Institute of Inorganic Chemistry and Analytical Chemistry, Johannes Gutenberg-University of Mainz, Mainz, Germany.
Institute of Pathology, Johannes Gutenberg-University of Mainz, Mainz, Germany.
J Tissue Eng Regen Med. 2018 Jul;12(7):1754-1768. doi: 10.1002/term.2703. Epub 2018 Jun 10.
We have previously described a promising alternative to conventional synthetic bone biomaterials using vaterite, a metastable CaCO polymorph that increases the local Ca concentration in vitro and leads to an oversaturation of phosphate, the primary bone mineral. This stimulates a natural bone-like mineralisation in a short period of time. In this study, sterile and endotoxin-free vaterite particles were synthesised in a nearly quantitative yield. The 500-1,000 nm vaterite particles did not exhibit any cytotoxic effects as measured by MTS, lactate dehydrogenase, or crystal violet assays on the human osteoblast cell line (MG-63) exposed to concentrations up to 500 μg/ml vaterite up to 72 hr. MG-63, primary human osteoblasts or human umbilical vein endothelial cells in the presence of vaterite up to 500 μg/ml for 7 days exhibited typical growth patterns. Endothelial cells exhibited a normal induction of E-selectin after exposure to LPS and MG-63 cells in osteogenic differentiation medium showed an increased expression of alkaline phosphatase compared with the respective control cells without vaterite. MG-63 cultured on a vaterite-containing degradable poly(ethylene glycol)-hydrogel exhibited strong adhesion and proliferation, similar to cells on cell culture plates. Cells did not attach to gels without vaterite. Our results demonstrate that vaterite particles are biocompatible, do not influence cell gene expression, and that vaterite in hydrogels may be able to serve for adhesion of osteoblasts and as a mineral substrate for natural bone formation by osteoblasts. These characteristics make vaterite particles a highly favourable compound for use in bone regeneration applications.
我们之前曾描述过一种有前途的替代传统合成骨生物材料的方法，即使用文石，一种亚稳 CaCO3 多晶型物，它可以增加体外局部 Ca 浓度，并导致磷酸盐过饱和，磷酸盐是主要的骨矿物质。这会在短时间内刺激自然骨样矿化。在这项研究中，无菌且无内毒素的文石颗粒以近乎定量的产率合成。500-1000nm 的文石颗粒在暴露于高达 500μg/ml 文石的浓度下，通过 MTS、乳酸脱氢酶或结晶紫测定，在人成骨细胞系（MG-63）上没有表现出任何细胞毒性作用，暴露时间长达 72 小时。MG-63、原代人成骨细胞或人脐静脉内皮细胞在高达 500μg/ml 的文石存在下培养 7 天，表现出典型的生长模式。内皮细胞在暴露于 LPS 后表现出 E-选择素的正常诱导，而在成骨分化培养基中的 MG-63 细胞与没有文石的相应对照细胞相比，碱性磷酸酶的表达增加。在含有文石的可降解聚乙二醇水凝胶上培养的 MG-63 表现出强烈的粘附和增殖能力，类似于细胞在细胞培养板上的粘附和增殖能力。没有文石的凝胶上细胞无法附着。我们的结果表明，文石颗粒具有生物相容性，不会影响细胞基因表达，并且水凝胶中的文石可能能够用于成骨细胞的粘附，并作为成骨细胞自然骨形成的矿物基质。这些特性使文石颗粒成为骨再生应用中非常有前途的化合物。
