Date of Completion

7-28-2020

Embargo Period

2-6-2021

Keywords

cartilage, biomechanics, collagen, microcrack, impact, cyclic loading

Major Advisor

David M. Pierce

Associate Advisor

George Lykotrafitis

Associate Advisor

Kristin Morgan

Associate Advisor

Anna Tarakanova

Field of Study

Biomedical Engineering

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Physical pain limits the quality of life for more than 20% of the adult population around the world. Joint injury and acute trauma account for a significant portion of this pain. The most common joint injuries include ankle sprains, ACL tears in the knee, Patellofemoral syndrome (injury resulting from the repetitive movement of the patella against the femur), and Tennis Elbow (Epicondylitis). There is strong evidence that suggest these injuries trigger a cascade of events that lead to post-traumatic osteoarthritis (PTOA). PTOA is a multifactorial disease that affects all aspects of joints, including ligaments, tendons, bones, menisci, and most prominently, the layers of articular cartilage. Articular cartilage is a complex tissue, comprised of solid and electrolytic fluid constituents that continuously interact to generate remarkable mechanical responses. In particular, collagen fibers (predominantly Type II) contribute to the majority of cartilage's mechanical function and integrity. Proteoglycans, a charged macromolecule, further contribute to regulating the collagen network density and overall compressive response. In this work we combined ex vivomechanical experiments with imaging modalities to determine how mechanical impacts affect the structure and function of articular cartilage. In particular, we used single low-energy impacts, often followed by cyclic compression to mimic walking, as mechanical treatments to study the evolution of microscale damage and mechanobiology. More specifically, we initiated and propagated microcracks, or cracks with widths smaller than that of lacunae (30\,$\mu$m), in the network of collagen to generate damage within cartilage. Three over-arching questions drive the studies presented herein: (1) How do microcracks propagate through networks of collagen? (2) Can impact loading produce positive (anabolic) cellular responses? (3) Can we prevent formation and/or propagation of microcracks? Broadly, we found:

  1. The microcracks we initiated under low-energy impact loading increased in length and width during subsequent cyclic compression that simulated walking. The extent of this propagation depended on the combination of impact and cyclic compression.
  2. Low-energy mechanical impacts generally stimulate time-dependent anabolic responses in the superficial zone of articular cartilage and catabolic responses in the middle and deep zones.
  3. The natural crosslinker genipin negatively influences microcrack initiation such that microcracks initiated in treated specimens are longer and deeper than untreated specimens, and two treatments with genipin significantly worsens propagation of microcracks during subsequent cyclic compression.

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