Development and characterization of a novel hybrid tissue engineering-based scaffold for spinal cord injury repair

摘要

Spinal cord injury (SCI) represents a significant health and social problem, and therefore it is vital to developnovel strategies that can specifically target it. In this context, the objective of the present work was to develop anew range of three-dimensional (3D) tubular structures aimed at inducing the regeneration within SCI sites. Upto six different 3D tubular structures were initially developed by rapid prototyping: 3D bioplotting–based on abiodegradable blend of starch. These structures were then further complemented by injecting Gellan Gum, apolysaccharide-based hydrogel, in the central area of structures. The mechanical properties of these structureswere assessed using dynamic mechanical analysis, under both dry and wet conditions, and their morphologies=porosities were analyzed using micro-computed tomography and scanning electron microscopy. Biologicalevaluation was carried out to determine their cytotoxicity, using both minimum essential medium (MEM)extraction and MTS tests, as well as by encapsulation of an oligodendrocyte-like cell (M03-13 cell line) within thehydrogel phase. The histomorphometric analysis showed a fully interconnected network of pores with porosityranging from 70% to 85%. Scaffolds presented compressive modulus ranging from 17.4 to 62.0MPa and 4.42 to27.4 MPa under dry and wet conditions, respectively. Cytotoxicity assays revealed that the hybrid starch=poly-ecaprolactone=Gellan Gum scaffolds were noncytotoxic, as they did not cause major alterations on cell morphology,proliferation, and metabolic viability. Moreover, preliminary cell encapsulation assays showed that thehybrid scaffolds could support the in vitro culture of oligodendrocyte-like cells. Finally, preliminary in vivostudies conducted in a hemisection rat SCI model revealed that the above-referred structures were well integratedwithin the injury and did not trigger chronic inflammatory processes. The results herein presentedindicate that these 3D systems might be of use in future SCI regeneration approaches.