Long-Gap Sciatic Nerve Regeneration Using 3D-Printed Nerve Conduits with Controlled FGF-2 Release.
Diego N Rodriguez-Sanchez1,2, Leticia A M de Carvalho1, Ingri Mancilla-Corzo3
1Laboratory of Nerve Regeneration, Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Sao Paulo 13083-970, Brazil.
ACS Applied Materials & Interfaces
|July 7, 2025
Summary
This study developed 3D-printed nerve guidance conduits (NGCs) using PCL and GelMA with FGF-2 to treat peripheral nerve injuries. These bioactive NGCs significantly improved nerve regeneration and functional recovery in rats.
Area of Science:
- Biomaterials Engineering
- Regenerative Medicine
- Neuroscience
Background:
- Peripheral nerve injuries (PNIs) often result in significant sensory and motor deficits.
- Current reconstructive surgeries for PNIs have variable outcomes.
- Three-dimensional (3D) printing offers a platform for creating advanced nerve guidance conduits (NGCs).
Purpose of the Study:
- To develop and evaluate 3D-printed NGCs using polycaprolactone (PCL) and gelatin methacryloyl (GelMA) for peripheral nerve repair.
- To incorporate fibroblast growth factor 2 (FGF-2) for enhanced neurotrophic support and controlled release.
- To assess the efficacy of these bioactive NGCs in a rat model of long-gap peripheral nerve injury.
Main Methods:
- Fabrication of NGCs using a 3D printing process with PCL and GelMA (10% w/v).
- Integration and controlled release of thermostable fibroblast growth factor 2 (FGF-2) within the GelMA matrix.
- In vitro assessment of cell viability, proliferation, and gene expression (Schwann cells, MSCs).
- In vivo implantation of NGCs in a rat model of long-gap peripheral nerve injury, followed by functional, electrophysiological, and histological analysis at 4 and 12 weeks.
Main Results:
- Optimized GelMA concentration (10% w/v) ensured excellent printing fidelity, mechanical properties, and rheology.
- FGF-2 incorporation led to sustained release over 30 days, enhanced cell metabolism, and promoted vascularization-related gene expression in MSCs.
- NGC implantation significantly improved sensory and motor recovery, electrophysiological function, and nerve regeneration in rats at 12 weeks.
- Early signs of regeneration at 4 weeks included Schwann cell proliferation, P75NTR expression, myelination, and neurofilament organization.
Conclusions:
- 3D-printed NGCs composed of PCL and GelMA, functionalized with FGF-2, are biocompatible and promote nerve regeneration.
- These bioactive NGCs demonstrate significant therapeutic potential for repairing long-gap peripheral nerve injuries.
- The developed NGCs represent a promising alternative to traditional nerve autografts.
