Characterization of hydrogel overlayers to improve implant biocompatibility.

摘要

The central hypothesis of this dissertation is that implant coatings incorporating local release strategies will alter the progression of the foreign body reaction by attenuating inflammation and increasing the vascularity of the surrounding tissue. The objectives of this research are: (1) to develop a glucose-permeable anti-fouling hydrogel coating for implants, (2) to incorporate drug release into hydrogels for modifying foreign body reaction and reduce barriers to glucose transport, and (3) to evaluate this drug-releasing strategy by assessing in vivo performance of hydrogel-coated polyethersulfone fibers implanted in rat subcutaneous tissue.;Anti-biofouling hydrogels were prepared from 2-hydroxyethyl methacrylate, N-vinyl pyrrolidinone, and polyethylene glycol. Hydrogels were characterized for monomer content, cytotoxicity and glucose permeability using microdialysis probes. Glucose uptake by microdialysis probes with and without hydrogels was found to occur quickly at the probe tip. Using numerical simulation of microdialysis, glucose uptake was predicted to reach steady state within one minute in perfusion fluid exiting the probe tip; however, Taylor dispersion in the outflow tubing delayed experimental detection of steady state by more than 3 minutes. In vivo microdialysis testing during 8-day implantation demonstrated no significant difference in glucose recovery over time between hydrogel-coated and bare microdialysis probe. Anti-biofouling coatings alone were not sufficient to prevent decline in glucose detection over time.;In order to address inflammation and vascularity surrounding implanted sensors, drug delivery was incorporated into the hydrogel coating design. Sustained release of tissue modifying drugs, dexamethasone (DX) and vascular endothelial growth factor (VEGF), was characterized for hydrogel, microsphere, and hydrogels with embedded microsphere drug delivery. The simplest coating format, drug release from hydrogels, was determined to be as effective at drug delivery as hydrogels with embedded microspheres. VEGF-releasing hydrogel-coated fibers increased vascularity and inflammation in surrounding tissue after two weeks implantation compared to bare fibers. DX-releasing hydrogel-coated fibers reduced inflammation compared to hydrogel-coated fibers. At six weeks, there were no significant differences between drug-releasing hydrogel-coated fibers and control fibers. These results indicate that hydrogel drug release would be effective to address the initial events of the foreign body response.