In recent years, synthetic calcium phosphate (CaP) ceramics have emerged as an alternative to bone grafts in the treatment of large critical-sized bone defects. To successfully substitute for bone grafts, materials must be osteoinductive, that is, they must induce osteogenic differentiation and subsequent bone formation in vivo. Although a set of osteoinductive CaP ceramics has been developed, the precise biological mechanism by which a material directs cells toward osteogenesis and the role of individual chemical and physical properties in this mechanism remain incompletely understood. Here, we used proteomics to compare serum protein adsorption to two CaP ceramics with different osteoinductive potential, namely an osteoinductive β-tricalcium phosphate (TCP) and a non-osteoinductive hydroxyapatite (HA). Moreover, we analyzed the protein profiles of human mesenchymal stromal cells (hMSCs) cultured on these two ceramics. The serum protein adsorption experiments in the absence of cells highlighted the proteins that are highly abundant in the serum and/or have a high affinity to CaP. The extent of adsorption was suggested to be affected by the available surface area for binding and by the ion exchange dynamics on the surface. Several proteins were uniquely expressed by hMSCs on TCP and HA surfaces. Proteins identified as enriched on TCP were involved in processes related to wound healing, cell proliferation, and the production of extracellular matrix. On the other hand, proteins that were enriched on HA were involved in processes related to protein production, translation, localization, and secretion. In addition, we performed a separate proteomics analysis on TCP, HA, and two biphasic calcium phosphates with known osteoinductive potential and performed a clustering analysis on a combination of a set of proteins found to be enriched on osteoinductive materials with a set of proteins already known to be involved in osteogenesis. This yielded two protein networks potentially involved in the process of osteoinduction – one consisting of collagen fragments and collagen-related enzymes and a second consisting of endopeptidase inhibitors and regulatory proteins. The results of this study show that protein profiling can be a useful tool to help understand the effect of biomaterial properties on the interactions between a biomaterial and a biological system. Such understanding will contribute to the design and development of improved biomaterials for (bone) regenerative therapies.

近年来，合成磷酸钙（CaP）陶瓷已经出现，可以替代大面积的临界骨缺损中的骨移植物。要成功替代骨移植，材料必须具有骨诱导性，也就是说，它们必须在体内诱导成骨分化和随后的骨形成。尽管已经开发出一组骨诱导性CaP陶瓷，但仍不能完全理解材料将细胞引导向骨形成的精确生物学机制以及单个化学和物理性质在该机制中的作用。在这里，我们使用蛋白质组学来比较两种具有不同骨诱导潜力的CaP陶瓷，即骨诱导性β-磷酸三钙（TCP）和非骨诱导性羟基磷灰石（HA）的血清蛋白吸附。此外，我们分析了在这两种陶瓷上培养的人间充质基质细胞（hMSCs）的蛋白质谱。在没有细胞的情况下进行的血清蛋白质吸附实验突出了蛋白质，这些蛋白质在血清中高度丰富和/或对CaP具有高亲和力。建议吸附的程度受可用结合表面积和表面上离子交换动力学的影响。hMSC在TCP和HA表面上独特表达了几种蛋白质。鉴定为富含TCP的蛋白质参与了与伤口愈合，细胞增殖和细胞外基质产生有关的过程。另一方面，富含HA的蛋白质参与了与蛋白质生产，翻译，定位和分泌有关的过程。此外，我们对TCP，HA，以及两个具有已知骨诱导潜力的双相磷酸钙，并对发现富含骨诱导材料的一组蛋白质与一组已知参与成骨的蛋白质的组合进行了聚类分析。这产生了可能与骨诱导过程有关的两个蛋白质网络-一个由胶原蛋白片段和与胶原蛋白相关的酶组成，另一个由内肽酶抑制剂和调节蛋白组成。这项研究的结果表明，蛋白质谱分析可能是帮助了解生物材料特性对生物材料与生物系统之间相互作用的有用工具。这种理解将有助于设计和开发用于（骨）再生疗法的改良生物材料。这产生了可能与骨诱导过程有关的两个蛋白质网络-一个由胶原蛋白片段和与胶原蛋白相关的酶组成，另一个由内肽酶抑制剂和调节蛋白组成。这项研究的结果表明，蛋白质谱分析可能是帮助了解生物材料特性对生物材料与生物系统之间相互作用的有用工具。这种理解将有助于设计和开发用于（骨）再生疗法的改良生物材料。这产生了可能与骨诱导过程有关的两个蛋白质网络-一个由胶原蛋白片段和与胶原蛋白相关的酶组成，另一个由内肽酶抑制剂和调节蛋白组成。这项研究的结果表明，蛋白质谱分析可能是帮助了解生物材料特性对生物材料与生物系统之间相互作用的有用工具。这种理解将有助于设计和开发用于（骨）再生疗法的改良生物材料。这项研究的结果表明，蛋白质谱分析可能是帮助了解生物材料特性对生物材料与生物系统之间相互作用的有用工具。这种理解将有助于设计和开发用于（骨）再生疗法的改良生物材料。这项研究的结果表明，蛋白质谱分析可能是帮助了解生物材料特性对生物材料与生物系统之间相互作用的有用工具。这种理解将有助于设计和开发用于（骨）再生疗法的改良生物材料。