Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische Universität Dresden, Germany.
Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus and Faculty of Medicine of Technische Universität Dresden, Germany; State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People's Republic of China.
Acta Biomater. 2015 Nov;27:264-274. doi: 10.1016/j.actbio.2015.08.036. Epub 2015 Aug 28.
Additive manufacturing allows to widely control the geometrical features of implants. Recently, we described the fabrication of calcium phosphate cement (CPC) scaffolds by 3D plotting of a storable CPC paste based on water-immiscible carrier liquid. Plotting and hardening is conducted under mild conditions allowing the (precise and local) integration of biological components. In this study, we have developed a procedure for efficient loading of growth factors in the CPC scaffolds during plotting and demonstrated the feasibility of this approach. Bovine serum albumin (BSA) or vascular endothelial growth factor (VEGF), used as model proteins, were encapsulated in chitosan/dextran sulphate microparticles which could be easily mixed into the CPC paste in freeze-dried state. In order to prevent leaching of the proteins during cement setting, usually carried out by immersion in aqueous solutions, the plotted scaffolds were aged in water-saturated atmosphere (humidity). Setting in humidity avoided early loss of loaded proteins but provided sufficient amount of water to allow cement setting, as indicated by XRD analysis and mechanical testing in comparison to scaffolds set in water. Moreover, humidity-set scaffolds were characterised by altered, even improved properties: no swelling or crack formation was observed and accordingly, surface topography, total porosity and compressive modulus of the humidity-set scaffolds differed from those of the water-set counterparts. Direct cultivation of mesenchymal stem cells on the humidity-set scaffolds over 21days revealed their cytocompatibility. Maintenance of the bioactivity of VEGF during the fabrication procedure was proven in indirect and direct culture experiments with endothelial cells.
Additive manufacturing techniques allow the fabrication of implants with defined architecture (inner pore structure and outer shape). Especially printing technologies conducted under mild conditions allow additionally the (spatially controlled) integration of biological components such as drugs or growth factors. That enables the generation of individualized implants which can better meet the requirements of a patient and of tissue engineering constructs. To our knowledge, simultaneous printing of biological components was up to now only described for hydrogel/biopolymer-based materials which suffer from poor mechanical properties. In contrast, we have developed a procedure (based on 3D plotting of a calcium phosphate cement paste) for the fabrication of designed and growth factor loaded calcium-phosphate-based scaffolds applicable for bone regeneration.
增材制造允许广泛控制植入物的几何特征。最近，我们描述了基于不混水载体液体的可储存磷酸钙水泥（CPC）糊剂的 3D 绘图来制造 CPC 支架。绘图和硬化是在温和条件下进行的，允许（精确和局部）整合生物成分。在这项研究中，我们开发了一种在绘图过程中有效加载 CPC 支架中生长因子的方法，并证明了该方法的可行性。牛血清白蛋白（BSA）或血管内皮生长因子（VEGF）被用作模型蛋白，被包封在壳聚糖/葡聚糖硫酸盐微球中，这些微球可以在冷冻干燥状态下很容易地混入 CPC 糊剂中。为了防止蛋白在水泥凝固过程中浸出（通常通过浸入水溶液中进行），绘制的支架在水饱和气氛（湿度）中老化。在湿度下凝固避免了负载蛋白的早期损失，但提供了足够的水以使水泥凝固，这可以通过与在水中凝固的支架相比的 XRD 分析和机械测试来指示。此外，湿度凝固的支架具有改变的甚至改善的特性：没有观察到肿胀或裂纹形成，因此，湿度凝固的支架的表面形貌、总孔隙率和压缩模量与水凝固的支架不同。在 21 天的时间里，将间充质干细胞直接培养在湿度凝固的支架上，证明了它们的细胞相容性。在与内皮细胞的间接和直接培养实验中，证明了 VEGF 的生物活性在制造过程中的保持。
增材制造技术允许制造具有定义的结构（内部孔结构和外部形状）的植入物。特别是在温和条件下进行的打印技术还允许（空间受控）整合生物成分，如药物或生长因子。这使得能够生成可以更好地满足患者和组织工程结构要求的个性化植入物。据我们所知，到目前为止，仅描述了用于水凝胶/生物聚合物基材料的同时打印，这些材料的机械性能较差。相比之下，我们已经开发了一种（基于磷酸钙水泥糊的 3D 绘图）制造可设计和负载生长因子的磷酸钙基支架的方法，适用于骨再生。
