Development of a 3D bioprinted model of airway smooth muscle — a novel paradigm to study airway mechanics in asthma
| dc.contributor.author | Osagie, Jeffery | |
| dc.contributor.examiningcommittee | Halayko, Andrew (Physiology & Pathophysiology) | en_US |
| dc.contributor.examiningcommittee | Keijzer, Richard (Surgery) | en_US |
| dc.contributor.examiningcommittee | Mookherjee, Neeloffer (Internal Medicine) | en_US |
| dc.contributor.supervisor | West, Adrian | |
| dc.date.accessioned | 2022-04-05T16:13:23Z | |
| dc.date.available | 2022-04-05T16:13:23Z | |
| dc.date.copyright | 2022-03-31 | |
| dc.date.issued | 2022-03-31 | |
| dc.date.submitted | 2022-03-31T19:59:02Z | en_US |
| dc.degree.discipline | Physiology and Pathophysiology | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | Asthma is a chronic obstructive airway disease characterized by exaggerated contraction of airway smooth muscle (ASM) and structural changes that modify the mechanical properties of the airways. I hypothesized that 3D bioprinting technology can be used to construct a physiologically-relevant model, explicitly designed to simulate airway narrowing in vitro. Additionally, this model would be used to elucidate the consequences of altered mechanical loads on ASM contractile phenotype and function. The ASM model consisted of a ring-shaped bundle of muscle constrained within a stiffness-modifiable acellular alginate support. ASM tissues bioprinted without acellular supports generated excessive baseline tension and rapidly lost structural integrity. The inclusion of acellular supports provided a mechanical preload that enabled baseline tone development, cellular organization, and muscle maturation. Contractility, assessed as a reduction in lumen area of constructs in response to various agonists, revealed differential contractile responses in ASM tissues fabricated across a stiffness range. Finally, although relative mRNA abundance of relevant contractile genes was modulated by structure, I was unable to detect statistically significant differences between the acellular stiffness groups tested. These results suggest that a 3D bioprinted model of ASM represents a suitable platform to study changes in airway mechanics associated with asthma. The variable functional responses in ASM tissues fabricated with different acellular stiffnesses support that mechanical cues profoundly alter cellular function. Moving forward, the molecular effectors/mechanisms through which aberrant mechanical loads produce putative defects in ASM would be characterized, potentially unmasking novel therapeutic strategies to manage disease progression in asthma. | en_US |
| dc.description.note | May 2022 | en_US |
| dc.description.sponsorship | Research Manitoba, Manitoba Lung Association Canada Foundation for Innovation, Natural Sciences and Engineering Research Council Aspect Biosystems. | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/36399 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Tissue Engineering | en_US |
| dc.subject | 3D Bioprinting | en_US |
| dc.subject | Airway Smooth Muscle | en_US |
| dc.title | Development of a 3D bioprinted model of airway smooth muscle — a novel paradigm to study airway mechanics in asthma | en_US |
| dc.type | master thesis | en_US |
| oaire.awardTitle | University of Manitoba Graduate Fellowship | en_US |
| project.funder.identifier | http://dx.doi.org/10.13039/100010318 | en_US |
| project.funder.name | University of Manitoba | en_US |