Biomimetic Mineralization of Mn-Doped Biphasic Calcium Phosphate in the GelMa Hydrogel Acting as a Functional 3D Bioscaffold for Osteo Defect Repair

Abstract

Multicomponent composite scaffolds are stimulating biomaterials that contribute to enhanced physical and mechanical properties and are able to induce or enhance cell differentiation toward specific lineages depending upon their composition. In the case of bone tissue engineering, ceramic components act as "osteoinductive", which, when incorporated into a polymer system, helps encapsulated cells undergo osteodifferentiation. However, formulating a tissue-personalized bioink to provide an appropriate cell niche is challenging. The reproducibility of the bioink and its in vitro characterization are crucial for a scaffold. Here, we show that the composite scaffold drives the human umbilical cord mesenchymal stem cells (hUMSCs) into osteogenic lineage without the addition of any growth factors. Our findings demonstrate that incorporation of Mn-doped BCP into the hydrogel system consisting of gelatin methacrylate and sodium alginate improved the printability and mechanical strength of the scaffold. The possible mechanism behind the enhancement in physical and mechanical properties of bioink is intermolecular ionic interaction and hydrogen bonding between the polymer and bioceramic. Biological results indicate that the composite scaffolds are biocompatible and support cell proliferation during the course of cell culture. Furthermore, RT-qPCR, alkaline phosphate, and alizarin red staining were also used to assess the differentiation ability of cells. The results show that Mn-doped BCP significantly accelerated the osteogenic differentiation of hUMSCs encapsulated within the composite scaffolds. Overall, these results validate the use of Mn-doped BCP bioink for osteo defect regeneration in vitro and provide intriguing opportunities for mineralized bone scaffolds to advance in bone tissue engineering using 3D bioprinting.