Bioengineering microspheres regulating mesenchymal stem cell fate accelerate spinal cord injury therapeutics

Stem cell therapies have shown significant promise in addressing spinal cord injury (SCI) due to their ability to protect, regenerate, and replace tissue. However, the efficacy of these therapies encounters post-transplantation challenges, including poor survival, inefficient retention, difficulty in neuron transdifferentiation, and difficulty connecting into the injured area. In this study, we introduce a bioengineering platform to address these problems through regulating of mesenchymal stem cell (MSC) fate. To fabricate this platform, extracellular matrix (ECM) was first obtained and optimized for effective phenotypic neuronal differentiation in vitro. To support stem cell survival and retention, porous microspheres were collected and selected with microfluidic fabrication. When incorporated into the bioengineered microsphere (BEM) platform, the loaded MSCs demonstrated improved survival, considerable retention rates, the ability to differentiate into neuronal cells, and effective tissue integration in contusive SCI models. More importantly, BEM-assisted MSC treatment reduces scar tissue formation, improves the regeneration of nearby tissues and axons, protects the synaptic structure, and enhances signal transduction, thereby accelerating post-SCI recovery. This advancement enhances therapeutic strategies for SCIs and related neuronal disorders.