Peptide-Cellulose Conjugates on Cotton-Based Materials Have Protease Sensor/Sequestrant Activity

The growing incidence of chronic wounds in the world population has prompted increased interest in chronic wound dressings with protease-modulating activity and protease point of care sensors to treat and enable monitoring of elevated protease-based wound pathology. However, the overall design features needed for the combination of a chronic wound dressing that lowers protease activity along with protease detection capability as a single platform for semi-occlusive dressings has scarcely been addressed. The interface of dressing and sensor specific properties (porosity, permeability, moisture uptake properties, specific surface area, surface charge, and detection) relative to sensor bioactivity and protease sequestrant performance is explored here. Measurement of the material’s zeta potential demonstrated a correlation between negative charge and the ability of materials to bind positively charged Human Neutrophil Elastase. Peptide-cellulose conjugates as protease substrates prepared on a nanocellulosic aerogel were assessed for their compatibility with chronic wound dressing design. The porosity, wettability and absorption capacity of the nanocellulosic aerogel were consistent with values observed for semi-occlusive chronic wound dressing designs. The relationship of properties that effect dressing functionality and performance as well as impact sensor sensitivity are discussed in the context of the enzyme kinetics. The sensor sensitivity of the aerogel-based sensor is contrasted with current clinical studies on elastase. Taken together, comparative analysis of the influence of molecular features on the physical properties of three forms of cellulosic transducer surfaces provides a meaningful assessment of the interface compatibility of cellulose-based sensors and corresponding protease sequestrant materials for potential use in chronic wound sensor/dressing design platforms.

[1]  G. Schultz,et al.  Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors , 1999, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[2]  N. Miyamoto,et al.  Functional porous carbon-ZnO nanocomposites for high-performance biosensors and energy storage applications. , 2016, Physical chemistry chemical physics : PCCP.

[3]  T. Lee,et al.  Contact Angle and Wetting Properties , 2013 .

[4]  A. Fisher,et al.  In vitro assessment of water vapour transmission of synthetic wound dressings. , 1995, Biomaterials.

[5]  T. Grzela,et al.  Modulation of matrix metalloproteinases MMP-2 and MMP-9 activity by hydrofiber-foam hybrid dressing – relevant support in the treatment of chronic wounds , 2015, Central-European journal of immunology.

[6]  Rachel Smith,et al.  Mechanism of action of PROMOGRAN, a protease modulating matrix, for the treatment of diabetic foot ulcers , 2002, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[7]  K. Harding,et al.  Defective extracellular matrix reorganization by chronic wound fibroblasts is associated with alterations in TIMP-1, TIMP-2, and MMP-2 activity. , 2000, The Journal of investigative dermatology.

[8]  R. Clark,et al.  Overview and General Considerations of Wound Repair , 1998 .

[9]  Yanbing Yang,et al.  Aptamer-functionalized carbon nanomaterials electrochemical sensors for detecting cancer relevant biomolecules , 2018 .

[10]  M. Carter,et al.  Defining a new diagnostic assessment parameter for wound care: Elevated protease activity, an indicator of nonhealing, for targeted protease‐modulating treatment , 2016, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[11]  D. Yager,et al.  The proteolytic environment of chronic wounds , 1999, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[12]  V. Falanga Occlusive wound dressings. Why, when, which? , 1988, Archives of dermatology.

[13]  Joachim Dissemond,et al.  Influence of pH on wound-healing: a new perspective for wound-therapy? , 2007, Archives of Dermatological Research.

[14]  Tim R. Dargaville,et al.  Sensors and imaging for wound healing: a review. , 2013, Biosensors & bioelectronics.

[15]  E. Dabelsteen,et al.  Proliferation and mitogenic response to PDGF-BB of fibroblasts isolated from chronic venous leg ulcers is ulcer-age dependent. , 1999, The Journal of investigative dermatology.

[16]  J. V. Edwards,et al.  Future Structure and Properties of Mechanism-Based Wound Dressings , 2006 .

[17]  Krystal R. Fontenot,et al.  Structure/Function Relations of Chronic Wound Dressings and Emerging Concepts on the Interface of Nanocellulosic Sensors , 2020 .

[18]  E. Ayello,et al.  Wound dressings: an evolving art and science. , 2012, Advances in skin & wound care.

[19]  J. V. Edwards,et al.  Synthesis and activity of NH2- and COOH-terminal elastase recognition sequences on cotton. , 1999, The journal of peptide research : official journal of the American Peptide Society.

[20]  E. Togawa,et al.  Crystal transition from cellulose II hydrate to cellulose II , 2011 .

[21]  T. Serena Development of a Novel Technique to Collect Proteases from Chronic Wounds. , 2014, Advances in wound care.

[22]  J. Tarlton,et al.  Use of modified superabsorbent polymer dressings for protease modulation in improved chronic wound care. , 2013, Wounds : a compendium of clinical research and practice.

[23]  J. VincentEdwards Protease Biosensors Based on Peptide-Nanocellulose Conjugates: From Molecular Design to Dressing Interface , 2016 .

[24]  J. Evans,et al.  The preclinical evaluation of the water vapour transmission rate through burn wound dressings. , 1987, Biomaterials.

[25]  Krystal R. Fontenot,et al.  Human neutrophil elastase peptide sensors conjugated to cellulosic and nanocellulosic materials: part I, synthesis and characterization of fluorescent analogs , 2016, Cellulose.

[26]  Monica C. Concha,et al.  Kinetic and structural analysis of fluorescent peptides on cotton cellulose nanocrystals as elastase sensors. , 2015, Carbohydrate polymers.

[27]  J. V. Edwards,et al.  Peptide conjugated cellulose nanocrystals with sensitive human neutrophil elastase sensor activity , 2013, Cellulose.

[28]  G. Winter,et al.  Formation of the Scab and the Rate of Epithelization of Superficial Wounds in the Skin of the Young Domestic Pig , 1962, Nature.

[29]  J. V. Edwards,et al.  Thrombin Production and Human Neutrophil Elastase Sequestration by Modified Cellulosic Dressings and Their Electrokinetic Analysis , 2011, Journal of functional biomaterials.

[30]  O. Stojadinović,et al.  Biology and Biomarkers for Wound Healing , 2016, Plastic and reconstructive surgery.

[31]  P. Kingshott,et al.  Electrospun nanofibers as dressings for chronic wound care: advances, challenges, and future prospects. , 2014, Macromolecular bioscience.

[32]  Krystal R. Fontenot,et al.  Human neutrophil elastase detection with fluorescent peptide sensors conjugated to cellulosic and nanocellulosic materials: part II, structure/function analysis , 2016, Cellulose.

[33]  J. Schroers,et al.  Nanopatterned Bulk Metallic Glass Biosensors. , 2017, ACS Sensors.

[34]  J. Vincent Edwards,et al.  Preparation, Characterization and Activity of a Peptide-Cellulosic Aerogel Protease Sensor from Cotton , 2016, Sensors.

[35]  R. Diegelmann,et al.  Ability of chronic wound fluids to degrade peptide growth factors is associated with increased levels of elastase activity and diminished levels of proteinase inhibitors , 1997, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[36]  John E. Murphy,et al.  Global Substrate Profiling of Proteases in Human Neutrophil Extracellular Traps Reveals Consensus Motif Predominantly Contributed by Elastase , 2013, PloS one.

[37]  J. Dumville,et al.  A 'test and treat' strategy for elevated wound protease activity for healing in venous leg ulcers. , 2016, The Cochrane database of systematic reviews.

[38]  Chengjun Zhou,et al.  Comparative properties of cellulose nano-crystals from native and mercerized cotton fibers , 2012, Cellulose.

[39]  T. Lindström,et al.  Aerogels from nanofibrillated cellulose with tunable oleophobicity , 2010 .

[40]  J. V. Edwards,et al.  Development of a Continuous Finishing Chemistry Process for Manufacture of a Phosphorylated Cotton Chronic Wound Dressing , 2009 .

[41]  Marco Romanelli,et al.  Wound bed preparation: a systematic approach to wound management , 2003, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[42]  Harry Brumer,et al.  Cellulose-Based Biosensors for Esterase Detection. , 2016, Analytical chemistry.

[43]  T. Phillips,et al.  Choosing a Wound Dressing Based on Common Wound Characteristics. , 2016, Advances in wound care.

[44]  Krystal R. Fontenot,et al.  Structure/Function Analysis of Cotton-Based Peptide-Cellulose Conjugates: Spatiotemporal/Kinetic Assessment of Protease Aerogels Compared to Nanocrystalline and Paper Cellulose , 2018, International journal of molecular sciences.

[45]  B. Schyrr,et al.  Fiber-optic protease sensor based on the degradation of thin gelatin films , 2015 .

[46]  I. K. Cohen,et al.  Modified cotton gauze dressings that selectively absorb neutrophil elastase activity in solution , 2001, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[47]  R. Ulijn,et al.  Hydrogels for the detection and management of protease levels. , 2010, Macromolecular bioscience.