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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=716595
• 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.

胶原纤维可以说是人类和动物最重要的结构蛋白，可以满足骨、肌腱、韧带和软骨等组织的抗张负荷要求。由于它们在我们的正常功能中起着关键作用，胶原纤维在过去的60年里一直是正在进行的研究的主题。肌腱经常用于胶原研究，因为与其他结缔组织相比，它们有一个基本的结构，主要由平行排列的胶原纤维组成，并沿着肌腱的长度定向。 胶原蛋白纤维的研究具有挑战性。纤维的直径通常在50到250纳米之间，大约是人类头发的1000倍。由于与可见光的波长相似，胶原纤维的结构细节不能用普通的光学显微镜可视化，这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，手背的指伸肌腱在低应力下工作，因为伸展手指通常阻力很小。与此同时，跟腱在高应力下工作，传递行走和跑步时推动我们前进所需的力量。最近的研究表明，生理上不同的肌腱是由具有显著结构和功能差异的胶原纤维组成的。纳米级纤维结构的差异是如何或何时出现的，目前尚不清楚。此外，具有不同结构的胶原纤维的肌腱所获得的功能优势尚不清楚，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。 利用广泛的纳米级结构表征技术，以及对单个胶原纤维的机械、热和酶降解能力测试，将探索在发育过程中功能不同的肌腱的胶原纤维结构何时、如何以及为什么会出现分歧的问题。所获得的知识将为结构组织如何发育并在一生中得到适当的维护提供新的理解。虽然所进行的研究不会探讨组织疾病或功能障碍的发展问题，但了解健康组织的正常生理过程是了解承载组织病理学的重要前提。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蛋白生物材料获得的胶原蛋白结构-功能知识，这些材料可以显著改进目前用于骨科手术中骨组织修复的那些材料。理想情况下，所创造的技术将导致加拿大这里的商业产品开发，最终通过改进的治疗方案使加拿大人在经济和医疗上受益。