| Description |
Phosphate-metal complex formation is a naturally occurring toughening mechanism in underwater materials and has been incorporated into the synthetic hydrogel material discussed in this dissertation. Polyphosphate hydrogels were loaded with Ca2+ which crosslinks OPO3 groups in the hydrogel which increase the initial modulus from 0.04 to 10.3 MPa and rupture at a critical force to dissipate strain energy and act as a sacrificial network to preserve the integrity of the hydrogel. Phosphate metal crosslinks are electrostatic domains that are easily recoverable, which adds to the durability and usefulness of the hydrogels. This toughening mechanism was borrowed from the underwater caddisfly larvae, which spin a tough, adhesive silk fiber to manufacture protective mobile cases from sticks, rocks and other advantageously gathered materials. The caddisfly silk also uses serial domains of phosphates crosslinked with Ca2+ to increase modulus and produce strain induced yield, energy dissipation, and recoverability. In addition to metal ions, positively charged aminoglycoside antibiotics such as tobramycin can also be used as crosslinking agents. Due to electrostatically delayed diffusion, tobramycin is gradually released and exchanged with metal ions in biologically relevant Ca2+ and Mg2+ containing solutions. In the polyphosphate hydrogel system, tobramycin was included with and without the presence of Ca2+ to form a hydrogel with the capability to sustain tobramycin release for up to 70 days and totally eradicate pseudomonas aeruginosa biofilms within 48 hours. In the case of hydrogels loaded with Ca2+ and tobramycin, the hydrogels retained their toughness, and durability and thus may be used as structural materials in total joint replacement to reduce incidence of infection. Complex coacervation is an alternative to the polyphosphate-tobramycin hydrogel system and occurs as a phase separation where a dense coacervate of polyphosphate and tobramycin is formed. The formation of clear, fluid coacervate phase is dependent on salt concentration and is maximized at ~1M NaCl. Polyphosphate-tobramycin coacervates have a sustained release assay for up to 60 days. Additionally, the coacervate can be resuspended into micro droplets by vortex and subsequently aerosolized for pulmonary delivery of tobramycin. Aerosolized coacervate is ideal for treating chronic pulmonary infection in cystic fibrosis. It could not only improve rates of pseudomonas aeruginosa infection but also reduce the number of required doses and thus improve patient compliance. |
