Preparation Of Bioglass-Polymer Composite Microsphere/Hydrogel And Their Application In Tissue Regeneration

Bioglass(BG)has not only good bioactivity for hard tissue repair such as bone and teeth,but also bioactiviyty to promote cell proliferation,migration,differentiation,and enhance angiogenesis for soft tissue repair.Studies have shown that bioglass may be used for the repair of soft tissues such as skin,blood vessels,nerves,intestines,stomach.However,the bioglass in the form of block and powder that commonly used in hard tissue repair may not be suitable for soft tissue repair due to the problems such as difficulty in fixing,shaping,and excessive alkalinity in wet environment.For this reason,we developped bioglass/polymer composite materials with good biocompatibility to meet the needs of soft tissue repair.However,there are still many scientific questions to be answered in applying bioglass composite hydrogels for soft tissue repair.(1)The effect of bioglass on the cell loading performance of tissue engineering materials(2)Whether the bioglass-containing composite hydrogel can activate cell-cell interactions in vitro and enhance tissue and organ repair in vivo such as the heart;(3)In addition to providing bioactivity,whether bioglass can endow hydrogel with other functions to meet the multiple needs for soft tissue repair.The purpose of this thesis is to explore the application of bioglass composite hydrogel for soft tissue repair,and propose the research topic of the preparation of bioglass composite hydrogel and its application in wound/myocardial tissue repair.First,a bioglass/polylactic acid(BG/PLA)composite microsphere with macroporous structure for the in vitro cell expansion for possible tissue engineering applications.Then,the application of bioglass for the repair of myocardial tissue was investigated including the activation of stem cells and the interaction between stem cells and myocardium by the bioglass composite hydrogel,and the application of the composite hydrogel for the treatment of myocardial infarction.At last,the effects of bioglass and its ions on the multifunctionality of hydrogels were explored,and a composite hydrogel suitable for wound clouture and accelerating chronic wounds healing was prepared.The main research contents and results are as follows:(1)Porous microcarrier with macroporous structure can not only amplify cells in vitro,but also serve as cell delivery tools to deliver cells to damaged tissues by injection.Bioglass is an inorganic material with excellent biological activity,however,it is difficult to directly prepare BG microcarriers with macroporous structure.Therefore,in this study,a novel BG/poly-lactic acid(PLA)porous microspheres was prepared by double emulsion method.The morphology and structure of the microsphere were characterized by SEM,and the content of BG in the composite microsphere was measured by thermo gravimetric analysis TGA and its ion release was detected by ICP.Cell proliferation experiments showed that cells could adhere and grow on the surface and inside of the microspheres.The results show that the microsphere with interconnected open-pore microstructure is suit for cell adhesion and proliferation.Bioglass can promote cell proliferation in the microspheres and the obtained BG/PLA composite microsphere has great potential applications in tissue engineering.(2)Stem cells therapy has been proved as a promising strategy for myocardial infarction(MI)treatment.However,the therapeutic efficacy has been mainly limited by cellular activity of transplanted mesenchymal stem cells(MSCs).In order to enhance the therapeutic effect of MSCs in the treatment of myocardial infarction,we developed a novel bioglass(BG)/?-polyglutamic acid(?-PGA)/chitosan(CS)hydrogel with self-healing property.The implantation of MSCs loaded BG/?-PGA/CS composite hydrogel in the mice acute myocardial infarction(AMI)model showed a significant improvement in the therapeutic efficacy with improved cardiac function,attenuation of heart remodeling,antiapoptosis of cardiomyocyte and accelerated vascularization.The in vitro cell experiments demonstrated that the BG/?-PGA/CS hydrogel activated the intercellular interaction between MSCs and Cardiomyocytes(CMs),which resulted in reduced cell apoptosis and enhanced angiogenesis.Our study suggests that activation of MSCs by silicate bioactive materials may be an effective approach for enhance stem cell therapy.(3)Dual-adhesiveness to both tissue and implant biomaterials and bioactivity to stimulate tissue regeneration are interesting properties for developing new generation of tissue repairing hydrogels with potential new clinical applications.In this study,we developed a unique bioglass(BG)/oxidized sodium alginate(OSA)composite hydrogel,in which BG played a multi-functional role to endow the hydrogel with both dual-adhesive and bioactive properties.On one side,the BG could improve the tissue bonding strength by creating alkaline environment to stimulate the chemical reaction between OSA and the amino groups on surrounding tissues.And on the other side,the BG endowed the hydrogel with the adhesiveness to implantable materials by releasing Ca ions which might be chelated with the carboxyl groups of the hydrogel matrix.In addition,the composite hydrogel also showed excellent bioactivity to stimulate angiogenesis and promote wound healing.This study demonstrates that multi-functional hydrogel can be designed by utilizing the multi-functional ions released from silicate BG,and the BG/OSA hydrogel showed good potential as adhesive and bioactive materials for wound healing applications.We found that compounding bioglass with hydrogel / microcarrier can meet the needs of soft tissue repair.On the one hand,bioglass can provide the biological activities required for soft tissue repair,such as: promoting the loading of cells on biological materials,activating the interaction between cells,promoting the expression of cell angiogenesis genes;On the other hand,bioglass can regulate the multifunction of composite materials,such as self-healing,injectability and adhesion.