Research On Antimicrobial Peptides-loaded Sodium Alginate/GelMA/HA Composite Hydrogel And Its Application In Infected Wound Repair

The skin is the first line of defense for organisms and it is easily damaged due to external mechanical stimulation or internal pathological factors.The natural healing process of wounds is relatively slow,and it is easy to delay the healing due to infection.The dressings are usually used clinically to promote the repair process.Traditional dressings such as gauze cannot provide a moist environment for the wound,and are easy to adhere and make the injury more serious.Therefore,the development of multifunctional skin wound dressings with good antibacterial effects and tissue repair effects has become a research hotspot in this field.Hydrogel material can keep the wound around moist,and its structure is similar to extracellular matrix,so it is used in wound dressings.However,most hydrogels have defects such as poor mechanical properties and weak anti-infective performance,which are limited in clinical applications.The purpose of this research is to develop a sodium alginate(SA)/Gel MA/HA composite hydrogel with good mechanical properties.By integrating antimicrobial peptides,the multifunctional composite materials that could promote wound repair and local sterilization can be constructed to provide an effective solution for the problem of wound repair.The main research contents and results are as follows:The micro/nano HA particles have good biocompatibility and a large specific surface area,and are often used as carriers for drugs or genes.In this study,by changing the concentration of the reaction system,three kinds of micro/nano hydroxyapatite particles(The surface microstructure was nanoneedles,nanorods and nanosheets,respectively)with mesoporous structure were prepared by using sodium citrate as a template.By loading antimicrobial peptides(AMPs),mesoporous material as a drug carrier,the effect of its hierarchical structure on the release performance of the drug was analyzed.The experimental results showed that HA particles with a flaky hierarchical structure have the highest loading efficiency,and could achieve an orderly controlled release of AMPs for up to 9 days.The results of circular dichroism and mass spectrometry indicated that the stability of the released AMPs was not affected.In addition,the results of antibacterial experiments showed that the composite microspheres with a flaky hierarchical structure The antibacterial activity of the composite microspheres with a flaky hierarchical structure against S.aureus and E.coli was still 30%and 22%at 7 day respectively.The SA/Gel MA hydrogels with double network structure were prepared by chemical and physical cross-linking methods.At the same time,different concentrations of HA microspheres with hierarchical structure were incorporated to explore the influence of the content of HA particles on the hydrogel mechanical property.The results showed that the HA particles doped with a concentration of 3%could increase the mechanical strength of the hydrogel by 50%.The polydopamine modified HA particles(PDA-HA composite microspheres)were incorporated into the hydrogel to explore its synergistic antibacterial activity and skin repair properties.The results showed that the composite hydrogel containing PDA-HA microspheres could increase the temperature to about 60°C within 10 minutes under near-infrared light irradiation with a power of 1.5W/cm~2,which could kill bacteria efficiently,and the presence of AMPs could make the composite hydrogel possess long-term antibacterial properties.The model of wound and infected wound in rats was established and the results of in vivo healing experiment showed that SA/Gel MA/HA and SA/Gel MA/PDA-HA@AMPs composite hydrogels exhibited good wound healing effects,and the healing rate could reach about 95%at14 days;SA/Gel MA/AMPs and SA The/Gel MA/PDA-HA@AMPs composite hydrogel showed a good healing effect on infected wounds,and the healing rate at 7 days could reach83%and 75%,respectively.Due to the fact that hydrogel can keep the environment moist around the wound,the above research has developed a multifunctional hydrogel wound dressing with better mechanical properties to achieve effective repair of infected wounds,which is expected to provide a new solution for clinically infected wounds.