Enzymatic Formation Of A Hydrogel From A Glycopeptide As A Biomimetic Scaffold For Tissue Engineering

Extracellular matrix(ECM)plays an important role in biological systems.It serves as a biological scaffold with biomechanical and chemical properties to supporting the adhesion and growth of cells.The preparation of biomimetic matrix materials with good biocompatibility,cell-adhesion and biological activity is an important direction in current tissue engineering research.Because certain peptide-based hydrogels have the disadvantages of low cell-adhesion and severe self-assembly conditions to work as biomimetic ECM,while glycopeptides have self-assembly properties,biological stability,biocompatibility and cell-adhesion as a class of biomolecules between glycoproteins and sugar amino acids.Therefore,glycopeptides have become one of the excellent choices for solving these problems and preparing novel biomimetic matrix materials.The main research contents of this paper are to use glucose and tyrosinephosphate(alkaline phosphatase substrate)to prepare a glycopeptide molecule,which can form supermolecular hydrogels through enzymatic reaction under physiological conditions for promoting cell adhesion and growth.At the same time,we also explored the potential of this glycopeptide hydrogel in tissue engineering applications by working as a biomimetic matrix material.In the first part of this thesis,we designed and synthesized a novel glycopeptide molecule,which can self-assemble into hydrogel by alkaline phosphatase inducing in the physiological condition.After the supramolecular self-assembly,the glucose moiety on the surface of the hydrogel acts as biomolecular clues to promote cell adhesion and growth through the interaction between the sugar and the receptor.After the inclusion of Deferoxamine(DFO),the self-assembled Gp gel serves as a reservoir for sustainably releasing DFO and inducing the generation of new blood capillaries in vitro and in vivo.The second part of this thesis focused on the use of ALP to induce biomineralization of hydrogel,to simulate the biomineralization process in natural bone mineral system.First,the glycopeptide hydrogel was soaked in a solution containing calcium ions and ?-phosphoglycerides(?-GP,a substrate for ALP),which could diffused into the hydrogel containing ALP.Then phosphate ions were released from from ?-glycerophosphate by ALP,and reacted with calcium ions to form insoluble calcium phosphate minerals(CaP).The presence of glucose moieties on the hydrogel surface promoted the adhesion,growth and osteogenic differentiation of mesenchymal stem cells.Therefore,in these processes,ALP can not only triggered the supramolecular self-assembly and formation of a supramolecular hydrogel from a glycopeptide,but also induced the in situ nucleation and growth of CaP.Due to the presence of mineral phase,the mineralized glycopeptide hydrogel exhibited significantly improved mechanical strengthes and bioactivities to mesenchymal stem cells.