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

Nanoadhesives can achieve tight wound closure by connecting biomacromolecules from both sides. However, 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 angiogenesis 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 nanoparticles with highly integrated polydopamine (MS-PDA) were prepared by templated synthesis. The entangling 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 bioactive SiO₄^4- by the disintegration of nanoparticles contributed 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. STATEMENT OF SIGNIFICANCE: PVA polymer entangled mesoporous nanoadhesives of polydopamine (PDA)/silica hybrids with the combination of excellent wound closure effect, boosted ROS-scavenging activity, and significant angiogenesis ability were developed for improving the suboptimal skin wound healing efficiency. This strategy not only greatly advances our ability to rationally integrate repairing elements in nanoadhesives for manipulating combined processes of interfacial events during wound healing, but also offers general implications toward application of polymers to reinforce the adhesion strength in nanoadhesive systems. In addition, our findings on the impacts of pore effects mediated ROS species conversion and polymer entanglement may also trigger great interests and facilitate the development/broad application of therapeutic adhesives.