Nanobiology Dependent Therapeutic Convergence between Biocompatibility and Bioeffectiveness of Graphene Oxide Quantum Dot Scaffold for Immuno‐Inductive Angiogenesis and Nerve Regeneration

The understanding of nanomaterial biology determines material selection and scaffold fabrication in regenerative medicine. The translational application of advanced functional nanomaterials, like graphene and derivatives, requires an in-depth investigation on the sophisticated material-cell action network. To achieve the therapeutic convergence between biocompatibility and bioeffectiveness, herein, series of graphene derivatives are screened and the superiority of graphene oxide quantum dots (GOQDs) is confirmed. Thereby, a GOQD functionalized nerve scaffold is fabricated for peripheral nerve repair with electrospinning and freeze-drying technology. The behavioral, electrophysiological, and pathological analysis confirms that GOQDs promote nerve structural reconstruction and attenuate denervation-induced myopathy. Macrophages perceive the implanted materials and initiate a variety of biological processes. GOQDs activate the macrophage ERK/CERB/VEGF pathway in vitro and in vivo, thereby contributing to intraneural vascularization. In addition, an enzyme-activated degradation route of GOQDs is explored and the implanted scaffolds trigger negligible scar formation and blood toxicity. These findings demonstrate the ability of the GOQD, a biocompatible graphene derivative, to facilitate intraneural vascularization and regeneration of injured peripheral nerves through a macrophage intracellular signaling-mediated mechanism. This enlightens the authors to continuously explore the mechanisms behind the material nanobiology-dependent therapeutic convergence between biocompatibility and bioeffectiveness for clinical translation.