Engineering fibrin polymers through engagement of alternative polymerization mechanisms

• Authors: Sarah E. Stabenfeldt, Emory University; Merek Gourley, Emory University; Laxminarayanan Krishnan, University of Louisville; James B. Hoying, University of Louisville; Thomas Barker, Emory University
• Journal Title: Biomaterials
• Volume: Volume 33, Number 2
• Publisher: Elsevier | 2012-01-01, Pages 535-544
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.biomaterials.2011.09.079
• Subjects: Engineering, Biomedical
• Keywords: Angiogenic Proteins; Animals; Cells, Cultured; Fibrin; Fibrinogen; Fibrinolysis; Humans; Male; Mechanical Phenomena; Microscopy, Confocal; Microvessels; Polyethylene Glycols; Polymerization; Polymers; Porosity; Rats; Rats, Sprague-Dawley; Regenerative Medicine; Thrombin; Tissue Engineering

Abstract

Fibrin is an attractive material for regenerative medicine applications. It not only forms a polymer but also contains cryptic matrikines that are released upon its activation/degradation and enhance the regenerative process. Despite this advantageous biology associated with fibrin, commercially available systems (e.g. TISSEEL) display limited regenerative capacity. This limitation is in part due to formulations that are optimized for tissue sealant applications and result in dense fibrous networks that limit cell infiltration. Recent evidence suggests that polymerization knob 'B' engagement of polymerization hole 'b' activates an alternative polymerization mechanism in fibrin, which may result in altered single fiber mechanical properties. We hypothesized that augmenting fibrin polymerization through the addition of PEGylated knob peptides with specificity to hole 'b' (AHRPYAAC-PEG) would result in distinct fibrin polymer architectures with grossly different physical properties. Polymerization dynamics, polymer architecture, diffusivity, viscoelasticity, and degradation dynamics were analyzed. Results indicate that specific engagement of hole 'b' with PEGylated knob 'B' conjugates during polymerization significantly enhances the porosity of and subsequent diffusivity through fibrin polymers. Paradoxically, these polymers also display increased viscoelastic properties and decreased susceptibility to degradation. As a result, fibrin polymer strength was significantly augmented without any adverse effects on angiogenesis within the modified polymers.