Dual Sustained-Release BMP7-Nanoparticle Hydrogel Scaffolds for Enhanced BMSC Neuronal Differentiation and Spinal Cord Injury Repair.

Abstract

Study design: Preclinical experimental study.

Objective: To explore the use of hydrogels as bioactive scaffolds for encapsulating bone marrow mesenchymal stem cells (BMSCs) to enhance their therapeutic potential in spinal cord injury (SCI). This study further aims to evaluate the added value of a BMP7 nanoparticle delivery system in overcoming the limitations of BMSCs alone for SCI repair.

Summary of background data: SCI leads to significant neuron loss and functional impairment. While BMSC-based stem cell therapies show promise, their efficacy is limited by challenges such as the instability of bone morphogenetic protein (BMP)-7 in inducing neuronal differentiation. High concentrations of BMP7, though effective in promoting neuronal differentiation, may cause inflammation, necessitating the development of a delivery system for sustained and localized release.

Methods: BMSCs were isolated from Sprague-Dawley rats, and BMP-7's effects on neuronal differentiation were assessed via western blotting. BMP7-loaded nanoparticles (NPs) and BMSCs were co-loaded into a gelatin methacrylate (Gel-MA) hydrogel scaffold, with a cell loading density of 1 × 10⁵ cells/μl. BMP7 was encapsulated at a 0.04% (w/V) concentration, corresponding to approximately 0.4 ng BMP7 per μl of hydrogel. Optimization was performed using mechanical, cytotoxicity, and neuronal marker analyses. Scaffold properties, including water absorption, BMP7 release, and BMSC morphology, were characterized. Therapeutic efficacy was evaluated in a rat SCI model using motor function recovery, histological analysis, and molecular assessments.

Results: BMP-7 effectively promoted BMSC differentiation into neurons while suppressing glial cell development. The BMP7-NPs/Gel-MA scaffold ensured sustained BMP7 release, achieving optimal differentiation at a 0.04% (w/V) BMP7 concentration. In vivo, the scaffold combined with BMSCs enhanced neuronal proliferation and differentiation, stimulated myelin regeneration, reduced lesion volume, and significantly improved motor function recovery.

Conclusion: The BMP7-NPs/Gel-MA scaffold provides sustained delivery of BMP-7, effectively directing BMSC differentiation into neuron-like cells while avoiding glial commitment. Combined with BMSCs, it offers a promising therapeutic strategy for SCI repair.