The New York Stem Cell Foundation Research Institute, New York, NY, USA.
Division of Applied Material Sciences, Uppsala University, Uppsala, Sweden.
J Tissue Eng Regen Med. 2018 Mar;12(3):715-726. doi: 10.1002/term.2491. Epub 2017 Sep 25.
Bone engineering opens the possibility to grow large amounts of tissue products by combining patient-specific cells with compliant biomaterials. Decellularized tissue matrices represent suitable biomaterials, but availability, long processing time, excessive cost, and concerns on pathogen transmission have led to the development of biomimetic synthetic alternatives. We recently fabricated calcium phosphate cement (CPC) scaffolds with variable macroporosity using a facile synthesis method with minimal manufacturing steps and demonstrated long-term biocompatibility in vitro. However, there is no knowledge on the potential use of these scaffolds for bone engineering and whether the porosity of the scaffolds affects osteogenic differentiation and tissue formation in vitro. In this study, we explored the bone engineering potential of CPC scaffolds with two different macroporosities using human mesenchymal progenitors derived from induced pluripotent stem cells (iPSC-MP) or isolated from bone marrow (BMSC). Biomimetic decellularized bone scaffolds were used as reference material in all experiments. The results demonstrate that, irrespective of their macroporosity, the CPC scaffolds tested in this study support attachment, viability, and growth of iPSC-MP and BMSC cells similarly to decellularized bone. Importantly, the tested materials sustained differentiation of the cells as evidenced by increased expression of osteogenic markers and formation of a mineralized tissue. In conclusion, the results of this study suggest that the CPC scaffolds fabricated using our method are suitable to engineer bone grafts from different cell sources and could lead to the development of safe and more affordable tissue grafts for reconstructive dentistry and orthopaedics and in vitro models for basic and applied research.
骨工程通过将患者特异性细胞与顺应性生物材料结合，为大量组织产品的生长提供了可能性。脱细胞组织基质代表了合适的生物材料，但可用性、长处理时间、过高的成本以及对病原体传播的担忧导致了仿生合成替代品的发展。我们最近使用一种简便的合成方法制造了具有可变大孔率的磷酸钙水泥 (CPC) 支架，该方法具有最少的制造步骤，并在体外证明了长期的生物相容性。然而，目前尚不清楚这些支架在骨工程中的潜在用途，以及支架的孔隙率是否会影响体外成骨分化和组织形成。在这项研究中，我们使用源自诱导多能干细胞 (iPSC-MP) 的人间充质祖细胞或从骨髓中分离的 iPSC-MP 和 BMSC 来探索具有两种不同大孔率的 CPC 支架的骨工程潜力。仿生脱细胞骨支架在所有实验中均用作参考材料。结果表明，无论其大孔率如何，本研究中测试的 CPC 支架均支持 iPSC-MP 和 BMSC 细胞的附着、存活和生长，与脱细胞骨相似。重要的是，所测试的材料支持细胞的分化，表现为成骨标志物的表达增加和矿化组织的形成。总之，这项研究的结果表明，使用我们的方法制造的 CPC 支架适合于不同细胞来源的工程骨移植物的构建，并可能导致安全且更经济实惠的组织移植物的发展，用于重建牙科和矫形外科以及基础和应用研究的体外模型。
