Tailoring gelation and mechanical properties of fibrin-based extracellular matrix using stimulus-responsive poly(Lactic-co-glycolic acid) microgelator

Statement of Purpose: Fibrin based matrices have been extensively used for three dimensional cell culture, tissue regeneration, and injectable cellular carrier due to their ability to support cell activities responsible for tissue regeneration¹. However, there are still grand needs to control the gelation rate and the mechanical strength for enhanced transports and therapeutic efficacy of cells. This challenge results from a difficulty in regulating the gelation time while maintaining the mechanical properties and microstructure of fibrin matrices due to the complex protein polymerization mechanism². To this end, this study demonstrates the stimulus-responsive poly (lactic-co-glycolic acid) (PLGA) microgelator that can activate fibrin fiber formation from their surfaces by actively ejecting thrombin in response to an external stimulus (i.e., hydrogen peroxide). The stimulus-responsive microgelator was assembled by simultaneously encapsulating MnO₂ nanosheets that decompose H₂O₂ to O₂ gas and thrombin into a spherical shell. We hypothesize that the microgelator would generates oxygen within the particles when exposed to H₂O₂. The oxygen gas will then act as force to pump out thrombin from the particles by increasing the internal pressure of particles. In the fibrinogen solution, the ejected thrombin molecules nucleate the fibrin fibers from the PLGA particle surface and finally form the interconnected fibrous networks with an increased elastic modulus, compared to the fibrin gel formed by mixing fibrinogen and thrombin in solution.