Collagen-mediated in situ mineralization-enhanced biomimetic bone tissue engineering scaffolds

Oriented poly(lactic acid) (PLA) fiber bone tissue engineering scaffolds are often limited by factors including poor material hydrophilicity and weak osteogenic activity. The introduction of in situ mineralization can address these issues, but it requires the assistance of hydrophilic materials to achieve optimal performance. Collagen, a nature-based ECM component, was adopted because it can enhance hydrophilicity, encourage cell adhesion, and biomimetrically induce mineralization, according to recent studies of ECM-mimicking scaffolds. Therefore, this study proposes a collagen-mediated in situ mineralization-enhanced scaffold design aimed at improving the hydrophilicity and osteogenic potential of oriented fiber scaffolds. Collagen (5-10 wt%) and phosphate-containing solutions (59.6 mM) were added to a PLA matrix, and scaffolds were electrospun at 12 kV. Subsequently, the scaffolds underwent in situ mineralization in a calcium ion-containing solution (101 mM), leading to the formation of calcium phosphate within the scaffold structure. The experimental results show that the introduction of collagen effectively promoted the formation of in situ mineralization, enhanced the hydrophilicity of the scaffold, and maintained good fiber orientation. The scaffolds exhibited significant mechanical anisotropy, with the Young's modulus parallel to the fiber direction reaching 5 MPa, which is 25 times greater than that in the direction perpendicular to the fibers. In vitro studies with rat bone marrow mesenchymal stem cells showed a 2.4-fold increase in osteogenic differentiation, as assessed by alkaline phosphatase activity. Micro-CT analysis showed that the increase of BV/TV was 3.26 times higher when compared to that of control scaffolds, while histological analysis revealed mature bone tissue formation characterized by well-organized collagen fibers. Overall, the present study describes a novel strategy of collagen-mediated in situ mineralization, first integrating enhanced hydrophilicity, mechanical anisotropy, and biomimetic bone-like properties to address major limitations associated with the current oriented fiber scaffolds.