Bioinspired Hybrid Scaffolds for Bone Tissue Engineering

骨组织由胶原纤维增强的羟基磷灰石（HAp）的分级结构组成，其由细胞（成骨细胞）产生，并且除其他外，能够实现具有足够延展性的高强度以及再生能力。功能性骨替代材料必须反映这种特性，从而反映仿生孔径、机械性能和生物相容性。到目前为止，技术解决方案需要在生物和机械性能之间进行折衷，因为现有的方法和材料无法同时以满足要求的方式进行复制。高比例的细胞成分使得骨结构的工程提取和模拟非常具有挑战性，然而，这是理想的骨替代材料所必需的。这里提出的项目旨在通过探索以玻璃海绵Euplectella aspergillum为模型的仿生方法来填补这一空白。这种海绵也是分层结构的，并表现出为骨替代材料产生积极特性的构造原理，例如高抗压强度、刚度和延展性。同时，所选材料方法旨在开发所需的生物学特性。这需要基于模拟的纤维增材制造（FAM）开发，用于生产用于骨置换的分层结构、高度多孔和承重支架，其首次在材料和结构水平上将联合收割机机械和再生增强生物特性相结合。这将特别克服骨缺损治疗中的现有挑战，并显着提高受影响患者的愈合成功率。将对开发的支架进行广泛的机械和生物学表征，以便为MDR合规性（医疗器械法规）风险评估奠定基础。目标值在很大程度上取决于随后的植入区域（例如，颌骨与股骨）。对于皮质骨的复制，将实现100 - 200 MPa的压缩强度/弯曲刚度和5 - 20 GPa的弹性模量;对于松质骨，将实现65 - 90%的孔隙率，由此待开发的技术使得可以在一个植入物中复制两者。最后，制造技术将在INNOTERE进行工业验证，从而将开发的技术从TRL 4提升到TRL 6。

Bone tissue consists of hierarchical structures of collagen fiber-reinforced hydroxyapatite (HAp), which are generated by cells (osteoblasts) and enable, among other things, high strengths with sufficient ductility, as well as regenerative capacity. Functional bone substitute materials must reflect this property profile and thus biomimetic pore sizes, mechanical properties and biocompatibility. Until now, technical solutions have required a compromise between biological and mechanical properties, since established methods and materials are not capable of reproducing both at the same time in a way that meets the requirements. The high proportion of cellular components makes an engineering abstraction and imitation of the bone structure very challenging, which is, however, necessary for an ideal bone substitute material. The project proposed here aims to fill this gap by exploring a biomimetic approach modeled on the glass sponge Euplectella aspergillum. This sponge is also hierarchically structured and exhibits construction principles that generate positive properties for bone substitution materials, such as high compressive strength, stiffness and ductility. At the same time, the chosen material approach is intended to develop the required biological properties. This requires the simulation-based development of Fiber Additive Manufacturing (FAM) for the production of hierarchically structured, highly porous and load-bearing scaffolds for bone replacement, which for the first time combine mechanical and regeneration-enhancing biological properties at the material and structural level. This should specifically overcome existing challenges in the therapy of bone defects and significantly increase the healing success of affected patients. The developed scaffolds will be extensively characterized mechanically and biologically in such a way that the basis for a MDR-compliant (medical device regulation) risk assessment will be laid. The target values are strongly dependent on the subsequent implantation region (e.g. jaw vs. femur). For the replication of the cortical bone, compressive strengths/bending stiffnesses of 100 - 200 MPa and elastic moduli of 5 - 20 GPa are to be achieved; for cancellous bone, porosities of 65 - 90 % are to be achieved, whereby the technology to be developed makes it possible to replicate both in one implant. Finally, the manufacturing technology will be industrially validated at INNOTERE, thus raising the developed technology from TRL4 to TRL6.