Innovative manufacturing of decellularised bone scaffolds
脱细胞骨支架的创新制造
基本信息
- 批准号:1958401
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:英国
- 项目类别:Studentship
- 财政年份:2017
- 资助国家:英国
- 起止时间:2017 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Musculoskeletal disorders are the second greatest cause of disability in the UK. For example, one third of people aged over 45 have sought treatment for osteoarthritis, costing the NHS over £5 billion per year.Diseases such as cancer or trauma through mechanical insult can lead to damage of the skeletal structures requiring surgical intervention. Graft materials are used to replace and restore the function of musculoskeletal tissues including bone, cartilage, menisci and tendons.In iMBE we have developed decellularised musculoskeletal tissue scaffolds from both human and animal tissues to address a range of clinical grafting needs. Decellularised scaffolds are advantageous over traditional human and animal grafts, as removal of cellular components renders the graft immune-compatible. The advantage over synthetic grafting materials is the retention of the native tissue composition, structure and function which acts as the optimal environment for regenerative stem and progenitor cells. Decellularised bone has the potential to repair bony defects, but also to act as a skeletal attachment site when incorporated into composite bone-soft tissue scaffolds for example in a bone-tendon graft for cruciate ligament reconstruction. Decellularised bone and tendon products have been shown to function as excellent regenerative scaffolds in large animal studies. Although appropriate to produce tissues in the research setting, the current decellularisation processing methods for bony tissues are not compatible with scale up for industrial manufacture and therefore prove a real barrier to the use of these scaffolds clinically in patients. Also, one size does not fit all; a range of decellularised bone grafts with differing properties is required to match with orthopaedic application, surgeon preference, and patient variability. The research challenge is to develop improved industry-compatible methods of bone decellularisation and to elucidate the biological and biomechanical variance in the end product that can be achieved through altering different bioprocess parameters. The specific research questions are:1. Can the manufacturing bioprocess be adapted to good manufacturing process (GMP) standards appropriate for clinical grade scaffold production at NHS BT facilities? 2. Can variation of the source tissue, storage and sterilisation method lead to a stratified range of decellularised bone products?This project will involve biological, biomechanical and CT analysis of bone along with the product design challenge of building a device to partly automate the bioprocess.This research has the potential to directly impact on industry practice and also contribute towards the production of improved decellularised scaffolds for use in bony tissue regeneration. Aim: To produce and characterise a range of decellularised bone products using industry compatible manufacturing processes to a standard suitable for clinical use.Objectives (manufacturing):1. To physically remove bone marrow in a way compatible with working in a grade B clean room.2. To develop a rig/device to contain and automate the tissue washing process.3. To reduce the duration of the decellularisation bioprocess.The manufacturing process will initially be optimised using porcine tissue prior to application to human tissue.Objectives (product variation):1. To determine the effect of the following parameters on resultant biological, material and biomechanical properties of the human bone scaffold.a. The size and shape of bone blocks which are processedb. The storage method used e.g. frozen vs lyophilisedc. The sterilisation method used e.g. irradiation vs chemical sterilisation This project will use decellularisation, histology, cell culture and biochemical assay facilities in FBS. Micro CT imaging and biomechanical testing facilities will be used in the school of mechanical engineering.
肌肉骨骼疾病是英国残疾的第二大原因。例如,45岁以上的人中有三分之一寻求骨关节炎的治疗,每年花费NHS超过50亿英镑。癌症或机械损伤造成的创伤等疾病可能导致骨骼结构受损,需要手术干预。移植材料用于替代和恢复肌肉骨骼组织的功能,包括骨、软骨、肌腱和肌腱。在iMBE中,我们开发了来自人类和动物组织的脱细胞肌肉骨骼组织支架,以满足一系列临床移植需求。脱细胞支架优于传统的人类和动物移植物,因为细胞组分的去除使得移植物具有免疫相容性。与合成移植材料相比,其优点是保留了天然组织的组成、结构和功能,这是再生干细胞和祖细胞的最佳环境。脱细胞骨具有修复骨缺损的潜力,但当结合到复合骨-软组织支架中时,例如在用于交叉韧带重建的骨-肌腱移植物中,脱细胞骨也可用作骨骼附着部位。在大型动物研究中,脱细胞骨和肌腱产品已被证明可作为优良的再生支架。尽管适合于在研究环境中生产组织,但目前用于骨组织的去细胞化处理方法与工业生产的规模扩大不相容,因此证明了这些支架在临床上用于患者的真实的障碍。此外,一种尺寸并不适合所有人;需要一系列具有不同特性的脱细胞骨移植物来匹配骨科应用、外科医生偏好和患者变异性。研究的挑战是开发改进的行业兼容的骨去细胞化方法,并阐明通过改变不同的生物工艺参数可以实现的最终产品的生物和生物力学差异。具体的研究问题是:1.生产生物工艺是否适用于在NHS BT工厂生产临床级支架的良好生产工艺(GMP)标准?2.来源组织、储存和灭菌方法的变化是否会导致脱细胞骨产品的分层?该项目将涉及骨的生物学、生物力学和CT分析沿着构建一种设备以部分自动化生物过程的产品设计挑战。该研究有可能直接影响行业实践,并有助于生产用于骨组织再生的改进脱细胞支架。目的:使用工业兼容的生产工艺生产和生产一系列脱细胞骨产品,以达到适用于临床使用的标准。以符合B级洁净室工作要求的方式进行骨髓物理清除。开发一种装置/设备,以包含和自动化组织清洗过程。为了减少去细胞生物过程的持续时间。在应用于人体组织之前,首先将使用猪组织优化生产过程。目的(产品变化):1.确定以下参数对人骨支架的生物学、材料和生物力学性能的影响。所处理的骨块的大小和形状b。使用的储存方法,例如冷冻vs冻干。使用的灭菌方法,例如辐照与化学灭菌。本项目将在FBS中使用去细胞化、组织学、细胞培养和生化测定设施。微型CT成像和生物力学测试设施将用于机械工程学院。
项目成果
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其他文献
吉治仁志 他: "トランスジェニックマウスによるTIMP-1の線維化促進機序"最新医学. 55. 1781-1787 (2000)
Hitoshi Yoshiji 等:“转基因小鼠中 TIMP-1 的促纤维化机制”现代医学 55. 1781-1787 (2000)。
- DOI:
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LiDAR Implementations for Autonomous Vehicle Applications
- DOI:
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2021 - 期刊:
- 影响因子:0
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吉治仁志 他: "イラスト医学&サイエンスシリーズ血管の分子医学"羊土社(渋谷正史編). 125 (2000)
Hitoshi Yoshiji 等人:“血管医学与科学系列分子医学图解”Yodosha(涉谷正志编辑)125(2000)。
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Effect of manidipine hydrochloride,a calcium antagonist,on isoproterenol-induced left ventricular hypertrophy: "Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,K.,Teragaki,M.,Iwao,H.and Yoshikawa,J." Jpn Circ J. 62(1). 47-52 (1998)
钙拮抗剂盐酸马尼地平对异丙肾上腺素引起的左心室肥厚的影响:“Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,
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