Date of Award

Fall 12-21-2011

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Bioengineering

First Advisor

Dr. Robert Mauck

Second Advisor

Dr. Jason Burdick

Third Advisor

Dr. Brian Sennett

Abstract

The knee meniscus is prone to damage, which leads to pain and inhibits mobility in the joint long term. Due to the minimal vascularity, low cellularity and large mechanical forces imparted on the meniscus with normal use, endogenous repair is limited. Resection of the damaged region of the tissue (meniscectomy) remains the most common treatment for a torn meniscus, but this procedure results in cartilage degradation and other adverse changes in the knee joint. Given the prevalence of meniscus damage, there is thus a pressing need for novel approaches to meniscus repair. To address this issue, this thesis developed in vitro techniques to analyze the time-varying properties of the aging meniscus, and to address how the meniscus repair interface might be modulated through the use of growth factors. Further, electrospun scaffolds were designed to replicate key architectures of the native tissue while providing controlled release of biologic factors. Our findings demonstrated marked biological, biochemical, and structural changes in meniscus with age. These findings pointed to key factors that could play a role in meniscus integration (ie repair) capacity after meniscus injury; these factors were evaluated in the context of meniscus repair using a mechanical in vitro model. To address situations where substantial meniscus tissue would be removed, we tested the integration capacity of electrospun scaffolds with native tissue and maturation of these scaffolds in response to growth factor regimens, as well as how changes in scaffold characteristics (i.e. porosity and organization) and cell seeding techniques influence integration potential. Finally, we developed novel techniques to deliver bioactive growth factors and other molecules from components of electrospun scaffolds, including entrapped microspheres, with distinct release profiles. These novel, bioactive scaffolds were utilized to orchestrate complex regenerative signaling cascades from the scaffolds, with demonstration of efficacy via improved vascular density in an in vivo model. This work provides new approaches for the treatment of meniscus tears using novel electrospun materials, bringing us one step closer to new clinical options for meniscus repair.

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