Abstract
Fibrin is a widely used biological scaffold in tissue engineering and regenerative medicine. While the polymerization dynamics from its soluble precursor fibrinogen has been studied for decades, few attempts have been made to modulate fibrin network structure through the addition of external agents that actively engage this process. We propose the use of polyethylene glycol (PEG)-based linkers that interact with fibrinogen via knob:hole affinity interactions as a means of controlling thrombin-mediated fibrin polymerization dynamics and resulting network structure. Using bivalent and tetravalent knob-PEG conjugates with sizes ranging from 2 to 20 kDa, we demonstrate that the clotting characteristics of fibrinogen solutions can be altered in a dose-dependent manner, with conjugate size playing a major role in altering fibrin network structure. Interestingly, factor XIIIa-catalyzed fibrin(ogen) crosslinking and plasmin-mediated degradation were not significantly impacted. This work demonstrates the feasibility of modulating fibrin network structure through the addition of knob-PEG conjugates that perturb the polymerization process through non-covalent knob:hole interactions.