Work

Controlled spatial and temporal release of neurotrophic growth factor from genetically modified tissue engineering living scaffolds

Year: 2025

Type: article

Abstract: Peripheral nerve injuries (PNIs) affect thousands of patients yearly, often resulting in loss of function, sensation, and chronic pain. In critical-size defects, advanced surgical repair strategies often fail to restore full function. A key limitation is the lack of sustained, localized delivery of biological cues for axonal regeneration, such as growth factors. Glial-cell line-derived neurotrophic factor (GDNF) is known to promote axonal growth, Schwann cell migration, and neuronal survival, but uncontrolled release may cause axonal entrapment. We previously developed tissue-engineered nerve grafts (TENGs) composed of two neuronal populations connected by stretch-grown axons. In this study, we genetically modified the distal population to express human GDNF under a Tet-on inducible promoter, temporally controlling GDNF release through doxycycline administration. Modified TENGs survived implantation in a 1.5-cm rat sciatic nerve defect, supporting future studies. This approach offers a promising platform for spatially and temporally controlled neurotrophic factor delivery from tissue-engineered living scaffolds.

Source: Journal of Tissue Engineering

DOI: 10.1177/20417314251389333