Synthetic osteoinductive materials that mimic the human osteogenic niche have emerged as ideal candidates to address this area of unmet clinical need. In this study, we evaluated the osteoinductive potential in a rabbit orthotopic model of a magnesium-doped hydroxyapatite/type I collagen ​(MHA/Coll) composite. The composite was fabricated to exhibit a highly fibrous structure of carbonated MHA with 70% (±2.1) porosity and a Ca/P ratio of 1.5 (±0.03) as well as a diverse range of elasticity separated to two distinct stiffness peaks of low (2.35 ​± ​1.16 ​MPa) and higher (9.52 ​± ​2.10 ​MPa) Young's Modulus. Data suggested that these specific compositional and nanomechanical material properties induced the deposition of de novo mineral phase, while modulating the expression of early and late osteogenic marker genes, in a 3D in vitro model using human bone marrow-derived mesenchymal stem cells (hBM-MSCs). When tested in the rabbit orthotopic model, MHA/Col1 scaffold induction of new trabecular bone mass was observed by DynaCT scan, only 2 weeks after implantation. Bone histomorphometry at 6 weeks revealed a significant amount of de novo bone matrix formation. qPCR demonstrated MHA/Coll scaffold full cellularization in vivo and the expression of both osteogenesis-associated genes (Spp1, Sparc, Col1a1, Runx2, Dlx5) as well as hematopoietic (Vcam1, Cd38, Sele, Kdr) and bone marrow stromal cell marker genes (Vim, Itgb1, Alcam). Altogether, these data provide ​evidence of the solid osteoinductive potential of MHA/Coll and its suitability for multiple approaches of bone regeneration.

模仿人类成骨生态位的合成骨诱导材料已成为解决这一尚未满足的临床需求领域的理想候选者。在这项研究中，我们评估了镁掺杂羟基磷灰石/ I型胶原（MHA / Coll）复合材料在兔原位模型中的骨诱导潜力。该复合材料经加工以显示出高纤维结构的碳酸MHA，孔隙率70％（±2.1），Ca / P比为1.5（±0.03），并且具有不同的弹性范围，分为两个不同的低硬度峰（ 2.35±1.16 MPa）和更高（9.52±2.10 MPa）的杨氏模量。数据表明，这些特定的成分和纳米机械材料特性导致了从头沉积矿物质相，同时调节早期和晚期成骨标记基因的表达，在3D体外模型中，使用人骨髓源性间充质干细胞（hBM-MSC）。在兔原位模型中进行测试时，仅在植入后2周，通过DynaCT扫描观察到了MHA / Col1支架诱导的新骨小梁。6周时的骨组织形态测定显示大量的从头开始形成骨基质。qPCR证实了MHA / Coll支架在体内完全细胞化以及成骨相关基因（Spp1，Sparc，Col1a1，Runx2，Dlx5）以及造血（Vcam1，Cd38，Sele，Kdr）和骨髓基质细胞标记物基因的表达（Vim，Itgb1，Alcam）。总而言之，这些数据提供了MHA / Coll的固体骨诱导潜力及其对多种骨再生方法的适用性的证据。