Novel designs of bone-like scaffolds using topology optimisation and additive manufacturing

在世界各地，骨折是住院的常见原因。仅在英国，2004至2014年间就有2,489,052人因骨折入院[1]。由于骨折的高发生率，骨组织再生领域引起了世界各地的研究人员的广泛关注。骨组织结构复杂、层次分明，具有机械、生物和化学等多种功能。这种骨组织的层次结构由宏观结构(如皮质骨和松质骨)、微观结构(如骨小梁)、亚微观结构(如片层)、纳米结构(如纤维状胶原)和亚纳米结构(如矿物和胶原分子)的优化不规则排列组成[2]。骨组织的机械功能需求由其组成阶段和其层次结构的组织来支持[3]。由创伤、肿瘤和/或感染引起的广泛骨缺损必须用功能性替代方法来替代[3]。自体移植(从患者身体不同部位采集的骨组织)已被广泛接受为小缺陷重建的标准方法[4]。然而，自体骨移植手术有一些局限性，如供骨部位发病率、有限的骨供应、解剖、结构和手术方面的限制[5]。其他生物来源，如同种异体骨(从一个个体获取的骨组织)和异种骨(从另一个物种获取的骨组织)也进行了评估，并在骨修复和再生方面取得了不同的临床成功。因此，使用合成材料是修复和再生丢失的骨组织的另一种方式。然而，获得更接近健康骨组织的物理和生物学特性的人造骨替代品仍然是具有挑战性的。在骨组织工程中，高度多孔的支架材料为细胞附着、骨生长和血管形成提供了一条途径。为了改善多孔支架材料与活骨组织的结合，必须将材料的孔隙率、孔径大小、孔几何形状和孔连通性控制在合适的范围内。在这个项目中，我们建议使用拓扑优化技术来设计不同层次的类骨支架的细胞结构，这些支架由从现成的软体动物贝壳中提取的羟基磷灰石亚微米颗粒制成，并使用数字光处理(DLP)添加剂制造技术制造。贝壳资源丰富，一年内全球水产养殖产量约为1500万吨，填埋成本为88.95 GB/吨。这些骨样支架将提供与预期植入部位相匹配的机械性能，并提供充分的多孔网络互连，有利于组织整合和血管形成。所得到的骨替代材料将表现出与天然骨组织更接近的生物相容性、成骨性能和机械性能，以避免导致不必要的骨吸收和种植体松动的应力遮挡。

Around the world, fractures are a common reason for admission to hospitals. In England only, there were 2,489,052 fracture admissions between 2004 and 2014 [1]. As a result of these high rates of bone fractures, the field of bone tissue regeneration has extensively attracted researchers worldwide. The complex and hierarchical structure of bone tissue serves its diverse functions including mechanical, biological and chemical. This hierarchical structure of bone tissue is composed of optimised irregular arrangements of macrostructures (such as cortical and cancellous bone), microstructures (such as osteons and trabeculae), sub-microstructures (like lamellae), nanostructures (such as fibrillar collagen), and sub-nanostructures (such as minerals and collagen molecules)[2]. The mechanical function needs of bone tissue is supported by its component phases and the organisation of its hierarchical structure [3]. Extensive bone defects caused by trauma, tumour, and/or infection must be replaced by a functional alternative [3]. Autografts (bone tissue harvested from various sites of the patient body) has been widely accepted as the standard method for small defect reconstruction [4]. However, there are some limitations associated with autogenous bone grafting procedures, such as donor site morbidity, limited bone supply, anatomical, structural, and surgical limitations [5]. Other biological sources such as allograft (bone tissue harvested from one individual to another) and xenogenic (bone tissue harvested from another species) bone also been evaluated and used with varying clinical success for bone repair and regeneration. Hence, the use of synthetic materials is another way to repair and regenerate lost bone tissue [5]. However, it is still challenging to obtain synthetic bone substitutes that mimic the physical and biological properties of the healthy bone tissue more closely. In bone tissue engineering, highly porous scaffold materials provide a pathway for cell attachment, bone in-growth, and vascularisation. To improve integration of porous scaffold material and the living bone tissue, material features like porosity, pore size, pore geometry and pore connectivity have to be controlled in a suitable range. In this project, we propose using topology optimisation techniques to design cellular structures for bone-like scaffolds with different hierarchical levels made from hydroxyapatite submicron particles extracted from readily available molluscs shells and manufactured using Digital Light Processing (DLP) additive manufacturing technology. The shells are available in abundance with a global aquaculture production of approximately 15 million tonnes in 1 year and costing £88.95/tonne to landfill. These resulting bone-like scaffolds will offer mechanical properties that match the intended site for implantation and provides sufficient interconnectivity of the porous network that favour tissue integration and vascularisation. The resulting bone substitutes will demonstrate biocompatibility, osteogenic properties, and mechanical properties closer to those of natural bone tissues to avoid stress shielding which results in unwanted bone resorption and implant loosening.