Fabrication And Properties Of Injectable Hyaluronic Acid Hydrogel Based On Phenyl Borate

With the intensification of aging and Increased injuries for exercise,cartilage damage is becoming more common clinically.However,because of the its special structure and dense extracellular matrix of cartilage,its self-repair ability is very limited.At present,there are some shortcomings in various methods used clinically to treat cartilage injury,including microfracture surgery,autologous/allogenic cartilage transplantation,autologous/allogenic cartilage cell transplantation,etc.Cartilage tissue engineering is considered one of the most potential methods for repairing cartilage damage.Many biomaterials have been developed as tissue engineering scaffolds.Among them,injectable hydrogel scaffolds have attracted widespread attention in cartilage tissue engineering due to their characteristics of minimally invasive transplantation,matching irregular defects,and easy to contain drugs and cells.In this paper,a variety of injectable hyaluronic acid-based hydrogels were designed based on phenylboronic acid esters by grafting 3-carboxyphenylboronic acid onto hyaluronic acid,and the mechanical properties of the hydrogels have been improved by double cross-linking,which can be used as cartilage tissue engineering scaffolds to better meet the needs of cartilage regeneration and repair.First,two hyaluronic acid derivatives were prepared,namely phenylboronic acid and furan-modified hyaluronic acid,dopamine and furan-modified hyaluronic acid.By simple blending of the two derivative solutions,a single crosslinked hydrogel can be formed under physiological conditions.By adding maleimide-terminated four-arm polyethylene glycol to further react with furan,a double-crosslinked hydrogel was obtained.The properties of single-crosslinked hydrogels and double-crosslinked hydrogels were characterized.The results showed that the furan group and dopamine group,furan group and phenylboronic acid group were successfully modified on the hyaluronic acid main chain by amidation reaction,and two modified products HA-Furan-DA and HA-Furan-PBA were obtained;SC hydrogels prepared with HA-Furan-DA and HA-Furan-PBA were p H sensitive,dissociated under acidic conditions,and formed gels under alkaline conditions.Dynamically reversible phenylboronicacid esters gave SC hydrogels self-healing properties and injectability.The introduction of dopamine made the hydrogel have good adhesive properties,so that the hydrogel and cartilage tissue could form a good interface combination;DC hydrogel had good mechanical properties;it exhibited different swelling rates at different p Hs,but there was no significant difference in compression modulus;DC hydrogels with phenylboronic acid groups had better resistance to enzymatic degradation.In vitro cell experiments showed that: DC hydrogel had good biocompatibility,could maintain ATDC-5 survival and promote its proliferation.Secondly,on the basis of ensuring the versatility,the multi-functional hydrogel prepared in the earlier stage was further optimized in the scheme.The vinyl and phenylboronic acid groups were modified onto the hyaluronic acid main chain.Under the guidance of the medium,phenylboronic acid and hyaluronic acid formed a self-crosslinking hydrogel,and then the four-arm PEG capped with thiol groups reacted with vinyl by photocrosslinking to obtain a double-crosslinkable injectable hyaluronic acid-based hydrogel.This study successfully modified the vinyl and phenylboronic acid groups on the hyaluronic acid main chain to obtain the modified product HA-MA-PBA,the degree of substitution of the two groups was DS(MA)= 21%,DS(PBA)= 15.8%;there are a variety of basic amino acids in the medium,which can stabilize the negatively charged phenylboronic acid ester under physiological conditions,promote the crosslinking of phenylboronic acid and hyaluronic acid to form a single crosslinked hydrogel,and the dynamic reversible phenylboronic acid ester gave the hydrogel self-healing properties and injectability;SC hydrogel has certain adhesion to biological tissues.In addition,double-crosslinked hydrogels were prepared by photocrosslinking.The difference between the gelation time of the photocrosslinking between thiol-ene and double bonds and the mechanical properties of the hydrogels were discussed.Both the prepared DC hydrogels had good biocompatibility and could promote the proliferation of BMSCs.Finally,in the form of photocrosslinking,microgels of different sizes were prepared through superhydrophobic surfaces.The microgels achieved self-assembly under the guidance of culture medium,and the injectability of self-assembled hydrogels was studied.The methodof preparing microgels on super-hydrophobic surfaces was universal and convenient for changing the raw materials of hydrogels and wrapping a variety of cells.In summary,in this paper,hyaluronic acid was used as the basic material of the scaffold.3-Carboxyphenylboronic acid was grafted onto hyaluronic acid.Based on phenylboronic acid ester,a variety of injectable hyaluronic acid-based hydrogels were designed.On the basis of giving the hydrogel self-healing properties and adhesion,the mechanical properties of hydrogels were improved through the form of double cross-linking.It could be used as a cartilage tissue engineering scaffold for cartilage regeneration and repair.