Topical Antibiotic Elution in a Collagen-Rich Hydrogel Successfully Inhibits Bacterial Growth and Biofilm Formation In Vitro

Abstract

Background: Chronic wounds are a prominent concern, accounting for $25 billion of healthcare costs annually. Biofilms have been implicated in delayed wound closure, but treatment options continue to be limited and susceptible to developing antibiotic resistance. A novel collagen-rich hydrogel derived from human extracellular matrix presents an avenue for treating chronic wounds by providing appropriate extracellular proteins for healing and promoting neovascularization. Using the hydrogel as a delivery system for localized secretion of therapeutic dosage of antibiotics presents an attractive means of maximizing delivery while minimizing systemic side-effects. We hypothesize that the hydrogel can provide controlled elution of antibiotics leading to inhibition of bacterial growth and disruption of biofilm formation. Method: The rate of antibiotic elution from the collagen-rich hydrogel and the efficacy of biofilm disruption was assessed with Pseudomonas aeruginosa. Bacterial growth inhibition, biofilm disruption, and mammalian cell cytotoxicity were quantified using in vitro models. Results: The antibiotic-loaded hydrogel showed sustained release of antibiotics for up to 24 hours at therapeutic levels. The treatment inhibited bacterial growth and disrupted biofilm formation at multiple time points. The hydrogel was capable of accommodating various classes of antibiotics and did not result in cytotoxicity in mammalian fibroblasts or adipose stem cells Conclusion: An antibiotic-loaded collagen-rich hydrogel is capable of controlled antibiotic release effective for bacteria cell death without native cell death. A human-derived hydrogel that is capable of eluting therapeutic levels of antibiotic is an exciting prospect in the field of chronic wound healing.

Collagen in Wound Healing

“…Collagen wound dressings contain collagen blended with natural and synthetic polymers such as polyethylene oxide, poly (L-lactic acid), hyaluronic acid, elastin and silk fibroin, alginate, chitosan, etc [ 73 , 81 , 82 , 83 , 84 , 85 ]. These blended fabrications have incorporated other additives such as insulin [ 86 ], antibiotics [ 87 , 88 , 89 , 90 , 91 , 92 ] or gold nanoparticles [ 93 , 94 , 95 ] and have been tested mostly in in vitro studies or small animal models of wound healing. An evidence-based review of clinical studies on antibacterial integrated collagen wound dressings indicated that most studies were limited by small sample sizes and mixed chronic wound etiologies [ 46 ].…”

“…Collagen is also used as a surface coating to enhance moisture retention and promote cell adhesion within scaffolds/matrices [ 73 , 81 , 82 , 83 , 84 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ]. Water retention is important to keep the wound bed moist.…”

Antibacterial Soy Protein Isolate Prepared by Quaternization

“…The H&E and Masson’s trichrome staining of the wound tissue on Day 10 and Day 20 were performed. As shown in Figure 5 f, less inflammatory cells in the QSPI-2.0 group and Alginate Ag group were observed compared with the Tegaderm TM film group on Day 10, which was probably due to QSPI-2.0 and Alginate Ag inhibiting bacterial infection-induced inflammation [ 25 ]. Granulation tissue formation is a critical stage during the wound healing process, where the injury is filled with a matrix of fibrous connective tissue and blood vessels.…”

Applications ofhydrogel‐baseddelivery systems in wound care and treatment: Anup‐to‐datereview

“…27 Collagen-rich hydrogels were used as a delivery vehicle to offer controlled elution of gentamycin for bacterial growth inhibition (Pseudomonas aeruginosa) and disruption of biofilm formation. 47 Silica-collagen Type I nanocomposite hydrogels were loaded with antibiotics, gentamicin, and rifamycin. 48 The developed formulations were assessed for antimicrobial efficiency against P. aeruginosa and Staphylococcus aureus.…”