(WHS-P40) COPPER NANOPARTICLE-BASED MULTIFUNCTIONAL SCAFFOLDS FOR WOUND HEALING
Friday, May 17, 2024
7:30 AM – 5:00 PM East Coast USA Time
The pathophysiology of non-healing wounds has been associated with the colonization of multispecies bacteria as well as poor vascularization in wounds. Thus far, each of the above aspects have been separately investigated and an integrated approach to simultaneously addressing these issues in a cost-effective single drug delivery platform has yet to emerge. The objective of this study was to develop copper nanoparticle (CuNPs)-based injectable scaffolds with antibacterial as well as proangiogenic properties for wound healing. Our strategy relies on the current scientific knowledge that (1) copper has great potential to as antimicrobial agent for both topical and systemic administration, while it is less harmful to the host cell because copper is an essential metal for life; (2) copper is a co-factor for many angiogenic promoters and mediators, and can switch on such molecules from the quiescent to pro-angiogenic state; (3) Ascorbic acid exhibits dual functions of pro-oxidative and antioxidative activities depending on its concentrations. In this study, CuNPs (20-120 nm) were synthesized using a green hydrothermal synthesis method. The antibacterial and proangiogenic capabilities of CuNPs were fine-tuned by optimizing the dose of vitamin C (VC) that reacts with CuNP. The antibacterial activity of CuNPs was significantly enhanced when combined with higher concentrations of (VC), which synergistically enhanced a Fenton reaction for reactive oxygen species generation (ROS). The threshold level of VC for triggering a Fenton reaction with CuNP was measured to be 10 mM, where the MICs of CuNPs were measured to be 20 mM for both (methicillin sensitive and methicillin-resistant S. aureus), and 5 mM for both (drug-sensitive and drug-resistant P. aeruginosa), suggesting a potent antibacterial activity of CuNP/VC cocktail against broad-spectrum bacterial species. The proangiogenic activity of CuNPs was assessed by tube formation assay, in which the treatment of CuNPs (80 nm) on HUVEC significantly increased endothelial tube formation in a dose dependent manner at lower doses of VC ( <100 mM). An injectable formulation of hydrogel scaffold was prepared by incorporating CuNP and VC (at 10xMIC) in a thermos-reversible Pluronic F-127 hydrogel (25%), which enabled controlled release of CuNPs and VC. The bactericidal capacities of the CuNP/VC-loaded hydrogel formulation was assessed using a standard well diffusion assay against S. aureus and P. aeruginosa. The results showed a significantly increased inhibition of bacterial growth for the gel with both CuNPs and VC, compared to the gel with either CuNP or VC only (p < 0.05). In summary, our results support the feasibility of CuNP-based multifunctional hydrogel scaffold that facilitates the eradication of bacterial pathogens as well as proangiogenic response for wound healing.