Research progress on mechanism of peptide hydrogels for promoting wound healing
[Background]Wounds caused by trauma,burns,diabetes and surgery have always posed a threat to human health,and treating these wound has become a serious clinical challenge and economic burden.The wound healing process is complex,including four stages:hemostasis,inflammation and infection,proliferation and remodeling.However,due to problems such as infection,excessive inflammation,and secondary injury,the healing process often deviates from its normal path,resulting in abnormal wound repair.Peptide hydrogels,known for their good biological functions and activities,biocompatibility,and biodegradability,have broad application prospects in different stages of wound healing.In recent years,the research and development of peptide hydrogels for different stages of wound healing and their corresponding mechanism have made breakthrough progress.Currently,while there are reviews on hydrogel dressings focusing on wound healing,there is a lack of comprehensive review on the role and mechanism of polypeptide hydrogels in different stages of wound healing.[Progress]This paper systematically reviews the roles and mechanisms of peptide hydrogels in hemostasis,inflammation and infection,and proliferation and remodeling of various wound healing processes.The positively charged amino group of polypeptide hydrogels attracts plasma fibrin,platelets and red blood cells through electrostatic action,inducing the release of physiological aggregators such as adenosine diphosphate(ADP)and thromboxane 2(TXA2),causing irreversible aggregation of platelets and promoting the formation of blood clots.At the same time,up on absorbing blood,these hydrogels expand to form a network that seals cracks in blood vessels or wounds,or they self-assemble to form a nanofiber barrier that acts as a physical hemostatic agent.Polypeptide hydrogels activate the function of the immune system through the immunomodulatory activity of the polypeptide itself or self-assemble to form a structure simulating extracellular matrix(ECM).On the other hand,polypeptide hydrogels can serve as a drug delivery platform within wound dressings,promoting the transformation of macrophages from the M1 type to the M2 type by loading anti-inflammatory drugs,thus balancing pro-inflammatory and anti-inflammatory responses.Polypeptide hydrogels affect bacterial cell membranes through their cationic,self-assembled nanostructures,causing the release of bacterial contents and thus killing bacteria.In addition,the bactericidal effects of antimicrobial peptides and the impacts of photothermal therapy(PTT)and photodynamic therapy(PDT)of photothermal substances can be synergistic by coupling with photothermal substances.By activating focal adhesion kinase/integrin linked kinase(FAK/ILK)signaling pathway and Wnt/β-catenin pathway,and by inhibiting the expression of matrix metalloproteinase-9(MMP-9),polypeptide hydrogel can promote the proliferation of human dermal fibroblast(HDF),activate growth factors and,thus promoting angiogenesis and collagen synthesis,and accelerate the wound healing process.Currently,some peptide hydrogel products for hemostasis and anti-inflammation have been applied in clinical practice.[Perspective]Although breakthrough progress has been made in the research and development of peptide hydrogels for different stages of wound healing,the issues of low mechanical strength and weak long-term stability in polypeptide hydrogels still hinder their clinical conversion applications.According to the characteristics of different types of wounds,it is necessary to make full use of the biological activity and drug delivery function of peptides to improve the wound microenvironment while solving key problems such as wound infection and excessive inflammation.The mechanisms of hydrogels for promoting wound healing still lack in-depth exploration.The application of polypeptide hydrogels in scar free tissue repair is insufficient and deserves more attention.While progress has been made in wound monitoring and responsive release of bioactive drugs at the wound site,hydrogels with sensing integrity and on-demand delivery in response to dynamic wound environments require further exploration.In the future,in-depth research aimed at improving the mechanical strength,long-term stability,dynamic wound responsiveness,and scarless wound repair mechanism of peptide hydrogels will be crucial for their clinical translation and application.
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