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

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Abstract
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.
Funding Information
  • National Postdoctoral Program for Innovative Talents (BX20230070)
  • Shenzhen Municipal Fundamental Research Program (JCYJ20190814093401920)
  • Shenzhen Municipal Fundamental Research Program (JCYJ20210324125608022)
  • Basic and Applied Basic Research Foundation of Guangdong Province (2023A1515011986)
  • China Postdoctoral Science Foundation (2023M740606)
  • Shenzhen Medical Research Fund (B2401007)
  • Beijing Municipal Natural Science Foundation (Z200019)
  • Jiangsu Funding Program for Excellent Postdoctoral Talent (2022ZB123)
  • Jiangsu Funding Program for Excellent Postdoctoral Talent (2023ZB597)
  • National Key Research and Development Program of China (2020YFA0112503)
  • National Key Research and Development Program of China (2021YFA1101300)
  • National Key Research and Development Program of China (2021YFA1101800)
  • National Natural Science Foundation of China (22302231)
  • National Natural Science Foundation of China (81970882)
  • National Natural Science Foundation of China (82030029)
  • National Natural Science Foundation of China (82330033)
  • National Natural Science Foundation of China (82341247)
  • National Natural Science Foundation of China (823B2021)
  • National Natural Science Foundation of China (82401376)
  • National Natural Science Foundation of China (82470097)
  • National Natural Science Foundation of China (82471164)
  • National Natural Science Foundation of China (82471182)
  • National Natural Science Foundation of China (82501418)
  • National Natural Science Foundation of China (92149304)
  • Open Project Fund of Guangdong Academy of Medical Sciences (YKY-KF202201)

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