Neuro-Inspired Biomimetic Microreactor for Sensory Recovery and Hair Follicle Neogenesis under Skin Burns.

Abstract

Deep burns are one of the most severe skin wounds, with typical symptoms being a contradiction between initial severe pain and a subsequent loss of sensation. Although it has long been known that sensory nerves promote skin regeneration and modulate skin function, no proven burn management strategies target sensory nerves. Here, a neuro-inspired biomimetic microreactor is designed based on the immune escape outer membrane of neuroblastoma cells and neural-associated intracellular proteins. The microreactor is constructed on a metal-organic framework (MOF) with a neuroblastoma membrane coating the surface and intracellular proteins loaded inside, called Neuro-MOF. It is loaded into a therapeutic hydrogel and triggers the release of its content proteins upon excitation by near-infrared light. The proteins compensate the skin microenvironment for permanent neurological damage after burns to initiate peripheral nerve regeneration and hair follicle niche formation. In addition, the neuroblastoma cell membrane is displayed on the surface of the Neuro-MOF microreactor, decreasing its immunogenicity and suppressing local inflammation. In a mouse model of deep skin burns, the Neuro-MOF microreactor exhibited significant functional skin regeneration effects, particularly sensory recovery and hair follicle neogenesis.