Electrospun Nanofibrous Biomimetic Scaffolds For Tendon Tissue Engineering

In recent years,tissue engineering strategies have been demonstrated as an innovative technique to repair damaged tendon by building engineered tendon tissues.Developing suitably engineered tendon tissues in vitro via tissue engineering strategies is urgently needed but remains a going challenge.In tissue engineering,scaffolds play an important role in guiding cell behaviors and served as a temporary extracellular matrix(ECM).Previous studies have shown that cell behaviors can be influenced by the various properties of scaffolds.Therefore,designing a scaffold that can precisely control cell behaviors is highly beneficial for tendon tissue engineering.Electrospun nanofibers have been widely studied due to their high resemblance to the nanostructure of ECM.By controlling the parameters during electrospinning,the diameters,structures,and ingredients of nanofibers can be precisely adjusted.Therefore,a biomimetic scaffold for promoting cell growth can be easily fabricated.The microanatomy revealed that tendon tissue is composed of various highly organized collagen fibers with three-dimensional structures and wrapped by the sheath.However,traditional electrospinning strategies failed to develop a scaffold that fully mimics the 3D structure of native tendon tissues.Additionly,tendon sheath infection is a major complication after tendon injury,which will cause tendon adhesion.Previous studies have focused on developing scaffolds that served as physical barriers to prevent tendon adhesion,which failed to functionally repair the tendon sheath.To mimic the hierarchical 3D structure of native collagen in tendon tissue,we used a dry-wet electrospinning technique to prepare nanofiber yams(NFYs)with 3D alignment.We first investigated the tendon stem/progenitor cell(TSPCs)behaviors on different diameters of NFYs.The results showed that different diameters of NFYs would significantly influence the proliferation and tenogenic differentiation of TSPCs.After implanting the bundled NFYs in rat tendon injury sites,the results suggested that these biomimetic scaffolds could induce the alignment of neo-collagen fibers and promote tendon regeneration.According to the above results,the hierarchical 3D aligned scaffold performed a promising potential in tendon tissue engineering.To address the difficulties of functional repairing the tendon sheath,we prepared celecoxib-loaded aligned nanofibers with the core-shell structure to develop a functionally engineered tendon sheath via coaxial electrospinning.The aligned structure of nanofibers could induce the alignment of TSPCs while releasing celecoxib to suppress the expression of the inflammatory cytokines.The inflammation at the early period of tendon repair was reduced due to the sustained release of celecoxib from nanofibers,thereby preventing tendon adhesion.These results demonstrated that celecoxib-loaded functional scaffolds showed great potential in tendon sheath repair.In conclusion,in this thesis,we confirmed the effects of the structure and diameters of NFYs on TSPCs behaviors,and design a biomimetic scaffold based on tendon structure,which could induce the alignment of cells and neo-collagen.Finally,we fabricated an engineered tendon sheath to promote tendon regeneration and antiadhesion by mimicking the function of the native tendon sheath.These nanofibrous scaffolds displayed wide prospects in tendon tissue engineering and offered a new method for tendon tissue engineering scaffolds.