Bridging the Gap between Nano and Macroscale Hierarchies in Collagen Assembly

Purdue University, West Lafayette IN

Investigators

Abstract

CBET-0754442 Akkus Collagen plays a central role as a biomaterial and as a scaffold in the regenerative tissue replacement strategies. Surgeries of load bearing tissues such as tendons and ligaments are occurring by hundreds of thousands annually and existing synthetic analogs of collagen have extremely poor biomechanical properties in comparison to the tissues they are targeted to replace. This shortcoming is due, in part, to the lack of orientation in hierarchical orders above the level of fibers. This project will improve the strength and viscoelasticity of synthetic collagenous constructs to match those of natural counterparts by: a) an unconventional electrochemical process to attain an unprecedented level of molecular alignment and molecular packing density persistent across all levels of structural hierarchies, and, 2) the control of interfibrillar attachment by use of a biomimetic decorin-like linkage molecule. Phase 1 of proposed studies will optimize the mechanical strength and stiffness of the construct by elucidating the mechanisms by which collagen solutions achieve long-range order under the effect of weak currents applied directly to the solutions. The effects of electric current amplitude and collagen concentration on the hierarchical organization of collagen will be investigated to optimize the synthesis process. The strength of resulting oriented collagen gels will be improved by identifying the appropriate type and concentration of crosslinking amongst glutaraldehyde, genipin, nordihydroguaiaretic acid (NDGA) or ribose. Phase 2 will modulate the viscoelastic properties of oriented and crosslinked gels by decorin mimics consisting of dermatan sulfate attached to peptide motifs which selectively bind to type I collagen molecules. Mechanical properties of resulting synthetic constructs will be assessed at the bundle and the fiber levels by macroscale mechanical tests and atomic force microscopy, respectively, and compared to those of rat tendon, a reference natural tissue. The third phase is going to assess the phenotypic and genotypic response of tendon fibroblasts seeded in three-dimensional networks of the oriented collagenous construct in vitro, and, by assessing the non-enzymatic and enzymatic degradation rates of constructs in vitro. The project will include the outreach component of familiarizing the minority middle-school student population with the emerging field of biomedical engineering. This aim will be attained by a summer activity during which students will conduct hands-on projects in the area of biomedical engineering through coordination with the Minority Engineering Program at Purdue University. Broader impacts will be further strengthened by creation of a laboratory module in an undergraduate biomechanics/biomaterials laboratory by incorporating outcomes of the proposed research and by way of accommodating 9 undergraduates for summer research during the course of the project through Summer Undergraduate Fellowship program (SURF) at Purdue. In the overall, the proposed study will develop a novel fabrication process towards the design of a new biomaterial which may play a key role in creating strategies towards replacement of tissues such as tendons, ligaments, skin, cornea and vascular walls.