Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14040-901, Brazil.
Departamento de Ciências Biomoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14040-901, Brazil.
ACS Appl Mater Interfaces. 2020 Sep 30;12(39):43422-43434. doi: 10.1021/acsami.0c12434. Epub 2020 Sep 16.
Calcium phosphate (CaP)-based ceramics are the most investigated materials for bone repairing and regeneration. However, the clinical performance of commercial ceramics is still far from that of the native tissue, which remains as the gold standard. Thus, reproducing the structural architecture and composition of bone matrix should trigger biomimetic response in synthetic materials. Here, we propose an innovative strategy based on the use of track-etched membranes as physical confinement to produce collagen-free strontium-substituted CaP nanotubes that tend to mimic the building block of bone, , the mineralized collagen fibrils. A combination of high-resolution microscopic and spectroscopic techniques revealed the underlying mechanisms driving the nanotube formation. Under confinement, poorly crystalline apatite platelets assembled into tubes that resembled the mineralized collagen fibrils in terms of diameter and structure of bioapatite. Furthermore, the synergetic effect of Sr and confinement gave rise to the stabilization of amorphous strontium CaP nanotubes. The nanotubes were tested in long-term culture of osteoblasts, supporting their maturation and mineralization without eliciting any cytotoxicity. Sr released from the particles reduced the differentiation and activity of osteoclasts in a Sr concentration-dependent manner. Their bioactivity was evaluated in a serum-like solution, showing that the particles spatially guided the biomimetic remineralization. Further, these effects were achieved at strikingly low concentrations of Sr that is crucial to avoid side effects. Overall, these results open simple and promising pathways to develop a new generation of CaP multifunctional ceramics that are active in tissue regeneration and able to simultaneously induce biomimetic remineralization and control the imbalanced osteoclast activity responsible for bone density loss.
基于磷酸钙（CaP）的陶瓷是研究最多的用于骨修复和再生的材料。然而，商业陶瓷的临床性能仍然远远低于天然组织，后者仍然是金标准。因此，复制骨基质的结构架构和组成应该会在合成材料中引发仿生反应。在这里，我们提出了一种基于使用轨道蚀刻膜作为物理限制的创新策略，以生产不含胶原蛋白的锶取代的 CaP 纳米管，这些纳米管倾向于模拟骨骼的构建块，即矿化胶原纤维。高分辨率显微镜和光谱技术的组合揭示了驱动纳米管形成的潜在机制。在受限条件下，结晶不良的磷灰石板组装成纳米管，在直径和生物磷灰石结构方面类似于矿化胶原纤维。此外，Sr 和限制的协同作用导致非晶态 SrCaP 纳米管的稳定化。纳米管在成骨细胞的长期培养中进行了测试，支持它们的成熟和矿化，而没有引起任何细胞毒性。纳米颗粒中释放的 Sr 以 Sr 浓度依赖的方式降低了破骨细胞的分化和活性。它们的生物活性在类似血清的溶液中进行了评估，表明颗粒在空间上指导了仿生再矿化。此外，这些效果是在 Sr 的浓度非常低的情况下实现的，这对于避免副作用至关重要。总的来说，这些结果为开发新一代具有多功能性的 CaP 陶瓷开辟了简单而有前途的途径，这些陶瓷在组织再生中具有活性，并且能够同时诱导仿生再矿化和控制导致骨密度丧失的不平衡破骨细胞活性。
