Chronic respiratory diseases affects many people worldwide with little known about the mechanisms diving the pathology, making it difficult to find a cure. Improving the understanding of smooth muscle and extracellular matrix (ECM) interaction is key to developing a remedy to this leading cause of death. With currently no relevant or controllable in vivo or in vitro model to investigate diseased and normal interactions of small airway components, the development of a physiologically relevant in vitro model with comparable cell attachment, signaling, and organization is necessary to develop new treatments for airway disease. The goal of this study is to create a mechanically, biologically and structurally relevant in vitro model of small airway smooth muscle tissue. Synthetic Poly-L-Lactic Acid (PLLA) and decellularized pig lung ECM (DPLECM) were electrospun to form nanofibrous mats that can closely mimic natural bronchial tissue. The addition of DPLECM significantly changed the PLLA scaffold mechanically, biologically, and physically to bring it closer to the characteristics of the human lung. DPLECM scaffolds exhibited a significant decrease in the elastic modulus compared with PLLA alone. Histological staining and SDS-PAGE showed that after scaffold fabrication, essential proteins or protein fragments in natural ECM are still present after processing. Human bronchial smooth muscle cells (HBSMCs) seeded onto PLECM scaffolds formed multiple layers of cells compared to scaffolds composed solely of PLLA. Phenotype of smooth muscle is better maintained when DPLECM is incorporated into the scaffold shown by enhanced contractile protein expression and increased collagen production for normal smooth muscle remodeling of the scaffold. In summary, this research demonstrates that a PLLA/DPLECM composite electrospun mat is a promising tool to produce an in vitro model with the potential to uncover unknown characteristics of bronchiole smooth muscle behavior in diseased or normal states.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-5351 |
| Date | 01 January 2016 |
| Creators | Young, Bethany M |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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