羟基磷灰石和硅灰石纳米粒子这两种主要的骨矿物质之间的协同相互作用，促进间充质干细胞的成骨分化。
Synergistic interplay between the two major bone minerals, hydroxyapatite and whitlockite nanoparticles, for osteogenic differentiation of mesenchymal stem cells.
机构信息
Division of Engineering in Medicine, Department of Medicine, Harvard Medical School, Brigham & Women's Hospital, Cambridge, MA 02139, USA; Division of Health Sciences & Technology, Harvard-Massachusetts Institute of Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Division of Engineering in Medicine, Department of Medicine, Harvard Medical School, Brigham & Women's Hospital, Cambridge, MA 02139, USA; Division of Health Sciences & Technology, Harvard-Massachusetts Institute of Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
出版信息
Acta Biomater. 2018 Mar 15;69:342-351. doi: 10.1016/j.actbio.2018.01.016. Epub 2018 Feb 13.
UNLABELLED
The inorganic part of human bone is mainly composed of hydroxyapatite (HAP: Ca(PO)(OH)) and whitlockite (WH: CaMg(HPO)(PO)) minerals, where the WH phase occupies up to 20-35% of total weight. These two bone minerals have different crystal structures and physicochemical properties, implying their distinguished role in bone physiology. However, until now, the biological significance of the presence of a certain ratio between HAP and WH in bone is unclear. To address this fundamental question, bone mimetic scaffolds are designed to encapsulate human mesenchymal stem cells (MSCs) for assessing their osteogenic activity depending on different ratios of HAP and WH. Interestingly, cellular growth and osteogenic differentiation are significantly promoted when MSCs are grown with a 3-1 ratio of HAP and WH nanoparticles, which is similar to bone. One of the reasons for this synergism between HAP and WH in hydrogel scaffolds is that, while WH nanoparticles can enhance osteogenic differentiation of MSCs compared to HAP, WH counterintuitively decreases the mechanical stiffness of nanocomposite hydrogels and hinders the osteogenic activity of cells. Taken together, these findings identify the optimal ratio between two major minerals in bone mimetic scaffolds to maximize the osteogenic differentiation of MSCs.
STATEMENT OF SIGNIFICANCE
Human bone minerals are composed of HAP and WH inorganic nanoparticles which have different material properties. However, the reason for the coexistence of HAP and WH in human bone is not fully identified, and HAP and WH composite biomaterial has not been utilized in the clinic. In this study, we have developed bone mimetic HAP and WH nanocomposite hydrogel scaffolds with various ratios. Importantly, we found out that HAP can promote the mechanical stiffness of the composite hydrogel scaffolds while WH can enhance the osteogenic activity of stem cells, which together induced synergism to maximize osteogenic differentiation of stem cells when mixed into 3-1 ratio that is similar to human bone.
未加标签
人体骨骼的无机部分主要由羟基磷灰石（HAP：Ca(PO)(OH))和白磷钙石（WH：CaMg(HPO)(PO))矿物质组成，其中 WH 相占总重量的 20-35%。这两种骨矿物质具有不同的晶体结构和物理化学性质，这意味着它们在骨骼生理学中具有不同的作用。然而，到目前为止，骨骼中 HAP 和 WH 之间存在一定比例的生物学意义尚不清楚。为了解决这个基本问题，设计了仿生骨支架来封装人骨髓间充质干细胞（MSCs），以评估它们的成骨活性，取决于 HAP 和 WH 的不同比例。有趣的是，当 MSCs 以 HAP 和 WH 纳米粒子 3-1 的比例生长时，细胞生长和成骨分化显著增强，这与骨骼相似。HAP 和 WH 在水凝胶支架中协同作用的原因之一是，虽然 WH 纳米粒子可以增强 MSCs 的成骨分化，但与 HAP 相比，WH 反直觉地降低了纳米复合水凝胶的机械刚度，并抑制了细胞的成骨活性。总之，这些发现确定了仿生骨支架中两种主要矿物质之间的最佳比例，以最大限度地提高 MSCs 的成骨分化。
意义声明
人体骨骼矿物质由 HAP 和 WH 无机纳米粒子组成，它们具有不同的材料特性。然而，HAP 和 WH 共同存在于人体骨骼中的原因尚不完全清楚，HAP 和 WH 复合材料尚未在临床上得到应用。在这项研究中，我们开发了具有不同比例的仿生 HAP 和 WH 纳米复合水凝胶支架。重要的是，我们发现 HAP 可以提高复合水凝胶支架的机械刚度，而 WH 可以增强干细胞的成骨活性，当以类似于人体骨骼的 3-1 比例混合时，这两者共同诱导协同作用，最大限度地提高干细胞的成骨分化。
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