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Tendon tissue engineering and its role on healing of the experimentally induced large tendon defect model in rabbits: a comprehensive in vivo study.

ABSTRACT: Healing of large tendon defects is challenging. We studied the role of collagen implant with or without polydioxanone (PDS) sheath on the healing of a large Achilles tendon defect model, in rabbits. Sixty rabbits were divided into three groups. A 2 cm gap was created in the left Achilles tendon of all rabbits. In the control lesions, no implant was used. The other two groups were reconstructed by collagen and collagen-PDS implants respectively. The animals were clinically examined at weekly intervals and their lesions were observed by ultrasonography. Blood samples were obtained from the animals and were assessed for hematological analysis and determination of serum PDGF level, at 60 days post injury (DPI). The animals were then euthanized and their lesions were assessed for gross and histopathology, scanning electron microscopy, biomechanical testing, dry matter and hydroxyproline content. Another 65 pilot animals were also studied grossly and histopathologically to define the host implant interaction and graft incorporation at serial time points. The treated animals gained significantly better clinical scoring compared to the controls. Treatment with collagen and collagen-PDS implants significantly increased the biomechanical properties of the lesions compared to the control tendons at 60DPI (P<0.05). The tissue engineered implants also reduced peritendinous adhesion, muscle fibrosis and atrophy, and increased ultrasonographical echogenicity and homogenicity, maturation and differentiation of the collagen fibrils and fibers, tissue alignment and volume of the regenerated tissue compared to those of the control lesions (P<0.05). The implants were gradually absorbed and substituted by the new tendon. Implantation of the bioimplants had a significant role in initiating tendon healing and the implants were biocompatible, biodegradable and safe for application in tendon reconstructive surgery. The results of the present study may be valuable in clinical practice.

SUBMITTER: Meimandi-Parizi A

PROVIDER: S-EPMC3764104 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Tendon tissue engineering and its role on healing of the experimentally induced large tendon defect model in rabbits: a comprehensive in vivo study.

Meimandi-Parizi Abdolhamid A Oryan Ahmad A Oryan Ahmad A Moshiri Ali A

PloS one 20130905 9

Healing of large tendon defects is challenging. We studied the role of collagen implant with or without polydioxanone (PDS) sheath on the healing of a large Achilles tendon defect model, in rabbits. Sixty rabbits were divided into three groups. A 2 cm gap was created in the left Achilles tendon of all rabbits. In the control lesions, no implant was used. The other two groups were reconstructed by collagen and collagen-PDS implants respectively. The animals were clinically examined at weekly inte ...[more]

PMID: 24039851

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Project description:Unlabelled: Tendon injuries are common and present a clinical challenge, as they often respond poorly to treatment and result in long-term functional impairment. Inferior tendon healing responses are mainly attributed to insufficient or failed tenogenesis. The main objective of this study was to establish an efficient approach to induce tenogenesis of bone marrow-derived mesenchymal stem cells (BMSCs), which are the most common seed cells in tendon tissue engineering. First, representative reported tenogenic growth factors were used as media supplementation to induce BMSC differentiation, and the expression of teno-lineage transcription factors and matrix proteins was compared. We found that transforming growth factor (TGF)-?1 significantly induced teno-lineage-specific gene scleraxis expression and collagen production. TGF-?1 combined with connective tissue growth factor (CTGF) elevated tenomodulin and Egr1 expression at day 7. Hence, a stepwise tenogenic differentiation approach was established by first using TGF-?1 stimulation, followed by combination with CTGF for another 7 days. Gene expression analysis showed that this stepwise protocol initiated and maintained highly efficient tenogenesis of BMSCs. Finally, regarding in situ rat patellar tendon repair, tendons treated with induced tenogenic BMSCs had better structural and mechanical properties than those of the control group, as evidenced by histological scoring, collagen I and tenomodulin immunohistochemical staining, and tendon mechanical testing. Collectively, these findings demonstrate a reliable and practical strategy of inducing tenogenesis of BMSCs for tendon regeneration and may enhance the effectiveness of cell therapy in treating tendon disorders.SignificanceThe present study investigated the efficiency of representative tenogenic factors on mesenchymal stem cells' tenogenic differentiation and established an optimized stepwise tenogenic differentiation approach to commit tendon lineage differentiation for functional tissue regeneration. The reliable tenogenic differentiation approach for stem cells not only serves as a platform for further studies of underlying molecular mechanisms but also can be used to enhance cell therapy outcome in treating tendon disorders and develop novel therapeutics for tendon injury.

Project description:BackgroundBone tissue engineering is not widely used in clinical treatment. Two main reasons hide behind this: (1) the seed cells are difficult to obtain and (2) the process of tissue engineering bone construction is too complex and its efficiency is still relatively low. It is foreseeable that in the near future, the problem of seed cell sources could be solved completely in tissue engineering bone repair. As for the complex process and low efficiency of tissue engineering bone construction, usually two strategies would be considered: (1) the construction strategy based on injectable bone tissue and (2) the construction strategy based on osteogenic cell sheets. However, the application of injectable bone tissue engineering (iBTE) strategy and osteogenic cell sheet strategy is limited and they could hardly be used directly in repairing defects of large segmental bone, especially load-bearing bone.MethodsIn this study, we built an osteogenic micro-tissue with simple construction but with a certain structure and composition. Based on this, we established a new iBTE repair strategy-osteogenic micro-tissue in situ repair strategy, mainly targeting at solving the problem of large segmental bone defect. The steps are as follows: (1) Build the biodegradable three-dimensional scaffold based on the size of the defect site with 3D printing rapid prototyping technology. (2) Implant the three-dimensional scaffold into the defect site. This scaffold is considered as the "steel framework" that could provide both mechanical support and space for bone tissue growth. (3) Inject the osteogenic micro-tissue (i.e., the "cell-extracellular matrix" complex), which could be considered as "concrete," into the three-dimensional scaffold, to promote the bone tissue regeneration in situ. Meanwhile, the digested cells were injected as the compared group in this experiment. After 3 months, the effect of in situ bone defect repair of osteogenic micro-tissue and digested cells was compared.ResultsIt is confirmed that osteogenic micro-tissue could achieve a higher efficiency on cell usage and has a better repair effect than the digested cells.ConclusionsOsteogenic micro-tissue repairing strategy would be a more promising clinical strategy to solve the problem of large segmental bone defect.

Project description:Background and objectiveTissue engineering is an option in reconstructing large tendon defects and managing their healing and regeneration. We designed and produced a novel xenogeneic-based bovine platelet, embedded it within a tissue-engineered collagen implant (CI) and applied it in an experimentally induced large tendon defect model in rabbits to test whether bovine platelets could stimulate tendon healing and regeneration in vivo.MethodsOne hundred twenty rabbits were randomly divided into two experimental and pilot groups. In all the animals, the left Achilles tendon was surgically excised and the tendon edges were aligned by Kessler suture. Each group was then divided into three groups of control (no implant), treated with CI and treated with collagen-platelet implant. The pilot groups were euthanized at 10, 15, 30 and 40 days post-injury (DPI), and their gross and histologic characteristics were evaluated to study host-graft interaction mechanism. To study the tendon healing and its outcome, the experimental animals were tested during the experiment using hematologic, ultrasonographic and various methods of clinical examinations and then euthanized at 60 DPI and their tendons were evaluated by gross pathologic, histopathologic, scanning electron microscopic, biophysical and biochemical methods.ResultsBovine platelets embedded within a CI increased inflammation at short term while it increased the rate of implant absorption and matrix replacement compared with the controls and CI alone. Treatment also significantly increased diameter, density, amount, alignment and differentiation of the collagen fibrils and fibers and approximated the water uptake and delivery behavior of the healing tendons to normal contralaterals (p < 0.05). Treatment also improved echogenicity and homogenicity of the tendons and reduced peritendinous adhesion, muscle fibrosis and atrophy, and therefore, it improved the clinical scores and physical activity related to the injured limb when compared with the controls (p < 0.05).ConclusionThe bovine platelet gel embedded within the tissue-engineered CI was effective in healing, modeling and remodeling of the Achilles tendon in rabbit. This strategy may be a valuable option in the clinical setting.

Dataset Information

Tendon tissue engineering and its role on healing of the experimentally induced large tendon defect model in rabbits: a comprehensive in vivo study.

Publications

Tendon tissue engineering and its role on healing of the experimentally induced large tendon defect model in rabbits: a comprehensive in vivo study.

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