6 research outputs found
Synthesis and Characterization of Thermally and Chemically Gelling Injectable Hydrogels for Tissue Engineering
Novel, injectable hydrogels were developed that solidify through a dual-gelation, physical and
chemical, mechanism upon preparation and elevation of temperature to 37°C. A thermogelling,
poly(N-isopropylacrylamide)-based macromer with pendant epoxy rings and a hydrolyticallydegradable
polyamidoamine-based diamine crosslinker were synthesized, characterized, and
combined to produce in situ forming hydrogel constructs. Network formation through the epoxyamine
reaction was shown to be rapid and facile, and the progressive incorporation of the
hydrophilic polyamidoamine crosslinker into the hydrogel was shown to mitigate the often
problematic tendency of thermogelling materials to undergo significant post-formation gel
syneresis. The results suggest that this novel class of injectable hydrogels may be attractive
substrates for tissue engineering applications due to the synthetic versatility of the component
materials and beneficial hydrogel gelation kinetics and stability
Prevention of Collagen-Induced Platelet Binding and Activation by Thermosensitive Nanoparticles
Peripheral artery disease is an atherosclerotic occlusion in the peripheral vasculature that is typically treated via percutaneous transluminal angioplasty. Unfortunately, deployment of the angioplasty balloon damages the endothelial layer, exposing the underlying collagen and allowing for the binding and activation of circulating platelets, which initiate an inflammatory cascade leading to eventual restenosis. Here, we report on the development of poly(NIPAm-MBA-AMPS-AAc) nanoparticles that have a collagen I-binding peptide crosslinked to their surface allowing them to bind to exposed collagen. Once bound, these particles mask the exposed collagen from circulating platelets, effectively reducing collagen-mediated platelet activation. Using collagen I-coated plates, we demonstrate that these particles are able to bind to collagen at concentrations above 0.5 mg/mL. Once bound, these particles inhibit collagen-mediated platelet activation by over 60%. Using light scattering and zeta potential measurements, we investigated the potential of the nanoparticles as a drug delivery platform. We have verified that the collagen-binding nanoparticles retain the temperature sensitivity common to poly(NIPAm)-based nanoparticles while remaining colloidally stable in aqueous environments. We also demonstrate that they are able to passively load and release anti-inflammatory cell penetrating peptides. Combined, we have developed a collagen-binding nanoparticle that has dual therapy potential, preventing collagen-mediated platelet activation while delivering water-soluble therapeutics directly to the damaged area