Research On Biological Safety Of Hyaluronan Hydrogel Cross-linked By Polyethylene Glycol

Hyaluronan (HA) is a glycosaminoglycan built from repeating disaccharide units withglucuronic acid and acetyl glucosamine, now widely used as materials for tissue engineering.The natural HA structure has been remodeled to its derivatives gel to enlarge its degradationcycle, as degradation rate of the natural HA in the body is fast, to expand its applications intissue engineering. The performances of crosslinked sodium hyaluronate (CHA) hydrogelproduct such as resistance to degradation, physical and chemical properties are better thannatural HA, meanwhile we need to study its biological safety to make the CHA gel meet therequirement for using as tissue engineering materials.The study of biological safety evaluation was completed for CHA hydrogel cross-linkedby polyethylene glycol (PEG) according to standard ISO10993biological evaluation ofmedical devices, and a evaluation method of biological safety applied to CHA hydrogel wasestablished.Evaluate the degradation rate of the CHA hydrogel and skin local inflammatory reactionby the observation of skin exterior where the CHA hydrogel implanted, evaluate thedegradation rate based on the area and height of the ridge, and judge the local inflammatoryreaction based on the abscess, escharosis, caking situation; Compare the feed-intake andbody weight increase of the mice before and after CHA hydrogel implant to judge theinfluence to growth of the mice from the implant, and evaluate the influence to behavioralresponses of the mice from the implant according to the observation of the mice’s local,systemic or action responses; Evaluate the local inflammatory reaction of the skin where theCHA hydrogel implanted according to the observation of tissue responses of the anatomizedskin, and evaluate the in vivo degradation rate of the CHA hydrogel by determine the amountof the residual CHA hydrogel in the anatomized skin use of the carbazole colorimetric method;Evaluate the local histopathological response by making the pathological sections and HEstaining of the mice skin where the CHA hydrogel implanted; Evaluate the in vivodegradation rate of the CHA hydrogel by measuring the hyaluronan content in the mice’sblood. A biological safety evaluation research of CHA hydrogel with the crosslinking agent PEG,HA content was1.5%and degree of cross-linking is6%was carried out with the establishedmethod above. The local and pathology observation of the mice’s skin without inflammatoryreaction, the trends of dermal thickness and hair follicle amount showed that the implantedCHA hydrogel with the crosslinking agent PEG have a good biocompatibility; The behaviorand metabolic monitoring of the mice showed no abnormalities; The degradation cycle bydetermining the amount of the residual CHA hydrogel in the anatomized skin of the CHAhydrogel was2months, the in vivo degradation resistance performance was better thannatural hyaluronan hydrogel (degradation cycle was14days); The degradation cycle bymeasuring the hyaluronan content in the mice’s blood was2months, which was same as theresult by determining the amount of the residual CHA hydrogel in the anatomized skin.The established method could be used for the evaluation of the CHA hydrogel inbiological safety and degradation resistance performances, and the method for characterizingin vivo degradation resistance by measuring the hyaluronan content trends in the mice’sblood with advantages of high reliability, ease of operation and high sensitivity, there wasn’tany similar method for CHA hydrogel performance evaluation has been reported.