Browsing by Author "Smith, Thomas L."
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- A Decellularized Porcine Xenograft-Derived Bone Scaffold for Clinical Use as a Bone Graft Substitute: A Critical Evaluation of Processing and StructureBracey, Daniel N.; Seyler, Thorsten M.; Jinnah, Alexander H.; Lively, Mark O.; Willey, Jeffrey S.; Smith, Thomas L.; Van Dyke, Mark E.; Whitlock, Patrick W. (MDPI, 2018-07-12)Background: Bone grafts are used in approximately one half of all musculoskeletal surgeries. Autograft bone is the historic gold standard but is limited in supply and its harvest imparts significant morbidity to the patient. Alternative sources of bone graft include allografts, synthetics and, less commonly, xenografts which are taken from animal species. Xenografts are available in unlimited supply from healthy animal donors with controlled biology, avoiding the risk of human disease transmission, and may satisfy current demand for bone graft products. Methods: In the current study, cancellous bone was harvested from porcine femurs and subjected to a novel decellularization protocol to derive a bone scaffold. Results: The scaffold was devoid of donor cellular material on histology and DNA sampling (p < 0.01). Microarchitectural properties important for osteoconductive potential were preserved after decellularization as shown by high resolution imaging modalities. Proteomics data demonstrated similar profiles when comparing the porcine bone scaffold against commercially available human demineralized bone matrix approved for clinical use. Conclusion: We are unaware of any porcine-derived bone graft products currently used in orthopaedic surgery practice. Results from the current study suggest that porcine-derived bone scaffolds warrant further consideration to serve as a potential bone graft substitute.
- Investigation of Keratin and Keratin-Containing Composite Biomaterials: Applications in Peripheral Nerve RegenerationPotter, Nils (Virginia Tech, 2019-11-22)Keratins are a family of structural proteins that can be extracted from a variety of sources including wool, nails, skin, hooves, and hair. Keratin can be processed into different constructs such as coatings, scaffolds, and hydrogels, and has shown favorable results when placed in in vitro and in vivo settings for different tissue regeneration applications. Over three decades, keratin extraction technology has been continuously modified, and these differences in extraction processes have distinct effects on the characteristics of the end product. In this work, we examine the effect of keratin aggregation during a widely-used purification step, dialysis ultra-filtration, on material characteristics of the final keratin product when fabricated into a hydrogel. Two distinct dialysis procedures were applied during the extraction of oxidized keratin (keratose): one promoting protein aggregation and the other mitigating it. Analyses of material properties such as mechanical and enzymatic stability were conducted in addition to observing the differences in solution behavior between products. Data revealed that protein aggregation during the extraction process has a profound effect on keratose hydrogel material properties. After determination of the effect of protein aggregation during extraction on keratose hydrogels, investigation of how a blended material comprised of said keratose and type I collagen was undertaken. It was hypothesized that a blend would result in mixing at the molecular level, resulting in improved properties compared to either pure material alone. A protocol was created to make stable keratose/type I collagen blends and material characterization techniques were applied to determine the inherent properties of samples with differing ratios. Crosslinking density, mechanical properties, enzymatic degradation properties, water uptake capacity, structural architecture, and thermal properties were all assessed. In addition, the ability of this material to maintain cell viability was conducted. Results showed that the addition of type I collagen has a significant effect on the properties of hydrogel blends with keratose compared to the pure keratose system. This was mostly evident with hydrogel mechanical stability and material architecture. Finally, the ability to use this hybrid material as a luminal filler for a nerve conduit during peripheral nerve regeneration was explored in an in vitro setting. The ability of this blend to promote Schwann cell viability was assessed in addition to determining the ability of these cells to attach and migrate through the material matrix. These experiments demonstrate proof-of-concept for the application of using keratose/type I collagen matrices as a luminal filler in peripheral nerve guidance conduits.