Bio-Inspired Self-Renewing Implant Surfaces With Sequential Biofunctional Adaptation for Infectious Diabetic Tissue Repair

Abstract

The clinical success of bioinert, tissue-interfacing metallic implants is greatly jeopardized by complications such as infections, inflammation, and poor regeneration or biointegration, especially concerning diabetics. Implants featuring self-renewable surfaces that sequentially dictate antibacterial/anti-inflammatory, immunomodulatory, and pro-healing/-regenerative functionalities represent an emerging solution. Herein, fusing triple marine bioinspirations, namely the multilayered interlocked interfaces of mollusk shells, the adhesive/reactive chemistries of mussels, and the self-renewing, release-active mucus layers of corals, a self-adaptive interfacial engineering strategy that imparts self-renovating surfaces and temporally-activatable biofunctionalities to various inert biometallic devices is presented. Specifically, sandwich-like multilayered coatings are in situ constructed, comprising a substrate-derived micro/nanostructured prelayer, a mussel-inspired bioadhesive interlayer, and a polyphenol–antibiotic dynamically-crosslinked therapeutic gel toplayer. The dynamic bonds within the gel allowed pH/reactive oxygen species-responsive surface degradation, localized release of multifunctional therapeutics, and conditional exposure of cell-supportive chemical moieties and micro/nanotopographies. Systematic in-vitro, in-ovo, and in-vivo (spanning osseous, subcutaneous, and wound-closure implantations) studies demonstrated that the functionalized bone implants or wound closure staples possessed adaptive biocompatibility (cyto-/hemo/-tissue-compatibility) and biofunctionalities to combat device-associated infections and spur diabetic tissue repair. This study underscores the potential of self-adaptive coating strategies for orchestrating complex (even contradictory) biological functions in addressing challenging medical conditions that require implant intervention.