Antimicrobial Peptides in Wound Healing and Skin Regeneration: Dual Roles in Immunity and Microbial Defense
Abstract
1. Introduction
2. Data Extraction Management
3. Complex Interplay of Immune Responses and Wound Healing
3.1. Overview of Immune Response in Acute Wound Healing
3.2. Overview of Immune Response in Chronic Wound Healing
4. Dual Role of Antimicrobial Peptides in Wound Healing and Skin Regeneration
4.1. AMPs Modulate Macrophage Polarization in Wound Healing
4.2. AMPs Modulate Cytokine and Chemokine Regulation in Wound Healing
4.3. AMPs Modulate Responses by NK Cells in Wound Healing
4.4. Other Immunomodulatory Mechanisms of AMPs in Wound Healing
4.5. Bridging Innate Immunity and Adaptive Immunity Using AMPs
5. AMPs in Clinical Development
6. Future Prospects and Challenges in Antimicrobial Peptide Research
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Antimicrobial Peptide | Antimicrobial Mechanisms | Immunomodulatory Function | References |
---|---|---|---|
Human β-defensins (hBDs) | Exhibit broad-spectrum antimicrobial activity against various pathogens (i.e., bacteria, fungi, and viruses) | Release pro-inflammatory cytokines and chemokines that attract immune cells such as neutrophils and macrophages to the wound site, modulate macrophage polarization, and suppress neutrophil apoptosis | [83,84,85,86] |
Tet213-CN | Improves bacterial phagocytosis | Promotes M1 macrophage polarization, increases intracellular ROS generation and proinflammatory cytokine secretion, and modulates macrophage polarization | [87,88] |
Human cathelicidins LL-37 | Directly kill bacteria, fungi, and viruses by disrupting their cell membranes | Regulate inflammation by balancing between pro-inflammatory and anti-inflammatory actions, modulate macrophage polarization, act as a chemoattractant to guide immune cells such as neutrophils to the wound site, stimulate cytokine production, bridge innate immunity and adaptive immunity, and suppress neutrophil apoptosis | [86,89,90] |
Mast-MO | Compromises bacterial cell membrane integrity | Stimulates cytokine production, reduces excessive inflammation promotes a balanced immune response by suppressing pro-inflammatory factors (e.g., TNF-α and IL-6) | [91] |
Andersonin-W1 (AW1) | Directly kills pathogens and prevents biofilm formation | Balances inflammation, enhances immune cell recruitment, promotes tissue repair, and modulates inflammation by macrophages via the TLR4/NF-κB molecular axis by directly binding to TLR4 in the macrophage extracellular region | [92] |
Antimicrobial peptide derived from insulin-like growth factor-binding protein 5 (AMP-IBP5) | Exhibits broad-spectrum antimicrobial effects against Gram-positive and Gram-negative bacteria, kills antibiotic-resistant strains such as MRSA and Pseudomonas aeruginosa, and inhibits biofilm formation | Regulates inflammation and induces macrophage polarization | [93,94] |
Human α-defensins | Directly kill or inhibit bacterial growth via membrane disruption and inhibition of bacterial cell wall synthesis | Act as chemokines to recruit cells such as neutrophils, eosinophils, mast cells, monocytes, and lymphocytes to the infection or wound site and suppress neutrophil apoptosis | [86,95] |
Thrombocidin-1-derived peptide TC19 | Eradicates superficial multidrug-resistant bacterial strains, including Staphylococcus aureus and Acinetobacter baumannii | Induces neutrophil chemotaxis | [96] |
Peptide-Based Antimicrobial Medication | Brand Name | Application | Target Species | References |
---|---|---|---|---|
Bacitracin | Neosporin | To treat skin infections | Mainly Gram-positive bacteria, including Staphylococcus, Streptococcus, Corynebacterium, Clostridium, and Actinomyces | [98] |
Vancomycin | Firvanq, Vancocin | To treat serious Gram-positive infections, including MRSA infections | Staphylococcus aureus | [116] |
Dalbavancin | Dalvance, Xydalba | To treat skin infections | Gram-positive pathogens, including Staphylococcus aureus (including MRSA), Streptococcus pyogenes, Streptococcus agalactiae, and Enterococcus faecalis (vancomycin-susceptible strains) | [116,119] |
Polymyxin E | Colistin | To treat multidrug-resistant (MDR) Gram-negative bacterial infections | Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae | [116,120] |
Bulevirtide | Hepcludex | To treat chronic Hepatitis D (HDV) infection in adults with compensated liver disease | Hepatitis D virus | [116,121] |
Enfuvirtide | Fuzeon | An HIV-1 fusion inhibitor used in the treatment of human immunodeficiency virus (HIV) infection, primarily prescribed for patients who have developed resistance to other antiretroviral therapies (ART) | Human immunodeficiency virus (HIV) | [116,122] |
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Adnan, S.B.; Maarof, M.; Fauzi, M.B.; Md Fadilah, N.I. Antimicrobial Peptides in Wound Healing and Skin Regeneration: Dual Roles in Immunity and Microbial Defense. Int. J. Mol. Sci. 2025, 26, 5920. https://doi.org/10.3390/ijms26135920
Adnan SB, Maarof M, Fauzi MB, Md Fadilah NI. Antimicrobial Peptides in Wound Healing and Skin Regeneration: Dual Roles in Immunity and Microbial Defense. International Journal of Molecular Sciences. 2025; 26(13):5920. https://doi.org/10.3390/ijms26135920
Chicago/Turabian StyleAdnan, Siti Balqis, Manira Maarof, Mh Busra Fauzi, and Nur Izzah Md Fadilah. 2025. "Antimicrobial Peptides in Wound Healing and Skin Regeneration: Dual Roles in Immunity and Microbial Defense" International Journal of Molecular Sciences 26, no. 13: 5920. https://doi.org/10.3390/ijms26135920
APA StyleAdnan, S. B., Maarof, M., Fauzi, M. B., & Md Fadilah, N. I. (2025). Antimicrobial Peptides in Wound Healing and Skin Regeneration: Dual Roles in Immunity and Microbial Defense. International Journal of Molecular Sciences, 26(13), 5920. https://doi.org/10.3390/ijms26135920