Development of a P(L-D,L)LA Foam as a Dura Substitute and Its In Vitro Evaluation

Abstract

Dura substitutes are used to reduce the risk of postoperative complications following neurosurgical interventions, and to facilitate the healing of dura damages or defects caused by injuries. Traditional tissue transplants have limitations like limited tissue availability, potential risk of immune rejection and disease transmission. The use of biomaterials composed of synthetic polymers as dura substitutes offers a promising approach to overcome these limitations to replace and treat damaged dura mater. Potential biocompatible porous scaffolds still need to be developed to minimize the risks of immune response and disease transmission, while also ensuring effective cell migration and cell ingrowth in three dimension. The aim of the present study was to develop a poly(L-lactide-co-D,L-lactide) (P(L-D,L)LA) foam with an optimal pore size for dura mater substitution, investigate its morphological characteristics, and evaluate its potential for dura mater regeneration by assessing the spreading and growth of meningeal cells within it through in vitro studies. Foams were produced by lyophilization using different concentrations of P(L-D,L)LA solution. A GMP-grade P(L-D,L)LA, suitable for medical device applications, was used in this study. Morphological analysis was performed using scanning electron microscopy, and porosity of the foams was studied with mercury porosimetry. In in vitro studies, meningeal cells were seeded onto the polymeric foams, and their behavior and proliferation in these scaffolds were investigated with cytoskeleton and nucleus staining, and colorimetric cell proliferation assay, respectively. Scanning electron microscopy results showed that the foams prepared with 2.5% and 3% polymer solutions displayed good structural integrity and convenient interconnectivity, with pore sizes ranging from 80 to 150 µm. However, the foams prepared with 2% and 4% polymer solution demonstrated poor structural integrity and low interconnectivity, respectively. In vitro studies showed that the foams prepared with 2.5% and 3% polymer solutions served effectively as scaffolds for meningeal cells, and the cells attached, spread and homogeneously distributed. In addition, the cells proliferated and increased in number over time within these polymeric scaffolds. These findings suggest that the foams produced with 2.5% and especially 3% P(L-D,L)LA polymer solutions could effectively serve as a suitable substitute for the dura mater, providing an appropriate environment for cell ingrowth and tissue integration. This indicates that the developed foam could be a promising treatment for dura mater damage or defects, with the potential approach to promote regeneration in future in vivo and clinical studies.