Thrombin Production and Human Neutrophil Elastase Sequestration by Modified Cellulosic Dressings and Their Electrokinetic Analysis

Abstract

Wound healing is a complex series of biochemical and cellular events. Optimally, functional material design addresses the overlapping acute and inflammatory stages of wound healing based on molecular, cellular, and bio-compatibility issues. In this paper the issues addressed are uncontrolled hemostasis and inflammation which can interfere with the orderly flow of wound healing. In this regard, we review the serine proteases thrombin and elastase relative to dressing functionality that improves wound healing and examine the effects of charge in cotton/cellulosic dressing design on thrombin production and elastase sequestration (uptake by the wound dressing). Thrombin is central to the initiation and propagation of coagulation, and elastase is released from neutrophils that can function detrimentally in a stalled inflammatory phase characteristic of chronic wounds. Electrokinetic fiber surface properties of the biomaterials of this study were determined to correlate material charge and polarity with function relative to thrombin production and elastase sequestration. Human neutrophil elastase sequestration was assessed with an assay representative of chronic wound concentration with cotton gauze cross-linked with three types of polycarboxylic acids and one phosphorylation finish; thrombin production, which was assessed in a plasma-based assay via a fluorogenic peptide substrate, was determined for cotton, cotton-grafted chitosan, chitosan, rayon/polyester, and two kaolin-treated materials including a commercial hemorrhage control dressing (QuickClot Combat Gauze). A correlation in thrombin production to zeta potential was found. Two polycarboxylic acid cross linked and a phosphorylated cotton dressing gave high elastase sequestration.

Preparation, Characterization and Activity of a Peptide-Cellulosic Aerogel Protease Sensor from Cotton

“…Another beneficial aspect of the aerogel is its biosensor function with high SSA that enables a higher loading of the elastase peptide on the porous nanofibrillar systems, which improves sensor sensitivity functions. Furthermore, the NA may behave as a potential sequestrant of the cationic serine protease, HNE, present in the wound fluid due to its negative surface charge that derives from cellulose [81,82]. …”

Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding

“…Cotton contains about 90% of this cellulosic polymer along with a small amount of hydrophobic waxes and pectin, while wood contains about 40–50% cellulosic polymer. The US military standard field dressing consists of two layers of gauze wrapped over densely packed cotton, such that it can absorb a large volume of blood while the cotton strands are thought to trigger platelet activation and aggregation due to high hydrophilicity, negative surface charge, and surface energy . The cotton gauze or pad, when directly placed over a bleeding injury, may provide high blood absorption, partial hemostatic reaction (thrombin generation via contact pathway), and additional tamponade effect with adjunctive compression components, but they can adhere to the wound tissue which may be an issue during their subsequent removal.…”

“…The cotton gauze or pad, when directly placed over a bleeding injury, may provide high blood absorption, partial hemostatic reaction (thrombin generation via contact pathway), and additional tamponade effect with adjunctive compression components, but they can adhere to the wound tissue which may be an issue during their subsequent removal. Nonetheless, in recent years interesting research is being focused on modulating the hemostatic characteristics of cotton dressings and gauze by modifying them with other hemostatic or strengthening materials like kaolin mineral, chitosan, viscose, rayon, etc . OC derived from cotton and oxidized regenerated cellulose (ORC) derived usually from wood pulp, refer to manipulation of the cellulose structure where primary and secondary alcohol moieties are oxidatively converted to aldehyde, ketone, or carboxyl groups, which significantly changes the physico‐chemical and mechanical properties of OC and ORC compared to native cellulose .…”

Development of an electrospun biomimetic polyurea scaffold suitable for vascular grafting

“…Activation of plasma factors is a critical variable to study while evaluating the hemocompatibility of biomaterials. Bovine plasma has been used to study blood coagulation due to contact activation because of its similarity to human plasma, availability and cost . The assays used in this study measure the time for clotting based on the activation of certain plasma factors, while coming in contact with a foreign material, involved in the clot formation via intrinsic and extrinsic pathways .…”

“…Bovine plasma has been used to study blood coagulation due to contact activation because of its similarity to human plasma, availability and cost. [55][56][57][58] The assays used in this study measure the time for clotting based on the activation of certain plasma factors, while coming in contact with a foreign material, involved in the clot formation via intrinsic and extrinsic pathways. 59,60 APTT measures the clotting time of recalcified citrated plasma upon addition of plasma thromboplastin as a phospholipid suspension and an activator such as kaolin.…”