Intrafibrillar Mineralized Collagen–Hydroxyapatite-Based Scaffolds for Bone Regeneration

As one of the major challenges in the field of tissue engineering, large skeletal defects have attracted wide attention from researchers. Collagen (Col) and hydroxyapatite (HA), the most abundant protein and the main component in natural bone, respectively, are usually used as a biomimetic composite material in tissue engineering due to their excellent biocompatibility and biodegradability. In this study, novel intrafibrillar mineralized Col–HA-based scaffolds, constructed in either cellular or lamellar microstructures, were established through a biomimetic method to enhance the new bone-regenerating capability of tissue engineering scaffolds. Moreover, iron (Fe) and manganese (Mn), two of the essential trace elements in the body, were successfully incorporated into the lamellar scaffold to further improve the osteoinductivity of these biomaterials. It was found that the lamellar scaffolds demonstrated better osteogenic abilities compared to both in-house and commercial Col–HA-based cellular scaffolds in vitro and in vivo. Meanwhile, Fe/Mn incorporation further amplified the osteogenic promotion of the lamellar scaffolds. More importantly, a synergistic effect was observed in the Fe and Mn dual-element-incorporated lamellar scaffolds for both in vitro osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and in vivo bone regeneration loaded with fresh bone marrow cells. This study provides a simple but practical strategy for the creation of functional scaffolds for bone regeneration.