Aligned Micro-nano Fibrous Scaffold And Tendon Stem/Progenitor Cells For Tendon Regeneration

Tendon injuries account 50% of sports injuries.However,natural healing of tendon tissue is extremely inefficient and remains a common clinical challenge.Various therapeutic strategies have been employed to improve tendon repair,while the treatment outcomes are unsatisfying,as the tendon repaired with poor mechanical properties and is prone to repeated fractures.Therefore,more efficient strategies are urgently needed for tendon repair and regeneration.With the development of stem cells and tissue engineering so far,tendon tissue engineering is one of the most promising strategies.Given that physical microenvironment regulates cell fate,therefore,scaffold is one of the crucial factors in tissue engineering.Previously,aligned topography has been proved to induce tenogenic differentiation of stem cells.This is because it resemble the unique physiological structure of the tendon tissue extracellular matrix which is consisted of aligned collagen nanofibers in structure.However,native tendon is made of multi-unit(multi-scale)physiological structure.Moreover,the fiber diameter has been shown to regulate cell adhesion,proliferation and differentiation.Fibrous scaffold with single scale is not bionic enough from the native tissue,and is likely to lead to poor repair.As mentioned above,we designed a biomimetic aligned PLLA-PEO micro-nanofiber scaffold with anisotropy and multi-scale for tendon tissue engineering,based on the ultrastructural characteristics of natural tendon.The stable jet electrospinning(SJES)technology can stably produce well-aligned fibers,and adjusting the SJES parameters can easily control fiber diameters,which is an ideal technique to fabricate multi-scale fibers.Here,we obtained aligned micro-nanofibers through SJES.The composite scaffold showed superior mechanical and hydrophilic properties than single fibers and effectively promoted the tenogenic differentiation of mouse tendon stem/progenitor cells(TSPCs)while inhibited its osteogenic differentiation.Additionally,in the nude mice ectopic model and the rat in situ Achilles tendon defect model,it revealed that aligned micro-nanofibers combined with TSPCs induced synthesis deposition and alignment of collagen fibers,promoted the expression of tendon-specific genes,improved the mechanical properties of repair tendon,thus ultimately promoted the regeneration and repair of tendon.In summary,this study demonstrates that biomimetic aligned micro-nanofiber scaffolds effectively induced tenogenic differentiation of tendon stem/progenitor cells in vitro and promoted tendon regeneration in vivo.Thus,this study provided important information for the future tissue engineering application with stem cells and biomaterials.