Dual-Chambered Membrane Bioreactor for the Dynamic Co-Culture of Dermal Stratified Tissues

dc.contributor.advisorFisher, John Pen_US
dc.contributor.authorNavarro Rueda, Javieren_US
dc.contributor.departmentBioengineeringen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2019-10-01T05:42:02Z
dc.date.available2019-10-01T05:42:02Z
dc.date.issued2019en_US
dc.description.abstractEvery year over 11 million patients suffer severe burns worldwide. Facial burn statistics include victims of violence (warfare, acid attacks, scalding) and trauma (flame, electrical, chemical). Skin is the first barrier against external mechanical and biochemical factors, such as burning agents, and is composed of the epidermis, dermis, and hypodermis layers. When burned, skin cannot regulate temperature or fluid transport, or stop bacterial infection. Due to the importance of the skin barrier, natural healing and grafting treatments aim to quickly close the wounds with fast proliferation of fibroblasts and collagen deposition, a process that results in scarring, loss of function, and disfigurement. Tissue engineering has produced epidermis-dermis skin scaffolds for clinical use and in vitro dermal models. Throughout this work we studied 3D printing and bioreactor strategies for the simultaneous physiologic and topographic reconstruction of burnt facial skin tissues. First, we formulated a keratin-based bioink that can be used for 3D printing on a lithography-based 3D printer. Second, we implemented the keratin bioink in the production of Halofuginone-laden face masks for the improvement of contracture, scarring, and aesthetics in severe skin wound healing in an animal model. Due to lack of collagen organization and microstructural development, we introduced a novel dual-chambered (DCB) bioreactor system to study stratified tissues. For this, crosslinking density of the keratin-based hydrogels was used to fine tune the transport properties of membranes for potential use in guided tissue regeneration applications. Then, we assessed the viability of our novel DCB for co-culturing adjacent cell populations with the inclusion of a regulatory keratin membrane. Last, having studied the DCB with flat interfaces, we assessed its viability for perfusing curved interfaces. The integration of both curvature and cell populations allowed to assess the synergistic development of adjacent dermis fibroblasts and hypodermis stem-cell-derived adipocytes and evaluate whether including topography parameters would alter cell viability in the DCB. The strategies developed here elucidate on tissue stratification and aesthetic reconstruction. Furthermore, the keratin-based bioink, the engineered membranes, and the DCBs can be extended to study other stratified or gradient tissues and to fine-tune communication between cell populations in complex 3D constructs.en_US
dc.identifierhttps://doi.org/10.13016/w8do-lhs5
dc.identifier.urihttp://hdl.handle.net/1903/25157
dc.language.isoenen_US
dc.subject.pqcontrolledBiomedical engineeringen_US
dc.subject.pqcontrolledBioengineeringen_US
dc.subject.pqcontrolledEngineeringen_US
dc.subject.pquncontrolled3D printingen_US
dc.subject.pquncontrolledBioreactoren_US
dc.subject.pquncontrolledKeratinen_US
dc.subject.pquncontrolledMesenchymal stem cellsen_US
dc.subject.pquncontrolledSkinen_US
dc.subject.pquncontrolledWound healingen_US
dc.titleDual-Chambered Membrane Bioreactor for the Dynamic Co-Culture of Dermal Stratified Tissuesen_US
dc.typeDissertationen_US

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