with placement of a 2-mm silastic spacer at the fracture site. Fracture healing was assessed with plain radiographs, 18 F-fluoride, and 18 F-FDG PET scans at 1, 2, 3, and 4-week time points after surgery. Femoral specimens were harvested for histologic analysis and manual testing of torsional and bending strength 4 weeks after surgery. All fractures in group I revealed abundant callus formation and bone healing, while none of the nonunion femurs were healed via assessment with manual palpation, radiographic, and histologic evaluation at the 4-week time point. 18 F-fluoride PET images of group I femurs at successive 1-week intervals revealed progressively increased signal uptake at the union site during fracture repair. In contrast, minimal tracer uptake was seen at the fracture sites in group II at all time points after surgery. Data analysis revealed statistically significant differences in mean signal intensity between groups I and II at each weekly interval. No significant differences between the two groups were seen using 18 F-FDG PET imaging at any time point. This study suggests that 18 F-fluoride PET imaging, which is an indicator of osteoblastic activity in vivo, can identify fracture nonunions at an early time point and may have a role in the

The use of 18F-fluoride and 18F-FDG PET scans to assess fracture healing in a rat femur model

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Hsu, W. K.; Feeley, B. T.; Krenek, L.; Stout, D. B.; Chatziioannou, A. F.; Lieberman, J. R.

2011-01-01

Purpose Currently available diagnostic techniques can be unreliable in the diagnosis of delayed fracture healing in certain clinical situations, which can lead to increased complication rates and costs to the health care system. This study sought to determine the utility of positron emission tomography (PET) scanning with 18F-fluoride ion, which localizes in regions of high osteoblastic activity, and 18F-fluorodeoxyglucose (FDG), an indicator of cellular glucose metabolism, in assessing bone healing in a rat femur fracture model. Methods Fractures were created in the femurs of immuno-competent rats. Animals in group I had a fracture produced via a manual three-point bending technique. Group II animals underwent a femoral osteotomy with placement of a 2-mm silastic spacer at the fracture site. Fracture healing was assessed with plain radiographs, 18F-fluoride, and 18F-FDG PET scans at 1, 2, 3, and 4-week time points after surgery. Femoral specimens were harvested for histologic analysis and manual testing of torsional and bending strength 4 weeks after surgery. Results All fractures in group I revealed abundant callus formation and bone healing, while none of the nonunion femurs were healed via assessment with manual palpation, radiographic, and histologic evaluation at the 4-week time point. 18F-fluoride PET images of group I femurs at successive 1-week intervals revealed progressively increased signal uptake at the union site during fracture repair. In contrast, minimal tracer uptake was seen at the fracture sites in group II at all time points after surgery. Data analysis revealed statistically significant differences in mean signal intensity between groups I and II at each weekly interval. No significant differences between the two groups were seen using 18F-FDG PET imaging at any time point. Conclusion This study suggests that 18F-fluoride PET imaging, which is an indicator of osteoblastic activity in vivo, can identify fracture nonunions at an early time point

Unicameral bone cysts: comparison of percutaneous curettage, steroid, and autologous bone marrow injections.

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Canavese, Federico; Wright, James G; Cole, William G; Hopyan, Sevan

2011-01-01

The purpose of this study was to compare the outcome of percutaneous curettage with intralesional injection of methylprednisolone and bone marrow for unicameral bone cysts (UBCs). This was a retrospective review of 46 children and adolescents with UBC treated with autologous bone marrow injection, methylprednisolone acetate injection or percutaneous curettage alone. Inclusion criteria were a radiological diagnosis of UBC and at least 24 months follow-up from the last procedure. Healing was determined using Neer/Cole 4-grades rating scale. The 3 treatment groups were comparable with regard to age, sex, location of the cyst, and the number of procedures undertaken. At 2 years follow-up, the proportion of patients with satisfactory healing (Neer/Cole grades I and II) was greatest among those who underwent percutaneous curettage (70%) compared with bone marrow injection (21%) and methylprednisolone acetate injection (41%) (P = 0.03). We found no association between healing and age (P = 0.80) nor between healing and sex (P = 0.61). These results suggest that mechanical disruption of the cyst membrane may be helpful in healing of cysts and that this technique may be preferred to simple intralesional injections. Level III.

Evaluating of bone healing around porous coated titanium implant and potential systematic bias on the traditional sampling method

DEFF Research Database (Denmark)

Babiker, Hassan; Ding, Ming; Overgaard, Søren

2013-01-01

Introduction: The mechanical properties of bone can largely be explained by bone density and the anisotropic orientation of the trabecular bone. The type of trabecular structure plays an important role in determining the mechanical properties of cancellous bone. Gap-healing and implant fixation...... (Biomet Inc.) of 10 mm in length and 6 mm in diameter were inserted bilaterally into the proximal humerus of 8 skeletally mature sheep. Thus two implants with a concentric gap of 2 mm were implanted in each sheep. The gap was filled with allograft. Standardised surgical procedure was used. At sacrifice, 6...... weeks after surgery, both proximal humeri were harvested. The specimens were randomized to superficial or profound groups. In the superficial group, mechanical testing or histological analysis was carried out on the superficial part of the implant. In the profound group, the mechanical testing...

Treatment of active unicameral bone cysts with percutaneous injection of demineralized bone matrix and autogenous bone marrow.

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Rougraff, Bruce T; Kling, Thomas J

2002-06-01

The treatment of unicameral bone cysts varies from open bone-grafting procedures to percutaneous injection of corticosteroids or bone marrow. The purpose of this study was to evaluate the feasibility and effectiveness of percutaneous injection of a mixture of demineralized bone matrix and autogenous bone marrow for the treatment of simple bone cysts. Twenty-three patients with an active unicameral bone cyst were treated with trephination and injection of allogeneic demineralized bone matrix and autogenous bone marrow. The patients were followed for an average of fifty months (range, thirty to eighty-one months), at which time pain, function, and radiographic signs of resolution of the cyst were assessed. The average time until the patients had pain relief was five weeks, and the average time until the patients returned to full, unrestricted activities was six weeks. Bone-healing at the site of the injection was first seen radiographically at three to six months. No patient had a pathologic fracture during this early bone-healing stage. Cortical remodeling was seen radiographically by six to nine months, and after one year the response was usually complete, changing very little from then on. Five patients required a second injection because of recurrence of the cyst, and all five had a clinically and radiographically quiescent cyst after an average of thirty-six additional months of follow-up. Seven of the twenty-three patients had incomplete healing manifested by small, persistent radiolucent areas within the original cyst. None of these cysts increased in size or resulted in pain or fracture. Percutaneous injection of allogeneic demineralized bone matrix and autogenous bone marrow is an effective treatment for unicameral bone cysts.

Analysis of new bone, cartilage, and fibrosis tissue in healing murine allografts using whole slide imaging and a new automated histomorphometric algorithm

OpenAIRE

Zhang, Longze; Chang, Martin; Beck, Christopher A; Schwarz, Edward M; Boyce, Brendan F

2016-01-01

Histomorphometric analysis of histologic sections of normal and diseased bone samples, such as healing allografts and fractures, is widely used in bone research. However, the utility of traditional semi-automated methods is limited because they are labor-intensive and can have high interobserver variability depending upon the parameters being assessed, and primary data cannot be re-analyzed automatically. Automated histomorphometry has long been recognized as a solution for these issues, and ...

An Experimental Animal Model for Abdominal Fascia Healing after Surgery

DEFF Research Database (Denmark)

Burcharth, J; Pommergaard, H-C; Klein, M

2013-01-01

be used to evaluate the actively healing fascia. Such an animal model may promote future research in the prevention of IH. Methods: 86 male Sprague-Dawley rats were used to establish a model involving six experiments (experiments A-F). Mechanical testing of the breaking strength of the healed fascia......Background: Incisional hernia (IH) is a well-known complication after abdominal surgical procedures. The exact etiology of IH is still unknown even though many risk factors have been suggested. The aim of this study was to create an animal model of a weakly healed abdominal fascia that could...... was performed by testing tissue strips from the healed fascia versus the unincised control fascia 7 and 28 days postoperatively. Results: During the six experiments a healing model was created that produced significantly weaker coherent fascia when compared with the control tissue measured in terms...

MCP/CCR2 signaling is essential for recruitment of mesenchymal progenitor cells during the early phase of fracture healing.

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Masahiro Ishikawa

Full Text Available OBJECTIVE: The purpose of this study was to investigate chemokine profiles and their functional roles in the early phase of fracture healing in mouse models. METHODS: The expression profiles of chemokines were examined during fracture healing in wild-type (WT mice using a polymerase chain reaction array and histological staining. The functional effect of monocyte chemotactic protein-1 (MCP-1 on primary mouse bone marrow stromal cells (mBMSCs was evaluated using an in vitro migration assay. MCP-1-/- and C-C chemokine receptor 2 (CCR2-/- mice were fractured and evaluated by histological staining and micro-computed tomography (micro-CT. RS102895, an antagonist of CCR2, was continuously administered in WT mice before or after rib fracture and evaluated by histological staining and micro-CT. Bone graft exchange models were created in WT and MCP-1-/- mice and were evaluated by histological staining and micro-CT. RESULTS: MCP-1 and MCP-3 expression in the early phase of fracture healing were up-regulated, and high levels of MCP-1 and MCP-3 protein expression observed in the periosteum and endosteum in the same period. MCP-1, but not MCP-3, increased migration of mBMSCs in a dose-dependent manner. Fracture healing in MCP-1-/- and CCR2-/- mice was delayed compared with WT mice on day 21. Administration of RS102895 in the early, but not in the late phase, caused delayed fracture healing. Transplantation of WT-derived graft into host MCP-1-/- mice significantly increased new bone formation in the bone graft exchange models. Furthermore, marked induction of MCP-1 expression in the periosteum and endosteum was observed around the WT-derived graft in the host MCP-1-/- mouse. Conversely, transplantation of MCP-1-/- mouse-derived grafts into host WT mice markedly decreased new bone formation. CONCLUSIONS: MCP-1/CCR2 signaling in the periosteum and endosteum is essential for the recruitment of mesenchymal progenitor cells in the early phase of fracture healing.

Characteristics of bone turnover in the long bone metaphysis fractured patients with normal or low Bone Mineral Density (BMD.

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Christoph Wölfl

Full Text Available The incidence of osteoporotic fractures increases as our population ages. Until now, the exact biochemical processes that occur during the healing of metaphyseal fractures remain unclear. Diagnostic instruments that allow a dynamic insight into the fracture healing process are as yet unavailable. In the present matched pair analysis, we study the time course of the osteoanabolic markers bone specific alkaline phosphatase (BAP and transforming growth factor β1 (TGFβ1, as well as the osteocatabolic markers crosslinked C-telopeptide of type-I-collagen (β-CTX and serum band 5 tartrate-resistant acid phosphatase (TRAP5b, during the healing of fractures that have a low level of bone mineral density (BMD compared with fractures that have a normal BMD. Between March 2007 and February 2009, 30 patients aged older than 50 years who suffered a metaphyseal fracture were included in our study. BMDs were verified by dual energy Xray absorptiometry (DXEA scans. The levels of BTMs were examined over an 8-week period. Osteoanabolic BAP levels in those with low levels of BMD were significantly different from the BAP levels in those with normal BMD. BAP levels in the former group increased constantly, whereas the latter group showed an initial strong decrease in BAP followed by slowly rising values. Osteocatabolic β-CTX increased in the bone of the normal BMD group constantly, whereas these levels decreased significantly in the bone of the group with low BMD from the first week. TRAP5b was significantly reduced in the low level BMD group. With this work, we conduct first insights into the molecular biology of the fracture healing process in patients with low levels of BMD that explains the mechanism of its fracture healing. The results may be one reason for the reduced healing qualities in bones with low BMD.

External fixation of tibial pilon fractures and fracture healing.

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Ristiniemi, Jukka

2007-06-01

Distal tibial fractures are rare and difficult to treat because the bones are subcutaneous. External fixation is commonly used, but the method often results in delayed union. The aim of the present study was to find out the factors that affect fracture union in tibial pilon fractures. For this purpose, prospective data collection of tibial pilon fractures was carried out in 1998-2004, resulting in 159 fractures, of which 83 were treated with external fixation. Additionally, 23 open tibial fractures with significant > 3 cm bone defect that were treated with a staged method in 2000-2004 were retrospectively evaluated. The specific questions to be answered were: What are the risk factors for delayed union associated with two-ring hybrid external fixation? Does human recombinant BMP-7 accelerate healing? What is the role of temporary ankle-spanning external fixation? What is the healing potential of distal tibial bone loss treated with a staged method using antibiotic beads and subsequent autogenous cancellous grafting compared to other locations of the tibia? The following risk factors for delayed healing after external fixation were identified: post-reduction fracture gap of >3 mm and fixation of the associated fibula fracture. Fracture displacement could be better controlled with initial temporary external fixation than with early definitive fixation, but it had no significant effect on healing time, functional outcome or complication rate. Osteoinduction with rhBMP-7 was found to accelerate fracture healing and to shorten the sick leave. A staged method using antibiotic beads and subsequent autogenous cancellous grafting proved to be effective in the treatment of tibial bone loss. Healing potential of the bone loss in distal tibia was at least equally good as in other locations of the tibia.

Healing of experimentally created defects: a review

DEFF Research Database (Denmark)

Aaboe, M; Pinholt, E M; Hjørting-Hansen, E

1995-01-01

Within cranio-maxillofacial surgery and orthopedic surgery a bone graft or a bone substitute is required to recontour or assist bony healing in repair of osseous congenital deformities, or in repair of deformity due to trauma or to surgical excision after elimination of osseous disease processes ...... proteins have with success been added as adjuncts to already known biomaterials. In the future, inductive materials together with a suitable carrier and a biodegradable membrane may be the choice of bone substitute used within cranio-maxillofacial and orthopaedic surgery.......Within cranio-maxillofacial surgery and orthopedic surgery a bone graft or a bone substitute is required to recontour or assist bony healing in repair of osseous congenital deformities, or in repair of deformity due to trauma or to surgical excision after elimination of osseous disease processes...... exceeding a certain size. An autogenous bone graft is the optimal material of choice, however its use is problematic due to donor site morbidity, sparse amounts and uncontrolled resorption. Immunological responses and risk of viral contamination of allogenous and xenogenous bone materials make the use...

Regenerative potential and healing dynamics of the periodontium: a critical-size supra-alveolar periodontal defect study.

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Polimeni, Giuseppe; Susin, Cristiano; Wikesjö, Ulf M E

2009-03-01

The nature and characteristics of the newly formed periodontium obtained following regenerative procedures remain a matter of controversy. The objective of this study was to evaluate the regenerative potential of the periodontal attachment and healing dynamics as observed from the spatial distribution of newly formed cementum, periodontal ligament (PDL) and alveolar bone following optimal circumstances for wound healing/regeneration in a discriminating animal model. Critical-size, 6-mm, supra-alveolar, periodontal defects were surgically created in six young adult Beagle dogs. Space-providing ePTFE devices with 300-microm laser-drilled pores were implanted to support wound stability and space provision in one jaw quadrant/animal. Treatments were alternated between left and right jaw quadrants in subsequent animals. The gingival flaps were advanced to submerge the defect sites for primary intention healing. Histometric analysis followed an 8-week healing interval. Healing was uneventful in all animals. The histometric analysis showed that cementum regeneration (2.99 +/- 0.22 mm) was significantly greater than PDL (2.54 +/- 0.18 mm, p=0.03) and bone regeneration (2.46 +/- 0.26 mm, p=0.03). The wound area showed significant positive non-linear effect on cementum (log beta=1.25, palveolar bone virtually regenerate in parallel under optimal circumstances for periodontal wound healing/regeneration. Moreover, space provision positively influences the extent of periodontal regeneration.

Low-energy extracorporeal shockwave therapy (ESWT improves metaphyseal fracture healing in an osteoporotic rat model.

Directory of Open Access Journals (Sweden)

Gina A Mackert

Full Text Available As result of the current demographic changes, osteoporosis and osteoporotic fractures are becoming an increasing social and economic burden. In this experimental study, extracorporeal shock wave therapy (ESWT, was evaluated as a treatment option for the improvement of osteoporotic fracture healing.A well-established fracture model in the metaphyseal tibia in the osteoporotic rat was used. 132 animals were divided into 11 groups, with 12 animals each, consisting of one sham-operated group and 10 ovariectomized (osteoporotic groups, of which 9 received ESWT treatment. Different energy flux intensities (0.15 mJ/mm2, 0.35 mJ/mm2, or 0.55 mJ/mm2 as well as different numbers of ESWT applications (once, three times, or five times throughout the 35-day healing period were applied to the osteoporotic fractures. Fracture healing was investigated quantitatively and qualitatively using micro-CT imaging, quantitative real-time polymerase chain reaction (qRT-PCR analysis, histomorphometric analysis and biomechanical analysis.The results of this study show a qualitative and quantitative improvement in the osteoporotic fracture healing under low-energy (energy flux intensity: 0,15 mJ/mm2 ESWT and with fewer treatment applications per healing period.In conclusion, low-energy ESWT seems to exhibit a beneficial effect on the healing of osteoporotic fractures, leading to improved biomechanical properties, enhanced callus-quantity and -quality, and an increase in the expression of bone specific transcription factors. The results suggest that low-energy ESWT, as main treatment or as adjunctive treatment in addition to a surgical intervention, may prove to be an effective, simple to use, and cost-efficient option for the qualitative and quantitative improvement of osteoporotic fracture healing.

Investigation of Peri-Implant Bone Healing Using Autologous Plasma Rich in Growth Factors in the Canine Mandible After 12 Weeks: A Pilot Study

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Birang, Reza; Tavakoli, Mohammad; Shahabouei, Mohammad; Torabi, Alireza; Dargahi, Ali; Soolari, Ahmad

2011-01-01

Introduction: Faster reconstruction of patients’ masticatory systems is the aim of modern dentistry. A number of studies have indicated that application of growth factors to the surface of a dental implant leads to accelerated and enhanced osseointegration. The objective of the present study was to investigate the effect of plasma rich in growth factors on peri-implant bone healing. Materials and Methods: For the purpose of this study, two healthy, mixed-breed canines were selected, and the premolars were extracted from both sides of the mandible. Three months after premolar removal, 12 implants, each 5 mm in diameter and 10 mm in length, were placed in osteotomy sites on both sides of the mandible. Prior to placement, plasma rich in growth factors was applied to the surfaces of six implants, while the other six were used without plasma rich in growth factors. The implants were removed after 12 weeks along with the bone surrounding the sites using a trephine bur. One mesiodistal section containing the surrounding bone from each implant block, 50 µm in diameter, was prepared for histologic and histomorphometric investigation with an optical microscope. Results: The sites with implants treated with plasma rich in growth factors showed more bone-to-implant contact compared to control sites. Also, higher values for bone trabecular thickness and bone maturity were recorded for the PRGF-treated sites than for the control sites. Conclusion: Application of plasma rich in growth factors to the surface of an implant may enhance the bone healing process as well as bone-to-implant contact, thereby helping to achieve faster osseointegration. PMID:22145011

Low-intensity pulsed ultrasound increases bone volume, osteoid thickness and mineral apposition rate in the area of fracture healing in patients with a delayed union of the osteotomized fibula

NARCIS (Netherlands)

Rutten, S.; Nolte, P.A.; Korstjens, C.M.; van Duin, M.A.; Klein-Nulend, J.

2008-01-01

Introduction Low-intensity pulsed ultrasound (LIPUS) accelerates impaired fracture healing, but the exact mechanism is unknown. The aim of this study was to investigate how LIPUS affects bone healing at the tissue level in patients with a delayed union of the osteotomized fibula, by using histology

Exogenous PTHrP Repairs the Damaged Fracture Healing of PTHrP+/− Mice and Accelerates Fracture Healing of Wild Mice

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Wang, Yinhe; Fang, Xin; Wang, Chun; Ding, Congzhu; Lin, Hua; Liu, Anlong; Wang, Lei; Cao, Yang

2017-01-01

Bone fracture healing is a complicated physiological regenerative process initiated in response to injury and is similar to bone development. To demonstrate whether an exogenous supply of parathyroid hormone–related protein (PTHrP) helps in bone fracture healing, closed mid-diaphyseal femur fractures were created and stabilized with intramedullary pins in eight-week-old wild-type (WT) PTHrP+/+ and PTHrP+/− mice. After administering PTHrP for two weeks, callus tissue properties were analyzed at one, two, and four weeks post-fracture (PF) by various methods. Bone formation–related genes and protein expression levels were evaluated by real-time reverse transcriptase–polymerase chain reaction and Western blots. At two weeks PF, mineral density of callus, bony callus areas, mRNA levels of alkaline phosphatase (ALP), type I collagen, Runt-related transcription factor 2 (Runx-2), and protein levels of Runx-2 and insulin-like growth factor-1 decreased in PTHrP+/− mice compared with WT mice. At four weeks PF, total collagen-positive bony callus areas, osteoblast number, ALP-positive areas, and type I collagen-positive areas all decreased in PTHrP+/− mice. At both two and four weeks PF, tartrate-resistant acid phosphatase–positive osteoclast number and surface decreased a little in PTHrP+/− mice. The study indicates that exogenous PTHrP provided by subcutaneous injection could redress impaired bone fracture healing, leading to mutation of activated PTHrP by influencing callus areas, endochondral bone formation, osteoblastic bone formation, and bone turnover. PMID:28178186

Exogenous PTHrP Repairs the Damaged Fracture Healing of PTHrP+/− Mice and Accelerates Fracture Healing of Wild Mice

Directory of Open Access Journals (Sweden)

Yinhe Wang

2017-02-01

Full Text Available Bone fracture healing is a complicated physiological regenerative process initiated in response to injury and is similar to bone development. To demonstrate whether an exogenous supply of parathyroid hormone–related protein (PTHrP helps in bone fracture healing, closed mid-diaphyseal femur fractures were created and stabilized with intramedullary pins in eight-week-old wild-type (WT PTHrP+/+ and PTHrP+/− mice. After administering PTHrP for two weeks, callus tissue properties were analyzed at one, two, and four weeks post-fracture (PF by various methods. Bone formation–related genes and protein expression levels were evaluated by real-time reverse transcriptase–polymerase chain reaction and Western blots. At two weeks PF, mineral density of callus, bony callus areas, mRNA levels of alkaline phosphatase (ALP, type I collagen, Runt-related transcription factor 2 (Runx-2, and protein levels of Runx-2 and insulin-like growth factor-1 decreased in PTHrP+/− mice compared with WT mice. At four weeks PF, total collagen-positive bony callus areas, osteoblast number, ALP-positive areas, and type I collagen-positive areas all decreased in PTHrP+/− mice. At both two and four weeks PF, tartrate-resistant acid phosphatase–positive osteoclast number and surface decreased a little in PTHrP+/− mice. The study indicates that exogenous PTHrP provided by subcutaneous injection could redress impaired bone fracture healing, leading to mutation of activated PTHrP by influencing callus areas, endochondral bone formation, osteoblastic bone formation, and bone turnover.

The effect of a composite of polyorthoester and demineralized bone on the healing of large segmental defects of the radius in rats

DEFF Research Database (Denmark)

Solheim, E; Pinholt, E M; Andersen, R

1992-01-01

The effect of a composite of demineralized bone mixed with polyorthoester on the healing of large segmental defects in the rat radius was studied. Sixty male Wistar rats were divided into four groups, A through D, and an osteoperiosteal diaphyseal defect of 50 per cent of the length of the bone....... The formation of bone in the defects was quantified with computer-assisted measurements of the area on radiographs. The host-tissue response was evaluated with light microscopy. Defects that had been filled with the composite of polyorthoester and demineralized bone or with demineralized bone alone showed...... regeneration of bone corresponding to 93.6 and 77.6 per cent of the area of the defect, respectively. Defects that had no implant or that had been filled with polyorthoester alone showed significantly less formation of bone. No inflammation was seen with light microscopy, and only traces of the polyorthoester...

The efficacy of hydrothermally obtained carbonated hydroxyapatite in healing alveolar bone defects in rats with or without corticosteroid treatment.

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Marković, Dejan; Jokanović, Vukoman; Petrović, Bojan; Perić, Tamara; Vukomanović, Biserka

2014-05-01

Autogenous bone grafting has been the gold standard in clinical cases when bone grafts are required for bone defects in dentistry. The study was undertaken to evaluate multilevel designed carbonated hydroxyapatite (CHA) obtained by hydrothermal method, as a bone substitute in healing bone defects with or without corticosteroid treatment in rats as assessed by histopathologic methods. Bone defects were created in the alveolar bone by teeth extraction in 12 rats. The animals were initially divided into two groups. The experimental group was pretreated with corticosteroids: methylprednisolone and dexamethasone, intramuscularly, while the control group was without therapy. Posterior teeth extraction had been performed after the corticosteroid therapy. The extraction defects were fulfilled with hydroxyapatite with bimodal particle sizes in the range of 50-250 μm and the sample from postextocactional defect of the alveolar bone was analyzed pathohystologically. The histopatological investigations confirmed the biologic properties of the applied material. The evident growth of new bone in the alveolar ridge was clearly noticed in both groups of rats. Carbonated HA obtained by hydrothermal method promoted bone formation in the preformed defects, confirming its efficacy for usage in bone defects. Complete resorption of the material's particles took place after 25 weeks. Hydroxyapatite completely meets the clinical requirements for a bone substitute material. Due to its microstructure, complete resorption took place during the observation period of the study. Corticosteroid treatment did not significantly affect new bone formation in the region of postextractional defects.

Effects of particle size and porosity on in vivo remodeling of settable allograft bone/polymer composites.

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Prieto, Edna M; Talley, Anne D; Gould, Nicholas R; Zienkiewicz, Katarzyna J; Drapeau, Susan J; Kalpakci, Kerem N; Guelcher, Scott A

2015-11-01

Established clinical approaches to treat bone voids include the implantation of autograft or allograft bone, ceramics, and other bone void fillers (BVFs). Composites prepared from lysine-derived polyurethanes and allograft bone can be injected as a reactive liquid and set to yield BVFs with mechanical strength comparable to trabecular bone. In this study, we investigated the effects of porosity, allograft particle size, and matrix mineralization on remodeling of injectable and settable allograft/polymer composites in a rabbit femoral condyle plug defect model. Both low viscosity and high viscosity grafts incorporating small (<105 μm) particles only partially healed at 12 weeks, and the addition of 10% demineralized bone matrix did not enhance healing. In contrast, composite grafts with large (105-500 μm) allograft particles healed at 12 weeks postimplantation, as evidenced by radial μCT and histomorphometric analysis. This study highlights particle size and surface connectivity as influential parameters regulating the remodeling of composite bone scaffolds. © 2015 Wiley Periodicals, Inc.

The influence of the anabolic agent flavichromin on osteotomy healing

International Nuclear Information System (INIS)

Schargus, G.

1982-01-01

In this work it was attempted to attain a quicker consolidation of bone fragments in rabbits after they had undergone a lower jaw osteotomy and fragment fixation and had been treated with the usual osteosynthetic medications as well as doses of the anabolic agent flavichromin to stimulate bone healing. The healing progress of the first four post-operative weeks was clinically, radiologically, and also histologically assessed and it was also attempted to test the value of densitometrically studying the X-ray pictures as a quantitative measurement of the re-mineralisation of the fracture line. Although animal-specific studies do not allow themselves to be directly applied to humans, because the osteogenesis rates differ too greatly from humans and though further studies on dogs should be undertaken, in order to make a more conclusive statement, flavichromin because of its easy applicability should be considered for future use on humans, especially in cases with healing complications. In the healing of bone defects, flavichromin should be considered. (TRV) [de

Computational model-informed design and bioprinting of cell-patterned constructs for bone tissue engineering.

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Carlier, Aurélie; Skvortsov, Gözde Akdeniz; Hafezi, Forough; Ferraris, Eleonora; Patterson, Jennifer; Koç, Bahattin; Van Oosterwyck, Hans

2016-05-17

Three-dimensional (3D) bioprinting is a rapidly advancing tissue engineering technology that holds great promise for the regeneration of several tissues, including bone. However, to generate a successful 3D bone tissue engineering construct, additional complexities should be taken into account such as nutrient and oxygen delivery, which is often insufficient after implantation in large bone defects. We propose that a well-designed tissue engineering construct, that is, an implant with a specific spatial pattern of cells in a matrix, will improve the healing outcome. By using a computational model of bone regeneration we show that particular cell patterns in tissue engineering constructs are able to enhance bone regeneration compared to uniform ones. We successfully bioprinted one of the most promising cell-gradient patterns by using cell-laden hydrogels with varying cell densities and observed a high cell viability for three days following the bioprinting process. In summary, we present a novel strategy for the biofabrication of bone tissue engineering constructs by designing cell-gradient patterns based on a computational model of bone regeneration, and successfully bioprinting the chosen design. This integrated approach may increase the success rate of implanted tissue engineering constructs for critical size bone defects and also can find a wider application in the biofabrication of other types of tissue engineering constructs.

The effects of LIPUS on soft-tissue healing: a review of literature.

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Khanna, Anil; Nelmes, Richard T C; Gougoulias, Nikolaos; Maffulli, Nicola; Gray, Jim

2009-01-01

Ultrasound is widely used for imaging purposes and as an adjunct to physiotherapy. Low-intensity pulsed ultrasound (LIPUS), having removed the thermal component found at higher intensities, is used to improve bone healing. However, its potential role in soft-tissue healing is still under investigation. We searched on Medline using the keywords: low-intensity pulsed ultrasound, LIPUS and LIPUS and soft-tissue healing. Thirty-two suitable articles were identified. Research, mainly pre-clinical, so far has shown encouraging result, with LIPUS able to promote healing in various soft tissues such as cartilage, inter-vertebral disc, etc. The effect on the bone-tendon junction, however, is primarily on bone. The role of LIPUS in treating tendinopathies is questionable. Adequately powered human studies with standardisation of intensities and dosages of LIPUS for each target tissue are needed.

Kinetics of gene expression of alkaline phosphatase during healing of alveolar bone in rats.

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Rodrigues, Willian Caetano; Fabris, André Luís da Silva; Hassumi, Jaqueline Suemi; Gonçalves, Alaíde; Sonoda, Celso Koogi; Okamoto, Roberta

2016-06-01

Immunohistochemical studies and molecular biology have enabled us to identify numerous proteins that are involved in the metabolism of bone, and their encoding genes. Among these is alkaline phosphatase (ALP), an enzyme that is responsible for the initiation of mineralisation of the extracellular matrix during alveolar bone repair. To evaluate the gene expression of ALP during this process, we studied nine healthy adult male rats, which had their maxillary central incisors extracted from the right side and were randomly divided into three groups. During three experimental periods, 7 days, 14 days, and 28 days, the alveoli were curetted, the rats killed, and samples analysed by real-time reverse transcription polymerase chain reaction (qRT-PCR). The RNAm that encodes the gene for the synthesis of ALP was expressed during the three periods analysed, but its concentration was significantly increased at 14 and 28 days compared with at 7 days. There was no significant difference between 14 and 28 days (p=0.0005). We conclude that genes related to ALP are expressed throughout the healing process and more intensively during the later periods (14 and 28 days), which coincides with the increased formation of mineralised bone. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

In vivo micro-CT analysis of bone remodeling in a rat calvarial defect model

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Umoh, Joseph U.; Sampaio, Arthur V.; Welch, Ian; Pitelka, Vasek; Goldberg, Harvey A.; Underhill, T. Michael; Holdsworth, David W.

2009-04-01

The rodent calvarial defect model is commonly used to investigate bone regeneration and wound healing. This study presents a micro-computed tomography (micro-CT) methodology for measuring the bone mineral content (BMC) in a rat calvarial defect and validates it by estimating its precision error. Two defect models were implemented. A single 6 mm diameter defect was created in 20 rats, which were imaged in vivo for longitudinal experiments. Three 5 mm diameter defects were created in three additional rats, which were repeatedly imaged ex vivo to determine precision. Four control rats and four rats treated with bone morphogenetic protein were imaged at 3, 6, 9 and 12 weeks post-surgery. Scan parameters were 80 kVp, 0.45 mA and 180 mAs. Images were reconstructed with an isotropic resolution of 45 µm. At 6 weeks, the BMC in control animals (4.37 ± 0.66 mg) was significantly lower (p small BMC changes in animals.

Evaluation of the Surface Treatment on Bone Healing in a Transmucosal 1-mm Area of Implant Abutment: An Experimental Study in the Rabbit Tibia.

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Gehrke, Sergio Alexandre; da Silva Neto, Ulisses Tavares

2016-06-01

The objective of the present study was to investigate the effect on bone tissue healing patterns in 1-mm area treated in the transmucosal surface of the abutment in the tibia of rabbits. Forty-six abutments were divided into two groups: control group (CG) with 14 abutments with smooth surface and experimental group (EG) with 32 abutments presenting a 1-mm area of the transmucosal surface treated through sandblasting with microparticles of titanium oxide followed by acid etching. Five samples of each group were analyzed using an optical laser profilometer for surface roughness characterization. Thirty-six Morse taper implants (3.5 mm in diameter and 7 mm in length) were inserted 1.5 mm subcrestal into the tibiae of nine rabbits. The implants were removed after 8, 10, and 12 weeks for histological analysis. The histological slides were prepared and analyzed qualitatively in relation to the new bone at the interface bone-abutment and quantitatively, in relation to bone height from the base of the implant. These data were computed and statistically compared inside the groups using analysis of variance and the U-test between groups for same time. Both groups exhibited bone growth in the direction and over the surface of the abutments, with good healing. However, the EG group showed an increased height of bone formation in the crestal direction, and highly significant differences were observed (p abutment with treatment of the surface facilitated the maintenance of bone height around the abutment compared with the same abutment with the totally smooth surface. © 2015 Wiley Periodicals, Inc.

Bone grafts in dentistry

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Prasanna Kumar

2013-01-01

Full Text Available Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation.

The development and morphogenesis of the tendon-to-bone insertion What development can teach us about healing

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Thomopoulos, Stavros; Genin, Guy M.; Galatz, Leesa M.

2013-01-01

The attachment of dissimilar materials is a major challenge because of the high levels of stress that develop at such interfaces. An effective solution to this problem develops at the attachment of tendon (a compliant “soft tissue”) to bone (a stiff “hard tissue”). This tissue, the “enthesis”, transitions from tendon to bone through gradations in structure, composition, and mechanical properties. These gradations are not regenerated during tendon-to-bone healing, leading to a high incidence of failure after surgical repair. Understanding the development of the enthesis may allow scientists to develop treatments that regenerate the natural tendon-to-bone insertion. Recent work has demonstrated that both biologic and mechanical factors drive the development and morphogenesis of the enthesis. A cascade of biologic signals similar to those seen in the growth plate promotes mineralization of cartilage on the bony end of the enthesis and the formation of fibrocartilage on the tendon end of the enthesis. Mechanical loading is also necessary for the development of the enthesis. Removal of muscle load impairs the formation of bone, fibrocartilage, and tendon at the developing enthesis. This paper reviews recent work on the development of the enthesis, with an emphasis on the roles of biologic and mechanical factors. PMID:20190378

Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits

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Živadinović Milka

2016-01-01

Full Text Available Background/Aim. The mechanism of impaired bone healing in diabetes mellitus includes different tissue and cellular level activities due to micro- and macrovascular changes. As a chronic metabolic disease with vascular complications, diabetes affects a process of bone regeneration as well. The therapeutic approach in bone regeneration is based on the use of osteoinductive autogenous grafts as well as osteoconductive synthetic material, like a β-tricalcium phosphate. The aim of the study was to determine the quality and quantity of new bone formation after the use of autogenous bone and β-tricalcium phosphate in the model of calvarial critical-sized defect in rabbits with induced diabetes mellitus type I. Methods. The study included eight 4-month-old Chincilla rabbits with alloxan-induced diabetes mellitus type I. In all animals, there were surgically created two calvarial bilateral defects (diameter 12 mm, which were grafted with autogenous bone and β-tricalcium phosphate (n = 4 or served as unfilled controls (n = 4. After 4 weeks of healing, animals were sacrificed and calvarial bone blocks were taken for histologic and histomorphometric analysis. Beside descriptive histologic evaluation, the percentage of new bone formation, connective tissue and residual graft were calculated. All parameters were statistically evaluated by Friedman Test and post hock Wilcoxon Singed Ranks Test with a significance of p < 0.05. Results. Histology revealed active new bone formation peripherally with centrally located connective tissue, newly formed woven bone and well incorporated residual grafts in all treated defects. Control samples showed no bone bridging of defects. There was a significantly more new bone in autogeonous graft (53% compared with β-tricalcium phosphate (30%, (p < 0.030 and control (7%, (p < 0.000 groups. A significant difference was also recorded between β-tricalcium phosphate and control groups (p < 0.008. Conclusion. In the present

High-Frequency, Low-Intensity Pulsed Ultrasound Enhances Alveolar Bone Healing of Extraction Sockets in Rats: A Pilot Study.

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Kang, Kyung Lhi; Kim, Eun-Cheol; Park, Joon Bong; Heo, Jung Sun; Choi, Yumi

2016-02-01

Most studies of the beneficial effects of low-intensity pulsed ultrasound (LIPUS) on bone healing have used frequencies between 1.0 and 1.5 MHz. However, after consideration of ultrasound wave characteristics and depth of target tissue, higher-frequency LIPUS may have been more effective on superficially positioned alveolar bone. We investigated this hypothesis by applying LIPUS (frequency, 3.0 MHz; intensity, 30 mW/cm(2)) on shaved right cheeks over alveolar bones of tooth extraction sockets in rats for 10 min/d for 2 wk after tooth extraction; the control group (left cheek of the same rats) did not receive LIPUS treatment. Compared with the control group, the LIPUS group manifested more new bone growth inside the sockets on histomorphometric analysis (maximal difference = 2.5-fold on the seventh day after extraction) and higher expressions of osteogenesis-related mRNAs and proteins than the control group did. These findings indicate that 3.0-MHz LIPUS could enhance alveolar bone formation and calcification in rats. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Design, Materials, and Mechanobiology of Biodegradable Scaffolds for Bone Tissue Engineering

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Velasco, Marco A.; Narváez-Tovar, Carlos A.; Garzón-Alvarado, Diego A.

2015-01-01

A review about design, manufacture, and mechanobiology of biodegradable scaffolds for bone tissue engineering is given. First, fundamental aspects about bone tissue engineering and considerations related to scaffold design are established. Second, issues related to scaffold biomaterials and manufacturing processes are discussed. Finally, mechanobiology of bone tissue and computational models developed for simulating how bone healing occurs inside a scaffold are described. PMID:25883972

Direct transplantation of native pericytes from adipose tissue: A new perspective to stimulate healing in critical size bone defects.

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König, Matthias A; Canepa, Daisy D; Cadosch, Dieter; Casanova, Elisa; Heinzelmann, Michael; Rittirsch, Daniel; Plecko, Michael; Hemmi, Sonja; Simmen, Hans-Peter; Cinelli, Paolo; Wanner, Guido A

2016-01-01

Fractures with a critical size bone defect (e.g., open fracture with segmental bone loss) are associated with high rates of delayed union and non-union. The prevention and treatment of these complications remain a serious issue in trauma and orthopaedic surgery. Autologous cancellous bone grafting is a well-established and widely used technique. However, it has drawbacks related to availability, increased morbidity and insufficient efficacy. Mesenchymal stromal cells can potentially be used to improve fracture healing. In particular, human fat tissue has been identified as a good source of multilineage adipose-derived stem cells, which can be differentiated into osteoblasts. The main issue is that mesenchymal stromal cells are a heterogeneous population of progenitors and lineage-committed cells harboring a broad range of regenerative properties. This heterogeneity is also mirrored in the differentiation potential of these cells. In the present study, we sought to test the possibility to enrich defined subpopulations of stem/progenitor cells for direct therapeutic application without requiring an in vitro expansion. We enriched a CD146+NG2+CD45- population of pericytes from freshly isolated stromal vascular fraction from mouse fat tissue and tested their osteogenic differentiation capacity in vitro and in vivo in a mouse model for critical size bone injury. Our results confirm the ability of enriched CD146+NG2+CD45- cells to efficiently generate osteoblasts in vitro, to colonize cancellous bone scaffolds and to successfully contribute to regeneration of large bone defects in vivo. This study represents proof of principle for the direct use of enriched populations of cells with stem/progenitor identity for therapeutic applications. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Callus remodelling model

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Miodowska, Justyna; Bielski, Jan; Kromka-Szydek, Magdalena

2018-01-01

The objective of this paper is to investigate the healing process of the callus using bone remodelling approach. A new mathematical model of bone remodelling is proposed including both underload and overload resorption, as well as equilibrium and bone growth states. The created model is used to predict the stress-stimulated change in the callus density. The permanent and intermittent loading programs are considered. The analyses indicate that obtaining a sufficiently high values of the callus density (and hence the elasticity) modulus is only possible using time-varying load parameters. The model predictions also show that intermittent loading program causes delayed callus healing. Understanding how mechanical conditions influence callus remodelling process may be relevant in the bone fracture treatment and initial bone loading during rehabilitation.

First Reported Cases of Biomechanically Adaptive Bone Modeling in Non-Avian Dinosaurs.

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Jorge Cubo

Full Text Available Predator confrontation or predator evasion frequently produces bone fractures in potential prey in the wild. Although there are reports of healed bone injuries and pathologies in non-avian dinosaurs, no previously published instances of biomechanically adaptive bone modeling exist. Two tibiae from an ontogenetic sample of fifty specimens of the herbivorous dinosaur Maiasaura peeblesorum (Ornithopoda: Hadrosaurinae exhibit exostoses. We show that these outgrowths are cases of biomechanically adaptive periosteal bone modeling resulting from overstrain on the tibia after a fibula fracture. Histological and biomechanical results are congruent with predictions derived from this hypothesis. Histologically, the outgrowths are constituted by radial fibrolamellar periosteal bone tissue formed at very high growth rates, as expected in a process of rapid strain equilibration response. These outgrowths show greater compactness at the periphery, where tensile and compressive biomechanical constraints are higher. Moreover, these outgrowths increase the maximum bending strength in the direction of the stresses derived from locomotion. They are located on the antero-lateral side of the tibia, as expected in a presumably bipedal one year old individual, and in the posterior position of the tibia, as expected in a presumably quadrupedal individual at least four years of age. These results reinforce myological evidence suggesting that Maiasaura underwent an ontogenetic shift from the primitive ornithischian bipedal condition when young to a derived quadrupedal posture when older.

First Reported Cases of Biomechanically Adaptive Bone Modeling in Non-Avian Dinosaurs.

Science.gov (United States)

Cubo, Jorge; Woodward, Holly; Wolff, Ewan; Horner, John R

2015-01-01

Predator confrontation or predator evasion frequently produces bone fractures in potential prey in the wild. Although there are reports of healed bone injuries and pathologies in non-avian dinosaurs, no previously published instances of biomechanically adaptive bone modeling exist. Two tibiae from an ontogenetic sample of fifty specimens of the herbivorous dinosaur Maiasaura peeblesorum (Ornithopoda: Hadrosaurinae) exhibit exostoses. We show that these outgrowths are cases of biomechanically adaptive periosteal bone modeling resulting from overstrain on the tibia after a fibula fracture. Histological and biomechanical results are congruent with predictions derived from this hypothesis. Histologically, the outgrowths are constituted by radial fibrolamellar periosteal bone tissue formed at very high growth rates, as expected in a process of rapid strain equilibration response. These outgrowths show greater compactness at the periphery, where tensile and compressive biomechanical constraints are higher. Moreover, these outgrowths increase the maximum bending strength in the direction of the stresses derived from locomotion. They are located on the antero-lateral side of the tibia, as expected in a presumably bipedal one year old individual, and in the posterior position of the tibia, as expected in a presumably quadrupedal individual at least four years of age. These results reinforce myological evidence suggesting that Maiasaura underwent an ontogenetic shift from the primitive ornithischian bipedal condition when young to a derived quadrupedal posture when older.

The role of ubiquinone supplementation on osteogenesis of nonvascularized autogenous bone graft

OpenAIRE

Taufiqurrahman, Irham; Harijadi, Achmad; Simanjuntak, Roberto M.; D, Coen Pramono; Istiati, Istiati

2015-01-01

Background: Ubiquinone is one of food supplement which is known have positive effect in wound healing. However the study to evaluate the possible role of ubiquinone in bone healing in autogenous bone grafting after mandibular resection has not been studied. An in vitro study is required to evaluate whether ubiquinone or coenzyme Q-10 (CoQ10) has a positive effect on osteogenesis. Viability test of CoQ10 and a model of osteogenic-induced and hypoxic-condition mesenchymal stem cell culture were...

Defect nonunion of a metatarsal bone fracture in a cow: successful management with bone plating and autogenous cancellous bone graft.

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Raghunath, M; Singh, N; Singh, T; Gopinathan, A; Mohindroo, J; Atri, K

2013-01-01

A two-and-half-year-old cow was presented with a defect nonunion of the right metatarsal III/IV bone following a severely comminuted open fracture two months previously. The animal underwent open fixation using a 4.5 mm, broad, 10-hole, dynamic compression plate and autogenous cancellous bone graft collected from the contralateral iliac shaft. The animal started partial weight bearing after the third postoperative day and resumed complete weight bearing after the 10th day. Fracture healing was complete and the implants were removed after the 120th postoperative day. Stable fixation by means of a bone plate in conjunction with a cancellous bone graft facilitated complete healing and restoration of the bone column of the defect and the metatarsal fracture. The animal made a complete recovery.

Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects

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Fu YC

2015-12-01

Full Text Available Yin-Chih Fu,1–4 Yan-Hsiung Wang,1,5 Chung-Hwan Chen,1,3,4 Chih-Kuang Wang,1,6 Gwo-Jaw Wang,1,3,4 Mei-Ling Ho1,3,7,8 1Orthopaedic Research Center, 2Graduate Institute of Medicine, 3Department of Orthopaedics, 4Department of Orthopaedics, College of Medicine, 5School of Dentistry, College of Dental Medicine, 6Department of Medicinal and Applied Chemistry, 7Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, TaiwanAbstract: Most allogenic bone graft substitutes have only osteoconductive properties. Developing new strategies to improve the osteoinductive activity of bone graft substitutes is both critical and practical for clinical application. Previously, we developed novel simvastatin-encapsulating poly(lactic-co-glycolic acid microspheres (SIM/PLGA that slowly release simvastatin and enhance fracture healing. In this study, we combined SIM/PLGA with a rapidly absorbable calcium sulfate (CS bone substitute and studied the effect on bone healing in critical-sized calvarial bone defects in a rat model. The cytotoxicity and cytocompatibility of this combination was tested in vitro using lactate dehydrogenase leakage and a cell attachment assay, respectively. Combination treatment with SIM/PLGA and the CS bone substitute had no cytotoxic effect on bone marrow stem cells. Compared with the control, cell adhesion was substantially enhanced following combination treatment with SIM/PLGA and the CS bone substitute. In vivo, implantation of the combination bone substitute promoted healing of critical-sized calvarial bone defects in rats; furthermore, production of bone morphogenetic protein-2 and neovascularization were enhanced in the area of the defect. In summary, the combination of SIM/PLGA and a CS bone substitute has osteoconductive and osteoinductive properties, indicating that it could be used for regeneration

The efficacy of hydrothermally obtained carbonated hydroxyapatite in healing alveolar bone defects in rats with or without corticosteroid treatment

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Marković Dejan

2014-01-01

Full Text Available Background/Aim. Autogenous bone grafting has been the gold standard in clinical cases when bone grafts are required for bone defects in dentistry. The study was undertaken to evaluate multilevel designed carbonated hydroxyapatite (CHA obtained by hydrothermal method, as a bone substitute in healing bone defects with or without corticosteroid treatment in rats as assessed by histopathologic methods. Methods. Bone defects were created in the alveolar bone by teeth extraction in 12 rats. The animals were initially divided into two groups. The experimental group was pretreated with corticosteroids: methylprednisolone and dexamethasone, intramuscularly, while the control group was without therapy. Posterior teeth extraction had been performed after the corticosteroid therapy. The extraction defects were fulfilled with hydroxyapatite with bimodal particle sizes in the range of 50-250 μm and the sample from postextocactional defect of the alveolar bone was analyzed pathohystologically. Results. The histopatological investigations confirmed the biologic properties of the applied material. The evident growth of new bone in the alveolar ridge was clearly noticed in both groups of rats. Carbonated HA obtained by hydrothermal method promoted bone formation in the preformed defects, confirming its efficacy for usage in bone defects. Complete resorption of the material’s particles took place after 25 weeks. Conclusion. Hydroxyapatite completely meets the clinical requirements for a bone substitute material. Due to its microstructure, complete resorption took place during the observation period of the study. Corticosteroid treatment did not significantly affect new bone formation in the region of postextractional defects. [Projekat Ministarstva nauke Republike Srbije, br. 172026

Chronic Degeneration Leads to Poor Healing of Repaired Massive Rotator Cuff Tears in Rats.

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Killian, Megan L; Cavinatto, Leonardo M; Ward, Samuel R; Havlioglu, Necat; Thomopoulos, Stavros; Galatz, Leesa M

2015-10-01

Chronic rotator cuff tears present a clinical challenge, often with poor outcomes after surgical repair. Degenerative changes to the muscle, tendon, and bone are thought to hinder healing after surgical repair; additionally, the ability to overcome degenerative changes after surgical repair remains unclear. The purpose of this study was to evaluate healing outcomes of muscle, tendon, and bone after tendon repair in a model of chronic rotator cuff disease and to compare these outcomes to those of acute rotator cuff injuries and repair. The hypothesis was that degenerative rotator cuff changes associated with chronic multitendon tears and muscle unloading would lead to poor structural and mechanical outcomes after repair compared with acute injuries and repair. Controlled laboratory study. Chronic rotator cuff injuries, induced via detachment of the supraspinatus (SS) and infraspinatus (IS) tendons and injection of botulinum toxin A into the SS and IS muscle bellies, were created in the shoulders of rats. After 8 weeks of injury, tendons were surgically reattached to the humeral head, and an acute, dual-tendon injury and repair was performed on the contralateral side. After 8 weeks of healing, muscles were examined histologically, and tendon-to-bone samples were examined microscopically, histologically, and biomechanically and via micro-computed tomography. All repairs were intact at the time of dissection, with no evidence of gapping or ruptures. Tendon-to-bone healing after repair in our chronic injury model led to reduced bone quality and morphological disorganization at the repair site compared with acute injuries and repair. SS and IS muscles were atrophic at 8 weeks after repair of chronic injuries, indicating incomplete recovery after repair, whereas SS and IS muscles exhibited less atrophy and degeneration in the acute injury group at 8 weeks after repair. After chronic injuries and repair, humeral heads had decreased total mineral density and an altered

A novel implantation model for evaluation of bone healing response to dental implants: the goat iliac crest.

NARCIS (Netherlands)

Schouten, C.; Meijer, G.J.; Beucken, J.J.J.P van den; Spauwen, P.H.M.; Jansen, J.A.

2010-01-01

OBJECTIVES: Despite the availability of numerous animal models for testing the biological performance of dental and orthopedic implants, the selection of a suitable model is complex. This paper presents a new model for objective and standardized evaluation of bone responses to implants using the

Healing from Childhood Sexual Abuse: A Theoretical Model

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Draucker, Claire Burke; Martsolf, Donna S.; Roller, Cynthia; Knapik, Gregory; Ross, Ratchneewan; Stidham, Andrea Warner

2011-01-01

Childhood sexual abuse is a prevalent social and health care problem. The processes by which individuals heal from childhood sexual abuse are not clearly understood. The purpose of this study was to develop a theoretical model to describe how adults heal from childhood sexual abuse. Community recruitment for an ongoing broader project on sexual…

A predictive model for pressure ulcer outcome: the Wound Healing Index.

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Horn, Susan D; Barrett, Ryan S; Fife, Caroline E; Thomson, Brett

2015-12-01

The purpose of this learning activity is to provide information regarding the creation of a risk-stratification system to predict the likelihood of the healing of body and heel pressure ulcers (PrUs). This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:1. Explain the need for a PrU risk stratification tool.2. Describe the purpose and methodology of the study.3. Delineate the results of the study and development of the Wound Healing Index. : To create a validated system to predict the healing likelihood of patients with body and heel pressure ulcers (PrUs), incorporating only patient- and wound-specific variables. The US Wound Registry data were examined retrospectively and assigned a clear outcome (healed, amputated, and so on). Significant variables were identified with bivariate analyses. Multivariable logistic regression models were created based on significant factors (P wound clinics in 24 states : A total of 7973 body PrUs and 2350 heel PrUs were eligible for analysis. Not applicable : Healed PrU MAIN RESULTS:: Because of missing data elements, the logistic regression development model included 6640 body PrUs, of which 4300 healed (64.8%), and the 10% validation sample included 709 PrUs, of which 477 healed (67.3%). For heel PrUs, the logistic regression development model included 1909 heel PrUs, of which 1240 healed (65.0%), and the 10% validation sample included 203 PrUs, of which 133 healed (65.5%). Variables significantly predicting healing were PrU size, PrU age, number of concurrent wounds of any etiology, PrU Stage III or IV, evidence of bioburden/infection, patient age, being nonambulatory, having renal transplant, paralysis, malnutrition, and/or patient hospitalization for any reason. Body and heel PrU Wound Healing Indices are comprehensive, user-friendly, and validated predictive models for

Hard tissue regeneration using bone substitutes: an update on innovations in materials.

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Sarkar, Swapan Kumar; Lee, Byong Taek

2015-05-01

Bone is a unique organ composed of mineralized hard tissue, unlike any other body part. The unique manner in which bone can constantly undergo self-remodeling has created interesting clinical approaches to the healing of damaged bone. Healing of large bone defects is achieved using implant materials that gradually integrate with the body after healing is completed. Such strategies require a multidisciplinary approach by material scientists, biological scientists, and clinicians. Development of materials for bone healing and exploration of the interactions thereof with the body are active research areas. In this review, we explore ongoing developments in the creation of materials for regenerating hard tissues.

Novel hybrid drilling protocol: evaluation for the implant healing--thermal changes, crestal bone loss, and bone-to-implant contact.

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Calvo-Guirado, José Luis; Delgado-Peña, Jorge; Maté-Sánchez, Jose E; Mareque Bueno, Javier; Delgado-Ruiz, Rafael Arcesio; Romanos, Georgios E

2015-07-01

To evaluate a new hybrid drilling protocol, by the analysis of thermal changes in vitro, and their effects in the crestal bone loss and bone-to-implant contact in vivo. Temperature changes during simulated osteotomies with a hybrid drilling technique (biologic plus simplified) (test) versus an incremental drilling technique (control) were investigated. One hundred and twenty random osteotomies were performed (60 by group) in pig ribs up to 3.75-mm-diameter drill to a depth of 10 mm. Thermal changes and time were recorded by paired thermocouples. In a parallel experiment, bilateral mandibular premolars P2, P3, P4, and first molar M1 were extracted from six dogs. After 2-month healing, implant sites were randomly prepared using either of the drilling techniques. Forty eight implants of 3.75 mm diameter and 10 mm length were inserted. The dogs were euthanized at 30 and 90 days, and crestal bone loss (CBL) and bone-to-implant contact (BIC) were evaluated. The control group showed maximum temperatures of 35.3 °C ± 1.8 °C, ΔT of 10.4 °C, and a mean time of 100 s/procedure; meanwhile, the test group showed maximum temperatures of 36.7 °C ± 1.2 °C, ΔT of 8.1 °C, and a mean time of 240 s/procedure. After 30 days, CBL values for both groups (test: 1.168 ± 0.194 mm; control: 1.181 ± 0.113 mm) and BIC values (test: 43 ± 2.8%; control: 45 ± 1.3%) were similar, without significant differences (P > 0.05). After 90 days, CBL (test: 1.173 ± 0.187 mm; control: 1.205 ± 0.122 mm) and BIC (test: 64 ± 3.3%; control: 64 ± 2.4%) values were similar, without significant differences (P > 0.05). The BIC values were increased at 90 days in both groups compared with the 30-day period (P drilling procedure in vitro. Crestal bone loss and bone-to-implant contact in the hybrid drilling protocol are comparable with the conventional drilling protocol and do not affect the osseointegration process in vivo. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Changes in the fractal dimension, feret diameter, and lacunarity of mandibular alveolar bone during initial healing of dental implants.

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Önem, Erinç; Baksı, B Güniz; Sogur, Elif

2012-01-01

To evaluate the combination of fractal dimension (FD), lacunarity, and Feret diameter (FeD) to quantitatively characterize structural changes of mandibular alveolar bone around dental implants during initial healing. Three standard-sized regions of interest (ROIs) (mesial and distal crest and apical area) around implants and three ROIs of the same size in the alveolar bone on the contralateral side were analyzed on digital panoramic images. FD was calculated using the box-counting method, and lacunarity was calculated using the FracLac plugin of Image J software. FeD was measured in the same ROIs. Comparisons of the groups were done with the Dunnett test. Forty-two implants in the posterior mandibles of 21 patients were used for FD measurements. A total of 189 ROIs was segmented into binary images. Mean FD values for mesial, distal, and apical ROIs around implants were 1.26, 1.36, and 1.4, respectively. The mean FD of alveolar bone around premolars/molars was 1.39 for all ROIs. The mean FeD for mesial, distal, and apical ROIs around implants was 7.63, 7.86, and 8.02, respectively, whereas it ranged between 7.88 and 8.13 for premolar teeth. Mean lacunarity values for mesial, distal, and apical ROIs around implants were 0.53, 0.51, and 0.48, respectively. Lacunarity values for ROIs around premolars ranged between 0.45 and 0.50. No significant differences were observed in FD, FeD, or lacunarity measurements between ROIs around implants and around teeth. The satisfactory healing of bone following implant placement may be monitored by calculating FD, lacunarity, and FeD using digital panoramic images. Although preliminary, these values may alert the practitioner to any implants with loss of stability.

Mandibular reconstruction using bone allografts

International Nuclear Information System (INIS)

Chang Joon Yim

1999-01-01

Further understanding of bone healing mechanisms, bone physiology and bone biology, transplantation immunology, and development of Tissue Banking procedures has enabled oral and maxillofacial surgeons to reconstruct even the most difficult bony defects successfully with the preserved allogeneic bone implant. Although it had been known that bone allografts were clinically effective, its application has not been widespread until the reports of Inclan (I 942), Hyatt and Butler (I 950), and Wilson (I 95 1). Tissue Banking provides the surgeon with a readily available, relatively inexpensive, and relatively safe selection of allogeneic bone for clinical use. Now autogenous bone and allogeneic bone implants present a wide variety of surgical options to surgeons, whether used separately or in combination. The surgeons are able to make judicious and fruitful choices, only with a thorough knowledge of the above-mentioned biological principles and skillful techniques. Many kinds of bone grafting techniques have been tried for reconstructing defective osseous tissues of the oral and maxillofacial region, though they have varying degrees of success. The osseous defects which require grafting include those of various size, shape, position, or amount. Unlike autogenous grafts, whose function is to provide osteogenic cells, allografts are purely passive, offering only a matrix for the inductive phase of bone healing. The condition of the recipient bed is of primary importance, because the host must produce all of the essential elements for the bone allograft to become incorporated. Depending on the processing methods of the allogeneic bone, the bone graft materials have different qualities, different healing potentials and different indications. Proper selection of grafts and surgical techniques requires an understanding of graft immunology and the mechanisms of graft healing. The surgeons should know about the biological principles to raise the clinical success rate

Healing models for organizations: description, measurement, and outcomes.

Science.gov (United States)

Malloch, K

2000-01-01

Healthcare leaders are continually searching for ways to improve their ability to provide optimal healthcare services, be financially viable, and retain quality caregivers, often feeling like such goals are impossible to achieve in today's intensely competitive environment. Many healthcare leaders intuitively recognize the need for more humanistic models and the probable connection with positive patient outcomes and financial success but are hesitant to make significant changes in their organizations because of the lack of model descriptions or documented recognition of the clinical and financial advantages of humanistic models. This article describes a study that was developed in response to the increasing work in humanistic or healing environment models and the need for validation of the advantages of such models. The healthy organization model, a framework for healthcare organizations that incorporates humanistic healing values within the traditional structure, is presented as a result of the study. This model addresses the importance of optimal clinical services, financial performance, and staff satisfaction. The five research-based organizational components that form the framework are described, and key indicators of organizational effectiveness over a five-year period are presented. The resulting empirical data are strongly supportive of the healing model and reflect positive outcomes for the organization.

Pasteurized intercalary autogenous bone graft: radiographic and scintigraphic features

International Nuclear Information System (INIS)

Ehara, Shigeru; Tamakawa, Yoshiharu; Nishida, Jun; Shiraishi, Hideo

2000-01-01

Objective. Pasteurized autogenous bone graft sterilized at a low temperature (60 C) is one option for reconstruction after resection of bone and soft tissue tumors. The purpose of this investigation was to assess the normal and abnormal radiographic and scintigraphic findings of pasteurized intercalary autogenous bone graft after resection of bone and soft tissue sarcomas.Design. This was a retrospective evaluation of the radiography and bone scintigraphy findings in patients after treatment of bone and soft tissue sarcomas using an intercalary pasteurized autogenous bone graft.Patients. Among 10 consecutive patients, eight had intercalary grafts, and they constitute the subjects of this study. All available radiography and bone scintigraphy findings were reviewed for the healing process and the possibility of complications.Results and conclusions. Healing and incorporation of the graft were observed in five patients during the follow-up, but the other three did not heal satisfactorily. Rapid incorporation of pasteurized autogenous bone graft can be demonstrated by means of radiography and bone scintigraphy. (orig.)

A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol

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Enrique Gómez-Barrena

2018-01-01

Full Text Available ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32 to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC treatments versus iliac crest autograft (ICA to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments. The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 106 hBM-MSCs is noninferior to that of 200 × 106 hBM-MSCs. The participants (n=108 will be randomly assigned to either the experimental low dose (n=36, the experimental high dose (n=36, or the comparator arm (n=36 using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.

A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol.

Science.gov (United States)

Gómez-Barrena, Enrique; Padilla-Eguiluz, Norma G; Avendaño-Solá, Cristina; Payares-Herrera, Concepción; Velasco-Iglesias, Ana; Torres, Ferran; Rosset, Philippe; Gebhard, Florian; Baldini, Nicola; Rubio-Suarez, Juan C; García-Rey, Eduardo; Cordero-Ampuero, José; Vaquero-Martin, Javier; Chana, Francisco; Marco, Fernando; García-Coiradas, Javier; Caba-Dessoux, Pedro; de la Cuadra, Pablo; Hernigou, Philippe; Flouzat-Lachaniette, Charles-Henri; Gouin, François; Mainard, Didier; Laffosse, Jean Michel; Kalbitz, Miriam; Marzi, Ingo; Südkamp, Norbert; Stöckle, Ulrich; Ciapetti, Gabriela; Donati, Davide Maria; Zagra, Luigi; Pazzaglia, Ugo; Zarattini, Guido; Capanna, Rodolfo; Catani, Fabio

2018-01-01

ORTHOUNION is a multicentre, open, comparative, three-arm, randomized clinical trial (EudraCT number 2015-000431-32) to compare the efficacy, at one and two years, of autologous human bone marrow-derived expanded mesenchymal stromal cell (hBM-MSC) treatments versus iliac crest autograft (ICA) to enhance bone healing in patients with diaphyseal and/or metaphysodiaphyseal fracture (femur, tibia, and humerus) status of atrophic or oligotrophic nonunion (more than 9 months after the acute fracture, including recalcitrant cases after failed treatments). The primary objective is to determine if the treatment with hBM-MSCs combined with biomaterial is superior to ICA in obtaining bone healing. If confirmed, a secondary objective is set to determine if the dose of 100 × 10 6 hBM-MSCs is noninferior to that of 200 × 10 6 hBM-MSCs. The participants ( n = 108) will be randomly assigned to either the experimental low dose ( n = 36), the experimental high dose ( n = 36), or the comparator arm ( n = 36) using a central randomization service. The trial will be conducted in 20 clinical centres in Spain, France, Germany, and Italy under the same clinical protocol. The confirmation of superiority for the proposed ATMP in nonunions may foster the future of bone regenerative medicine in this indication. On the contrary, absence of superiority may underline its limitations in clinical use.

Osteoprogenitor cell therapy in an equine fracture model.

Science.gov (United States)

McDuffee, Laurie A; Pack, LeeAnn; Lores, Marcos; Wright, Glenda M; Esparza-Gonzalez, Blanca; Masaoud, Elmabrok

2012-10-01

To compare the efficacy of osteoprogenitors in fibrin glue to fibrin glue alone in bone healing of surgically induced ostectomies of the fourth metacarpal bones in an equine model. Experimental. Adult horses (n = 10). Segmental ostectomies of the 4th metacarpal bone (MC4) were performed bilaterally in 10 horses. There was 1 treatment and 1 control limb in each horse. Bone defects were randomly injected with either fibrin glue and osteoprogenitor cells or fibrin glue alone. Radiography was performed every week until the study endpoint at 12 weeks. After euthanasia, bone healing was evaluated using radiography and histology. Analysis of radiographic data was conducted using a linear-mixed model. Analysis of histologic data was conducted using a general linear model. Statistical significance was set at P bone healing revealed no significant difference between treatment and control limbs. Radiographic scoring results also showed that the treatment effect was not significant. Histologic analysis was consistent with radiographic analysis showing no significant difference between the area of bone present in treatment and control limbs. Injection of periosteal-derived osteoprogenitors in a fibrin glue carrier into surgically created ostectomies of MC4 does not accelerate bone healing when compared with fibrin glue alone. © Copyright 2012 by The American College of Veterinary Surgeons.

Flexible bipolar nanofibrous membranes for improving gradient microstructure in tendon-to-bone healing.

Science.gov (United States)

Li, Xiaoxi; Cheng, Ruoyu; Sun, Zhiyong; Su, Wei; Pan, Guoqing; Zhao, Song; Zhao, Jinzhong; Cui, Wenguo

2017-10-01

Enthesis is a specialized tissue interface between the tendon and bone. Enthesis structure is very complex because of gradient changes in its composition and structure. There is currently no strategy to create a suitable environment and to regenerate the gradual-changing enthesis because of the modular complexities between two tissue types. Herein, a dual-layer organic/inorganic flexible bipolar fibrous membrane (BFM) was successfully fabricated by electrospinning to generate biomimetic non-mineralized fibrocartilage and mineralized fibrocartilage in tendon-to-bone integration of enthesis. The growth of the in situ apatite nanoparticle layer was induced on the nano hydroxyapatite-poly-l-lactic acid (nHA-PLLA) fibrous layer in simulated body solution, and the poly-l-lactic acid (PLLA) fibrous layer retained its original properties to induce tendon regeneration. The in vivo results showed that BFM significantly increased the area of glycosaminoglycan staining at the tendon-bone interface and improved collagen organization when compared to the simplex fibrous membrane (SFM) of PLLA. Implanting the bipolar membrane also induced bone formation and fibrillogenesis as assessed by micro-CT and histological analysis. Biomechanical testing showed that the BFM group had a greater ultimate load-to-failure and stiffness than the SFM group at 12weeks after surgery. Therefore, this flexible bipolar nanofibrous membrane improves the healing and regeneration process of the enthesis in rotator cuff repair. In this study, we generated a biomimetic dual-layer organic/inorganic flexible bipolar fibrous membrane by sequential electrospinning and in situ biomineralization, producing integrated bipolar fibrous membranes of PLLA fibrous membrane as the upper layer and nHA-PLLA fibrous membrane as the lower layer to mimic non-mineralized fibrocartilage and mineralized fibrocartilage in tendon-to-bone integration of enthesis. Flexible bipolar nanofibrous membranes could be easily fabricated

The Effect of Aloe, Gelfoam, Plaster on Bone Formation in applying to the bone defect

International Nuclear Information System (INIS)

Choi, Eui Hwan; Kim, Su Gwan

1999-01-01

This study was to evaluate the effects of Aloe, Gelfoam, and Plaster of Paris on bone healing. Four experimental defects were created for placement of the three materials in the right femur of dogs. One defect served as an empty control site. The evaluation was performed at 1-, 6-, and 12-weeks by light microscopy and NIH image program. Radiographic and Histologic examinations showed new bone formation in the presence of Aloe, Gelfoam, and Plaster of Paris and similar bone healing reactions. On the basis of these findings, it was concluded that Aloe, Gelfoam, and Plaster of Paris may be adequate agents for use in bone procurement.

Lack of endogenous parathyroid hormone delays fracture healing by inhibiting vascular endothelial growth factor‑mediated angiogenesis.

Science.gov (United States)

Ding, Qingfeng; Sun, Peng; Zhou, Hao; Wan, Bowen; Yin, Jian; Huang, Yao; Li, Qingqing; Yin, Guoyong; Fan, Jin

2018-07-01

Intermittent low‑dose injections of parathyroid hormone (PTH) have been reported to exert bone anabolic effects and to promote fracture healing. As an important proangiogenic cytokine, vascular endothelial growth factor (VEGF) is secreted by bone marrow mesenchymal stem cells (BMSCs) and osteoblasts, and serves a crucial regulatory role in the process of vascular development and regeneration. To investigate whether lack of endogenous PTH causes reduced angiogenic capacity and thereby delays the process of fracture healing by downregulating the VEGF signaling pathway, a PTH knockout (PTHKO) mouse fracture model was generated. Fracture healing was observed using X‑ray and micro‑computerized tomography. Bone anabolic and angiogenic markers were analyzed by immunohistochemistry and western blot analysis. The expression levels of VEGF and associated signaling pathways in murine BMSC‑derived osteoblasts were measured by quantitative polymerase chain reaction and western blot analysis. The expression levels of protein kinase A (PKA), phosphorylated‑serine/threonine protein kinase (pAKT), hypoxia‑inducible factor‑1α (HIF1α) and VEGF were significantly decreased in BMSC‑derived osteoblasts from PTHKO mice. In addition, positive platelet endothelial cell adhesion molecule staining was reduced in PTHKO mice, as determined by immunohistochemistry. The expression levels of HIF1α, VEGF, runt‑related transcription factor 2, osteocalcin and alkaline phosphatase were also decreased in PTHKO mice, and fracture healing was delayed. In conclusion, lack of endogenous PTH may reduce VEGF expression in BMSC‑derived osteoblasts by downregulating the activity of the PKA/pAKT/HIF1α/VEGF pathway, thus affecting endochondral bone formation by causing a reduction in angiogenesis and osteogenesis, ultimately leading to delayed fracture healing.

Advances and Perspectives on Tissue Repair and Healing

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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.

Microencapsulation of 2-octylcyanoacrylate tissue adhesive for self-healing acrylic bone cement.

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Brochu, Alice B W; Chyan, William J; Reichert, William M

2012-10-01

Here, we report the first phase of developing self-healing acrylic bone cement: the preparation and characterization of polyurethane (PUR) microcapsules containing a medical cyanoacrylate tissue adhesive. Capsules were prepared by interfacial polymerization of a toluene-2,4-diisocyanate-based polyurethane prepolymer with 1,4-butanediol to encapsulate 2-octylcyanoacrylate (OCA). Various capsule characteristics, including: resultant morphology, average size and size distribution, shell thickness, content and reactivity of encapsulated agent, and shelf life are investigated and their reliance on solvent type and amount, surfactant type and amount, temperature, pH, agitation rate, reaction time, and mode of addition of the oil phase to the aqueous phase are presented. Capsules had average diameters ranging from 74 to 222 μm and average shell thicknesses ranging from 1.5 to 6 μm. The capsule content was determined via thermogravimetric analysis and subsequent analysis of the capsules following up to 8 weeks storage revealed minimal loss of core contents. Mechanical testing of OCA-containing capsules showed individual capsules withstood compressive forces up to a few tenths of Newtons, and the contents released from crushed capsules generated tensile adhesive forces of a few Newtons. Capsules were successfully mixed into the poly(methyl methacrylate) bone cement, surviving the mixing process, exposure to methyl methacrylate monomer, and the resulting exothermic matrix curing. Copyright © 2012 Wiley Periodicals, Inc.

A human model of small fiber neuropathy to study wound healing.

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Illigens, Ben M W; Gibbons, Christopher H

2013-01-01

The aim of this study was to develop a human model of acute wound healing that isolated the effects of small fiber neuropathy on the healing process. Twenty-five healthy subjects had the transient receptor vanilloid 1 agonist capsaicin and placebo creams topically applied to contralateral areas on the skin of the thigh for 48 hours. Subjects had shallow (1.2 millimeter) and deep (>3 millimeter) punch skin biopsies from each thigh on days 1 and 14. Biopsy wound healing was monitored photographically until closure. Intra-epidermal and sweat-gland nerve fiber densities were measured for each biopsy. Shallow wounds in capsaicin-treated sites healed more slowly than in placebo treated skin with biopsies taken on day 1 (PDeep biopsies in the capsaicin and placebo areas healed at similar rates at both time points. Nerve fiber densities were reduced only in capsaicin treated regions (Pshallow, but not deep wounds. This novel human model may prove valuable in the study of wound healing in patients with neuropathy.

A study of 23 unicameral bone cysts of the calcaneus: open chip allogeneic bone graft versus percutaneous injection of bone powder with autogenous bone marrow.

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Park, Il-Hyung; Micic, Ivan Dragoljub; Jeon, In-Ho

2008-02-01

The treatment of unicameral bone cyst varies from percutaneous needle biopsy, aspiration and local injection of steroid, autologous bone marrow, or demineralized bone matrix to curettage and open bone-grafting. The purpose of this study was to compare the results of open chip allogeneic bone graft versus percutaneous injection of demineralized bone powder with autogenous bone marrow in management of calcaneal cysts. Twenty-three calcaneal unicameral cysts in 20 patients were treated. Lyophilized irradiated chip allogeneic bone (CAB) and autogenous bone marrow were used for treatment of 13 cysts in 11 patients, and 10 cysts in 9 patients were treated with percutaneous injection of irradiated allogeneic demineralized bone powder (DBP) and autogenous bone marrow. There were 11 males and 9 female patients with mean age of 17 years. The patients were followed for an average of 49.4 months. Complete healing was achieved in 9 cysts treated with chip allogeneic bone and in 5 cysts treated with powdered bone. Four cysts treated with CAB and 3 cysts treated with DBP healed with a defect. Two cysts treated with powdered bone and autogenous bone marrow were classified as persistent. No infections or pathological fractures were observed during the followup period. Percutaneous injection of a mixture of allogeneic bone powder with autogenous bone marrow is a minimal invasive method and could be an effective alternative in the treatment of unicameral calcaneal bone cysts. The postoperative morbidity was low, the hospital stay was brief, and patient's comfort for unrestricted activity was enhanced.

Warning About the Use of Critical-Size Defects for the Translational Study of Bone Repair: Analysis of a Sheep Tibial Model.

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Lammens, Johan; Maréchal, Marina; Geris, Lisbet; Van der Aa, Joshua; Van Hauwermeiren, Hadewych; Luyten, Frank P; Delport, Hendrik

2017-11-01

The repair of large long bone defects requires complex surgical procedures as the bone loss cannot simply be replaced by autologous grafts due to an insufficient bone stock of the human body. Tissue engineering strategies and the use of Advanced Therapy Medicinal Products (ATMPs) for these reconstructions remain a considerable challenge, in particular since robust outcomes in well-defined large animal models are lacking. To be suitable as a model for treatment of human sized bone defects, we developed a large animal model in both skeletally immature and mature sheep and made close observations on the spontaneous healing of defects. We warn for the spontaneous repair of large defects in immature animals, which can mask the (in)effectiveness of ATMP therapies, and propose the use of large 4.5 cm defects that are pretreated with a polymethylmethacrylate (PMMA) spacer in skeletally mature animals.

Flexible intramedullary nailing for the treatment of unicameral bone cysts in long bones.

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Roposch, A; Saraph, V; Linhart, W E

2000-10-01

Unicameral bone cyst is characterized by its tenacity and risk of recurrence. Pathological fracture is common and is often the presenting symptom. The objective of the present study was to evaluate the results of flexible intramedullary nailing for the treatment of a unicameral bone cyst with or without a pathological fracture. Flexible intramedullary nailing for the treatment of a unicameral bone cyst was performed in thirty-two patients. Thirty of these patients presented with a pathological fracture; twenty-four were managed immediately with intramedullary nailing, and the other six had been managed conservatively at other clinics before they were referred to our department. The remaining two cysts were detected incidentally. The cyst was located in the humerus in twenty-one patients, in the femur in nine, and in the radius in two. The mean age of the patients at the time of surgery was 9.8 years, and the mean duration of follow-up was 53.7 months. Radiographic evaluation was performed according to the criteria of Capanna et al., and the cyst was classified as completely healed, healed with residual radiolucency (osteolysis), recurred, or having no response. The healing period ranged from three to 105 months. Fourteen cysts healed completely, and sixteen healed with residual radiolucent areas visible on radiographs. There was recurrence of two cysts that had healed with residual radiolucency. All of the cysts in the present study responded to treatment. A change of nails was necessary in nine patients, as the nails had become too short after bone growth. No major complications were observed. Flexible intramedullary nailing provides early stability, which allows early mobilization and thus obviates the need for a plaster cast and decreases the prevalence of the most common complication: a pathological fracture. This method of treatment also allows for an early return to normal activity.

The effects of Anadara granosa shell-Stichopus hermanni on bFGF expressions and blood vessel counts in the bone defect healing process of Wistar rats

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Rima Parwati Sari

2017-12-01

Full Text Available Background: Bone damage can be caused by various factors with treatment usually involving graft materials being applied to the defective area. Moreover, in the bone defect healing process, blood vessels are also considered to be an important energy source for cell proliferation. One of the angiogenic factors playing an important role in blood vessel formation is basic fibroblast growth factor (bFGF. Furthermore, synthesized hydroxyapatite derived from Anadara granosa (AG shells constitutes one of the potential materials for use in bone graft. The gold sea cucumber genus Stichopus hermanni (SH possesses the ability to stimulate endothelial progenitor cells inducing bFGF. Purpose: This study aims to investigate the effects of AG shells and SH on bFGF expressions and blood vessel counts within the bone healing process. Methods: Twenty four male Wistar rats were divided into three groups, namely: a control group (C, a treatment group was administered with blood cockle shell (AG, and a treatment group with blood cockle shell and golden sea cucumber (AG+SH. Defects were made on their femurs measuring half the diameter of a circular, no. 018. bur These rats were subsequently sacrificed on day 7 after surgery. The expressions of bFGF were measured by means of IHC technique, while the number of blood vessels was quantified using HE technique. The resulting data was subjected to statistical analysis using an Anova test followed by an LSD test (p < 0.05. Results: The one-way Anova test results combined with those of an LSD test showed there to be significant differences in bFGF expressions and blood vessel counts between the control group (K and the treatment group (AG as well as between the treatment group (AG and the treatment group (AG+SH. Conclusions: A combination of Anadara granosa shell and Stichopus hermanni can increase the expression of bFGF and the number of blood vessels on day 7 during the bone healing process in Wistar rats.

Bone tissue engineering: the role of interstitial fluid flow

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Hillsley, M. V.; Frangos, J. A.

1994-01-01

It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.

Effects of salmon calcitonin on fracture healing in ovariectomized rats.

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Li, Xiaolin; Luo, Xinle; Yu, Nansheng; Zeng, Bingfang

2007-01-01

To explore the effects of salmon calcitonin on the healing process of osteoporotic fractures in ovariectomized rats. We performed this study in The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China, during the period March 2002 to December 2004. We used 120 female adult Wistar rats in this experiment, among which 90 underwent ovariectomy (OVX) and the other 30 had sham-operation. All rats had their left tibias fractured 3 months later. The 90 OVX rats were randomly divided into 3 groups with 30 in each, while the 30 sham-operated rats served as control group. After the fracture the rats had subcutaneous injection of normal saline, salmon calcitonin and estrogen, respectively. X-ray film, histological examination, bone mineral density (BMD) measurement and biomechanics testing were carried out to evaluate the fracture healing. Compared with OVX rats treated with normal saline, the rats with salmon calcitonin had significantly higher BMD values in the left tibia, higher max torque, shear stress of the left tibia 8 weeks after fracture (pnormalization of microstructure of bone trabeculae. Salmon calcitonin can, not only increase BMD in osteoporotic bone, but also enhance the bone biomechanical properties and improve the process of fracture healing in fractured osteoporotic bone.

Role of Fas and Treg Cells in Fracture Healing as Characterized in the Fas-Deficient (lpr) Mouse Model of Lupus†

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Al-Sebaei, Maisa O; Daukss, Dana M; Belkina, Anna C; Kakar, Sanjeev; Wigner, Nathan A; Cusher, Daniel; Graves, Dana; Einhorn, Thomas; Morgan, Elise; Gerstenfeld, Louis C

2014-01-01

Previous studies showed that loss of tumor necrosis factor α (TNFα) signaling delayed fracture healing by delaying chondrocyte apoptosis and cartilage resorption. Mechanistic studies showed that TNFα induced Fas expression within chondrocytes; however, the degree to which chondrocyte apoptosis is mediated by TNFα alone or dependent on the induction of Fas is unclear. This question was addressed by assessing fracture healing in Fas-deficient B6.MRL/Faslpr/J mice. Loss of Fas delayed cartilage resorption but also lowered bone fraction in the calluses. The reduced bone fraction was related to elevated rates of coupled bone turnover in the B6.MRL/Faslpr/J calluses, as evidenced by higher osteoclast numbers and increased osteogenesis. Analysis of the apoptotic marker caspase 3 showed fewer positive chondrocytes and osteoclasts in calluses of B6.MRL/Faslpr/J mice. To determine if an active autoimmune state contributed to increased bone turnover, the levels of activated T cells and Treg cells were assessed. B6.MRL/Faslpr/J mice had elevated Treg cells in both spleens and bones of B6.MRL/Faslpr/J but decreased percentage of activated T cells in bone tissues. Fracture led to ∼30% to 60% systemic increase in Treg cells in both wild-type and B6.MRL/Faslpr/J bone tissues during the period of cartilage formation and resorption but either decreased (wild type) or left unchanged (B6.MRL/Faslpr/J) the numbers of activated T cells in bone. These results show that an active autoimmune state is inhibited during the period of cartilage resorption and suggest that iTreg cells play a functional role in this process. These data show that loss of Fas activity specifically in chondrocytes prolonged the life span of chondrocytes and that Fas synergized with TNFα signaling to mediate chondrocyte apoptosis. Conversely, loss of Fas systemically led to increased osteoclast numbers during later periods of fracture healing and increased osteogenesis. These findings suggest that retention

Effect of bone-soft tissue friction on ultrasound axial shear strain elastography.

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Tang, Songyuan; Chaudhry, Anuj; Kim, Namhee; Reddy, J N; Righetti, Raffaella

2017-07-12

Bone-soft tissue friction is an important factor affecting several musculoskeletal disorders, frictional syndromes and the ability of a bone fracture to heal. However, this parameter is difficult to determine using non-invasive imaging modalities, especially in clinical settings. Ultrasound axial shear strain elastography is a non-invasive imaging modality that has been used in the recent past to estimate the bonding between different tissue layers. As most elastography methods, axial shear strain elastography is primarily used in soft tissues. More recently, this technique has been proposed to assess the bone-soft tissue interface. In this paper, we investigate the effect of a variation in bone-soft tissue friction coefficient in the resulting axial shear strain elastograms. Finite element poroelastic models of bone specimens exhibiting different bone-soft tissue friction coefficients were created and mechanically analyzed. These models were then imported to an ultrasound elastography simulation module to assess the presence of axial shear strain patterns. In vitro experiments were performed to corroborate selected simulation results. The results of this study show that the normalized axial shear strain estimated at the bone-soft tissue interface is statistically correlated to the bone-soft tissue coefficient of friction. This information may prove useful to better interpret ultrasound elastography results obtained in bone-related applications and, possibly, monitor bone healing.

How prayer heals: a theoretical model.

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Levin, J S

1996-01-01

This article presents a theoretical model that outlines various possible explanations for the healing effects of prayer. Four classes of mechanisms are defined on the basis of whether healing has naturalistic or supernatural origins and whether it operates locally or nonlocally. Through this framework, most of the currently proposed hypotheses for understanding absent healing and other related phenomena-hypotheses that invoke such concepts as subtle energy, psi, consciousness, morphic fields, and extended mind-are shown to be no less naturalistic than the Newtonian, mechanistic forces of allopathic biomedicine so often derided for their materialism. In proposing that prayer may heal through nonlocal means according to mechanisms and theories proposed by the new physics, Dossey is almost alone among medical scholars in suggesting the possible limitations and inadequacies of hypotheses based on energies, forces, and fields. Yet even such nonlocal effects can be conceived of as naturalistic; that is, they are explained by physical laws that may be unbelievable or unfamiliar to most physicians but that are nonetheless becoming recognized as operant laws of the natural universe. The concept of the supernatural, however, is something altogether different, and is, by definition, outside of or beyond nature. Herein may reside an either wholly or partly transcendent Creator-God who is believed by many to heal through means that transcend the laws of the created universe, both its local and nonlocal elements, and that are thus inherently inaccessible to and unknowable by science. Such an explanation for the effects of prayer merits consideration and, despite its unprovability by medical science, should not be dismissed out of hand.

The healing process of intracorporeally and in situ devitalized distal femur by microwave in a dog model and its mechanical properties in vitro.

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Zhenwei Ji

Full Text Available BACKGROUND: Limb-salvage surgery has been well recognized as a standard treatment and alternative to amputation for patients with malignant bone tumors. Various limb-sparing techniques have been developed including tumor prosthesis, allograft, autograft and graft-prosthesis composite. However, each of these methods has short- and long-term disadvantages such as nonunion, mechanical failures and poor limb function. The technique of intracorporeal devitalization of tumor-bearing bone segment in situ by microwave-induced hyperthermia after separating it from surrounding normal tissues with a safe margin is a promising limb-salvage method, which may avoid some shortcomings encountered by the above-mentioned conventional techniques. The purpose of this study is to assess the healing process and revitalization potential of the devitalized bone segment by this method in a dog model. In addition, the immediate effect of microwave on the biomechanical properties of bone tissue was also explored in an in vitro experiment. METHODS: We applied the microwave-induced hyperthermia to devitalize the distal femurs of dogs in situ. Using a monopole microwave antenna, we could produce a necrotic bone of nearly 20 mm in length in distal femur. Radiography, bone scintigraphy, microangiography, histology and functional evaluation were performed at 2 weeks and 1, 2, 3, 6, 9 and 12 months postoperatively to assess the healing process. In a biomechanical study, two kinds of bone specimens, 3 and 6 cm in length, were used for compression and three-point bending test respectively immediately after extracorporeally devitalized by microwave. FINDINGS: An in vivo study showed that intracorporeally and in situ devitalized bone segment by microwave had great revitalization potential. An in vitro study revealed that the initial mechanical strength of the extracorporeally devitalized bone specimen may not be affected by microwave. CONCLUSION: Our results suggest that the

Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis

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Vittorio Locatelli

2014-01-01

Full Text Available Background. Growth hormone (GH and insulin-like growth factor (IGF-1 are fundamental in skeletal growth during puberty and bone health throughout life. GH increases tissue formation by acting directly and indirectly on target cells; IGF-1 is a critical mediator of bone growth. Clinical studies reporting the use of GH and IGF-1 in osteoporosis and fracture healing are outlined. Methods. A Pubmed search revealed 39 clinical studies reporting the effects of GH and IGF-1 administration on bone metabolism in osteopenic and osteoporotic human subjects and on bone healing in operated patients with normal GH secretion. Eighteen clinical studies considered the effect with GH treatment, fourteen studies reported the clinical effects with IGF-1 administration, and seven related to the GH/IGF-1 effect on bone healing. Results. Both GH and IGF-1 administration significantly increased bone resorption and bone formation in the most studies. GH/IGF-1 administration in patients with hip or tibial fractures resulted in increased bone healing, rapid clinical improvements. Some conflicting results were evidenced. Conclusions. GH and IGF-1 therapy has a significant anabolic effect. GH administration for the treatment of osteoporosis and bone fractures may greatly improve clinical outcome. GH interacts with sex steroids in the anabolic process. GH resistance process is considered.

Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis

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Locatelli, Vittorio; Bianchi, Vittorio E.

2014-01-01

Background. Growth hormone (GH) and insulin-like growth factor (IGF-1) are fundamental in skeletal growth during puberty and bone health throughout life. GH increases tissue formation by acting directly and indirectly on target cells; IGF-1 is a critical mediator of bone growth. Clinical studies reporting the use of GH and IGF-1 in osteoporosis and fracture healing are outlined. Methods. A Pubmed search revealed 39 clinical studies reporting the effects of GH and IGF-1 administration on bone metabolism in osteopenic and osteoporotic human subjects and on bone healing in operated patients with normal GH secretion. Eighteen clinical studies considered the effect with GH treatment, fourteen studies reported the clinical effects with IGF-1 administration, and seven related to the GH/IGF-1 effect on bone healing. Results. Both GH and IGF-1 administration significantly increased bone resorption and bone formation in the most studies. GH/IGF-1 administration in patients with hip or tibial fractures resulted in increased bone healing, rapid clinical improvements. Some conflicting results were evidenced. Conclusions. GH and IGF-1 therapy has a significant anabolic effect. GH administration for the treatment of osteoporosis and bone fractures may greatly improve clinical outcome. GH interacts with sex steroids in the anabolic process. GH resistance process is considered. PMID:25147565

The use of CT for evaluate to healing of segmental replantation in rabbits' tibia

International Nuclear Information System (INIS)

Liu Yifan; Hong Tianlu

2000-01-01

Objective: To study the value of CT in the bone healing. Methods: The rabbit's tibia segments were resected and replanted X-ray and CT photograph were taken after operation at 2,4,8,12 week. Results: CT is more clear than X-ray. Conclusion: CT is superior to X-ray photography in observed bone healing

Autonomous self-healing structural composites with bio-inspired design.

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D'Elia, Eleonora; Eslava, Salvador; Miranda, Miriam; Georgiou, Theoni K; Saiz, Eduardo

2016-05-05

Strong and tough natural composites such as bone, silk or nacre are often built from stiff blocks bound together using thin interfacial soft layers that can also provide sacrificial bonds for self-repair. Here we show that it is possible exploit this design in order to create self-healing structural composites by using thin supramolecular polymer interfaces between ceramic blocks. We have built model brick-and-mortar structures with ceramic contents above 95 vol% that exhibit strengths of the order of MPa (three orders of magnitude higher than the interfacial polymer) and fracture energies that are two orders of magnitude higher than those of the glass bricks. More importantly, these properties can be fully recovered after fracture without using external stimuli or delivering healing agents. This approach demonstrates a very promising route towards the design of strong, ideal self-healing materials able to self-repair repeatedly without degradation or external stimuli.

Interfacial Healing and Transport Phenomena Modeling ff Biopolymers

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Lebron, Karla

This research focuses on the characterization of bioplastics joined using ultrasonic welding and modeling of temperature distributions and interfacial healing. Polylactic acid (PLA), which is typically derived from starch-rich crops such as corn, was studied. While the measurement of activation energy for interfacial healing at weld interfaces of PLA films has been reported, here, this information is used to predict the weld strength of rigid PLA samples welded by ultrasonics. A characterization of the mechanical properties was completed with a tensile test to determine the effects of amplitude, melt velocity and collapse distance on weld strength. From previous interfacial healing activation energy measurements based on an impulse welding method, it was also possible to predict weld strength. It was found that the most influential parameters were weld time, collapse distance and weld velocity. In general, the model predicted weld strength reasonably well with r2 values between 0.77 and 0.78.

Biomechanical comparison of single-row, double-row, and transosseous-equivalent repair techniques after healing in an animal rotator cuff tear model.

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Quigley, Ryan J; Gupta, Akash; Oh, Joo-Han; Chung, Kyung-Chil; McGarry, Michelle H; Gupta, Ranjan; Tibone, James E; Lee, Thay Q

2013-08-01

The transosseous-equivalent (TOE) rotator cuff repair technique increases failure loads and contact pressure and area between tendon and bone compared to single-row (SR) and double-row (DR) repairs, but no study has investigated if this translates into improved healing in vivo. We hypothesized that a TOE repair in a rabbit chronic rotator cuff tear model would demonstrate a better biomechanical profile than SR and DR repairs after 12 weeks of healing. A two-stage surgical procedure was performed on 21 New Zealand White Rabbits. The right subscapularis tendon was transected and allowed to retract for 6 weeks to simulate a chronic tear. Repair was done with the SR, DR, or TOE technique and allowed to heal for 12 weeks. Cyclic loading and load to failure biomechanical testing was then performed. The TOE repair showed greater biomechanical characteristics than DR, which in turn were greater than SR. These included yield load (p repair of a chronic, retracted rotator cuff tear, the TOE technique was the strongest biomechanical construct after healing followed by DR with SR being the weakest. Copyright © 2013 Orthopaedic Research Society.

Rotator cuff repair with a tendon-fibrocartilage-bone composite bridging patch.

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Ji, Xiaoxi; Chen, Qingshan; Thoreson, Andrew R; Qu, Jin; An, Kai-Nan; Amadio, Peter C; Steinmann, Scott P; Zhao, Chunfeng

2015-11-01

To compare the mechanical performance of a rotator cuff repaired with a novel tendon-fibrocartilage-bone composite bridging patch vs the traditional Mason-Allen repair in an in vitro canine model. Twenty shoulders and 10 bridging patches from patellar tendon were harvested. The patches were trimmed and sliced into 2 layers. An infraspinatus tendon tear was created in each shoulder. Modified Mason-Allen sutures were used to repair the infraspinatus tendon to the greater tuberosity, with or without the bridging patch (bridging patch group and controls, respectively). Shoulders were loaded to failure under displacement control at a rate of 0.5mm/s. The ultimate tensile load was significantly higher in the bridging patch group than control (mean [SD], 365.46 [36.45] vs 272.79 [48.88] N; Pfibrocartilage-bone composite bridging patch achieved higher ultimate tensile load and stiffness at the patch-greater tuberosity repair site compared with traditional repair in a canine model. This composite tissue transforms the traditional tendon-to-bone healing interface (with dissimilar tissues) into a pair of bone-to-bone and tendon-to-tendon interfaces, which may improve healing quality and reduce retear rate. Copyright © 2015 Elsevier Ltd. All rights reserved.

Boron containing poly-(lactide-co-glycolide) (PLGA) scaffolds for bone tissue engineering

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Doğan, Ayşegül; Demirci, Selami [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University 34755 Istanbul (Turkey); Bayir, Yasin [Department of Biochemistry, Faculty of Pharmacy, Ataturk University, 25240, Erzurum (Turkey); Halici, Zekai [Department of Pharmacology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Karakus, Emre [Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ataturk University, 25240, Erzurum (Turkey); Aydin, Ali [Department of Orthopedics and Traumatology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Cadirci, Elif [Department of Pharmacology, Faculty of Pharmacy, Ataturk University, 25240, Erzurum (Turkey); Albayrak, Abdulmecit [Department of Pharmacology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Demirci, Elif [Department of Pathology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Karaman, Adem [Department of Radiology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Ayan, Arif Kursat [Department of Nuclear Medicine, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Gundogdu, Cemal [Department of Pathology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Şahin, Fikrettin, E-mail: fsahin@yeditepe.edu.tr [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University 34755 Istanbul (Turkey)

2014-11-01

Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calcium mineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highly warranted for the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics. The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering. - Highlights: • Boron containing PLGA scaffolds were developed for bone tissue engineering. • Boron incorporation increased cell viability and mineralization of stem cells. • Boron containing scaffolds increased bone-related protein expression in vivo. • Implantation of stem cells on boron containing scaffolds improved bone healing.