Xpand Biotechnology BV, 3723 MB Bilthoven, The
Eur Cell Mater. 2014 Apr 15;27:281-97; discussion 296-7. doi: 10.22203/ecm.v027a20.
A current challenge of synthetic bone graft substitute design is to induce bone formation at a similar rate to its biological resorption, matching bone's intrinsic osteoinductivity and capacity for remodelling. We hypothesise that both osteoinduction and resorption can be achieved by altering surface microstructure of beta-tricalcium phosphate (TCP). To test this, two TCP ceramics are engineered with equivalent chemistry and macrostructure but with either submicron- or micron-scale surface architecture. In vitro, submicron-scale surface architecture differentiates larger, more active osteoclasts--a cell type shown to be important for both TCP resorption and osteogenesis--and enhances their secretion of osteogenic factors to induce osteoblast differentiation of human mesenchymal stem cells. In an intramuscular model, submicrostructured TCP forms 20 % bone in the free space, is resorbed by 24 %, and is densely populated by multinucleated osteoclast-like cells after 12 weeks; however, TCP with micron-scale surface architecture forms no bone, is essentially not resorbed, and contains scarce osteoclast-like cells. Thus, a novel submicron-structured TCP induces substantial bone formation and is resorbed at an equivalent rate, potentially through the control of osteoclast-like cells.
目前，合成骨移植替代物设计的一个挑战是，以与其生物吸收相匹配的速度诱导骨形成，从而匹配骨的固有成骨活性和重塑能力。我们假设通过改变β-磷酸三钙（TCP）的表面微观结构，可以同时实现成骨诱导和吸收。为了验证这一点，我们用具有相同化学组成和宏观结构但具有亚微米或微米级表面结构的两种 TCP 陶瓷进行了工程设计。在体外，亚微米级表面结构区分出更大、更活跃的破骨细胞——这种细胞类型被证明对 TCP 的吸收和骨生成都很重要——并增强其分泌成骨因子，以诱导人间充质干细胞的成骨细胞分化。在肌肉内模型中，亚微结构 TCP 在自由空间中形成 20%的骨，24%被吸收，12 周后被多核破骨样细胞密集占据；然而，具有微米级表面结构的 TCP 没有形成骨，基本上没有被吸收，并且含有稀少的破骨样细胞。因此，一种新型的亚微米结构 TCP 可诱导大量骨形成，并以相当的速度被吸收，这可能是通过控制破骨样细胞来实现的。
