Development and Characterization of a PHB-HV-based 3D Scaffold for a Tissue Engineering and Cell-therapy Combinatorial Approach for Spinal Cord Injury Regeneration

Spinal cord injury (SCI) leads to devastating neurological deficits and disabilities. Several tissue engineering (TE)-based approaches have been investigated for management of this condition. However, to date no single repair strategy has successfully induced full functional recovery following SCI. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV) is found to be particularly attractive for TE applications due to its properties, such as biodegradability, biocompatibility, thermoplasticity and piezoelectricity. Hence, this report addresses the development and characterization of a PHB-HV-based 3D scaffold produced by freeze-drying aimed for SCI treatment. The scaffolds obtained revealed an anisotropic morphology with a fully interconnected network of open pores presenting high porosity and large pore sizes. Its mechanical properties with compressive modulus values between 1.4 and 2.9MPa confirmed its anisotropic characteristics, as revealed by SEM analysis. In vitro studies demonstrated a lack of cytotoxic effect of PHB-HV scaffolds over Central Nervous System (CNS)-derived primary cell cultures. Direct contact assays revealed the ability of these structures to support the culture of CNS-derived cells and Mesenchymal Stem Cells from different sources attesting their potential as carriers for delivering MSCs to the injury site. Histocompatibility studies showed that PHB-HV scaffolds were well tolerated by the host tissue, and did not negatively impacted the left hindlimb locomotor function recovery as demonstrated by the BBB test results. Therefore results herein presented suggest that PHB-HV scaffolds may be suitable for SCI treatment.