de Melo Pereira Daniel, Davison Noel, Habibović Pamela
Department of Instructive Biomaterials Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6229 ER, Maastricht, The Netherlands.
Bioact Mater. 2021 Jul 15;8:241-252. doi: 10.1016/j.bioactmat.2021.06.036. eCollection 2022 Feb.
Biomineralized collagen composite materials pose an intriguing alternative to current synthetic bone graft substitutes by offering a biomimetic composition that closely resembles native bone. We hypothesize that this composite can undergo cellular resorption and remodeling similar to natural bone. We investigate the formation and activity of human osteoclasts cultured on biomineralized collagen and pure collagen membranes in comparison to cortical bone slices. Human monocytes/macrophages from peripheral blood differentiate into multinucleated, tartrate-resistant alkaline phosphatase (TRAP)-positive osteoclast-like cells on all substrates. These cells form clear actin rings on cortical bone, but not on biomineralized collagen or pure collagen membranes. Osteoclasts form resorption pits in cortical bone, resulting in higher calcium ion concentration in cell culture medium; however, osteoclast resorption of biomineralized collagen and collagen membranes does not measurably occur. Activity of osteoclast enzymes - TRAP, carbonic anhydrase II (CA-II), and cathepsin-K (CTS-K) - is similar on all substrates, despite phenotypic differences in actin ring formation and resorption. The mesh-like structure, relatively low stiffness, and lack of RGD-containing binding domains are likely the factors responsible for preventing formation of stable actin rings on and resorption of (biomineralized) collagen membranes. This insight helps to guide further research toward the optimized design of biomineralized collagen composites as a more biomimetic bone-graft substitute.
生物矿化胶原蛋白复合材料通过提供一种与天然骨非常相似的仿生成分，为当前的合成骨移植替代物提供了一种引人入胜的选择。我们假设这种复合材料可以经历类似于天然骨的细胞吸收和重塑。我们研究了与皮质骨切片相比，在生物矿化胶原蛋白和纯胶原蛋白膜上培养的人破骨细胞的形成和活性。来自外周血的人单核细胞/巨噬细胞在所有底物上都分化为多核、抗酒石酸酸性磷酸酶（TRAP）阳性的破骨细胞样细胞。这些细胞在皮质骨上形成清晰的肌动蛋白环，但在生物矿化胶原蛋白或纯胶原蛋白膜上则不形成。破骨细胞在皮质骨中形成吸收坑，导致细胞培养基中钙离子浓度升高；然而，生物矿化胶原蛋白和胶原蛋白膜的破骨细胞吸收并未明显发生。尽管在肌动蛋白环形成和吸收方面存在表型差异，但破骨细胞酶——TRAP、碳酸酐酶II（CA-II）和组织蛋白酶-K（CTS-K）——在所有底物上的活性相似。网状结构、相对较低的硬度以及缺乏含RGD的结合域可能是阻止（生物矿化）胶原蛋白膜上形成稳定肌动蛋白环和吸收的原因。这一见解有助于指导进一步的研究，以优化生物矿化胶原蛋白复合材料的设计，使其成为更仿生的骨移植替代物。
