Browsing by Author "Hogan, Katie JoAnna"

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    Development of Extracellular Matrix-Based Biomaterials for Musculoskeletal Tissue Engineering
    (2023-08-08) Hogan, Katie JoAnna; Mikos, Antonios G
    Extracellular matrix (ECM)-based materials, which provide tissue-specific biochemical cues for cell recruitment, proliferation, and differentiation, have been the subject of significant research for cartilage, bone, and muscle tissue engineering. The use of advanced fabrication techniques such as 3D-printing (3DP) and electrospinning enable the fabrication of scaffolds with macro- and microarchitecture that further aids in these applications. In the initial aims of this thesis, decellularized cartilage ECM (cdECM) and demineralized bone matrix (DBM) were adapted into composite colloidal 3DP inks for the fabrication of 3DP constructs with tunable tissue-specific ECM content and photocrosslinking for cartilage and bone regeneration. First, photo-reactive cdECM was combined with photo-reactive gelatin nanoparticles (GNPs) in composite hydrogel-colloidal composite inks. Increased GNP content increased cdECM-GNP ink printability, and increased photocrosslinking was found to decrease cdECM-GNP scaffold swelling and degradation rates and increase biomolecule retention, demonstrating control over scaffold physicochemical properties. Next, photo-reactive DBM nanoparticles (DBM-NPs) were synthesized and combined with photo-reactive GNPs to create colloidal composite 3DP inks and scaffolds. The addition of DBM-NPs into composite colloidal inks did not impact ink printability, and photocrosslinking was demonstrated to decrease scaffold swelling and degradation kinetics, showing the tunability of these properties. An in vitro assessment of mesenchymal stem cell osteogenesis showed the osteoconductivity of DBM-NP-incorporating 3DP constructs. In the final component of this thesis, electrospun aligned decellularized skeletal muscle ECM (mdECM) microfiber meshes with variable crosslinking densities were implanted in an in vivo rat model of volumetric muscle loss, and increased crosslinking was associated with increased expression of markers for angiogenesis and myogenesis. This difference was thought to be related to more prolonged release of biochemical cues over time, emphasizing the importance of crosslinking in controlling presentation of mechanical and biochemical cues. Together, these studies present a variety of strategies for adapting ECM-based materials for high-throughput, precise fabrication methods suitable for the tissues of interest. The completion of this thesis and development of these techniques has resulted in fabrication platforms for ECM-derived biomaterial scaffolds with crosslinking systems for tunable physicochemical properties and biomolecule presentation which have broad applications across the field of tissue engineering.