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

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.