Using Hyaluronic Acid Based Hydrogel For The Investigation Of Inflammation Regulation Effect To Wound Healing

The skin,as the surface of the body,is a barrier which protect the body from external threats.The transition between the four main phases of the healing process is of great importance for wound repair.The inflammation phase is an important transition phase that leads the subsequent healing process.The transition of pro/anti-inflammatory behaviors makes the inflammatory response extremely modifiable.Therefore,it has become a main regulation target for researchers when they design the repair strategies.Hydrogels could provide wet healing conditions for wound,while they could get different biological functions through various construction strategies.Therefore,inflammation modulating hydrogel has gradually become a focused field in the research of wound repair.Currently,most of the inflammation modulating hydrogels are focused on promoting wound healing by inflammation inhibition due to the concern of chronic wounds induced by excessive inflammation.However,it has been demonstrated that activated inflammation can also accelerate wound healing.But the mechanism of it still lacks in further investigation.In this study,two types of hyaluronic acid(HA)based hydrogels were prepared to activate inflammatory response in different ways,which were based on the effect of microenvironmental temperature and bioactive compound on the inflammatory response during wound healing process.Furthermore,the effect of activated inflammatory response induced by hydrogel on wound healing was investigated.In the first part of the work,a chemically cross-linked hydrogel with nearinfrared light photothermal responsiveness was prepared using HA and graphene oxide,which was inspired by the potential associations between inflammation and local temperature of wound site.The optimal temperature of photothermal therapy(PTT)to accelerate wound healing was selected by in vitro and in vivo experiments.Then,the inflammatory response was investigated.The PTT results in a more rapid “activation-regulation” response during the inflammation phase,which makes the transition from the inflammation phase to the proliferation phase earlier.Eventually,it can promote angiogenesis,collagen deposition and accelerate wound healing.In the second part of the work,in order to fully use the different biological functions of two molecular weights of HA,a hydrogel composited by high and low molecular weight HA was prepared.By modifying low molecular weight HA(LHA)with a reduction-responsive disulfide bond,the hydrogel was able to partially dissolve in the presence of exogenous glutathione to release LHA with pro-inflammatory function.The hydrogel has certain functions of promoting fibroblast proliferation and wound healing because of the presence of high molecular weight HA(HHA).And when it releases LHA under the presence of glutathione,it can activate the inflammatory response of macrophages and wound effectively,and promote the transition of the inflammation phase,which further accelerates wound healing.In summary,HA-based hydrogels with different strategies to activate the inflammatory response in wound site are prepared in this study.The work is instructive for hydrogel photothermal treatment strategy in wound healing.In addition,it provides a new way to use the biological function of HA.Furthermore,the strategy of promoting wound healing by activated and accelerated inflammatory response also provides innovative idea for the therapeutic method of wound healing.