Synergising mechanical and osteogenic properties for personalized bone tissue engineering via co-3D printing with fibre reinforced composite and blood

通过纤维增强复合材料和血液的协同 3D 打印，协同机械和成骨特性，实现个性化骨组织工程

• 批准号: 2739766
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2739766
• 关键词: Synergising; mechanical; osteogenic; properties; personalized

An ideal biomaterial scaffold for healing load-bearing large bone defects should have cortical bone matching mechanical properties and osteogenic properties for promoting new bone regeneration. Scaffolds possessing these two traits currently do not exist. Current scaffolds made of bioglasses, bioceramics and particle reinforced composites have only achieved mechanical properties in the cancellous bone range. Cortical bone is an order of magnitude stronger than cancellous bone. Metals, such as titanium, are widely used in orthopaedic surgeries where high mechanical properties are sought. However, they are much stiffer than bone. The Young's modulus of titanium is approximately 10 times of cortical bone. This mismatch in mechanical properties shields the physiological stresses from the surrounding bone, which weakens them and makes them prone to fracture over time. Therefore, scaffolds matching human cortical bone mechanical properties are urgently needed.Potent osteogenic biomolecules such as bone morphogenic protein 2 (BMP2) are now widely used in various orthopaedic surgeries such as treating non-union fractures. However, the supraphysiological dosage used in clinic has caused various complications such as uncontrolled excessive bone growth and cancer. The adverse effects associated with supraphysiological dosage of BMP2 has led to a FDA warning to a spinal fusion device (Infuse-BMP2 loaded collagen in a titanium cage) and subsequent rejection of similar products. This has prompted researchers to investigate other means to enhance osteogenesis. Human beings have evolved to fully heal bone fractures at small scales. This process is triggered and regulated by the Regenerative Hematoma/Clot (RHC), which comprises a rich source of endogenous factors and cell populations that are critical for stem/progenitor cell recruitment, immunomodulation, osteogenic differentiation, and ultimate bone healing. However, the RHC is often disturbed or removed during fracture reduction, internal fixation, and debridement in orthopaedic surgeries, leading to poor bone regeneration. Rebuilding the RHC in bone fractures using the patient's own blood could potentially overcome major current limitations in fracture treatment and enable personalized regenerative implants that are low in cost, easily deployable, and low risk to patients compared to stem cell therapies or bone marrow aspiration.The aim of this project is to produce 3D printed continuous fibre reinforced composite scaffolds combined with engineered human blood gels to obtain osteogenic scaffolds with mechanical properties matching cortical bone.The specific objectives are:1. Develop a 3D printing process to fabricate continuous fibre reinforced composite scaffolds. Test the mechanical properties of the printed scaffolds with tuneable architectural parameters.2. Engineer blood gels with tuneable mechanical properties. Co-printing of fibre reinforced composite and blood gel.3. Test in vitro osteogenic differentiation of bone marrow stem cells in blood-composite scaffolds.

理想的修复承重性大骨缺损的生物材料支架应具有皮质骨的力学性能和成骨性能，以促进新骨再生。具有这两个特性的支架目前还不存在。目前，由生物玻璃、生物陶瓷和颗粒增强复合材料制成的支架只能在松质骨范围内获得力学性能。皮质骨比松质骨强一个数量级。钛等金属被广泛用于寻求高机械性能的整形外科手术中。然而，它们比骨头要硬得多。钛的杨氏模数约为皮质骨的10倍。这种机械性能的不匹配将生理应力与周围的骨骼隔离开来，从而削弱了它们，使它们随着时间的推移容易骨折。骨形态发生蛋白2(BMP2)等潜在的成骨生物分子目前被广泛应用于各种骨科手术中，如治疗骨不连。然而，临床上使用的超生理剂量会导致各种并发症，如失控的骨过度生长和癌症。BMP2的不良反应与超生理剂量的BMP2相关，已导致FDA警告脊柱融合装置(Inuse-BMP2在钛笼中负载胶原)，并随后拒绝使用类似产品。这促使研究人员研究其他方法来促进成骨。人类已经进化到能够完全治愈小规模的骨折。这一过程由再生血肿/凝块(RHC)触发和调节，RHC由丰富的内源性因子和细胞群组成，对干细胞/祖细胞招募、免疫调节、成骨分化和最终骨愈合至关重要。然而，在骨科手术中，在骨折复位、内固定和清创过程中，RHC经常被干扰或移除，导致骨再生不良。使用患者自身的血液重建骨折中的RHC可能会克服目前骨折治疗中的主要限制，并实现个性化的再生植入物，与干细胞治疗或骨髓抽吸相比，这种方法成本低，易于部署，对患者的风险较低。本项目的目标是生产3D打印的连续纤维增强复合支架，并与工程人血凝胶相结合，获得力学性能与皮质骨匹配的成骨支架。具体目标是：1.开发3D打印工艺来制造连续纤维增强复合支架。用可调的建筑参数测试打印支架的力学性能。设计出机械性能可调的血液凝胶。纤维增强复合材料与血液凝胶的共印花。骨髓干细胞在血液复合支架中的体外成骨分化实验。