University Research

Extracellular matrix repair and organization of chronic infected diabetic wounds treated with methacrylated chitosan-based hydrogels

Author 1 OrcID

https://orcid.org/0000-0002-6356-7691

Academic department

Department of Biomedical Engineering

Description

Diabetic foot ulcers (DFUs) are a multifactorial medical problem that require multifaceted approaches for effective healing. Most research on DFU healing has concentrated on promoting wound closure, with less emphasis on the quality of repaired tissue. This is problematic, however, since quality of the repaired tissues can have potential to improve wound healing outcomes and limit re-ulceration. If more functionally active dermis replaces the lost tissue, this can effectively maximize strength, organization, and overall structure of the plantar surface. Additionally, DFUs commonly show multi-strain infection, which further exacerbates the non-healing status of these wounds. Treatment of chronic wounds can be benefitted by application of oxygen and localized infection treatment, both can be achieved via our methacrylated chitosan-based (MACF) hydrogel. A non-healing diabetic infected wound model was used to explore extracellular matrix (ECM) organization, tensile strength, and metabolomic profiles at a 21-day endpoint as a marker for maturation and improved functionality of repaired tissues over normal scar formation. Effective remediation of infection was achieved with 14 days of polyhexamethylene biguanide (PHMB) application with improved wound repair compared to continuous treatment. Prolonged (21 day) application of PHMB showed resulting necrosis, although standard application times for patients with infected wounds can reach up to 28 continuous days. Biaxial mechanical analysis showed improved isotropic strength of infected tissues treated with MACF with PHMB stopped on D14, supported by collagen fiber orientation in second harmonics generation (SHG) imaging. Oxygenating MACF treatments also improved collagen deposition through the enhancement of the hydroxyproline fibrillary collagen synthesis pathway. These structural and mechanical results demonstrate a promising potential treatment for infected diabetic foot ulcers which shows improved dermal functionality.

Publisher name

Elsevier

Document Type

Article

Publication Date

6-1-2025

Publication Title

Acta Biomaterialia

Volume

199

First Page

166

Last Page

177

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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