Study On Engineering And Application Of Three-dimensional Tendon Scaffold With Bioadaptability

Tendon is an important connective tissue that maintains joint stability and mechanical transfer in the musculoskeletal system.Tendon injury caused by diseases,sports,traffic accidents and aging is a common clinical problem.The hypocellular and hypovascular nature of the tendon leads to poor self-repair and regeneration.As a result,the current clinical treatment still cannot fully restore the structure and mechanical properties of the tendon tissue.Tissue engineering that combines stem cells and functional biomaterials is a promising strategy for repair and treatment of tendon injuries.More recently,electrohydrodynamic jet printing(EHD-3DP)technology has been applied to the fabrication of tendon scaffold.However,the current fibre scaffolds fabricated by EHD-3DP cannot regulate efficient and stable cells alignment,and their mechanical properties cannot meet the requirements of tendon tissue engineering applications.In view of the above problems,this thesis aims to engineer threedimensional tendon scaffold with bioadaptability based on the strategy of simulating the anisotropic topological structure and mechanical properties of tendon tissue for repair and regeneration of tendon.The main research contents include:(1)Engineering and performance study of scaffold’s core with micro-pattern.Composite fibre sheet with anisotropic micropatterns was designed and engineered based on COL-I and PCL.The preparation mechanism of EHD-3DP fabricted PCL/COL-I fibre(including the tip-collector distance,ink feed rate,nozzle size and stage speed,ink concentration and solute composition)was systematically studied.The surface morphology,composition and phase,surface hydrophilicity,mechanical properties,degradation performance and biological response of the composite fibre sheet was analyzed.The results showed that the composite fibre sheet had biodegradability and biocompatibility,supported the adhesion and proliferation of human bone marrow mesenchymal stem cells(h BMSCs),regulated the effective and stable alignment of h BMSCs,and promoted the expression of tendon related genes and the synthesis of COL-I protein,which was expected to achieve the reconstruction of tendon like ECM.(2)Engineering and performance study of scaffold’s shell as mechanical support.A porous film with strain enhancement effect(UL-PCL)was designed and engineered based on PCL.The preparation mechanism of UL-PCL was systematically studied,including the effect of draw ratio and temperature on the surface ridge/groove structure,and the effect of laser processing pattern by laser on the distribution of perforation structure.The surface morphology,composition and phase,surface hydrophilicity,mechanical properties,degradation performance and biological response of UL-PCL were analyzed.The results show that UL-PCL has perfect mechanical properties,including Young’s modulus of 240.2 MPa and ultimated stress of 142.2 MPa.UL-PCL also has good biocompatibility,which can support the adhesion and proliferation of h BMSCs and regulate the alignment of h BMSCs.UL-PCL is expected to provide mechanical support and protection for tendon regeneration.(3)Study on the assembly and performance of core-shell tendon scaffold.Based on PCL fibre sheet with micropattern,a multi-layer cylindrical scaffold’s core was engineered.Based on porous PCL film,the scaffold’s shell of a single round tubular was engineered.Based on the core and shell,an integrated core-shell scaffold assembly process was established.The surface morphology,mechanical properties,degradation performance and biocompatibility of core-shell scaffolds were analyzed.The Young’s modulus of core-shell scaffold was 130.1 MPa,which was close to the lower limit of human patella tendon.The preferential degradation of the core portion releases space for the ingrowth of neotissue,and the slow degradation of the shell provides long-term mechanical support.Core-shell scaffolds allow the infiltration,migration and ingrowth of h BMSCs,which is expected to achieve the regeneration of tendon tissue from the inside out.