Preparation Of Hydrogel Based On Michael-addition And Their Applicationin Cartilage Tissue Engineering

Cartilage disease caused by cartilage damage or cartilage degradation is a relatively common disease,because the cartilage tissue has no blood supply and low capacity to repair itself,so we need to repair cartilage disease by means.Cartilage tissue engineering provides a new technique to solve the problem.Highly hydrated hydrogels can better mimic the viscoelasticity of cartilage extracellular matrix(ECM),maintain the chondrocyte phenotype and its injectable features in-situ avoiding the operation complexity.Therefore,hydrogel is an ideal biomaterial for cartilage regeneration.However hydrogel should be personalized designed and built to aim at solving the big problems existing in the cartilage tissue repair process not just a 3D support role for cells,such as poor mechanical properties,long gel time,poor self-healing capacity and non-binding ability with organization and so on.Therefore we designed this paper based on these problems.Click chemistry reaction is a new method in recent years for preparation of the hydrogel which is efficient.Compared to other reactions commonly used of click chemistry such as DA reaction,azide-alkyne reaction,light-initiated radical reaction,Michael-addition reaction needs no chemical initiator or catalyst which is harmful to cells,and it can react rapidly under physiological conditions without any other byproducts,so we exploited Michael-addition reaction for this paperFirstly,in order to improve the mechanical property of hydrogels,we have prepared well-defined hyaluronic/PEG network by Michael-addition click chemistry.By changing the degree of substitution of double bond and pH value of solution,the compressive modulus of hydrogel could be controlled from 35 KPa to 79 kPa.Due to the low internal friction,the hydrogel owned outstanding shape recovery.Meanwhile,the gel time of hydrogel was short ranging from 16 min to 62 min.Preliminary cytological experiments proved that the hydrogel had good cell compatibility and capacity to promote cell proliferation.Secondly,considering the poor interfacial bonding capacity of articular cartilage tissue,we oxidized hydroxyl group of hyaluronic acid to aldehyde group by sodium periodate and then reacted with cartilage tissue with Schiff-base crosslinking.Experiments showed that hyaluronic acid with aldehyde group could react with tissue.Meanwhile hydrogel ofhyaluronic acid polymer with aldehyde group could be chemical bonded to cartilage tissue and had a good ability of interface bonding.Finally,in order to improve the mechanical property of hydrogel further,we designed a dual network cross-linked hydrogels by two Michael-addition reactions,it proved that compared to SN hydrogel,DN hydrogel has better mechanical strength and deformation recovery property.Additionally,DN hydrogel with different molecular weight had different mechanical performance,hydrogel with smaller molecular weight had better mechanical strength.