Manufacturing of biofunctional nervous constructs by three-dimensional (3D) bioprinting

• Grant number: 21/08006-4
• Support Opportunities: Regular Research Grants
• Duration: December 01, 2021 - May 31, 2024
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Alexandre Leite Rodrigues de Oliveira
• Grantee: Alexandre Leite Rodrigues de Oliveira
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Diego Noé Rodríguez Sánchez
• Associated grant(s): 23/01380-3 - Neuroprotection and muscle preservation by modulation of KCC2 in combination with pregabalin in MDX mice, AP.R; 21/13472-4 - Multi-user Equipment approved in grant 2021/08006-4: 3D bioprinter, AP.EMU

Abstract

Functional recovery of the peripheral nervous system (PNS) injured is frequently and highly variable, leading to persistent sensory/motor deficits with poor quality of life and productivity. Biomimetic biomaterials that release continuously bioactive molecules offer a promising approach to optimizing the microenvironment during nerve regeneration. New technologies such as three-dimensional (3D) bioprinting allow the preparation of nervous constructs incorporated with neurotrophic factors, cells or drugs with advantages such as repeatability and geometric freedom. In this study, constructs will be biofabricated from methacrylate gelatin and alginate (GMA) bioink, incorporated with stable fibroblast growth factor-2 (FGF2 STAB) or embryonic stem cells overexpressing FGF2 (FGF2-hESC). The printability, bioprinting accuracy, rheological and mechanical parameters of bioink is going to evaluate. Subsequently, the GMA constructs incorporated with FGF2 STAB or FGF2-hESC will be bioprinted by extrusion and measured FGF2 release. Then, nerve wraps and nerve guidance conduits (NGCs) are going to assemble from the constructs and the interaction and neurotrophic potential of human mesenchymal stem cells (hMSCs) in vitro. In vivo, functional, electrophysiological and morphometric recovery after injury and repair of sciatic nerve using bandages or NGCs are going to analyze. Finally, the response of Schwann cells and in vivo kinetic release of FGF2 in the regenerated nerve will be evaluated. We believe that the proposed biomimetic biomanufactured constructs with controlled release of FGF2, will be able to optimize the regenerative results, avoiding perineural fibrosis and providing a suitable microenvironment for axonal homeostasis. Bandages or NGCs could be a translational alternative to neurorrhaphy or nerve autograft. (AU)