Local delivery of dual stem cell-derived exosomes using an electrospun nanofibrous platform for the treatment of traumatic brain injury

Traumatic brain injury (TBI) stands as a significant health challenge, affecting millions worldwide with its profound physical, psychological, and economic impacts. Recent advancements in regenerative medicine have introduced stem cell-derived exosomes as a promising therapeutic approach for TBI. However, challenges such as systemic administration drawbacks and nonspecific organ accumulation have prompted innovative solutions.

Researchers at Tongji University have now developed an electrospun nanofibrous scaffold designed for the sustained delivery of dual exosomes derived from mesenchymal stem cells (MSCs) and neural stem cells (NSCs). This scaffold incorporates a functionalized layer of polydopamine on poly(ε-caprolactone) nanofibers, enhancing the efficient incorporation of exosomes through adhesive forces, hydrogen bonding, and electrostatic interactions.

The study revealed two critical benefits of the dual exosome delivery system:

  1. Therapeutic Mechanisms: MSC-derived exosomes and NSC-derived exosomes were found to induce microglial polarization towards an anti-inflammatory M2 phenotype, modulate inflammatory responses, and promote axonal outgrowth and neural repair.
  2. Preclinical Efficacy: In a murine model of TBI, the nanofibrous scaffold loaded with dual exosomes (Duo-Exo@NF) accelerated functional recovery by reducing reactive astrocytes and microglia, while enhancing levels of growth-associated protein-43 (GAP-43) and doublecortin (DCX), markers of neural regeneration.

Furthermore, multiomics analysis provided insights into the underlying mechanisms of action, highlighting the therapeutic potential of dual stem cell-derived exosomes in TBI treatment.

These findings underscore the potential of the Duo-Exo@NF system as an effective therapeutic strategy for TBI. By enabling localized delivery, the scaffold minimizes off-target effects and maximizes therapeutic efficacy, offering hope for improved outcomes in TBI patients. Future research aims to refine this technology further and explore its translation into clinical settings, potentially revolutionizing the treatment landscape for traumatic brain injuries.

The development of advanced biomaterials like electrospun nanofibrous scaffolds represents a significant leap forward in regenerative medicine. With continued innovation and clinical validation, dual stem cell-derived exosomes delivered via such platforms hold promise for addressing the complex challenges of TBI, paving the way towards enhanced recovery and improved quality of life for patients worldwide.

Li J, Li X, Li X, Liang Z, Wang Z, Shahzad KA, Xu M, Tan F. (2024) Local Delivery of Dual Stem Cell-Derived Exosomes Using an Electrospun Nanofibrous Platform for the Treatment of Traumatic Brain Injury. ACS Appl Mater Interfaces [Epub ahead of print]. [abstract]

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