Design and Bench‐Top Testing of 3D Multilayered Electrospun Frameworks to Bridge the Injured Spinal Cord

ABSTRACT

Electrospinning persists as a popular microfabrication technique for producing neural scaffolds. However, standard electrospinning setups are inadequate for engineering tailored 3D architectures that match spinal cord injury (SCI) sites. Herein, an advanced electrospinning technology assembles three multilayered electrospun frameworks (MEFs) via automated layer‐by‐layer deposition to recapitulate the fourth thoracic segment of the human spinal cord. Their 3D designs show distinct biomimetic features intended to promote bridging of contusive SCI. To validate key requirements for SCI implants, MEFs undergo bench‐top tests to assess morphology and surface chemistry, mechanical properties, and in vitro biocompatibility. Results show that MEF‐9, featuring nine channels to support tissue ingrowth, is the best candidate to combine millimetric resemblance to both gray and white matters with nanotopographic cues that mimic the extracellular matrix. Mechanical characterization demonstrates compliance with the human spinal cord, with simulations showing that MEF‐9 better resists structural damage. Concerning biocompatibility, MEF‐9 supports adhesion of embryonic neural progenitor cells and favors their preferential differentiation into neurons rather than glia. After 14 days of culture, viable neural cells form a highly interconnected network with resemblance to gray matter. Overall, MEFs provide a solid foundation for patient‐specific electrospun SCI implants, enabling scalability, design precision, and biomimetic functionality.