| Hydrogels are water-loving polymers that are useful in many areas of medicine such as drug delivery and tissue scaffolding. Their fragility, however, has made it difficult to apply them as artificial substitutes for natural load-bearing tissues. Building upon recent pioneering work in the field of interpenetrating polymer networks, we have developed a new "hydrogel alloy" with dramatically enhanced mechanical properties despite being composed of two otherwise weak polymer networks of poly(ethylene glycol) (PEG) and poly(acrylic acid) (PAA). PEG and PAA networks are soft, biocompatible hydrogels that not only mix well with water but also interact favorably with each other. As a result, PEG, PAA, and water combine to form clear, homogeneous hydrogel alloys of independently crosslinked, water-swollen networks. While PAA is best known as the pH-sensitive, super-absorbent material found in infant diapers, PEG is renowned for its passivating effect when incorporated into drugs and implanted devices. Neither hydrogel is known, however, for its mechanical strength. Yet under physiologic conditions, PEG/PAA hydrogel alloys exhibit elastic modulus and fracture strength values that rival those of load-bearing anatomical structures such as the cornea and articular cartilage. Our hypothesis is that the strain hardening behavior exhibited by these materials is largely a consequence of hydrogen bonding between the physically entangled PEG and PAA networks.; The overall objective of this dissertation is two-fold: (1) to elucidate the structural basis for the dramatic biomechanical enhancement observed in PEG/PAA hydrogel alloys, and (2) to optimize their properties to mimic those of natural tissues for the purpose of replacing them. In the case of the latter, we have utilized a photochemical coupling strategy to site-specifically tether biomolecules to the material's surface in order to promote the adhesion and growth of cells. Cell adhesion is one of the keys to functionally integrating these artificial substrates with surrounding host tissue. In the case of an artificial cornea, however, rapid transport of nutrients is also required to maintain the health of the attached cells. Therefore, hydrogel alloys must be not only strong, transparent, and biocompatible, but also permeable to small molecules in order to function properly in vivo.; Presented are equilibrium swelling measurements, tensile and compression tests, diffusion experiments, surface characterization studies, and a series of in vitro and in vivo assays for biocompatibility and cellular adhesion. The results from these experiments provide an integrated assessment of the network, mechanical, transport, and biointerfacial properties of PEG/PAA hydrogel alloys as they pertain, in particular, to the development of a biointegrable artificial cornea. |
