Synthesis of Degradable poly-HEMA Hydrogels for Tissue Engineering

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Wescoe, Zachary Lawrence

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Porous materials have been used as implants to mitigate the foreign body response and improve integration into the host tissue. The foreign body response is characterized by a dense collagen capsule and a chronic inflammatory environment surrounding the implant. This response is mainly mediated by macrophages. Macrophages demonstrate plasticity in phenotype depending on the signals present. The classically activated macrophages are termed M1 and are pro-inflammatory; the alternatively activated macrophages are termed M2 and are pro-healing. Porous materials have been shown to influence macrophage phenotype in a size-dependent manner with 40m porous materials showing reduced collagen deposition, increased cellular infiltration, and neovascularization. The positive healing results of non-degradable polyHEMA scaffolds has motivated the construction of degradable scaffolds. A degradable caprolactone-based polyHEMA was previously developed in the Ratner lab, but after one year of implantation intramuscularly, the scaffold had not fully degraded. Ideally, the degradation rate of the material will match the rate of tissue reformation. This work focuses on the development of another degradable caprolactone-based polyHEMA to explore the tunability of the degradation rate and a new degradable glycolide-based polyHEMA to explore the potential of other degradable esters. The synthesized caprolactone-based polyHEMA performed similarly in degradation studies to the previous caprolactone polyHEMA, indicating minor tunability of degradation rate. There were issues in synthesizing the glycolide-based polyHEMA. These issues arose from the faster degradation rate of the glycolide compared to the caprolactone. Limiting the exposure of the polymer to water was difficult, which lead to premature degradation of the construct. The synthesis reactions need to be further optimized to generate the intended product.

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Thesis (Master's)--University of Washington, 2018

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