Preparation Of Anti-inflammatory,Anti-oxidative,And Self-adhesive Gallic Acid-gelatin Composite Hydrogeland Its Application For Diabetic Wound Healing

The continuous inflammatory response in the diabetic skin wound leads to excessive production of reactive oxygen species,which cause a vicious circle of long-term inflammation,and thus the diabetic wound healing is slow and even unable to heal completely.Hydrogel based wound dressing is a new type of wound dressing that has attracted much attention in recent years.To promote the diabetic skin wound repair,It is necessary to develop a multifunctional hydrogel dressing with anti-oxidation,anti-inflammatory and other biological activities.Because the skin of diabetic patients is relatively fragile,it is very important to design an adhesive and soft hydrogel dressing.In order to meet all the required characteristics for the treatment of chronic diabetic skin wounds,this study designed a biodegradable self-adhesive multifunctional hydrogel with antioxidant and anti-inflammatory capabilities.The formation mechanism of the hydrogel was discussed;the mechanical properties and tissue adhesion properties of the hydrogel were characterized;the interactions of the hydrogel with cells was studied;Prove the anti-oxidation and anti-inflammatory ability of hydrogel in vitro and in vivo;and evaluated the ability of hydrogel to promote diabetic skin wound repair.The specific research content can be divided into the following parts:(1)Inspired by the biological activity of natural plant polyphenols,pre-polymerized gallic acid(PGA)was complexed into a methacryloyl gelatin(GelMA)network to obtain the gallic acid-gelatin composite(PGA-GelMA)hydrogel.Firstly,gallic acid(GA)was pre-polymerized to form PGA oligomers in an alkaline and oxygen environment;secondly,PGA was added into the GelMA solution and then GelMA was polymerized through free radical reactions to form PGA-GelMA hydrogel.The PGA contains a large amount of phenolic hydroxyl and quinone groups,which imparted sufficient tissue adhesion to the hydrogel.In addition,the non-covalent bond interactions between the phenolic hydroxyl groups on the PGA and the amino groups on the GelMA chain endowed the PGA-GelMA hydrogel with high toughness and good flexibility.The experimental results of mechanical performances and adhesion test proved that the PGA-GelMA hydrogel has good flexibility and excellent tissue adhesion.(2)PGA was introduced into the hydrogel system due to its multiple biological activities,such as anti-inflammatory and anti-oxidant,and therefore the obtained PGA-GelMA hydrogel exhibit excellent antioxidant and anti-inflammatory.The DPPH free radical scavenging experiments proved that PGA-GelMA hydrogel had highly efficient free radical scavenging ability.In vitro ROS removal experiments showed that PGA-GelMA hydrogel can remove ROS and protect cells from excessive ROS damage.In vitro macrophage culture experiments proved that PGA-GelMA hydrogel has the ability to inhibit the secretion of inflammatory factors from macrophages.PGA also enriched with cate The fibroblasts culture experiments showed that PGA-GelMA hydrogel can promote cell adhesion and proliferation.In summary,the PGA-GelMA hydrogel meets the required characteristics of hydrogel wound dressings for diabetic skin wounds.(3)The hydrogel is employed as a wound dressing to repair the full-thickness skin wound on the back of diabetic rats.The results show that PGA-GelMA hydrogel has excellent anti-oxidation and anti-inflammatory abilities,alleviating chronic inflammation in the wound microenvironment caused by oxidative stress and increased expression of pro-inflammatory cytokines in the early stage of skin wound healing.The PGA-GelMA hydrogel exhibits excellent tissue repair ability and accelerates wound healing during the skin wound repair stage.In summary,this study developed multifunctional gallic acid-gelatin(PGA-GelMA)composite hydrogel with antioxidant,anti-inflammatory,and tissue adhesion properties.This natural polymers-based hydrogel has superior biodegradability.The PGA-GelMA hydrogel has inherent antioxidant,anti-inflammatory and promoting cell generation ability in a drug free manner.Therefore,the hydrogel can provide an effective and safe treatment strategy for promoting the healing of chronic wounds.