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Biotextiles for ligament repair using biofunctionalisation to aid regeneration

利用生物功能化帮助再生的韧带修复生物纺织品

基本信息

批准号：
1735234
负责人：
金额：
--
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1735234
关键词：
Biotextiles ligament repair using biofunctionalisation

项目摘要

The project will be integrated into the UKRMP Acellular approaches for therapeutic delivery Hub, a collaboration between Manchester, Nottingham, Imperial, Southampton, Keele and others.http://www.ukrmp.org.uk/hubs/Anterior cruciate ligament (ACL) ruptures are a common problem and occur mostly as a result of sports injuries. Around 200,000 ACL ruptures per year occur in the United States and it is estimated that more than 100,000 ACL repairs are performed annually in the United States.Such ruptures can subsequently lead to other, serious degenerative joint diseases and for this reason it is important to treat and tackle ACL injuries efficiently and effectively. The current gold standard for ACL repair involves the use of patellar tendon autografts; this treatment has many limitations including: donor site morbidity and more importantly the inability of the graft to fully integrate with the bone tunnel site (area often referred to as the enthesis). High failure rates often occur particularly at this enthesis site subsequently leading to patient revisits for further improved surgeries. Hence, an intervention is required which could be coupled with the current gold standard method to act as a dual technology, which could provide more robust graft integration.Some research has been performed in developing alternative grafts fabricated from synthetic FDA approved materials including Poly-e-Caprolactone (PCL) and PET with the hope to manufacture tissue-engineered grafts that would provide the required mechanical properties. However, limitations associated with such constructs include their lack of bio-interaction, lack of functional neo-matrix lay down and remodeling, leading to failure at the enthesis site. Therefore, the problem of graft failure (autograft or synthetic) at the enthesis site is yet to be fully resolved. For this reason this study aims to improve graft integration at the enthesis site through improved healing rate.In this case, we aim to develop a synthetic graft, which is able to precisely mimic the nano-and micro- architecture of native tissue ACL extracellular matrix along with the appropriate mechanical properties and degradation rate. Working in collaboration with Professor Eithne Comerford (University of Liverpool), we aim to identify key extracellular matrix (ECM) protein fragments within the different regions of the ACL (particularly the enthesis) and functionalise these onto the synthetic graft. We have identified fibrillin-1 as a starting point and preliminary results have shown significantly more rapid attachment and alignment along the electrospun fibres with fibrillin present. Further molecules have been identified and will be explored along with signalling pathways.Cell behavior will be assessed in terms of cell viability, morphology, proliferation, differentiation, intra- and extracellular signalling pathways and neo-matrix secretion. These will be validated and identified using via immunocytochemistry, ELISA, RT-PCR and histology.Additionally the electrospun system could be used as a platform technology for other ligaments and also tendon repair.

该项目将被整合到由曼彻斯特、诺丁汉、帝国理工学院、南安普敦大学、基尔大学等公司合作的英国http://www.ukrmp.org.uk/hubs/Anterior无细胞疗法治疗传递中心。前十字韧带断裂是一种常见问题，主要由运动损伤引起。在美国，每年约有20万例前交叉韧带断裂，据估计，美国每年进行的前交叉韧带修复超过10万例。这种断裂会导致其他严重的退行性关节疾病，因此，有效和有效地治疗和处理前交叉韧带损伤非常重要。目前修复前交叉韧带的黄金标准包括使用自体髌腱移植；这种治疗有许多局限性，包括：供区发病率，更重要的是移植物不能与骨隧道部位(通常被称为末端)完全结合。高失败率经常发生，特别是在这个吻合部位，随后导致患者再次就诊，以进一步改进手术。因此，需要一种干预措施，与目前的金标准方法相结合，作为一种双重技术，可以提供更强大的移植物整合。一些研究已经在开发由FDA批准的合成材料(包括聚己内酯(PCL)和PET)制成的替代移植物，希望制造出能够提供所需机械性能的组织工程移植物。然而，与这些结构相关的局限性包括它们缺乏生物相互作用，缺乏功能性新基质的铺设和重塑，导致端部失败。因此，吻合处的移植失败(自体移植或人工合成)的问题尚未完全解决。因此，本研究旨在通过提高愈合率来改善植骨在愈合部位的整合。在这种情况下，我们的目标是开发一种人工合成的移植物，它能够精确地模拟天然组织ACL细胞外基质的纳米和微结构，以及适当的机械性能和降解率。与利物浦大学的Eithne Comerford教授合作，我们的目标是识别前交叉韧带不同区域(特别是末端)中的关键细胞外基质(ECM)蛋白质片段，并将这些片段功能化到合成移植物上。我们已经确定了纤维蛋白-1作为起点，初步结果表明，在纤维蛋白存在的情况下，电纺纤维的附着和排列速度明显加快。更多的分子已经确定，并将与信号通路一起探索。细胞行为将从细胞活力、形态、增殖、分化、细胞内和细胞外信号通路以及新基质分泌方面进行评估。这些材料将通过免疫细胞化学、酶联免疫吸附试验、逆转录聚合酶链式反应和组织学进行验证和鉴定。此外，电纺系统还可以作为其他韧带和肌腱修复的平台技术。