Development, control, and functional significance of variations in collagen fibril nanostructure, with application to the creation of novel biomaterials

胶原纤维纳米结构变化的开发、控制和功能意义，及其在新型生物材料创建中的应用

• 批准号: RGPIN-2020-06035
• 负责人: Veres, Samuel
• 金额: $ 2.04万
• 依托单位: Saint Mary's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=740991
• 关键词: Development; control; functional; significance; variations

Collagen fibrils are arguably the most important structural protein to both humans and animals, fulfilling the tensile load-bearing requirements of tissues such as bone, tendon, ligament, and cartilage. Due to their critical role in our normal function, collagen fibrils have been the subject of ongoing research for the past six decades. Tendons are often used for collagen research, because compared to other connective tissues they have a basic architecture, consisting primarily of collagen fibrils packed in parallel and oriented along the tendon's length. Collagen fibrils are challenging to study. Fibrils typically have diameters ranging from 50 to 250 nm, about 1000 times thinner than a human hair. Being of similar scale to the wavelength of visible light, the structural details of collagen fibrils can't be visualized with normal light microscopy, requiring techniques like electron or atomic force microscopy. Despite being anatomically similar, different tendons serve different physiologic functions. For example, the digital extensor tendons on the back of the hand operate under low stress, as there is usually little resistance to extending the fingers. Meanwhile the Achilles tendon operates under high stress, transmitting the forces needed to propel us during walking and running. Recent research has shown that physiologically distinct tendons are composed of collagen fibrils with significant structural and functional differences. How or when differences in nanoscale fibril structure arise remains unknown. Further, the functional advantages gained by tendons with differently structured collagen fibrils remains unclear, as our recent research has shown that the fibrils from high stress tendons are no stronger than those from low stress tendons.? Using a wide array of nanoscale structural characterization techniques, and mechanical, thermal, and enzymatic degradability testing of individual collagen fibrils, questions regarding when, how, and why the collagen fibril structures of functionally distinct tendons diverge during development will be explored. The knowledge gained will provide new understandings of how structural tissues develop and are properly maintained throughout life. While the research conducted will not explore issues concerning the development of tissue disease or disfunction, understanding the normal physiologic processes in healthy tissues is an important prerequisite to understanding load-bearing tissue pathology. Such issues are of global importance. The research program will also make use of the collagen structure-function knowledge gained through development of novel mineralized collagen biomaterials that could offer significant improvements to those materials currently used for bone tissue repair in orthopaedic surgery. The technologies created will ideally lead to commercial product developments here in Canada, eventually benefiting Canadians both economically and medically via improved treatment options.

胶原原纤维可以说是人类和动物最重要的结构蛋白，满足组织如骨、肌腱、韧带和软骨的拉伸承载要求。由于它们在我们的正常功能中的关键作用，胶原纤维在过去六十年中一直是持续研究的主题。肌腱通常用于胶原蛋白研究，因为与其他结缔组织相比，它们具有基本的结构，主要由平行排列并沿沿着肌腱长度定向的胶原纤维组成。胶原纤维的研究具有挑战性。原纤维通常具有50至250 nm的直径，比人的头发细约1000倍。由于与可见光的波长相似，胶原纤维的结构细节无法用普通光学显微镜观察，需要电子或原子力显微镜等技术。尽管在解剖学上相似，但不同的肌腱具有不同的生理功能。例如，手背上的指伸肌肌腱在低应力下操作，因为通常伸展手指的阻力很小。与此同时，跟腱在高应力下运作，传递在行走和跑步时推动我们所需的力量。最近的研究表明，生理上不同的肌腱是由胶原纤维组成的，具有显着的结构和功能差异。纳米纤维结构的差异如何或何时出现仍然未知。此外，具有不同结构的胶原纤维的肌腱所获得的功能优势仍然不清楚，因为我们最近的研究表明，来自高应力肌腱的纤维并不比来自低应力肌腱的纤维更强。使用广泛的纳米级结构表征技术，和机械，热，和酶的降解性测试的个人胶原纤维，有关何时，如何，以及为什么功能不同的肌腱的胶原纤维结构在发展过程中分歧的问题将进行探讨。所获得的知识将为结构组织如何发展和在整个生命过程中正确维护提供新的理解。虽然所进行的研究不会探讨有关组织疾病或功能障碍的发展问题，但了解健康组织中的正常生理过程是了解承重组织病理学的重要先决条件。这些问题具有全球重要性。该研究计划还将利用通过开发新型矿化胶原生物材料获得的胶原结构-功能知识，这些材料可以为目前用于骨科手术中骨组织修复的材料提供显着改进。所创造的技术将理想地导致加拿大的商业产品开发，最终通过改善治疗方案使加拿大人在经济和医疗上受益。