Combination wound healing using polymer entangled porous nanoadhesive hybrids with robust ROS scavenging and angiogenesis properties

Nanoadhesives can achieve tight wound closure by connecting biomacromolecules from both sides. How-ever, previously developed adhesive systems suffered from suboptimal wound healing efficiency due to the lack of interparticle cohesion, sufficient reactive oxygen species (ROS)-scavenging sites, and angiogen-esis consideration. Herein, we developed a polymer entangled porous nanoadhesive system to address the above challenge by synergy of three functional components. Firstly, hybrid mesoporous silica nanoparti-cles with highly integrated polydopamine (MS-PDA) were prepared by templated synthesis. The entan-gling between PVA polymer and MS-PDA contributed to much stronger cohesion between nanoparticles, which led to 75% larger adhesion strength. As confirmed by in vitro and in vivo evaluations, the highly exposed catechol groups boosted the scavenging activity of ROS (1.8-4.1 fold enhancement as compared with nonporous counterpart). Consequently, more macrophages exhibited anti-inflammatory phenotype, leading to 2-2.6 fold lower pro-inflammatory cytokine levels. Moreover, the sustained release of bioac-tive SiO4 4 - by the disintegration of nanoparticles contributed to similar to 3-fold higher expression of VEGF and enhanced new blood vessel formation, as well as better wound repair. This platform can provide a new paradigm for developing multifunctional nanoadhesive systems in treating skin wounds.