Co-delivery of Two Growth Factors From Combined PLGA and PLLA/PCL Microsphere Scaffolds for Spinal Cord Injury Repairs

Abstract

The purpose of this study is to demonstrate the effectiveness of spheres-in-tube structured scaffolds to sequentially deliver two biomolecules during two phases of tissue regeneration following spinal cord injury (SCI). Scaffolds were synthesized of a poly (lactic-co-glycolic acid) (PLGA) base combined with Poly (L-lactic acid) / Poly (ε-caprolactone) (PLLA/PCL) microspheres. The scaffolds are constructed by leveraging the different solubilities of PLGA, PLLA and PCL in super critical carbon dioxide and ethyl acetate during fabrication processes. Microspheres can reduce the pore size and porosity of PLGA scaffolds; this enhances their mechanical strength and enables them to provide long-term treatment without collapse. The release of the epidermal growth factor (EGF) and basic fibroblast growth factor (FGF-b) are being used to study the release profiles of the designed scaffolds. The analysis shows that FGF-b is released from high porosity PLGA base as the first delivery vehicle and completes the release in the first week. PLLA or PCL microspheres, having the property of sustainably delivering encapsulated EGF in 36 days, are used as the second drug delivery vehicle. FGF-b released within the first week can mimic biomolecules used to protect the surviving neurons and promote the development of sprout axons. The sustained release of EGF from microspheres is used for long-term therapy to differentiate multipotent cells into determined types at the injury site. The results demonstrate that these enhanced parameters along with the ability of sequential co-delivery of growth factors, make these designed scaffolds a promising candidate in SCI studies.