Access Type

Open Access Dissertation

Date of Award

January 2017

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Biomedical Engineering

First Advisor

Mai T. Lam

Abstract

This body of work sets to investigate some of these mechanical interventions that are designed to promote wound healing, repair, or even replace an injured tissue. By investigating three separate tissues and three separate mechanical interventions, we can draw conclusions about the implications of including mechanical interventions in biomedical research and clinical treatments. The use of sutures to close wounds is highly common, however the effects of sutures on the tensile mechanics of human skin are largely unknown. To evaluate how sutures may affect uniaxial tensile mechanics, human skin samples were sutured and loaded in tension in multiple orientations. The data suggested that the sutured skin had a lower fracture strength and higher elastic modulus than the intact skin, particularly when loaded in-line with the injury. Next, the inflammatory effects of a decellularized ECM patch in a myocardial infarction model were analyzed. A commercially available decellularized material, porcine small intestine submucosa, was evaluated as a patch treatment in a rat myocardial infarction model, a treatment that is common in cardiac research. As anticipated, the addition of the patch in the injury area increased local inflammation as indicated by gene expression and leukocyte population and density. However, the patch did not appear to extend the inflammation response nor affect the response in a manner that would suggest hindrance to wound healing. Thirdly, a unique biochemical and mechanical approach was used to direct human adipose stem cells to differentiate towards a meniscus-like phenotype. By using a variety of media formulations and a variation of uniaxial tensile parameters, a protocol to maximize meniscus gene expression was concluded. A chondrogenic media formulation with 10% uniaxial strain at 1 Hz for 3 hours was found to have the greatest increase in meniscus gene expression of all of the parameters tested. Together, each of these individual works contributes to the conclusion that mechanical interventions can have a significant impact on the restructuring, repair, and replacement of soft tissues.

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