Wound Healing Promotion via Release of Therapeutic Metallic Ions from Phosphate Glass Fibers: An In Vitro and Ex Vivo Study

Hoxha, Agron; Nikolaou, Athanasios; Wilkinson, Holly N.; Hardman, Matthew J.; Gutierrez-Merino, Jorge; Felipe-Sotelo, Monica; Carta, Daniela

Abstract

Biomaterials capable of promoting wound healing and preventing infections remain in great demand to address the global unmet need for the treatment of chronic wounds. Phosphate-based glasses (PG) have shown potential as bioresorbable materials capable of inducing tissue regeneration, while being replaced by regenerated tissue and releasing therapeutic species. In this work, phosphate-glass-based fibers (PGF) in the system P2O5-CaO-Na2O added with 1, 2, 4, 6, and 10 mol % of the therapeutic metallic ions (TMI) Ag+, Zn2+, and Fe3+ were manufactured via electrospinning of coacervate gels. Coacervation is a sustainable, cost-effective, water-based method to produce PG. All TMI are effective in promoting wound closure (re-epithelialization) in living human skin ex vivo, where the best-performing system is PGF containing Ag+. In particular, PGF with ≥4 mol % of Ag+ is capable of promoting 84% wound closure over 48 h. These results are confirmed by scratch test migration assays, with the PGF-Ag systems containing ≥6 mol % of Ag+, demonstrating significant wound closure enhancement (up to 72%) after 24 h. The PGF-Ag systems are also the most effective in terms of antibacterial activity against both the Gram-positive Staphylococcus aureus and the Gram-negative Escherichia coli. PGF doped with Zn2+ shows antibacterial activity only against S. aureus in the systems containing Zn2+ ≥ 10 mol %. In addition, PGF doped with Fe3+ rapidly accelerates ex vivo healing in patient chronic wound skin (>30% in 48 h), demonstrating the utility of doped PGF as a potential therapeutic strategy to treat chronic wounds.

Citation

Hoxha, A., Nikolaou, A., Wilkinson, H. N., Hardman, M. J., Gutierrez-Merino, J., Felipe-Sotelo, M., & Carta, D. (2024). Wound Healing Promotion via Release of Therapeutic Metallic Ions from Phosphate Glass Fibers: An In Vitro and Ex Vivo Study. ACS Applied Materials & Interfaces, 16(29), 37669-37682. https://doi.org/10.1021/acsami.4c07035

• Journal Article Type: Article
• Acceptance Date: Jul 7, 2024
• Online Publication Date: Jul 15, 2024
• Publication Date: Jul 24, 2024
• Deposit Date: Sep 2, 2024
• Publicly Available Date: Sep 2, 2024
• Journal: ACS Applied Materials and Interfaces
• Print ISSN: 1944-8244
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 16
• Issue: 29
• Pages: 37669-37682
• DOI: https://doi.org/10.1021/acsami.4c07035
• Keywords: Wound healing; Phosphate-based glass fibers; Antibacterial; Soft tissue regeneration; Controlled release
• Public URL: https://hull-repository.worktribe.com/output/4783867