An ultrasmall infinite coordination polymer nanomedicine-composited biomimetic hydrogel for programmed dressing-chemo-low level laser combination therapy of burn wounds

Abstract

To programmatically promote burn wound healing in a way that was tailored to the complex healing phases of hemostasis, anti-inflammation, proliferation, and remolding, we proposed a combined therapeutic strategy of dressing management-chemotherapy-low level laser therapy (LLLT), and designed a highly integrated and simply-structured nanocomposite hydrogel with properties of transparency, self-monitored pH-responsive drug release, and burn wound-adaptability (shape-remodeling, self-healing, and tissue-adhesion). This nanocomposite hydrogel was composed of oxidized hyaluronic acid (OHA), ε-poly-L-lysine grafted human-like collagen (HLC-EPL) and a versatile curcumin-Fe(III) infinite coordination polymer nanomedicines (Cur-Fe(III) ICPs), which were dual dynamically cross-linked via imine bonds and nanoparticle-polymer interactions. The minimized light scattering and absorption of carrier-free and ultrasmall (9.14 ± 1.25 nm) Cur-Fe(III) ICPs and the low refractive index contrast with water of HLC-EPL and OHA endowed the nanocomposite hydrogel with a light transmittance of ≥ 90.1% at 904 nm, which made it compatible with LLLT. The dynamic crosslinking site-rich surface of the Cur-Fe(III) ICPs improved the shape-remodeling and self-healing efficiency of dressing, which resulted in an 84.6% cross-linking reconstruction efficiency within 10 min, thus making it more adaptive to burn wounds. The programmed therapy was implemented by the autoprogressed intrinsic procoagulant activity of HLC-EPL and physical sealing effect in the hemostasis phase, pH-responsive chemotherapy of Cur-Fe(III) ICPs in the inflammation phase, and spatiotemporally controllable LLLT in the proliferation and remodeling phases. As a result, the closure period of full-thickness burn wounds was greatly shortened from 21 to 9 days, and the reconstruction of skin structure was accelerated.