{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:24:59Z","timestamp":1793147099939,"version":"4.5.0"},"reference-count":104,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFB"],"abstract":"<jats:p>Osteomyelitis, a severe bone infection, poses a significant therapeutic challenge in both human and veterinary medicine, especially due to the increasing prevalence of antibiotic-resistant pathogens like methicillin-resistant Staphylococcus aureus (MRSA). Conventional treatments, including surgical debridement and systemic antibiotics, often prove inadequate due to the ability of bacteria to form biofilms and evade host immune responses. Antimicrobial peptides (AMPs), such as LL-37 and \u03b2-defensins, have emerged as a promising alternative therapeutic strategy. AMPs exhibit broad-spectrum antimicrobial activity, including efficacy against resistant strains, and possess immunomodulatory properties that can promote bone regeneration. This article comprehensively reviews AMP applications in treating osteomyelitis across both human and veterinary medicine. We discuss diverse therapeutic approaches, including free AMPs, their conjugation with biomaterials such as collagen and chitosan to enhance delivery and stability, and the development of AMP-based nanoparticles. Furthermore, we analyze preclinical and clinical findings, highlighting the efficacy and safety of AMPs in combating osteomyelitis in both human and animal patients. Finally, we explore future perspectives and challenges, such as optimizing delivery, stability, and efficacy, while minimizing cytotoxicity, and in translating AMP-based therapies into clinical practice to effectively manage this debilitating disease.<\/jats:p>","DOI":"10.3390\/jfb16030090","type":"journal-article","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T05:54:38Z","timestamp":1741154078000},"page":"90","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Application of Antimicrobial Peptides (AMPs) in Treatment of Osteomyelitis in Human and Veterinary Orthopedics"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7339-0554","authenticated-orcid":false,"given":"Dominika","family":"Nguyen Ngoc","sequence":"first","affiliation":[{"name":"Sub-Department of Pathophysiology, Department of Preclinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Life Sciences, 20-033 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Latalski","sequence":"additional","affiliation":[{"name":"Children\u2019s Orthopaedic Department, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0884-7498","authenticated-orcid":false,"given":"Anna","family":"Danielewicz","sequence":"additional","affiliation":[{"name":"Children\u2019s Orthopaedic Department, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Szponder","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Clinical Sciences, Faculty of Veterinary Medicine, University of Agriculture in Krakow, 31-120 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8815-0630","authenticated-orcid":false,"given":"Joanna","family":"Wessely-Szponder","sequence":"additional","affiliation":[{"name":"Sub-Department of Pathophysiology, Department of Preclinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Life Sciences, 20-033 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Mazur","sequence":"additional","affiliation":[{"name":"Sub-Department of Pathophysiology, Department of Preclinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Life Sciences, 20-033 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jor.2016.10.004","article-title":"Osteomyelitis: Recent Advances in Pathophysiology and Therapeutic Strategies","volume":"14","author":"Birt","year":"2017","journal-title":"J. Orthop."},{"key":"ref_2","unstructured":"Schaefer, S., Johnston, S.A., and Decamp, C.E. (2015). Brinker, Piermattei and Flo\u2019s Handbook of Small Animal Orthopedics and Fracture Repair, Elsevier Ltd.. [6th ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1099\/jmm.0.000952","article-title":"Animal Models of Orthopaedic Infections. A Review of Rabbit Models Used to Induce Long Bone Bacterial Infections","volume":"68","author":"Bottagisio","year":"2019","journal-title":"J. Med. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/j.ajpath.2020.02.007","article-title":"Current Concepts of Osteomyelitis: From Pathologic Mechanisms to Advanced Research Methods","volume":"190","author":"Hofstee","year":"2020","journal-title":"Am. J. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Seebach, E., and Kubatzky, K.F. (2019). Chronic Implant-Related Bone Infections\u2014Can Immune Modulation Be a Therapeutic Strategy?. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01724"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0140-6736(04)16727-5","article-title":"Osteomyelitis","volume":"364","author":"Lew","year":"2004","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"nihpa116823","DOI":"10.3810\/psm.2008.12.11","article-title":"Osteomyelitis: Approach to Diagnosis and Treatment","volume":"36","author":"Fritz","year":"2008","journal-title":"Phys. Sportsmed."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s00590-025-04184-w","article-title":"Clinical and Epidemiological Differences in Staphylococcal Osteoarticular Infections: Insights for Developing Hospital-Based Infection Control Interventions","volume":"35","author":"Figueiredo","year":"2025","journal-title":"Eur. J. Orthop. Surg. Traumatol."},{"key":"ref_9","unstructured":"Wing, E.J., and Schiffman, F.J. (2021). Cecil Essentials of Medicine, Elsevier."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/s41579-022-00686-0","article-title":"Skeletal Infections: Microbial Pathogenesis, Immunity and Clinical Management","volume":"20","author":"Masters","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1097\/QCO.0000000000000155","article-title":"Current Concepts in Pathogenesis of Acute and Chronic Osteomyelitis","volume":"28","author":"Smeets","year":"2015","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1089\/ars.2020.8027","article-title":"Spatial Properties of Reactive Oxygen Species Govern Pathogen-Specific Immune System Responses","volume":"32","author":"To","year":"2020","journal-title":"Antioxid. Redox Signal."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhao, A., Sun, J., and Liu, Y. (2023). Understanding Bacterial Biofilms: From Definition to Treatment Strategies. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1137947"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Arciola, C.R., Ravaioli, S., Mirzaei, R., Dolzani, P., Montanaro, L., Daglia, M., and Campoccia, D. (2023). Biofilms in Periprosthetic Orthopedic Infections Seen through the Eyes of Neutrophils: How Can We Help Neutrophils?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242316669"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zdziennicka, J., Junkuszew, A., Latalski, M., \u015awieca, M., and Wessely-Szponder, J. (2021). Long-Term Interactions of Circulating Neutrophils with Titanium Implants, the Role of Platelets in Regulation of Leukocyte Function. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221810060"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1007\/s00018-024-05311-2","article-title":"Age-Related Dysregulation of CXCL9\/10 in Monocytes Is Linked to Impaired Innate Immune Responses in a Mouse Model of Staphylococcus aureus Osteomyelitis","volume":"81","author":"Lin","year":"2024","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Hao, Z., Chen, R., Chai, C., Wang, Y., Chen, T., Li, H., Hu, Y., Feng, Q., and Li, J. (2022). Antimicrobial Peptides for Bone Tissue Engineering: Diversity, Effects and Applications. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.1030162"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e00932-19","DOI":"10.1128\/IAI.00932-19","article-title":"Staphylococcus aureus Osteomyelitis: Bone, Bugs, and Surgery","volume":"88","author":"Urish","year":"2020","journal-title":"Infect. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Xie, X., Li, J., Gu, F., Zhang, K., Su, Z., Wen, Q., Sui, Z., Zhou, P., and Yu, T. (2021). Genetic Determinants for Bacterial Osteomyelitis: A Focused Systematic Review of Published Literature. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.654792"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Granata, V., Possetti, V., Parente, R., Bottazzi, B., Inforzato, A., and Sobacchi, C. (2022). The Osteoblast Secretome in Staphylococcus aureus Osteomyelitis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1048505"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1093\/cid\/ciad377","article-title":"Risk Factors and Outcomes of Hematogenous Vertebral Osteomyelitis in Patients with Staphylococcus aureus Bacteremia","volume":"77","author":"Kinamon","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e01140-22","DOI":"10.1128\/aac.01140-22","article-title":"Neutralization of Staphylococcus aureus Protein A Prevents Exacerbated Osteoclast Activity and Bone Loss during Osteomyelitis","volume":"67","author":"Gehrke","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/01652176.2021.2022244","article-title":"Microbiological Aspects of Osteomyelitis in Veterinary Medicine: Drawing Parallels to the Infection in Human Medicine","volume":"42","author":"Silva","year":"2022","journal-title":"Vet. Q."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.tvjl.2019.06.003","article-title":"Bacterial Osteomyelitis in Veterinary Orthopaedics: Pathophysiology, Clinical Presentation and Advances in Treatment across Multiple Species","volume":"250","author":"Gieling","year":"2019","journal-title":"Vet. J."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Meroni, G., Tsikopoulos, A., Tsikopoulos, K., Allemanno, F., Martino, P.A., and Soares Filipe, J.F. (2022). A Journey into Animal Models of Human Osteomyelitis: A Review. Microorganisms, 10.","DOI":"10.3390\/microorganisms10061135"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/ame2.12149","article-title":"Innovations in Osteomyelitis Research: A Review of Animal Models","volume":"4","author":"Roux","year":"2021","journal-title":"Anim. Models Exp. Med."},{"key":"ref_27","unstructured":"Johnston, S.A., and Tobias, K.M. (2017). Veterinary Surgery: Small Animal Expert Consult, Saunders. [2nd ed.]."},{"key":"ref_28","unstructured":"Zachary, J.F. (2021). Pathologic Basis of Veterinary Disease, Mosby."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3415\/VCOT-10-07-0116","article-title":"Haematogenous Osteomyelitis: Clinical Presentation and Outcome in Three Dogs","volume":"24","author":"Rabillard","year":"2017","journal-title":"Vet. Comp. Orthop. Traumatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.cveq.2017.03.002","article-title":"Septic Arthritis, Physitis, and Osteomyelitis in Foals","volume":"33","author":"Glass","year":"2017","journal-title":"Vet. Clin. N. Am. Equine Pract."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e301","DOI":"10.1002\/vrc2.301","article-title":"Use of Antimicrobial Impregnated Calcium Sulphate Beads in the Surgical Management of Mandibular Osteomyelitis in an 8-Year-Old Huacaya Alpaca","volume":"10","author":"Po","year":"2022","journal-title":"Vet. Rec. Case Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1007\/s10096-023-04640-7","article-title":"Osteomyelitis Caused by Streptococcus intermedius in Immunocompetent Adults\u2014A Case Report and Systematic Literature Review","volume":"42","author":"Brunink","year":"2023","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.2147\/IDR.S272733","article-title":"Methicillin-Resistant Staphylococcus aureus (MRSA): One Health Perspective Approach to the Bacterium Epidemiology, Virulence Factors, Antibiotic-Resistance, and Zoonotic Impact","volume":"13","author":"Algammal","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Corbisiero, M.F., Smyth, A., Stellern, J., Leoniak, S., Raines, M.M., Axford, B., and Dobbie, A.M. (2023). Mitigating Infectious Complications of Injection Pharyngoplasty with Calcium Hydroxyapatite for Velopharyngeal Insufficiency: Retropharyngeal Abscess and Osteomyelitis. Cleft Palate Craniofacial J., 10556656231207468.","DOI":"10.1177\/10556656231207468"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.1532-950X.1992.tb00082.x","article-title":"Anaerobic Bacteria Isolated from Osteomyelitis in Dogs and Cats","volume":"21","author":"Muir","year":"1992","journal-title":"Vet. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1590\/1678-4162-10917","article-title":"Chronic Osteomyelitis in Canine Penile Bone: Case Report","volume":"72","author":"Silveira","year":"2020","journal-title":"Arq. Bras. Med. Vet. Zootec."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Billings, C., and Anderson, D.E. (2022). Role of Animal Models to Advance Research of Bacterial Osteomyelitis. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.879630"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Jiang, C., Zhu, G., and Liu, Q. (2024). Current Application and Future Perspectives of Antimicrobial Degradable Bone Substitutes for Chronic Osteomyelitis. Front. Bioeng. Biotechnol., 12.","DOI":"10.3389\/fbioe.2024.1375266"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.ymthe.2022.09.006","article-title":"PD-1\/PD-L1 Blockade Is a Potent Adjuvant in Treatment of Staphylococcus aureus Osteomyelitis in Mice","volume":"31","author":"Li","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ortega, M.A., Fraile-Martinez, O., Garc\u00eda-Montero, C., Callej\u00f3n-Pel\u00e1ez, E., S\u00e1ez, M.A., \u00c1lvarez-Mon, M.A., Garc\u00eda-Honduvilla, N., Monserrat, J., \u00c1lvarez-Mon, M., and Bujan, J. (2021). A General Overview on the Hyperbaric Oxygen Therapy: Applications, Mechanisms and Translational Opportunities. Medicina, 57.","DOI":"10.3390\/medicina57090864"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Surendar, J., Hackenberg, R.K., Schmitt-S\u00e1nchez, F., Ossendorff, R., Welle, K., Stoffel-Wagner, B., Sage, P.T., Burger, C., Wirtz, D.C., and Strauss, A.C. (2024). Osteomyelitis Is Associated with Increased Anti-Inflammatory Response and Immune Exhaustion. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1396592"},{"key":"ref_42","first-page":"395","article-title":"Osteomyelitis: Diagnosis and Treatment","volume":"104","author":"Bury","year":"2021","journal-title":"Am. Fam. Physician"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Wang, G., Cui, Y., Liu, H., Tian, Y., Li, S., Fan, Y., Sun, S., Wu, D., and Peng, C. (2023). Antibacterial Peptides-Loaded Bioactive Materials for the Treatment of Bone Infection. Colloids Surf. B Biointerfaces, 225.","DOI":"10.1016\/j.colsurfb.2023.113255"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.pupt.2005.01.001","article-title":"The Human Cathelicidin LL-37: A Multifunctional Peptide Involved in Infection and Inflammation in the Lung","volume":"18","author":"Tjabringa","year":"2005","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Alford, M.A., Baquir, B., Santana, F.L., Haney, E.F., and Hancock, R.E.W. (2020). Cathelicidin Host Defense Peptides and Inflammatory Signaling: Striking a Balance. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.01902"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/nri.2016.29","article-title":"The Immunology of Host Defence Peptides: Beyond Antimicrobial Activity","volume":"16","author":"Hancock","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ghosh, S.K., Feng, Z., Fujioka, H., Lux, R., McCormick, T.S., and Weinberg, A. (2018). Conceptual Perspectives: Bacterial Antimicrobial Peptide Induction as a Novel Strategy for Symbiosis with the Human Host. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.00302"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Wessely-Szponder, J., Zdziennicka, J., Junkuszew, A., Latalski, M., \u015awieca, M., and Szponder, T. (2022). Prospects and Applications of Natural Blood-Derived Products in Regenerative Medicine. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010472"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41413-019-0061-z","article-title":"Evolving Concepts in Bone Infection: Redefining \u201cBiofilm\u201d, \u201cAcute vs. Chronic Osteomyelitis\u201d, \u201cthe Immune Proteome\u201d and \u201cLocal Antibiotic Therapy\u201d","volume":"7","author":"Masters","year":"2019","journal-title":"Bone Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/SLA.0000000000005508","article-title":"Efficacy and Safety of PL-5 (Peceleganan) Spray for Wound Infections: A Phase IIb Randomized Clinical Trial","volume":"277","author":"Wei","year":"2023","journal-title":"Ann. Surg."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2206602","DOI":"10.1002\/advs.202206602","article-title":"Advances of Antimicrobial Peptide-Based Biomaterials for the Treatment of Bacterial Infections","volume":"10","author":"Li","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Haddad, N., Ajaz, J., Mansour, L., Kasemodel, R., Jarvis, J., Jarad, J., Gorski, H., and Carr, M. (2023). A Review of the Clinical Utilization of Oral Antibacterial Therapy in the Treatment of Bone Infections in Adults. Antibiotics, 13.","DOI":"10.3390\/antibiotics13010004"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e38392","DOI":"10.1016\/j.heliyon.2024.e38392","article-title":"Nano-Scaffold-Based Delivery Systems of Antimicrobial Agents in the Treatment of Osteomyelitis; A Narrative Review","volume":"10","author":"Yekani","year":"2024","journal-title":"Heliyon"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Tripathi, A.K., Singh, J., Trivedi, R., and Ranade, P. (2023). Shaping the Future of Antimicrobial Therapy: Harnessing the Power of Antimicrobial Peptides in Biomedical Applications. J. Funct. Biomater., 14.","DOI":"10.20944\/preprints202309.1916.v1"},{"key":"ref_55","first-page":"599","article-title":"Nanoparticles Associated with Antimicrobial Peptides (AMPs)\u2014Promising Combination for Biomedical and Veterinary Applications","volume":"79","author":"Szymczak","year":"2023","journal-title":"Med. Weter."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Purohit, K., Reddy, N., and Sunna, A. (2024). Exploring the Potential of Bioactive Peptides: From Natural Sources to Therapeutics. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031391"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1002\/jor.24689","article-title":"Therapeutics and Delivery Vehicles for Local Treatment of Osteomyelitis","volume":"38","author":"Cobb","year":"2020","journal-title":"J. Orthop. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1007\/s10989-019-09963-8","article-title":"New Engineered Fusion Peptide with Dual Functionality: Antibacterial and Strong Binding to Hydroxyapatite","volume":"26","author":"Fateme","year":"2020","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.biomaterials.2016.01.063","article-title":"Antimicrobial Peptide Melimine Coating for Titanium and Its in Vivo Antibacterial Activity in Rodent Subcutaneous Infection Models","volume":"85","author":"Chen","year":"2016","journal-title":"Biomaterials"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2015.12.003","article-title":"Prevention of Staphylococcus aureus Biomaterial-Associated Infections Using a Polymer-Lipid Coating Containing the Antimicrobial Peptide OP-145","volume":"222","author":"Riool","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5739","DOI":"10.1021\/acsabm.9b00776","article-title":"Single Step Plasma Process for Covalent Binding of Antimicrobial Peptides on Catheters To Suppress Bacterial Adhesion","volume":"2","author":"Tran","year":"2019","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zhang, J., Gao, T., Zhang, N., He, J., and Wu, F. (2021). Covalent Immobilization of DJK-5 Peptide on Porous Titanium for Enhanced Antibacterial Effects and Restrained Inflammatory Osteoclastogenesis. Colloids Surf. B Biointerfaces, 202.","DOI":"10.1016\/j.colsurfb.2021.111697"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"46733","DOI":"10.1039\/C6RA06778F","article-title":"Covalent Immobilization of KR-12 Peptide onto a Titanium Surface for Decreasing Infection and Promoting Osteogenic Differentiation","volume":"6","author":"Nie","year":"2016","journal-title":"RSC Adv."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10863","DOI":"10.1007\/s10853-022-07266-w","article-title":"Peptide-Coating Combating Antimicrobial Contaminations: A Review of Covalent Immobilization Strategies for Industrial Applications","volume":"57","author":"Stillger","year":"2022","journal-title":"J. Mater. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.progpolymsci.2011.08.001","article-title":"ATRP in the Design of Functional Materials for Biomedical Applications","volume":"37","author":"Siegwart","year":"2012","journal-title":"Prog. Polym. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"35830","DOI":"10.1021\/acsami.8b14534","article-title":"Temperature-Controlled Reversible Exposure and Hiding of Antimicrobial Peptides on an Implant for Killing Bacteria at Room Temperature and Improving Biocompatibility in Vivo","volume":"10","author":"Zhan","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e02447-19","DOI":"10.1128\/mBio.02447-19","article-title":"Staphylococcus aureus Infects Osteoclasts and Replicates Intracellularly","volume":"10","author":"Krauss","year":"2019","journal-title":"mBio"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s11914-019-00548-4","article-title":"Mechanisms of Immune Evasion and Bone Tissue Colonization That Make Staphylococcus aureus the Primary Pathogen in Osteomyelitis","volume":"17","author":"Muthukrishnan","year":"2019","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"28764","DOI":"10.1021\/acsami.1c04895","article-title":"Antimicrobial Peptide-Loaded Pectolite Nanorods for Enhancing Wound-Healing and Biocidal Activity of Titanium","volume":"13","author":"Zhang","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.msec.2018.08.069","article-title":"Nanostructured Titanium Surfaces Fabricated by Hydrothermal Method: Influence of Alkali Conditions on the Osteogenic Performance of Implants","volume":"94","author":"Huang","year":"2019","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1021\/acsbiomaterials.8b01046","article-title":"Antimicrobial Titanium Surface via Click-Immobilization of Peptide and Its in Vitro\/Vivo Activity","volume":"5","author":"Chen","year":"2019","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"11428","DOI":"10.1021\/acsami.6b16779","article-title":"Mussel-Inspired Multifunctional Hydrogel Coating for Prevention of Infections and Enhanced Osteogenesis","volume":"9","author":"Cheng","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"109","DOI":"10.7150\/thno.38388","article-title":"On-Demand Storage and Release of Antimicrobial Peptides Using Pandora\u2019s Box-like Nanotubes Gated with a Bacterial Infection-Responsive Polymer","volume":"10","author":"Chen","year":"2020","journal-title":"Theranostics"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Islam, T., Tamanna, N.T., Sagor, M.S., Zaki, R.M., Rabbee, M.F., and Lackner, M. (2024). Antimicrobial Peptides: A Promising Solution to the Rising Threat of Antibiotic Resistance. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16121542"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1039\/D0BM01584A","article-title":"Based on the Synergistic Effect of Mg2+ and Antibacterial Peptides to Improve the Corrosion Resistance, Antibacterial Ability and Osteogenic Activity of Magnesium-Based Degradable Metals","volume":"9","author":"Zhou","year":"2021","journal-title":"Biomater. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"20417314241303818","DOI":"10.1177\/20417314241303818","article-title":"Bioinspired Synthetic Peptide-Based Biomaterials Regenerate Bone through Biomimicking of Extracellular Matrix","volume":"15","author":"Azadi","year":"2024","journal-title":"J. Tissue Eng."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Melicher\u010d\u00edk, P., Ne\u0161uta, O., and \u010ce\u0159ovsk\u00fd, V. (2018). Antimicrobial Peptides for Topical Treatment of Osteomyelitis and Implant-Related Infections: Study in the Spongy Bone. Pharmaceuticals, 11.","DOI":"10.3390\/ph11010020"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1021\/acsabm.0c00250","article-title":"Bioactive and Elastic Nanocomposites with Antimicrobial Properties for Bone Tissue Regeneration","volume":"3","author":"Ibrahim","year":"2020","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"He, Y., Jin, Y., Wang, X., Yao, S., Li, Y., Wu, Q., Ma, G., Cui, F., and Liu, H. (2018). An Antimicrobial Peptide-Loaded Gelatin\/Chitosan Nanofibrous Membrane Fabricated by Sequential Layer-by-Layer Electrospinning and Electrospraying Techniques. Nanomaterials, 8.","DOI":"10.3390\/nano8050327"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4945","DOI":"10.1021\/acs.biomac.0c01163","article-title":"Dual Oral Tissue Adhesive Nanofiber Membranes for pH-Responsive Delivery of Antimicrobial Peptides","volume":"21","author":"Boda","year":"2020","journal-title":"Biomacromolecules"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/rb\/rbaa015","article-title":"Development of an Antimicrobial Peptide-Loaded Mineralized Collagen Bone Scaffold for Infective Bone Defect Repair","volume":"7","author":"He","year":"2020","journal-title":"Regen. Biomater."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Monteiro, C., Fernandes, H., Oliveira, D., Vale, N., Barbosa, M., Gomes, P., and Martins, M.C.L. (2020). AMP\u2013Chitosan Coating with Bactericidal Activity in the Presence of Human Plasma Proteins. Molecules, 25.","DOI":"10.3390\/molecules25133046"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1099\/jmm.0.001000","article-title":"Antimicrobial Peptides Prevent Bacterial Biofilm Formation on the Surface of Polymethylmethacrylate Bone Cement","volume":"68","year":"2019","journal-title":"J. Med. Microbiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"124432","DOI":"10.1016\/j.matchemphys.2021.124432","article-title":"Melittin Antimicrobial Peptide Thin Layer on Bone Implant Chitosan-Antibiotic Coatings and Their Bactericidal Properties","volume":"263","author":"Zarghami","year":"2021","journal-title":"Mater. Chem. Phys."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Chen, J., Hu, G., Li, T., Chen, Y., Gao, M., Li, Q., Hao, L., Jia, Y., Wang, L., and Wang, Y. (2021). Fusion Peptide Engineered \u201cStatically-Versatile\u201d Titanium Implant Simultaneously Enhancing Anti-Infection, Vascularization and Osseointegration. Biomaterials, 264.","DOI":"10.1016\/j.biomaterials.2020.120446"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Li, Y., Na, R., Wang, X., Liu, H., Zhao, L., Sun, X., Ma, G., and Cui, F. (2017). Fabrication of Antimicrobial Peptide-Loaded PLGA\/Chitosan Composite Microspheres for Long-Acting Bacterial Resistance. Molecules, 22.","DOI":"10.3390\/molecules22101637"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s42826-022-00128-1","article-title":"Role of Animal Models in Biomedical Research: A Review","volume":"38","author":"Mukherjee","year":"2022","journal-title":"Lab. Anim. Res."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Shi, X., Wu, Y., Ni, H., Chen, X., and Xu, Y. (2022). Comparing the Efficacy of Different Antibiotic Regimens on Osteomyelitis: A Network Meta-Analysis of Animal Studies. Front. Med., 9.","DOI":"10.3389\/fmed.2022.975666"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1293\/tox.2020-0041","article-title":"Treatment of Contaminated Radial Fracture in Sprague-Dawley Rats by Application of a Degradable Polymer Releasing Gentamicin","volume":"34","author":"Ramot","year":"2021","journal-title":"J. Toxicol. Pathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.4049\/jimmunol.1701574","article-title":"Innate Immunity to Staphylococcus aureus: Evolving Paradigms in Soft Tissue and Invasive Infections","volume":"200","author":"Brandt","year":"2018","journal-title":"J. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Lovati, A.B., Drago, L., Monti, L., De Vecchi, E., Previdi, S., Banfi, G., and Roman\u00f2, C.L. (2013). Diabetic Mouse Model of Orthopaedic Implant-Related Staphylococcus aureus Infection. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067628"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Kim, J., Yoo, G., Lee, T., Kim, J.H., Seo, D.M., and Kim, J. (2022). Classification Model for Diabetic Foot, Necrotizing Fasciitis, and Osteomyelitis. Biology, 11.","DOI":"10.3390\/biology11091310"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"111842","DOI":"10.1016\/j.injury.2024.111842","article-title":"In Vivo Models of Infection: Large Animals\u2014Mini Review on Human-Scale One-Stage Revision in a Porcine Osteomyelitis Model","volume":"55","author":"Henriksen","year":"2024","journal-title":"Injury"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e1142","DOI":"10.1002\/jsp2.1142","article-title":"Preclinical Models of Vertebral Osteomyelitis and Associated Infections: Current Models and Recommendations for Study Design","volume":"4","author":"Joyce","year":"2021","journal-title":"JOR Spine"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1302\/2046-3758.103.BJR-2019-0193.R3","article-title":"Development of a Large Animal Rabbit Model for Chronic Periprosthetic Joint Infection","volume":"10","author":"Yagi","year":"2021","journal-title":"Bone Jt. Res."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Zdziennicka, J., Szponder, T., and Wessely-Szponder, J. (2021). Application of Natural Neutrophil Products for Stimulation of Monocyte-Derived Macrophages Obtained before and after Osteochondral or Bone Injury. Microorganisms, 9.","DOI":"10.3390\/microorganisms9010124"},{"key":"ref_97","first-page":"47","article-title":"Choosing the Right Animal Model for Osteomyelitis Research: Considerations and Challenges","volume":"43","author":"Huang","year":"2023","journal-title":"J. Orthop. Transl."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41413-024-00332-w","article-title":"Prospects and Challenges for the Application of Tissue Engineering Technologies in the Treatment of Bone Infections","volume":"12","author":"Qin","year":"2024","journal-title":"Bone Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.jacbts.2019.10.008","article-title":"Limitations of Animal Studies for Predicting Toxicity in Clinical Trials","volume":"4","year":"2019","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_100","first-page":"E255","article-title":"Ethical Considerations Regarding Animal Experimentation","volume":"63","author":"Kiani","year":"2022","journal-title":"J. Prev. Med. Hyg."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1002\/jbm.a.37432","article-title":"Injectable Hydrogel as a Carrier of Vancomycin and a Cathelicidin-Derived Peptide for Osteomyelitis Treatment","volume":"110","author":"Machado","year":"2022","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1146\/annurev-pathol-052016-100332","article-title":"Humanized Mouse Models of Clinical Disease","volume":"12","author":"Walsh","year":"2017","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00005-018-0506-x","article-title":"Humanized Mice as Unique Tools for Human-Specific Studies","volume":"66","author":"Yong","year":"2018","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Yazdanpanah, Z., Johnston, J.D., Cooper, D.M.L., and Chen, X. (2022). 3D Bioprinted Scaffolds for Bone Tissue Engineering: State-Of-The-Art and Emerging Technologies. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.824156"}],"container-title":["Journal of Functional Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4983\/16\/3\/90\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:47:21Z","timestamp":1760028441000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4983\/16\/3\/90"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,5]]},"references-count":104,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["jfb16030090"],"URL":"https:\/\/doi.org\/10.3390\/jfb16030090","relation":{},"ISSN":["2079-4983"],"issn-type":[{"value":"2079-4983","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,5]]}}}