A new TGF‐β3 controlled‐released chitosan scaffold for tissue engineering synovial sheath

Abstract

The post-operative outcome of flexor tendon healing remains limited by flexor tendon adhesion that reduces joint range of motion. Despite improvement in different methods, peritendinous adhesion formation continues to present a formidable challenge. Recent studies showed that transforming growth factor-β3 (TGF-β3) may be the key factor to reducing adhesion formation in skin or tendon. In this study, we designed a novel type of tissue engineering synovial sheath containing TGF-β3, to prevent flexor tendon adhesion. First, to achieve a stable release of TGF-β3, chitosan microspheres, prepared by crosslinking-emulsion, were used for the delivery of TGF-β3. Second, a three-dimensional chitosan scaffold was prepared by lyophilization, and TGF-β3 microspheres were carefully introduced into the scaffold. Then, synovial cells were cultured and then seeded into the TGF-β3 loaded scaffold to produce TGF-β3 controlled-released tissue engineering synovial sheath. Tests clearly demonstrated that the scaffold has good structure and compatibility with cells. These results expand the feasibility of combinative strategies of controlled protein release and tissue-engineered synovial sheath formation. Application of this scaffold to tendon repair sites may help to prevent adhesion of tendon healing.

Effect of transforming growth factor-β3 on the expression of Smad3 and Smad7 in tenocytes

“…Previous studies have established a role for TGF-β signaling in tendon healing by demonstrating that inhibition of neutralization of TGF-β1 and β2, or the addition of TGF-β3 can decrease adhesion formation (8,26,27). A novel TGF-β3 controlled-released chitosan scaffold has been developed for tissue engineering of the synovial sheath (28). The present study focused on the effect of TGF-β3, and the underlying the TGF-β/Smad signaling pathway on wound healing.…”

Tendon Reconstruction with Tissue Engineering Approach—A Review

“…168 Hence, it is thought that the incorporation of this factor in scaffolds may be vital in reducing adhesion formation in healing tendons. 169 PDGF-BB and FGF were shown to significantly increase canine flexor tendon fibroblast proliferation and collagen production when tested in-vitro and in-vivo. 170 171 Transfer of an exogenous PDGF-B gene to rat tenocytes has also been shown to increase collagen I gene expression in-vitro, suggesting that PDGF gene transfer may offer a novel way of promoting flexor tendon healing.…”

Application of stem cells derived from the periodontal ligament or gingival tissue sources for tendon tissue regeneration

“…To induce tenogenic differentiation, encapsulated PDLSCs and GMSCs as well as hBMMSCs (2×10 6 cells in 1 mL of TGF-β3-loaded alginate microspheres) were cultured in a tenogenic medium containing DMEM with 15% FBS, 2 mM L-glutamine, 100 nM Dex, 100 3M ascorbic acid, 2 mM sodium pyruvate (R&D Systems Inc), 100 U/mL penicillin, and 100 μg/mL streptomycin [26]. Cell-free RGD-coupled alginate microspheres without TGF-β3 were used as the negative control.…”

“…Moreover, TGFβ signaling is a potent inducer of Scleraxis (Scx), a basic helix-loop-helix (bHLH) transcription factor gene that is a unique marker for the tendon cell fate in vitro and in vivo , demonstrating a vital role for the TGF-β signaling pathway in tendon repair and regeneration [23–25]. Among the members of the TGF-β superfamily, TGF-β3 is of particular interest as it is an isoform that has been associated with promoting dermal wound and tendon healing without fibrotic scar formation [26,27]. Other studies have confirmed that differentiation of MSCs driven by TGF-β3 can promote tendon tissue formation and may provide a promising modality of treatment for tendon regeneration and repair [24–27].…”