Multifunctional Inverse Opal Nerve Guidance Conduits Loaded with Mesenchymal Stem Cells for Peripheral Nerve Repair

Nerve guidance conduits (NGCs) hold considerable value in the field of nerve regeneration, yet current approaches display constraints regarding the diversity of loaded factors and their short sustained-release duration. Herein, a type of multifunctional inverse opal NGC integrating bone marrow mesenchymal stem cells (BMSCs) is presented for peripheral nerve repair. The generation of inverse opal scaffolds leverages the inversion of a monodisperse emulsion droplet template crafted by microfluidic technique. Ascribed to the biocompatibility and the cell-concentrating properties of the inverse opal scaffold, coupled with the inherent capabilities of BMSCs, such an NGC enables the secretion of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor, promoting the migration of rat Schwann cells and differentiation of pheochromocytoma 12 cells. Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) further revealed that three-dimensional (3D) BMSC spheroid culture in the inverse opal scaffold significantly upregulated bFGF, PDGF, and VEGF mRNA expression relative to two-dimensional (2D) culture. Further in vivo experimentation confirms the promising efficacy of NGCs loaded with BMSCs in repairing 10 mm sciatic nerve defects. These results underscore the substantial potential of this innovative design for peripheral nerve regeneration.