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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Advisor: Dr. Thomas Barker
Committee: Dr. Andrew Lyon, Dr. Valeria Milam
The need to control bleeding and wound healing presents a significant clinical need in surgery, trauma, and emergency medicine. Fibrin is the body’s natural provisional matrix activated in response to vascular injury, and fails in traumatic hemorrhaging due to mass dilution effects, the inability to concentrate clotting factors, and failure to generate tissue compressive forces. Noncovalent knob:hole interactions between fibrin monomers are critical for the assembly of fibrin that leads to network and clot formation. In this study we aimed to exploit fibrin knob:hole affinity interactions with swelling, space filling microgels for the development of a robust bio-synthetic hybrid polymer system with superior hemostatic properties. Previous work has explored the inherent binding interactions of various fibrin knobs and their complementary polymerization holes, which have led to the development of fibrin knob peptide mimic (GPRPFPAC) with enhanced binding affinity for fibrin(ogen) holes. By coupling this enhanced fibrinogen binding peptide with a pNIPAm microgel system capable of being dynamically tuned and self-assembled, we hypothesized the specific and rapidly triggered formation of a bulk hydrogel in a wound environment (i.e. in the presence of fibrinogen).
Additionally for fibrin-based hemostatics, there is a need to control the final macroscopic properties of the matrix to enhance cell infiltration and matrix degradation while maintaining mechanical integrity to produce hydrogels with more regenerative properties for enhanced wound healing. In this study we also sought to demonstrate the effect of fibrin knob peptide-functionalized microgels on fibrin polymerization, structure, and mechanical properties using three objectives. 1) Synthesize and characterize fibrin knob peptide-functionalized microgels 2) Characterize fibrin polymerization, degradation, composition, and structure in the presence of fibrin knob peptide-labeled microgels 3) Determine the mechanical properties of hybrid fibrin-microgel networks. We hypothesized that fibrin polymerized in the presence of fibrin knob peptide-functionalized microgels, with specificity for fibrin(ogen) via knob:hole interactions, will result in altered polymerization dynamics, distinct fibrin polymer architectures, and altogether different physical properties of the final fibrin-microgel network.
The results of this study showed that at the microgel and peptide conjugation concentrations used, the fibrinogen triggered formation of a microgel gel did not occur. Further optimization of knob peptide-functionalized microgels should facilitate the development of a fibrinogen triggered colloidal assembly of microgels into a bulk hydrogel for hemostatic applications. We also demonstrated that fibrin network polymerization, structure, and viscoelastic properties were greatly altered in the presence of knob peptide-conjugated microgels. Further investigation of hybrid microgel-fibrin systems in vitro will help determine the viability of these systems for different tissue engineering applications.
