Additive manufacturing of a novel class of implants with heterogeneous structures, combining different biomaterials and printing methods

结合不同的生物材料和打印方法，增材制造具有异质结构的新型植入物

• 批准号: 525055411
• 负责人: Professor Dr. Michael Gelinsky
• 金额: --
• 依托单位: Zentrum für Translationale Knochen-, Gelenk- und Weichgewebeforschung
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/525055411?language=en
• 关键词: Additive; manufacturing; novel; class; implants

The additive method of micro-extrusion can be operated at room temperature and a multitude of biodegradable biomaterials is available in the meanwhile for this method. Here, we aim at creating new types of implants and tissue constructs that support full regeneration of common defects that occur at tissue interfaces like the osteochondral unit (bone and articular cartilage) or the tendon-bone interface (enthesis). Novel solutions will be developed by combining biomaterials that are specifically adapted to the respective tissues by means of multi-channel extrusion printing. Operation at room temperature will enable integration of tissue-specific, sensitive bioactive factors directly in the printing process. A major innovation of this project is the development and utilization of new printing patterns. Influence of the printing design is still a mostly unexplored topic in micro-extrusion printing, where so far commonly basic wood pile geometries are printed. Focus for the development is the generation of a maximum of concave surfaces as those have been proven to support cell adhesion and migration better than planar and convex surfaces. In addition, size and accessibility of the pores will be taken into account that are crucial for O2 and nutrient supply, both during cell culture and after implantation into the tissue defects. The mechanical properties of the scaffold resulting from the designed pattern will be included in the optimization processes, supported by computational modelling. Besides micro-extrusion, the AM technology of Melt Electrowriting (MEW) of thermoplastic polymers will be integrated in the scaffold design. As shown in preliminary experiments by the applicants, micro-extrusion (strand diameter >= 200 Mikrometer) and MEW (fiber diameter ca. 0.5-20 micromters) can be combined within one printing process. As with MEW highly defined microfiber meshes can be produced, the combination of both AM technologies allows the fabrication of scaffolds with hierarchical structures that provide suitable surfaces for cell attachment and development - but also microfiber networks that mimic the extracellular matrices of mammalian tissues. Integration of MEW meshes can enhance the mechanical stability of calcium phosphate scaffolds, improve the connection of different, extrusion-printed biomaterials and provide guiding structures for alignment of cells. Overall, a new generation of scaffolds and tissue constructs will be developed that consists of several biodegradable biomaterials and are fabricated by innovative combination of two AM technologies in one printing process. The resulting constructs will be thoroughly investigated concerning their structural, mechanical and biological properties, utilizing microscopy, mechanical testing, and state-of-the-art in vitro tests with primary human cells and human mesenchymal stem cells. All this data will be deeply analyzed to conclude about structure-property relation.

微挤压添加法可在室温下操作，同时该方法可制备多种可生物降解的生物材料。在这里，我们的目标是创造新型植入物和组织结构，支持骨软骨单位（骨和关节软骨）或肌腱-骨界面（附着点）等组织界面处常见缺陷的完全再生。通过多通道挤出印刷结合专门适合各自组织的生物材料，将开发出新颖的解决方案。在室温下操作将使组织特异性、敏感的生物活性因子直接整合到打印过程中。该项目的一大创新在于新型印刷图案的开发和利用。印刷设计的影响在微挤压印刷中仍然是一个尚未探索的话题，迄今为止，微挤压印刷通常印刷基本的木堆几何形状。开发的重点是生成最大程度的凹面，因为这些凹面已被证明比平面和凸面更好地支持细胞粘附和迁移。此外，还将考虑孔的大小和可及性，这对于细胞培养期间和植入组织缺损后的氧气和营养供应至关重要。由设计模式产生的支架的机械性能将包含在优化过程中，并由计算模型支持。除了微挤出之外，热塑性聚合物的熔融电写入（MEW）增材制造技术也将被集成到支架设计中。如申请人的初步实验所示，微挤出（线材直径>=200微米）和MEW（纤维直径约0.5-20微米）可以在一个印刷过程中结合起来。与 MEW 可以生产高度定义的微纤维网一样，两种增材制造技术的结合可以制造具有分层结构的支架，为细胞附着和发育提供合适的表面，而且还可以制造模仿哺乳动物组织细胞外基质的微纤维网络。 MEW 网格的集成可以增强磷酸钙支架的机械稳定性，改善不同的挤出印刷生物材料的连接，并为细胞排列提供引导结构。总体而言，将开发新一代支架和组织结构，由多种可生物降解的生物材料组成，并通过在一个打印过程中创新地组合两种增材制造技术来制造。将利用显微镜、机械测试以及对原代人类细胞和人类间充质干细胞进行最先进的体外测试，对所得构建体的结构、机械和生物特性进行彻底研究。所有这些数据将被深入分析，以得出结构-性能关系的结论。