Antibiotic Eluting Collagen-based Hydrogel Improves Wound Healing in Murine Model of Biofilm Infected Wounds

Introduction: In 2018 it was estimated that 8.2 million people had wounds accounting for an estimated associated cost of $28.1 billion to $96.8 billion.1 It is believed that over 90% of chronic wounds contain biofilms, making them difficult to treat due to increasing antibiotic resistance and a constantly evolving microbiome.2 Collagen-rich hydrogel (cHG), a biocompatible hydrogel that is simple to manufacture and enhances neovascularization, is a promising way to treat these challenging wounds. This study assesses the efficacy of an antibiotic-eluting collagen-rich hydrogel (cHG+abx) for the topical treatment of a wound colonized with Methicillin-Resistant Staphylococcus aureus (MRSA) using an established murine model of biofilms.

Methods: Using a stented wound model, 120 mice were divided into four groups: control (wound only), infection only (IO), infection+cHG (IcHG), and infection+cHG augmented with antibiotic (IcHG+ABX). On post-operative day (POD) 2, infection groups were inoculated with MRSA biofilms; on POD 4, a standard occlusive dressing with or without cHG or cHG+ABX was applied. Group specific dressings were replaced every other day until sacrifice on POD 5, 8, 14, or 17. Rate and quality of wound healing was assessed via wound histology. Systemic symptoms were monitored with temperature, weight, and hematologic labs.

Results: Histological analysis demonstrated the IcHG+ABX group had significantly shorter wound lengths than the IO group at POD 5 (3263.97μm ± 79.10μm vs 3518.87μm ± 160.82μm, p<0.001), POD 8 (1408.06μm ± 104.037μm vs 3096.07μm ± 91.29μm, p<0.001) , and POD 14 (1057.19μm ± 133.70μm vs 240.19μm ± 153.08μm, p<0.001). Additionally, the IcHG+ABX group had significantly decreased inflammatory tissue thickness at POD 5 (251.05μm ± 53.73μm vs 313.32μm ± 169.71μm, p=0.0126), POD 8 (199.83μm ± 112.19μm vs 388.49μm ± 179.11μm, p<0.0001), and POD 14 (39.39μm ± 30.80μm vs 134.61μm ± 137.55μm, p<0.0001). No animals were sacrificed due to illness or signs of distress during the experiment. Diagnostic labs showed normal renal and liver function for all IcHG+ABX mice.

Conclusion: Human-derived collagen hydrogels are a promising carrier of antibiotics to topically treat biofilm-colonized wounds. We demonstrated that human-derived collagen hydrogel effectively eliminated MRSA biofilms in vivo and accelerated wound closure rate while reducing inflammation without adverse systemic effects. cHG offers a biocompatible, topical option with dual functionality; antibiotic-augmented collagen hydrogels eliminate wound biofilms while accelerating wound healing.

Citations:
1. Nussbaum SR, Carter MJ, Fife CE, DaVanzo J, Haught R, Nusgart M, Cartwright D. An Economic Evaluation of the Impact, Cost, and Medicare Policy Implications of Chronic Nonhealing Wounds. Value Health. 2018 Jan;21(1):27-32. doi: 10.1016/j.jval.2017.07.007. Epub 2017 Sep 19. PMID: 29304937.
2. Attinger C, Wolcott R. Clinically Addressing Biofilm in Chronic Wounds. Adv Wound Care (New Rochelle). 2012 Jun;1(3):127-132. doi: 10.1089/wound.2011.0333. PMID: 24527292; PMCID: PMC3839004.

Research and Technology

PSTM 2024