A superabsorbent polymer-containing wound dressing efficiently sequesters MMPs and inhibits collagenase activity in vitro
25 Jun 2013-Journal of Materials Science: Materials in Medicine (Springer US)-Vol. 24, Iss: 10, pp 2473-2478
TL;DR: In vitro data confirm the positive effect of the SAP wound dressing observed in vivo and suggest that it should be specifically useful for highly exuding wounds with an elevated proteolytic activity that needs to be reduced to support healing.
Abstract: Superabsorbent polymer (SAP)-containing wound dressings present a valuable and unique category of wound management products. An in vitro approach was used to assess the effects of a new SAP dressing in treatment of non-healing wounds. It was shown that the SAP dressing possesses a significant binding capacity for MMP-2 and MMP-9 in vitro (P < 0.001). The inclusion of the bound proteases was so strong that no MMP-2 and only marginal amounts of MMP-9 were released from the dressing samples in a subsequent elution step. In addition, the SAP dressing was able to take up collagenase and reduce its activity in vitro. However, collagenase was not completely inactivated upon binding and enzyme-mediated substrate turnover could be observed at the dressings. In conclusion, in vitro data confirm the positive effect of the SAP wound dressing observed in vivo. The findings suggest that it should be specifically useful for highly exuding wounds with an elevated proteolytic activity that needs to be reduced to support healing.
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TL;DR: In this paper, the MMP-knockout mouse models display altered wound healing responses, but these are often subtle phenotypic changes indicating the overlapping MMP substrate specificity and inter-MMP compensation.
Abstract: Significance: Matrix metalloproteinases (MMPs) are present in both acute and chronic wounds. They play a pivotal role, with their inhibitors, in regulating extracellular matrix degradation and deposition that is essential for wound reepithelialization. The excess protease activity can lead to a chronic nonhealing wound. The timed expression and activation of MMPs in response to wounding are vital for successful wound healing. MMPs are grouped into eight families and display extensive homology within these families. This homology leads in part to the initial failure of MMP inhibitors in clinical trials and the development of alternative methods for modulating the MMP activity. MMP-knockout mouse models display altered wound healing responses, but these are often subtle phenotypic changes indicating the overlapping MMP substrate specificity and inter-MMP compensation. Recent Advances: Recent research has identified several new MMP modulators, including photodynamic therapy, protease-absorbing dressing, micr...
543 citations
TL;DR: This review summarizes the progress in microfluidic 3D cancer models, their benefits, and their broad application to basic cancer biology, drug screening, and drug discovery.
151 citations
TL;DR: The presence of free water may not be detrimental to healing, but any adverse effects of wound fluid on tissues is more likely related to the biological components contained within chronic wound exudate, for example elevated protease levels.
Abstract: Balancing skin hydration levels is important as any disruption in skin integrity will result in disturbance of the dermal water balance. The discovery that a moist environment actively supports the healing response when compared with a dry environment highlights the importance of water and good hydration levels for optimal healing. The benefits of 'wet' or 'hyper-hydrated' wound healing appear similar to those offered by moist over a dry environment. This suggests that the presence of free water may not be detrimental to healing, but any adverse effects of wound fluid on tissues is more likely related to the biological components contained within chronic wound exudate, for example elevated protease levels. Appropriate dressings applied to wounds must not only be able to absorb the exudate, but also retain this excess fluid together with its protease solutes, while concurrently preventing desiccation. This is particularly important in the case of chronic wounds where peri-wound skin barrier properties are compromised and there is increased permeation across the injured skin. This review discusses the importance of appropriate levels of hydration in skin, with a particular focus on the need for optimal hydration levels for effective healing. Declaration of interest: This paper was supported by Paul Hartmann Ltd. The authors have provided consultative services to Paul Hartmann Ltd.
108 citations
09 Feb 2015
TL;DR: The roles of MMPs in acute and chronic wound healing are discussed and current therapeutic approaches aiming at inhibiting aberrant MMP activities in healing disorders are summarized.
Abstract: Cutaneous wound healing is a complex tissue response that requires a coordinated interplay of multiple cells in orchestrated biological processes to finally re-establish the skin's barrier function upon injury. Proteolytic enzymes and in particular matrix metalloproteinases (MMPs) contribute to all phases of the healing process by regulating immune cell influx, facili - tating migration of fibroblasts and keratinocytes, and remodeling of the scar tissue. As a result of these pleiotropic functions in the healing skin wound, uncontrolled activities of MMPs are associated with impaired wound healing, a growing health problem in Western countries due to increased life expectancies and rising rates of underlying diseases, such as diabetes. However, detailed mechanisms have been only partially unraveled, and new diagnostic tools and more targeted therapies are urgently needed. In this review, we discuss the roles of MMPs in acute and chronic wound healing and summarize current therapeutic approaches aiming at inhibiting aberrant MMP activities in healing disorders.
46 citations
Cites background from "A superabsorbent polymer-containing..."
...A similar effect on removal of detrimental MMPs from chronic wound environments has been demonstrated for superabsorbent hydrogel wound dressings.(70,71) Through their capacity to very efficiently absorb large amounts of fluids, these dressings are very effective in the cleansing phase of wound treatment, when MMP activity is particularly high....
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TL;DR: In this article, the authors evaluate the impact of moisture management for optimal wound care and assess current wound management strategies relating to antisepsis and moist wound healing utilizing the wound bed preparation paradigm 2015 update.
Abstract: Objective: To provide an overview of moisture management and its importance in wound care. The authors evaluate the impact of moisture management for optimal wound care and assess current wound management strategies relating to antisepsis and moist wound healing utilizing the wound bed preparation paradigm 2015 update. The discussion distinguishes the form and function of wound care dressing classes available for optimal moisture management.
Conclusion: Moisture management for chronic wounds is best achieved with modern moist interactive dressings if the wound has the ability to heal.
40 citations
References
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01 Jan 1981TL;DR: In this article, the authors discuss the history of polymers and their application in the field of chemical engineering, including the origins of polymer science and the Polymer Industry, as well as a discussion of the role of elastic deformation in polymers.
Abstract: CONCEPTS, NOMENCLATURE AND SYNTHESIS OF POLYMERS Concepts and Nomenclature The Origins of Polymer Science and the Polymer Industry Basic Definitions and Nomenclature Molar Mass and Degree of Polymerization Principles of Polymerization Introduction Classification of Polymerization Reactions Monomer Functionality and Polymer Skeletal Structure Functional Group Reactivity and Molecular Size: The Principle of Equal Reactivity Step Polymerization Introduction Linear Step Polymerization Non-Linear Step Polymerization Radical Polymerization Introduction to Radical Polymerization The Chemistry of Conventional Free-Radical Polymerization Kinetics of Conventional Free-Radical Polymerization Free-Radical Polymerization Processes Reversible-Deactivation ('Living') Radical Polymerizations Non-Linear Radical Polymerizations Ionic Polymerization Introduction to Ionic Polymerization Cationic Polymerization Anionic Polymerization Group-Transfer Polymerization Stereochemistry and Coordination Polymerization Introduction to Stereochemistry of Polymerization Tacticity of Polymers Geometric Isomerism in Polymers Prepared from Conjugated Dienes Ziegler-Natta Coordination Polymerization Metallocene Coordination Polymerization Ring-Opening Polymerization Introduction to Ring-Opening Polymerization Cationic Ring-Opening Polymerization Anionic Ring-Opening Polymerization Free-Radical Ring-Opening Polymerization Ring-Opening Metathesis Polymerization Specialized Methods of Polymer Synthesis Introduction Solid-State Topochemical Polymerization Polymerization by Oxidative Coupling Precursor Routes to Intractable Polymers Supramolecular Polymerization (Polyassociation) Copolymerization Introduction Step Copolymerization Chain Copolymerization Block Copolymer Synthesis Graft Copolymer Synthesis CHARACTERIZATION OF POLYMERS Theoretical Description of Polymers in Solution Introduction Thermodynamics of Polymer Solutions Chain Dimensions Frictional Properties of Polymer Molecules in Dilute Solution Number-Average Molar Mass Introduction to Measurements of Number-Average Molar Mass Membrane Osmometry Vapour Pressure Osmometry Ebulliometry and Cryoscopy End-Group Analysis Effects of Low Molar Mass Impurities upon Mn Scattering Methods Introduction Static Light Scattering Dynamic Light Scattering Small-Angle X-Ray and Neutron Scattering Frictional Properties of Polymers in Solution Introduction Dilute Solution Viscometry Ultracentrifugation Molar Mass Distribution Introduction Fractionation Gel Permeation Chromatography Field-Flow Fractionation Mass Spectroscopy Chemical Composition and Molecular Microstructure Introduction Principles of Spectroscopy Ultraviolet and Visible Light Absorption Spectroscopy Infrared Spectroscopy Raman Spectroscopy Nuclear Magnetic Resonance Spectroscopy Mass Spectroscopy PHASE STRUCTURE AND MORPHOLOGY OF BULK POLYMERS The Amorphous State Introduction The Glass Transition Factors Controlling the Tg Macromolecular Dynamics The Crystalline State Introduction Determination of Crystal Structure Polymer Single Crystals Semi-Crystalline Polymers Liquid Crystalline Polymers Defects in Crystalline Polymers Crystallization Melting Multicomponent Polymer Systems Introduction Polymer Blends Block Copolymers PROPERTIES OF BULK POLYMERS Elastic Deformation Introduction Elastic Deformation Elastic Deformation of Polymers Viscoelasticity Introduction Viscoelastic Mechanical Models Boltzmann Superposition Principle Dynamic Mechanical Testing Frequency Dependence of Viscoelastic Behaviour Transitions and Polymer Structure Time-Temperature Superposition Effect of Entanglements Non-Linear Viscoelasticity Elastomers Introduction Thermodynamics of Elastomer Deformation Statistical Theory of Elastomer Deformation Stress-Strain Behaviour of Elastomers Factors Affecting Mechanical Behaviour Yield and Crazing Introduction Phenomenology of Yield Yield Criteria Deformation Mechanisms Crazing Fracture and Toughening Introduction Fundamentals of Fracture Mechanics of Fracture Fracture Phenomena Toughened Polymers Polymer Composites Introduction to Composite Materials Matrix Materials Types of Reinforcement Composite Composition Particulate Reinforcement Fibre Reinforcement Nanocomposites Electrical Properties Introduction to Electrical Properties Dielectric Properties Conduction in Polymers Polymer Electronics Answers to Problems Index Problems and Further Reading appear at the end of each chapter.
1,348 citations
TL;DR: The elevated levels of matrix metalloproteinase activity decreased significantly as healing occurs in chronic leg ulcers, which parallels the processes observed in normally healing acute wounds and supports the case for the addition of protease inhibitors in chronic wounds in conjunction with any treatments using growth factors.
Abstract: To assess the differences in proteolytic activity of acute and chronic wound environments, wound fluids were collected from acute surgical wounds (22 samples) and chronic wounds (25 samples) of various etiologies, including mixed vessel disease ulcers, decubiti and diabetic foot ulcers. Matrix metalloproteinase (MMP) activity measured using the Azocoll assay was significantly elevated by 30 fold in chronic wounds (median 22.8 microg MMP Eq/ml) compared to acute wounds (median 0.76 microg MMP Eq/ml) (p < 0.001). The addition of the matrix metalloproteinase inhibitor Illomostat decreased the matrix metalloproteinase activity by approximately 90% in all samples, confirming that the majority of the activity measured was due to matrix metalloproteinases. Gelatin zymograms indicated predominantly elevated matrix metalloproteinase-9 with smaller elevations of matrix metalloproteinase-2. In addition tissue inhibitor of metalloproteinase-1 levels were analyzed in a small subset of acute and chronic wounds. When tissue inhibitor of metalloproteinase-1 levels were compared to protease levels there was an inverse correlation (p = 0.02, r = - 0.78). In vitro degradation of epidermal growth factor was measured by addition of 125I labelled epidermal growth factor to acute and chronic wound fluid samples. There was significantly higher degradation of epidermal growth factor in chronic wound fluid samples (mean 28.1%) compared to acute samples (mean 0.6%). This also correlated to the epidermal growth factor activity of these wound fluid samples (p < 0. 001, r = 0.64). Additionally, the levels of proteases were assayed in wound fluid collected from 15 venous leg ulcers during a nonhealing and healing phase using a unique model of chronic wound healing in humans. Patients with nonhealing venous leg ulcers were admitted to the hospital for bed rest and wound fluid samples were collected on admission (nonhealing phase) and after 2 weeks (healing phase) when the ulcers had begun to heal as evidenced by a reduction in size (median 12%). These data showed that the elevated levels of matrix metalloproteinase activity decreased significantly as healing occurs in chronic leg ulcers (p < 0.01). This parallels the processes observed in normally healing acute wounds. This data also supports the case for the addition of protease inhibitors in chronic wounds in conjunction with any treatments using growth factors.
867 citations
"A superabsorbent polymer-containing..." refers background in this paper
...Several studies have shown that exudates from these chronic wounds are characterized by elevated levels of matrix metalloproteinases (MMPs) [1, 2], contain excessive amounts of polymorphonuclear granulocyte-derived elastase (PMN elastase) [3–5], and high concentrations of free radicals [6]....
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TL;DR: The results suggest that non-healing ulcers develop an environment containing high levels of activated metalloproteinases, which may result in chronic tissue turnover and failed wound closure.
721 citations
"A superabsorbent polymer-containing..." refers background in this paper
...Several studies have shown that exudates from these chronic wounds are characterized by elevated levels of matrix metalloproteinases (MMPs) [1, 2], contain excessive amounts of polymorphonuclear granulocyte-derived elastase (PMN elastase) [3–5], and high concentrations of free radicals [6]....
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TL;DR: The current understanding of the proteolytic enzymes found in chronic wounds is discussed and attempts to relate this information to the abundant presence of neutrophils.
Abstract: A consistent feature of chronic leg and pressure ulcers is chronic inflammation associated with an elevated infiltration of neutrophils. Neutrophils and their proteases have been implicated in mediating the tissue damage associated with a variety of chronic inflammatory diseases. This review discusses our current understanding of the proteolytic enzymes found in chronic wounds and attempts to relate this information to the abundant presence of neutrophils. In addition, the implications that the proteolytic environment may have for current and future treatment strategies of chronic nonhealing wounds are discussed.
388 citations
TL;DR: The ability of some chronic nonhealing wounds to rapidly degrade exogenously added growth factors has important implications with regard to past and future clinical attempts to use peptide growth factors to treat these types of problem wounds.
Abstract: The stability of peptide growth factors exposed to fluids from healing surgical wounds and from nonhealing chronic wounds was examined in vitro. (125)I-Labeled transforming growth factor-beta1 or platelet-derived growth factor-BB was incubated with fluids from healing surgical wounds and fluids from venous stasis or pressure ulcers. Fluids from healing surgical wounds had no appreciable effect on the level of (125)I corresponding to intact growth factor. In contrast, incubation with fluids from several venous stasis or pressure ulcers resulted in significant degradation of these growth factors. Degradation was blocked by broad-spectrum serine proteinase inhibitors and by specific inhibitors of neutrophil elastase. Levels of elastase activity in wound fluids correlated with the ability to degrade peptide growth factors. Further comparisons showed qualitative and quantitative differences in the endogenous proteinase inhibitors, alpha2-macroglobulin and alpha1-antiproteinase. These results could explain, in part, the variable growth factor levels which have been found in chronic wounds. More importantly, the ability of some chronic nonhealing wounds to rapidly degrade exogenously added growth factors has important implications with regard to past and future clinical attempts to use peptide growth factors to treat these types of problem wounds.
288 citations
"A superabsorbent polymer-containing..." refers background in this paper
...The disproportionate action of proteases leads to considerable reduced amounts of growth factors [7] and proteinase inhibitors like tissue inhibitors of matrix metalloproteases [8]....
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