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1. Rapid fabrication of collagen bundles mimicking tumor-associated collagen architectures

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   Gong, Xiangyu; Kulwatno, Jonathan; Mills, K.L. (May 2020, Acta Biomaterialia)

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2. Collagen biomineralization: pathways, mechanisms, and thermodynamics

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   Sorokina, Lioudmila V.; Shahbazian-Yassar, Reza; Shokuhfar, Tolou (June 2021, Emergent Materials)

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3. MICROMECHANICAL MODEL OF MECHANOSENSITIVE COLLAGEN TISSUES

   Kalyn G. Younger, William Cortes (June 2023, Summer Biomechanics, Bioengineering and Biotransport Conference Foundation)
4. Collagen-Peptide-Based Drug Delivery Strategies

   https://doi.org/10.21300/21.4.2020.9  

   Jayaraman, Arthi; Price, Christopher; Sullivan, Millicent O.; Kiick, Kristi L. (December 2020, Technology & Innovation)

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   Collagen-targeting strategies have proven to be an effective method for targeting drugs to pathological tissues for treatment of disease. The use of collagen-like peptides for controlling the assembly of drug delivery vehicles, as well as their integration into collagen-containing matrices, offers significant advantages for tuning the morphologies of assembled structures, their thermoresponsiveness, and the loading and release of both small-molecule and macro-molecular cargo. In this contribution, we summarize the design and development of collagen-peptide-based drug delivery systems introduced by the Kiick group and detail the expansion of our understanding and the application of these unique molecules through collaborations with experts in computational simulations (Jayaraman), osteoarthritis (Price), and gene delivery (Sullivan). Kiick was inducted as a Fellow of the National Academy of Inventors in 2019 and was to deliver an address describing the innovations of her research. Given the cancellation of the NAI Annual Meeting as a result of coronavirus travel restrictions, her work based on collagen-peptide-mediated assembly is instead summarized in this contribution. 

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5. MICROMECHANICAL MODEL OF MECHANOSENSITIVE COLLAGEN TISSUES

   Younger, Kalyn G; Cortes, William; Reich, Daniel H; Nguyen, Thao D (June 2022, Summer Biomechanics, Bioengineering and Biotransport Conference)

   The mechanical behavior of soft collagenous tissues is largely influenced by the reinforcing collagen fiber microstructure. The anisotropic collagen microstructure can remodel in response to changes in mechanical loading, which can dramatically alter the mechanical properties of the tissues and the mechanical environment of the resident cells. It is important to study the remodeling mechanisms of collagen tissues to understand the pathophysiology of various connective tissue diseases. We hypothesize that the collagen structure actively changes in response to mechanical stimuli through concurrent processes of collagen deposition and degradation and that the rates of these processes are altered by collagen mechanochemistry, mechanosensitive collagen production, and cellular contraction. In prior studies, we developed micromechanical models of collagen tissues to investigate the role of collagen mechanochemistry and mechanosensitive collagen production in remodeling the collagen fiber structure and tissue growth.[1,2] We found that stress inhibition of enzymatic degradation and stimulation of collagen production can explain many phenomena, including remodeling the anisotropic collagen structure along the directions of the maximum principal stress and the development of stress homeostasis. The goal of this study is to investigate the effect of mechanical loading on the active behavior of the cells. Our approach uses a model 3D microtissue systems, self-assembled on a magnetically actuated two-pillar system (µTUG), to investigate these cell-collagen interactions and effects of mechanical loading. The micropillar support allows for measurement of the active cellular contraction, while the magnetic tweezer allows for mechanical testing of the microtissue under a controlled stress rate. Digital image analysis is applied to measure the local two-dimensional (2D) strain field. To analyze the mechanical measurements for mechanical properties of the collagen structure and active behavior of the cells, we developed a micromechanical model for the mechanical behavior of the microtissue. The micromechanical model includes the elastic behavior of the anisotropic collagen structure and the anisotropic active behavior of the cells. To describe mechanosensitive cellular contraction, we assume concurrent polymerization/depolymerization of actin filaments, where the polymerization rate increases with the fiber stress. In this paper, we will briefly summarize the model and describe an initial model validation by comparing to µTUG experiments measuring the stress-strain behavior of the microtissue to load-unload tests. 

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