Study On Mechanical Stretching Of Film Materials And The Application Of Promoting Bone Regeneration

Periosteum offers the key regulatory factors for bone development and growth.Recently,the tissue-engineering strategy of artificial periostium confirms its feasibility to help the repair of bone defects.However,the studies rarely achieve an integration of the key functions of natural periosteum,which is associated with the limitation of bone regeneration.Physically,a natural periosteum is composed of highly oriented multilayer and interlaced collagen fiber bundles,which serves to induce bone formation,protect the bone from the peripheral tissue as well as provide abundant blood supply for the bone tissue.Based on bionic design and engineering principles,this thesis aims to construct tissue-engineered periosteum(TEPO)and develop the technology for integrating key periosteum's functions.(1)Constructing the biomimetic TEPO based on bioactive ions and geometric cues.Through electrofluid spinning technology,the degradable copper dopped tricalcium phosphate(Cu-TCP)was integrated with the bioabsorbable polymer material polycaprolactone(PCL),to fabricate a fiber membrane TEPO with ionic bone-forming signals(Ca²⁺,PO₄^3-),angiogenic signals(Cu²⁺)and geometric cues.In the electrofluid spinning process,Cu-TCP doping and mechanical stretching affect the fiber diameter and arrangement.Cu-TCP doping improved the surface wettability of this type of TEPO,while mechanical stretching made the surface wettability of TEPO present anisotropy.Meanwhile,the two manufacturing parameters enhanced the mechanical propertiesof TEPO in the direction of fiber orientation(Young's modulus,yield stress and ultimate stress),but did not significantly decrease the mechanics along the direction perpendicular to the fiber orientation.The results of cell experiments showed that TEPO had good cytocompatibility and could induce the deposition of calcium phosphate-like nodules and matrix-like fibers.(2)Constructing TEPO with functional modules based on bioactive ions and geometric cues,to realize multilevel structure in natural periosteum.The highly oriented PCL fiber was prepared by a combination of electrofluidic direct writing,spinning and uniaxial stretching to obtain anisotropic geometric cues.The functional module of TEPO was designed based on the bionic principle.T In the process of fiber reorientation,the stretching temperature,draw ratio and support layer structure affected both diameter and rearrangement of the PCL fibers,making the fiber layer present mechanical anisotropy.Along the uniaxial stretching direction,the fiber layer obtained the Young's modulus of 19.2 MPa,the yield stress of 5.2 MPa,the elastic strain of 27%and the ultimate stress of 10.5 MPa.Cell experiment results showed that functional modules of TEPO had good cytocompatibility and could quickly establish a linear arrangement of cells,cytoskeleton,and nucleus similar to those of natural periosteum,respectively.The changes in cell morphology could induce the up-regulation of the osteogenic expression,including Colla1,RUNX2,ALP,OCN and OPN,and further promoted the formation of osteoid calcium nodules.(3)Constructing TEPO with functional integration based on bioactive drugs,ions and geometric cues.TEPO was prepared based on the bionic principle and modular design to integrate the key biofunctions of natural periosteum:osteogenesis,vascularization,protective barrier,as well as the antibacterial,anti-inflammatory and anti-fibrotic effects.This TEPO showed mechanical anisotropy and improved stability against degradation.Cell experiment results showed that the functionally integrated TEPO obtained good cell compatibility to promote cell proliferation,guide the linear arrangement of cells and sub-cellular organelles effectively,thereby enhancing the deposition of bone-like mineralization.