Preparation And Basic Research On The Application Of Self-healing Hydrogels For Burn Wound Healing

Hydrogels,which consist of hydrophilic three-dimensional networks that can accelerate wound healing,are considered the most promising modern dressings.Self-healing hydrogels can self-repair damage and restore their original structure and function due to their reversible dynamic bonds,and have a relatively long service life.Through molecular and chemical structure design,self-healing hydrogels can have excellent tissue adhesion,mechanical properties and biological efficacy.Both hyaluronic acid and gelatin are the main components of the extracellular matrix,have good biocompatibility.Hyaluronic acid has moisture retention,and can promote wound healing.Gelatin has excellent biodegradability and low immunogenicity.Therefore,hyaluronic acid and gelatin were selected as the main chains to prepare hydrogels.Schiff base chemical cross-linked self-healing hydrogels,catechol-Fe³⁺coordination physical cross-linked self-healing hydrogels and physicochemical double cross-linked self-healing hydrogels were prepared respectively.The properties of physicochemical double cross-linked hydrogels and single cross-linked hydrogels were compared,and the application basis of the double cross-linked self-healing hydrogels as burn wound dressing was explored.The main research results are as follows:（1）Oxidized hyaluronic acid（OHA）and amino-gelatin（AG）were prepared by modifying hyaluronic acid（HA）and gelatin respectively.Schiff base cross-linked hydrogels（AG-OHA）with different R values were prepared by changing the ratio of aldehyde group in OHA and amino group in AG（R value）.The physical and chemical properties of AG-OHA hydrogels did not show regular changes with the increase of R value,but were mainly affected by the number of imine bonds.The more the number of imine bonds,the higher the cross-linking density of hydrogel.AG-OHA-1.0 hydrogel had the highest cross-linking density,the shortest gelation time（250±3 s）,the strongest mechanical property（G’=61.5 k Pa）and the largest adhesion strength（4.79±0.95 k Pa）.（2）Catechol grafted-OHA（OD）was prepared by modifying OHA.Coordination cross-linked self-healing hydrogels（OD-Fe（III））were prepared by changing the molar ratio of Fe³⁺and catechol.The relatively low molar ratio of Fe³⁺and catechol enables Fe³⁺to coordinate with catechol to the greatest extent,which makes the hydrogels show the characteristics of fast bond formation and dynamic equilibrium reconstruction.OD-Fe（III）-1 hydrogel had the highest adhesion strength（8.86±0.42 k Pa）,the gelation time was 31±4 s,and its G’was 2850 Pa.（3）The physicochemical double cross-linked self-healing hydrogels（AG-OD-Fe（III））were prepared by combining Schiff base cross-linking and coordination cross-linking.By comparing the properties of physicochemical double cross-linked self-healing hydrogels and single cross-linked self-healing hydrogels,the results showed that physicochemical double cross-linking greatly improved the physical and chemical properties of the self-healing hydrogels.The double cross-linking shortened the gelation time of AG-OD-Fe（III）hydrogel,and enhanced the mechanical and adhesive properties of the hydrogels while maintaining good self-healing properties.AG-OD/1.0-Fe（III）hydrogel had the highest cross-linking density,the shortest gelation time（52±2 s）,the strongest mechanical properties（G’=535k Pa）,the maximum adhesion strength（19.3±1.01 k Pa）,and the recovery rate of G’was97.1±1.3%.This made the hydrogel suitable for dynamic wound with high frequency movement,such as groin and joints.Physicochemical double cross-linking can not only improve the physical and chemical properties of AG-OD-Fe（III）hydrogels,but also effectively improve the biological efficacy of the hydrogels,enhance the hemostatic properties and the inherent antibacterial ability of the hydrogels.The AG-OD/1.0-Fe（III）hydrogel was applied to the treatment of deep second-degree burn wounds.The results showed that the hydrogel can accelerate the reconstruction of skin structure and function,and shorten the healing time of burn wound to 13 days.The AG-OD/1.0-Fe（III）hydrogel is a potential burn wound dressing.