Decellularized periosteum and sodium alginate-based photoresponsive dressing with copper selenide nanoparticles for infected-wound healing in diabetic mice

Zhiwen Su; Yan Chen; Haifeng Liang; Zhongxun Liu; Deguang Wu; Jian Li; Hao Su; Yiran Yan; Zhi Huang; Bo Yu

doi:10.1016/j.ijbiomac.2024.131895

Decellularized periosteum and sodium alginate-based photoresponsive dressing with copper selenide nanoparticles for infected-wound healing in diabetic mice

Int J Biol Macromol. 2024 Apr 25;268(Pt 2):131895. doi: 10.1016/j.ijbiomac.2024.131895. Online ahead of print.

Authors

Zhiwen Su¹, Yan Chen², Haifeng Liang¹, Zhongxun Liu¹, Deguang Wu¹, Jian Li¹, Hao Su¹, Yiran Yan¹, Zhi Huang³, Bo Yu⁴

Affiliations

¹ Zhujiang Hospital, Southern Medical University, Orthopedic and Traumatology Department, Guangzhou 510282, China.
² Zhujiang Hospital, Southern Medical University, Ultrasound Medical Center, Guangzhou 510282, China.
³ Institute of Biomedical Engineering, School of Basic Medical Sciences, Central South University, Changsha 410083, China. Electronic address: biomaterials@csu.edu.cn.
⁴ Zhujiang Hospital, Southern Medical University, Orthopedic and Traumatology Department, Guangzhou 510282, China. Electronic address: gzyubo@163.com.

PMID: 38677700
DOI: 10.1016/j.ijbiomac.2024.131895

Abstract

Diabetes-related skin ulcers are of significant clinical concern. Although conventional dressings have been developed, their outcomes have not been adequate, indicating the need to investigate functional dressings for the treatment of diabetic ulcers. Copper selenide nanoparticles (Cu₂Se NPs) demonstrate outstanding photoresponsiveness, which is critical to the healing process. However, their limited solubility in water restricts their application. To synthesize the ODT-PMMA@Cu₂Se NP-doped decellularized periosteum‑sodium alginate functional dressing-ODT-PMMA@Cu₂Se/ECM-S (OP@Cu₂Se/ECM-S), Cu₂Se NPs were modified by n-octadecanethiol (ODT) end-functionalized poly (methacrylic acid) (PMAA) ligands homogeneously dispersed in a decellularized periosteum/sodium alginate matrix. This process improved the water solubility and stability. Moreover, under near-infrared irradiation (NIR), ODT-PMMA@Cu₂Se demonstrated robust photo-responsiveness along with photothermal and photodynamic effects, leading to rapid heating and stimulation of reactive oxygen species (ROS) generation. These two processes work in concert to exhibit excellent antibacterial ability; at 20 μg/mL concentration of Cu₂Se NPs, the bacterial activities of S. aureus and E. coli were 5.40 % and 0.96 %, respectively. Without the NIR laser irradiation, OP@Cu₂Se/ECM-S rapidly increased the vascular endothelial growth factor (VEGF) expression, triggered the phosphatidylinositide 3-kinases (PI3K) and protein kinase B (AKT) signaling pathway, affected the expression of bFGF and CD31, and promoted neovascularization, proliferation, and cell migration. In a diabetic mouse wound model, OP@Cu₂Se/ECM-S exhibited good biocompatibility and promoted epidermal regeneration, collagen deposition, and neovascularization. In a mouse model of subcutaneous abscesses, OP@Cu₂Se/ECM-S also showed excellent antibacterial activity, in vivo experiments confirmed a decrease in bacterial activity to 1.97 %. Thus, OP@Cu₂Se/ECM-S is a potentially useful approach for healing diabetic wounds.

Keywords: Antibacterial and angiogenesis; Cu(2)Se nanoparticles; Diabetic wound healing; Photo- responsiveness.