Design,Fabrication,and Application Of Hydrogel-Based Burn Wound Dressing

Burns,especially extensive burns,are related to the severe morbidity and mortality,and accompanied by the inflammatory response,body temperature unbalance,and hypotensive shock.High-performance,low-cost burn wound dressings can possibly avoid or mitigate devastating effects（severe pain,infection,tissue necrosis,and permanent disabilities/disfigurements）to patients.However,burn wounds pose new challenges to burn wound care for their large burn area,irregular shape,hypersensitive anguish,massive exudate,and susceptibility to infection.The rational design and fabrication of high-performance,low-cost burn wound dressings are the key factors restricting the development of wound care.Existing burn wound dressings,such as traditional gauzes and absorbent cottons,autografts,tissue-engineering biological scaffolds,topical agents,and hydrogels,etc.,still suffer from insufficient therapeutic effect,inferior thermoregulation performance,and weak wound protection.These deficiencies may cause increased mortality,complications,and delayed healing.Recently,biomimetic polymer materials and hydrogel composite materials have attracted much attention,and multifunctional requirements of dressings,emergency care application,and intelligent development are still serious challenges.Based on the above problems,we use commercial and cost-effective materials to prepare the fast cooling and effective anti-inflammatory hydrogel-based first aid patch,stretchable and thermoregulatory hydrogel-based interactive bandage,and adaptive and electroactive hydrogel-based smart wound dressing by metamaterial,dual network,and molecular modularization design,respectively.Mechanical,electrical,thermodynamic,and biological properties of hydrogels,the structure-performance correlation of materials,and the assembly and application of selected high-performance hydrogels have been systematically studied,which greatly promote the development and commercial application of multifunctional biomaterials.Additionally,it is expected to facilitate further acceptance of society to high-quality biomaterials in health care.The specific work is as follows:1.Innovatively introducing the metamaterial design into the field of medical dressing,preparing a multi-layered topological structured first-aid burn wound patch to integrate rapid cooling,effective anti-inflammation,and wound protection,and achieving a breakthrough in the field of first-aid burn wound dressing.Inspired by the typical topological heterogeneous structure and multiple functions（i.e.,immune defense,automatic temperature regulation,and protection）of human skin,we design a cost-effective hydrogel-based multi-layered first-aid burn wound patch（FBP）to simultaneously integrate soft,cooling,and anti-inflammatory performances by employing commercial and affordable materials.Such a FBP contains a mesh topological poly（vinyl alcohol）-chitosan（PVA-CS）tough hydrogel layer,a poly（acrylamide）-chitosan（PAAm-CS）hydrogel layer,and poly（ethylene）films as the top and bottom encapsulation layers to prevent the dehydration.Among them,the high EO water-containing PAAm-CS hydrogel layer is designed to be a soft skin protective barrier to realize both fast cooling and anti-inflammation and reduce the irritation against damaged skin tissues;the mesh topological PVA-CS tough hydrogel layer is expected to provide the mechanical support for patients’body movements and also enhance the cooling performance by accelerating the water evaporation through enlarged contact surface.As-fabricated FBP exhibits a unique combination of intriguing mechanical,thermal,and biological properties,including softness（Young’s modulus:83 k Pa）,stretchability（fracture stain:>106%）,high thermal conductivity(0.54 W m^-1 K^-1),instant cooling（120 s）,effective antibacterial activity（96.2%for S.aureus,92.2%for E.coli）,and excellent biocompatibility(94.04%cell viability at 20 mg m L^-1 extract in 24 h).A second-degree scald rat model further demonstrates that fast-cooling and anti-inflammatory FBP can effectively reduce the tissue damage and inflammation levels by showing less edema formation and higher collagen/blood vessel ratios.With a set of these interesting performances,the FBP may be useful as a first-aid burn wound product to alleviate patients’sufferings and even rescue more lives in critical situation.2.Proposing a concept of interactive dressing for negative-pressure wound therapy and mechanically driven regeneration.An interactive hydrogel-based burn wound bandage with dual-network is prepared by chemical and physical crosslinking to integrate softness,thermoregulation,heat-induced driving effect.Achieving a breakthrough in the performance of temperature-responsive bulk material in the field of hydrogel-based burn wound dressing.Inspired by the biomechanical strategy of embryonic wound contraction and perfect regeneration,we employ a temperature-responsive hydrogel matrix（poly（N-isopropylacrylamide）,PNIPAAm）and stretchable polysaccharide polymer（sodium alginate,SA）by dual network design to develop a stretchable and thermoregulatory interactive hydrogel burn wound bandage with a view to negative-pressure wound therapy and mechanically driven regeneration.As-prepared PNIPAAm-SA hydrogel has excellent mechanical and thermodynamic properties,and exhibits a unique temperature-driven effect,including softness（Young’s modulus:9.9-16.7 k Pa）,stretchability（fracture strain:59.8-101.1%）,and thermoregulation（UCST:30-40°C）and driving effect（thermal bending angle:118°,thermal shrinkage rate:45%）.The above results prove the feasibility of interactive dressing in burn wound care,which is expected to lay an effective foundation for the smart application of hydrogel-based materials in wound dressing.3.Proposing a concept of smart dressing for personalized management and health monitoring.The smart hydrogel-based burn wound dressing is prepared by molecularly modular design,and its actuator/sensor integration application is realized by its temperature-responsive and strain sensing characteristics,which greatly promotes the development of intelligent and telemedicine field.Smart hydrogel-based burn wound dressing that can interact with the wounds,sense and react to the wound condition or environment changing by employing built-in sensors and/or smart materials（such as stimuli-responsive materials and self-healing materials）,have been proposed to effectively facilitate wound healing.In this work,a conductive polymer（poly（3,4-ethylenedioxythiophene）:poly（styrenesulfonate）,PEDOT:PSS）and a temperature-responsive hydrogel matrix（poly（N-isopropylacrylamide）,PNIPAAm）are used to prepare an adaptive（Young’s modulus:10.6-18.4 k Pa,fracture strain:42.0-114.2%）,electroactive(electrical conductivity:15.2 m S m^-1,impedance:46.46Ω,103 Hz),and thermoregulatory（UCST:35°C）smart hydrogel.The electroactive and thermoregulatory smart hydrogel-based burn wound dressing adapts to irregular,deep,or complex burn wounds with spontaneous shape changes,provides an electrical stimulation（ES）therapy by rehabilitating endogenous electrical current conduction,and realizes human health movement monitoring with its strain sensing properties,thus solving the core challenge of wound healing promotion and monitoring applications.It provides effective technical support and theoretical guidance for the application and development of hydrogel-based materials in smart wound dressing.In summary,the concept of passive,interactive,and smart wound dressing is firstly proposed in this paper.Three kinds of high-performance and cost-effective hydrogel-based burn wound dressings are designed and prepared by metamaterial,dual-networked,and molecularly modular designs.The material correlation of structure-performance and an efficient integration/assembly strategy of hydrogel-based burn wound dressing have been revealed.Additionally,the development,optimization,and estimation of various hydrogel-based wound dressings have been completed,and achieving a breakthrough in wound protection,body temperature regulation,efficient healing,and wound management of hydrogel-based burn wound dressing.