Engineered isopeptide bond stabilized fibrin inspired nanoscale peptide based sealants for efficient blood clotting

Abstract

Designing biologically inspired nanoscale molecular assembly with desired functionality is a challenging endeavour. Here we report the designing of fibrin-inspired nanostructured peptide based sealants which facilitate remarkably fast entrapping of blood corpuscles (~28 seconds) in contrast to fibrin (~56 seconds). Our engineered sealants are stabilized by lysine-aspartate ionic interactions and also by Nε(γ-glutamyl) lysine isopeptide bond mediated covalent interaction. Each sealant is formed by two peptides having complementary charges to promote lysine-aspartate ionic interactions and designed isopeptide bond mediated interactions. Computational analysis reveals the isopeptide bond mediated energetically favourable peptide assemblies in sealants 1–3. Our designed sealants 2 and 3 mimic fibrin-mediated clot formation mechanism in presence of transglutaminase enzyme and blood corpuscles. These fibrin-inspired peptides assemble to form sealants having superior hemostatic activities than fibrin. Designed sealants feature mechanical properties, biocompatibility, biodegradability and high adhesive strength. Such nature-inspired robust sealants might be potentially translated into clinics for facilitating efficient blood clotting to handle traumatic coagulopathy and impaired blood clotting.

Peptide-based topical agents and intravenous hemostat for rapid hemostasis

“…4). 53 The ionic sealant, sealant 2, has exhibited much higher nanomechanical force (22 ± 2.7 nN) compared to fibrin (13.6 ± 1.3 nN). The ex vivo Hayem method demonstrates that the designed sealant 2 (∼28 s) exhibits much faster sealing ability than natural fibrin (∼56 s) and entraps blood corpuscles, like fibrin, and is biodegradable (Fig.…”

“…This journal is © The Royal Society of Chemistry 2020 residues. 53 The Gln residues were incorporated in peptide 3 to engineer intermolecular isopeptide linkages with the Lys residue of peptide 2. Such an intermolecular isopeptide bond is also observed in fibrin.…”

“…5). 53 Such designed enzymatically modified peptide-based self-assembled sealant is biocompatible, as well as biodegradable, and has enormous potential to be translated in the clinics.…”

“…59,60 The significant contribution of this work is that this group has demonstrated that RGD-functionalized sealants have the potential to specifically perform on-demand sealing of the blood at the site of any internal injury. 53 This journal is © The Royal of Chemistry 2020 3.2.2 Platelets. Platelets are the first candidate to initiate the hemostatic mechanism upon vascular injury, and platelet substitutes exist as a significant class of intravenous hemostats.…”

“…Bertram et al prepared synthetic platelet peptide conjugates for intravenous hemostasis. 63 They have synthesized polymer PLGA (poly(lactic-co-glycolic acid))-based 53 platelets and conjugated them with the RGD (Arg-Gly-Asp) peptide sequence. The rat femoral artery model showed that the bleeding time for synthetic particles was effectively less than the control saline.…”