Fabrication Of Hyaluronic Acid Hydrogel Films With Differetn Modulus For The Guidance Of Cellular Adhesion And Migriation

Cell behavior and function are regulated by a variety of environmental signals,including soluble factors,extracellular matrix(ECM)-mediated signals,and intercellular interactions.In these environmental signals,the Young's modulus of a material is an important factor governing the cell fate by altering the biomechanical properties of the ECM.In this thesis,we prepared methacrylic acid-functionalized hyaluronic acid hydrogels(MeHA)hydrogel films with different modulus and modulus gradients by controlling the degree of photopolymerization of MeHA,and investigated the effect of modulus of MeHA hydrogel films on the adhesion of H9C2 cells and the collective durotaxis migration of H9C2 cell cluster,respectively.In Chapter 2,we used the natural polysaccharide hyaluronic acid as a base material to introduce photocrosslinking sites by chemical modification.Five MeHA hydrogel films with different modulus were prepared by controlling the different UV illumination times.Then modified the cell-adhesive peptide on the surface of the MeHA hydrogel films.Modulus variability was characterized by atomic force microscopy(AFM)and peptide modification uniformity was characterized by fluorescence microscopy.H9C2 cells were cultured on the surface of five different modulus MeHA hydrogel films.The effect of modulus on cell adhesion behavior was obtained by counting cell spreading area.And immunofluorescence staining was used to observe actin,adhesion plaque protein and fibronectin,which are closely related to cell adhesion.As well as the mechanisms by which modulus differences affect cell adhesion behavior were explored by inhibiting the activity of the cell membrane surface integrin?v?3.In Chapter 3,we prepared MeHA hydrogel films with modulus gradients based on the results of Chapter 2.The range of modulus gradients of MeHA hydrogel films can be precisely controlled by means of the composition of precursors and photomask moving speed.Formation of H9C2 cell clusters in the modulus gradient region using PDMS templates to limit cell growth regions.The collective durotaxis migration behavior of H9C2 cell clusters was studied.In this thesis,we systematically investigated the effect of modulus factors of the MeHA hydrogel films on the adhesion and migration of H9C2 cells.The results of this study shed light on understanding the molecular mechanisms in the cell adhesion and collective cell migration,and may find applications in the engineering of novel scaffold materials.