The Regulatory Effects Of Alginate Hydrogel On Neural Stem Cell Differentiation

Ocean provides abundant resources for marine biomaterials,which have excellent bioactivities,and are widely used in food,pharmaceutical,and biomedical sciences.Alginate,a marine polysaccharide derived from brown algae,can be cross-linked with divalent cations under mild conditions to form a three-dimensional hydrogel structure,similar to physiological tissues.With good biocompatibility,low immunogenicity,and soft mechanical property,the alginate hydrogel has been increasingly used in the research fields of neural tissue engineering and biomechanics.This work focuses on the alginate hydrogel biomaterial,and attempts to develop and investigate its function in neural tissue regeneration.Firstly,we optimized the preparation method of alginate hydrogel through the "thaw-induced gelation" and a delicate control of the gel mechanical properties,constructing a hydrogel platform suitable for neural cell cultivation and differentiation.Next,we used the alginate hydrogel as a substrate and achieved efficient in vitro differentiation of human neural stem cells to astrocytes.Finally,we investigated the cellular and molecular mechanism of neural stem cell differentiation facilitated by the hydrogel,and found that the cell’s mechanosensing of the hydrogel triggered activation the Piezo1 calcium channel and YAP/TEAD-mediated transcription,promoting neural stem differentiation and astrocytic development.The ways of preparation and application of the alginate hydrogel demonstrated in this study provide a bioactive platform for the research in neuroscience and mechanobiology.Meanwhile,this work provides novel insights into the regulatory mechanisms of human neural stem cell differentiation,which will benefit future studies on the role of astrocytes in physiology and diseases.This thesis consists of five parts:Chapter 1 provides an overview of marine biomedical materials and the fate regulation mechanism of neural stem cells,with a focus on the regulation of neural cells by alginate hydrogel;Chapter 2 introduces the materials and methods used in this thesis;Chapters 3 and 4 are the major parts of this thesis,in which Chapter 3 introduces the design principles and preparation methods of the alginate hydrogel-based neural cell culture and differentiation platform,with a focus on the analysis of hydrogel properties,biological compatibility and applicability;Chapter 4 explores the biological mechanisms of the alginate hydrogel material to promote neural stem cell differentiation;Chapter 5 summarizes this thesis and discusses its weaknesses and future outlook.