Preparation Of Multifunctional Oriented Porous Composite Electrospun Fiber And Its Application In Soft Tissue Repair

Soft tissue damage caused by trauma and metabolic diseases,which is one of common clinical disease in the whole world,poses a serious threat to human survival and health.There are some traditional techniques for repairing soft tissue damage,for example autotransplantation,allotransplantation and so on.However,each of these techniques has some shortcomings,such as the limit of autologous donor,secondary injury and the immune reactions.Therefore,it is very significant to find a reliable,safe and effective method to repair cartilage defects.Currently,the fast-developing soft tissue engineering has provided a promising strategy to replace or repair damaged soft tissue.The electrospun fibrous membrane,which possesses many attractive structural advantages such as extracellular matrix(ECM)-like architecture,porous interconnected 3D network,large surface-to-volume ratio and tunable surface structure,has recently received significant attention in the tissue regeneration.In order to improve the activity of electrospun scaffolds,we designed an aligned porous fibrous scaffold with a bio-mimic surface for cartilage tissue engineering and an aligned porous electrospun fibrous membrane with controlled drug delivery for diabetic wound healing.The main contents of this thesis include the following two parts:(1)An aligned porous fibrous scaffold with a bio-mimic surface for cartilage tissue engineeringAn articular cartilage defect is usually difficult to self-repair and regeneration because of the avascularity and low cellularity.The exploration of efficient strategy to significantly induce chondrocytes differentiation,improve the formation of ECM in the cartilage defect site,and thereby accelerate cartilage tissue regeneration is still a significant challenge.Herein,we reported a kind of aligned porous poly(L-lactic acid)(PLLA)electrospun fibrous scaffold with polydopamine(PDA)and chondroitin sulfate(CS)incorporated for articular cartilage defect repair.The PLLA electrospun fibers aligned in a single direction and there were ellipse-shaped nano-pores in situ generated onto the surface of fibers,while the PDA as well as CS were well coated on the surface of each fiber and the CS could be released from the scaffolds.The in vitro results revealed that the bio-mimic surface aligned porous composite scaffolds(PL/PDA and PL/PDA/CS)could stimulate the proliferation,attachment and chondrogenic gene expression of chondrocytes and rabbit bone marrow mesenchym stem cells(r BMSCs)compared with the pure PLLA scaffolds.The in vivo study further demonstrated that the prepared PL/PDA/CS scaffolds significantly improved the differentiation of chondrocytes and the formation of ECM in the defect area,which eventually stimulated the repairing of articular cartilage defect.(2)An aligned porous electrospun fibrous membrane with controlled drug delivery-an efficient strategy to accelerate diabetic wound healing with improved angiogenesisA chronic wound in diabetic patients is usually characterized by poor angiogenesis and delayed wound closure.The exploration of efficient strategy to significantly improve angiogenesis in the diabetic wound bed and thereby accelerate wound healing is still a significant challenge.Herein,we reported a kind of aligned porous PLLA electrospun fibrous membranes containing dimethyloxalylglycine(DMOG)-loaded mesoporous silica nanoparticles(DS)for diabetic wound healing.The PLLA electrospun fibers aligned in a single direction and there were ellipse-shaped nano-pores in situ generated onto the surface of fibers,while the DS were well distributed in the fibers and the DMOG as well as Si ion could be controlled released from the nanopores on the fibers.The in vitro results revealed that the aligned porous composite membranes(DS-PL)could stimulate the proliferation,migration and angiogenesis-related gene expression of human umbilical vein endothelial cells(HUVECs)compared with the pure PLLA membranes.The in vivo study further demonstrated that the prepared DS-PL membranes significantly improved neo-vascularization,re-epithelialization and collagen formation as well as inhibited inflammatory reaction in the diabetic wound bed,which eventually stimulated the healing of the diabetic wound.Collectively,these results suggest that the combination of hierarchical structures(nanopores on the aligned fibers)with the drugs as well as ions from the membranes,which could create a synergetic effect on the rapid stimulation of soft tissue defect,is a potential novel therapeutic strategy for highly efficient soft tissue require.