Preparation Of Natural Polymer Based Hydrogel And Its Application In Tissue Repair

Millions of people worldwide die each year from tissue damage caused by injury or disease.Tissue damage can severely reduce the quality of life of patients and impose a huge medical burden on them.Traditional methods of organ tissue transplantation treatment are greatly limited by the shortage of donors,and the emergence and development of tissue engineering has opened up new avenues for tissue repair.The selection of suitable and biocompatible scaffold materials is particularly important in tissue repair treatment,among which natural polymer-based hydrogels have attracted much attention because of their physical and biological properties similar to those of extracellular matrix.The development of natural polymer-based hydrogels with good biocompatibility and their application in tissue repair after loading with drugs and cells is of great importance to promote the development of regenerative medicine.In this paper,two types of natural polymer-based composite hydrogels,polysaccharide and protein,were prepared by selecting two natural polymers,chitosan and bovine serum albumin,as substrates,respectively,based on which they were functionally modified for different tissue repair applications,and their potential applications in the field of alveolar ridge preservation and spinal cord injury repair were evaluated,respectively.The main studies are as follows.(1)CS/PEG composite hydrogels were prepared by chemically cross-linking a four-arm polyethylene glycol active ester(4-arm-PEG-NHS)with chitosan(CS),and a gradient concentration of polyhexamethylene guanidine hydrochloride(PHMB)was added to the hydrogel system as an antimicrobial agent to prepare CS/PEG/PHMB hydrogels with antimicrobial properties.The hydrogel showed a uniform three-dimensional porous structure with pore size distribution between 50 and 100 μm;the alkali-treated hydrogel had excellent mechanical properties with a compressive strength of 450 kPa;the prepared chitosan-based hydrogel exhibited degradation properties under weak acidic and alkaline environments,and the degradation rate reached about 37%in a 28-day in vitro degradation experiment,and PHMB The antibacterial performance of the prepared CS/PEG/PHMB hydrogels was related to the concentration of PHMB in the system,and it could effectively inactivate all bacteria when its concentration reached 1%.(2)BSA/PEG composite hydrogels were prepared by chemical cross-linking of 4-arm-PEG-NHS with bovine serum albumin(BSA),and microglia were resuspended in the pre-gel solution before gel formation to achieve three-dimensional encapsulation of microglia.The pore size and porosity of the prepared BSA/PEG hydrogel decreased with the increase of 4-arm-PEG-NHS concentration in the system,and the average pore size of the hydrogel was distributed between 10 μm and 50 μm for each concentration.The modulus of 5%BSA/PEG hydrogel is 1073.95±6.2 Pa,which is closest to the spinal cord modulus(～1000 Pa),and can provide microglia with a three-dimensional mechanical microenvironment similar to that in living organisms;the prepared BSA/PEG hydrogel is non-cytotoxic and compatible with microglia,and microglia can maintain normal proliferation inside the hydrogel;the microglia-loaded BSA/PEG hydrogel The BSA/PEG hydrogel loaded with microglia could be transplanted to the spinal cord injury site by injection to reduce scar formation;the introduction of microglia could also alleviate the inflammatory response at the injury site and stimulate tissue regeneration;the recovery of motor function of the hind limbs of mice could be significantly improved after implanting the hydrogel scaffold into the treatment.