(267f) Tailoring Gelation and Mechanical Properties of Fibrin-Based Extracellular Matrix Using Stimulus-Responsive Poly(Lactic-co-Glycolic Acid) Microgelator

Fibrin gels have been extensively used for three-dimensional cell culture, bleeding control, and molecular and cell therapies because the fibrous networks facilitate biomolecular and cell transport. However, a small window for gelation makes it difficult to handle the gels for desired preparation and transport. Several methods developed to control gelation rates often alter the microstructure, thereby affecting the mechanical response. To this end, we hypothesized that a catalytic microgelator designed to discharge thrombin cargos continuously in response to an external stimulus, such as H₂O₂, would provide control of the gelation rate over a broad range while strengthening the gel. We examined this hypothesis by assembling poly (lactic-co-glycolic acid) (PLGA) particles loaded with thrombin and MnO₂ nanosheets that decompose H₂O₂ to O₂ gas and mixing them with fibrinogen solution or blood containing 0.2 mM H₂O₂. Due to the increased internal pressure, these particles released a 3-fold larger mass of thrombin than PLGA particles loaded only with thrombin. As a consequence, catalytic microgelators increased the gelation time by one order of magnitude and the elastic modulus by a factor of two compared with the fibrin gel formed by directly mixing fibrinogen and thrombin in solution. These catalytic microgelators also served to clot blood unlike PLGA particles loaded with thrombin. The resulting blood clot was also more rigid than the blood clot formed by thrombin solution. The results of this study would serve as a new paradigm in controlling gelation kinetics of pre-gel solution and mechanical properties of the post-gel matrix.