ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Germany.
Int Rev Cell Mol Biol. 2014;313:27-77. doi: 10.1016/B978-0-12-800177-6.00002-5.
In recent years a paradigm shift in understanding of human bone formation has occurred that starts to change current concepts in tissue engineering of bone and cartilage. New discoveries revealed that fundamental steps in biomineralization are enzyme driven, not only during hydroxyapatite deposition, but also during initial bioseed formation, involving the transient deposition and subsequent transformation of calcium carbonate to calcium phosphate mineral. The principal enzymes mediating these reactions, carbonic anhydrase and alkaline phosphatase, open novel targets for pharmacological intervention of bone diseases like osteoporosis, by applying compounds acting as potential activators of these enzymes. It is expected that these new findings will give an innovation boost for the development of scaffolds for bone repair and reconstruction, which began with the use of bioinert materials, followed by bioactive materials and now leading to functional regenerative tissue units. These new developments have become possible with the discovery of the morphogenic activity of bioinorganic polymers, biocalcit, bio-polyphosphate and biosilica that are formed by a biogenic, enzymatic mechanism, a driving force along with the development of novel rapid-prototyping three-dimensional (3D) printing methods and bioprinting (3D cell printing) techniques that may allow a fabrication of customized implants for patients suffering in bone diseases in the future.
近年来，人们对人类骨骼形成的理解发生了范式转变，这开始改变骨和软骨组织工程的当前概念。新的发现揭示了生物矿化的基本步骤是酶驱动的，不仅在羟磷灰石沉积期间，而且在初始生物种子形成期间也是如此，涉及碳酸钙向磷酸钙矿物的短暂沉积和随后的转化。介导这些反应的主要酶，碳酸酐酶和碱性磷酸酶，为骨质疏松症等骨骼疾病的药物干预提供了新的靶点，通过应用作为这些酶的潜在激活剂的化合物。预计这些新发现将为骨修复和重建支架的开发提供创新动力，骨修复和重建支架的开发始于使用生物惰性材料，随后是生物活性材料，现在引领功能性再生组织单位。这些新的发展随着生物无机聚合物、生物钙、生物多磷酸盐和生物硅的形态发生活性的发现而成为可能，这些物质是通过生物、酶促机制形成的，这是一种驱动力，同时还开发了新型快速原型三维（3D）打印方法和生物打印（3D 细胞打印）技术，这些技术可能允许为患有骨骼疾病的患者制造定制植入物。
