In Vitro Coculture of Primary Human Cells to Analyze Angiogenesis, Osteogenesis, and the Inflammatory Response to Newly Developed Osteosynthesis Material for Pediatric Maxillofacial Traumatology: A Potential Pretesting Model before In Vivo Experiments

Abstract

During the present study, an in vitro coculture bone tissue mimic based on primary osteoblasts and primary endothelial cells was used for a complex and broad evaluation of a newly developed material for applications in pediatric maxillofacial traumatology. The biomaterial was composed of PDLLA (poly(D,L-lactide)) in various combinations with calcium carbonate (CC), magnesium (Mg), and chitosan (CH). Besides classical biocompatibility analyses, the present study evaluated material-dependent effects on fundamental processes that are essential for successful material integration and regeneration. Therefore, inflammation-associated factors such as E-selectin and interleukins were analyzed in the in vitro model system on gene expression and protein level depending on the different materials. Furthermore, in order to test the capability of vascularization of the material, the effect of the different materials on the formation of microvessel-like structures as well as the expression and release of proangiogenic factors was investigated in vitro in the bone coculture model. In addition, the mineralization capacity as well as the relative gene expression of osteogenic differentiation factors was analyzed in response to the different materials. As a result, the authors could assess the material combination PDLLA: CC CH as the most functionally tested material with regard to biocompatibility, inflammatory response, and microvessel-like structure formation as well as osteogenic differentiation in the in vitro coculture system. In conclusion, by using tissue-engineered human bone tissue equivalents as proposed here in an in vitro coculture model, biomaterial-mediated effects can be readily investigated. Moreover, it is proposed that these complex in vitro evaluations could contribute to the understanding and improvement of the development of novel materials for pediatric traumatological care for prospective clinical applications.

Poly(dl-lactide) Polymer Blended with Mineral Phases for Extrusion 3D Printing—Studies on Degradation and Biocompatibility

“…Dohle et al recently reported on in vitro investigations of the PDLLA + CaCO 3 blend using primary osteoblasts, primary endothelial cells, and primary dermal fibroblasts. For all three cell types, they observed high cell viability as well as excellent cell adhesion and expression of their typical markers in contact with the sample surface [30]-these cell responses were comparable to the results obtained for PDLLA + CaCO 3 and PDLLA in the present study. For 3D-printed scaffolds of PDLLA + β-TCP, excellent cell attachment, viability, proliferation, and osteogenic differentiation of adipose-derived stem cells seeded on these scaffolds were confirmed by Rezai Rad et al [31].…”