Effect of Tendon Stem Cells in Chitosan/β-Glycerophosphate/Collagen Hydrogel on Achilles Tendon Healing in a Rat Model

Abstract

BackgroundThe aim of this study was to determine whether the local application of tendon stem cells (TSCs) with chitosan/b-glycerophosphate/collagen(C/GP/Co) hydrogel promotes healing after an acute Achilles tendon injury in a rat model.Material/MethodsNinety-six Sprague-Dawley (SD) rats were used to make an Achilles tendon defect model, then the animals were randomly divided into 4 groups consisting of 8 rats each: control group, hydrogel group, TSCs group, and TSCs with hydrogel group. At 2, 4, and 6 weeks after treatment, tendon samples were harvested, and the quality of tendon repair was evaluated based on histology, immunohistochemistry, and biomechanical properties.ResultsCombining TSCs with C/GP/Co hydrogel significantly enhances tendon healing compared with the control, hydrogel, and TSCs groups. The improved healing was indicated by the improvement in histological and immunohistochemistry outcomes and the increase in the biomechanical properties of the regenerated tissue at both 4 and 6 weeks post-injury.ConclusionsThis study demonstrates that the transplantation of TSCs combined with C/GP/Co hydrogel significantly improved the histological, immunohistochemistry, and biomechanical outcomes of the regenerated tissue at 4 and 6 weeks after implantation. TSCs with C/GP/Co hydrogel is a potentially effective treatment for tendon injury.

Tendon stem progenitor cells: Understanding the biology to inform therapeutic strategies for tendon repair

“…Recent work developing biomaterials for TSPCs showed that seeding TSPCs in fibrin gels, collagen hydrogels or engineered tendon matrix (ETM) films or gels, can induce in vitro tenogenic differentiation. In addition, these scaffolds serve as successful in vivo delivery vehicles for TSPCs into a tendon defect.…”

“…The collagen matrix produced by TSPCs in vitro also remains immature (small uniform fibrils) and mechanical properties can only approach that of embryonic tendons . However, these scaffolds support TSPC expansion, limited tenogenic differentiation in vitro, and in vivo implantation (alone or in combination with growth factor or small molecule treatments) . In general, several studies suggest that combining chemical supplementation (including growth factors such as CTGF or small molecules such as TSA) with 3D culture best enhances tenogenic differentiation and improves subsequent healing after implantation of constructs .…”

“…96 Biomimetic scaffolds that mimic native tendon architecture (in terms of aligned fibers) and mechanical properties can also support TSPC culture, ECM deposition, and initiate a tendon-specific gene response. 97 Recent work developing biomaterials for TSPCs showed that seeding TSPCs in fibrin gels, 43,58,60,98 collagen hydrogels 99,100 or engineered tendon matrix (ETM) films or gels, 101 can induce in vitro tenogenic differentiation. In addition, these scaffolds serve as successful in vivo delivery vehicles for TSPCs into a tendon defect.…”

“…42,59,104 However, these scaffolds support TSPC expansion, limited tenogenic differentiation in vitro, and in vivo implantation (alone or in combination with growth factor or small molecule treatments). [58][59][60]64,90,[95][96][97][98][99]101,105 In general, several studies suggest that combining chemical supplementation (including growth factors such as CTGF or small molecules such as TSA) with 3D culture best enhances tenogenic differentiation and improves subsequent healing after implantation of constructs. 59,90,95 Consistent with almost all tendon differentiation research however, the media formulations for 3D constructs are also serum-based and functional properties are rarely assessed.…”

Tissue Regeneration

“…Chitosan in combination with collagen has also been investigated to serve as a material for tissue engineering: addition of chitosan to bovine and salmon collagen scaffolds improved the mechanical properties by increasing the compressive strength and the swelling ratio [73]. Moreover, a rat Achilles tendon study, where a scaffold based on chitosan-β-glycerophosphate-collagen was used, demonstrated the effectiveness of this composite material for this purpose [74].…”