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

在世界各地，骨折是入院的常见原因。仅在英格兰，2004年至2014年间就有2,489,052例骨折入院。由于这些高骨折率，骨组织再生领域广泛吸引了世界各地的研究人员。骨组织结构复杂、层次分明，具有机械、生物、化学等多种功能。骨组织的这种分层结构由宏观结构（如皮质骨和松质骨）、微观结构（如骨骨和骨小梁）、亚微观结构（如片层）、纳米结构（如纤维胶原）和亚纳米结构（如矿物质和胶原分子）[2]的优化不规则排列组成。骨组织的机械功能需求是由其组成阶段和其分层结构的组织[3]支持的。外伤、肿瘤和/或感染引起的大面积骨缺损必须用功能性的替代骨块代替。自体移植物（取自患者身体各个部位的骨组织）已被广泛接受为小缺损重建的标准方法。然而，自体植骨术存在一些局限性，如供体部位发病率、骨供应有限、解剖、结构和手术限制等。其他生物来源，如同种异体骨（从一个人身上采集到另一个人的骨组织）和异种骨（从另一个物种采集的骨组织）也被评估并用于骨修复和再生，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骨组织的另一种方法。然而，获得更接近健康骨组织的物理和生物特性的人工骨替代品仍然具有挑战性。在骨组织工程中，高多孔支架材料为细胞附着、骨生长和血管化提供了途径。为了提高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、孔隙几何形状和孔隙连通性等特征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具有不同层次的骨样支架的细胞结构，这些支架由羟基磷灰石亚微米颗粒制成，这些颗粒从现成的贝类贝壳中提取，并使用数字光处理（DLP）增材制造技术制造。这种贝壳储量丰富，每年全球水产养殖产量约为1500万吨，每吨填埋成本为88.95英镑。这些骨样支架将提供与预定植入部位相匹配的机械性能，并提供有利于组织整合和血管化的多孔网络的充分互联性。由此产生的骨替代物将表现出更接近天然骨组织的生物相容性、成骨特性和机械特性，以避免应力屏蔽导致不必要的骨吸收和植入物松动。

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.