Metal Organic Framework-Modified Bioadaptable Implant Potentiates the Reconstruction of Nerve Microenvironment Via Immunometabolism Reprogramming

Abstract

Whereas immune homeostasis and metabolic reprogramming are recognized as fundamental players in the restoration of posttraumatic nerve microenvironment, much less is known about the immunometabolism in this progress. In the nerve tissue, the immune identity of resident macrophages contributes to the reshaping of metabolic states. In turn, rapid metabolic shifts and on-demand energy production are also needed to support versatile macrophage functions. Here, we develop a self-powered nerve bridging scaffold by integrating metal organic frameworks (MOFs) and reduced graphene oxide (rGO) nanoparticles into polycaprolactone (PCL) substrates. This provides a bioadaptable neural interface to enable the improved oxidative metabolism in injured nerves and phenotypic switch of infiltrated macrophages. The unique molecular identity of reprogrammed macrophages is also identified, with macrophages displaying enhanced oxidative phosphorylation, mitochondrial bioenergetics and suppressed calcium signaling. Thus, our piezoelectric scaffolds have matched bioadaptability with nerve immunometabolism and facilitate nerve repair.

Keywords: metal organic framework, immunometabolism reprogramming, nerve microenvironment, macrophage polarization, nerve regeneration.