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Extracellular matrix chronic wounds

Scott E Geiger, Olivier A Deigni, John Tracy Watson, Bruce A Kraemer
: Open wounds of the distal third of the leg and foot with an exposed tendon present a challenge in wound management and in attaining stable, durable coverage. The mobility of the tendon often leads to chronic inflammation that impedes wound closure, while the desiccation of the exposed tendon leads to progressive tendon necrosis. For the authors' cases, the ability of extracellular matrix (ECM) products to modulate wound bed inflammation and facilitate constructive remodeling of a wound seemed a reasonable approach in treating these wounds, especially in patients who are often poor surgical candidates for more advanced reconstructive procedures...
September 2016: Wounds: a Compendium of Clinical Research and Practice
Sarthak Sinha, Samuel Su, Matthew Workentine, Natacha Agabalyan, Min Cheng, Vincent Gabriel, Jeff Biernaskie
Marjolin's ulcer (MU) is an aggressive malignancy arising within chronic wounds. A major cause is unhealed burn injuries. This results in well-differentiated squamous cell carcinoma (SCC). This study aimed to elucidate transcriptional changes leading to malignancy by investigating differentially expressed genes in squamous cells present in a SCC compared with MU. MU tumor cells were isolated from histologically confirmed biopsy of SCC within an unhealed burn scar. Epithelial cells (ECs) adjacent to the tumor were co-isolated and a SCC cell line was commercially purchased...
September 20, 2016: Journal of Burn Care & Research: Official Publication of the American Burn Association
Ganping Bai, Guohe Yan, Guojian Wang, Ping Wan, Ronghua Zhang
Hepatic fibrosis (HF), a wound-healing response to a variety of chronic stimuli, is characterized by the excessive synthesis of extracellular matrix (ECM) proteins by hepatic stellate cells (HSC) and eventually the development of hepatic cirrhosis. Turtle shell pill (TSP) is a common traditional Chinese medicine used for preventing and treating HF and early hepatic cirrhosis, but its side-effects and the shortage of ingredients limit its clinical application. In addition, its mechanism of action is not clear...
September 9, 2016: Oncology Reports
Olivia B Hughes, Adele Rakosi, Flor Macquhae, Ingrid Herskovitz, Joshua D Fox, Robert S Kirsner
BACKGROUND: Wound healing is a dynamic process whereby cells, growth factors (GFs), and the extracellular matrix (ECM) interact to restore the architecture of damaged tissue. Chronic wounds can be difficult to treat due to the increased presence of inflammatory cells that degrade the ECM, GF, and cells necessary for wound healing to occur. Cellular and acellular matrix products can be used in the management of a variety of chronic wounds including venous, diabetic, and pressure ulcers and other conditions such as burns, epidermolysis bullosa, pyoderma gangrenosum, and surgical wounds...
September 2016: Plastic and Reconstructive Surgery
Panagiotis Flevaris, Douglas Vaughan
Extracellular matrix (ECM) deposition during wound healing is a physiological response to an insult. Wound healing becomes deregulated in the setting of chronic injury or long-standing metabolic disease, leading to the accumulation of ECM components and fibrosis. Matrix protein turnover is determined by the rate of synthesis as well as the rate of proteolytic degradation and clearance by matrix metalloproteinases (MMPs). The persistent activation of interstitial myofibroblasts, coupled with defects in matrix proteolysis, ultimately disrupts tissue architecture and leads to biochemical and mechanical organ dysfunction with eventual organ failure...
August 24, 2016: Seminars in Thrombosis and Hemostasis
Laura E Dickinson, Sharon Gerecht
Skin regeneration requires the coordinated integration of concomitant biological and molecular events in the extracellular wound environment during overlapping phases of inflammation, proliferation, and matrix remodeling. This process is highly efficient during normal wound healing. However, chronic wounds fail to progress through the ordered and reparative wound healing process and are unable to heal, requiring long-term treatment at high costs. There are many advanced skin substitutes, which mostly comprise bioactive dressings containing mammalian derived matrix components, and/or human cells, in clinical use...
2016: Frontiers in Physiology
Sandra Rother, Sergey A Samsonov, Tommy Hofmann, Joanna Blaszkiewicz, Sebastian Köhling, Stephanie Moeller, Matthias Schnabelrauch, Jörg Rademann, Stefan Kalkhof, Martin von Bergen, M Teresa Pisabarro, Dieter Scharnweber, Vera Hintze
: An imbalance between tissue-degrading matrix metalloproteinases (MMPs) and their counterparts' tissue inhibitors of metalloproteinases (TIMPs) causes pathologic extracellular matrix (ECM) degradation in chronic wounds and requires new adaptive biomaterials that interact with these regulators to re-establish their balance. Sulfated glycosaminoglycans (GAGs) and TIMP-3 are key modulators of tissue formation and remodeling. However, little is known about their molecular interplay. GAG/TIMP-3 interactions were characterized combining surface plasmon resonance, ELISA, molecular modeling and hydrogen/deuterium exchange mass spectrometry...
November 2016: Acta Biomaterialia
Refaat Omar, Jiaqi Yang, Haoyuan Liu, Neal M Davies, Yuewen Gong
Hepatic fibrosis is a reversible wound-healing response to either acute or chronic liver injury caused by hepatitis B or C, alcohol, and toxic agents. Hepatic fibrosis is characterized by excessive accumulation and reduced degradation of extracellular matrix (ECM). Excessive accumulation of ECM alters the hepatic architecture leading to liver fibrosis and cirrhosis. Cirrhosis results in failure of common functions of the liver. Hepatic stellate cells (HSC) play a major role in the development of liver fibrosis as HSC are the main source of the excessive production of ECM in an injured liver...
August 18, 2016: Reviews of Physiology, Biochemistry and Pharmacology
Vijay K Kuna, Arvind M Padma, Joakim Håkansson, Jan Nygren, Robert Sjöback, Sarunas Petronis, Suchitra Sumitran-Holgersson
Herein, we report the fabrication of a novel composite gel from decellularized gal-gal-knockout porcine skin and human peripheral blood mononuclear cells (hPBMC) for full-thickness skin wound healing. Decellularized skin extracellular matrix (ECM) powder was prepared via chemical treatment, freeze-drying and homogenization. The powder was mixed with culture medium containing hyaluronic acid to generate a pig skin gel (PSG). The effect of the gel in regeneration of full-thickness wound was studied in nude mice...
August 5, 2016: Cell Transplantation
J Kim, Y Jung
Liver fibrosis, a major characteristic of chronic liver disease, is inappropriate tissue remodeling caused by prolonged parenchymal cell injury and inflammation. During liver injury, hepatic stellate cells (HSCs) undergo transdifferentiation from quiescent HSCs into activated HSCs, which promote the deposition of extracellular matrix proteins, leading to liver fibrosis. Thymosin beta 4 (Tβ4), a major actin-sequestering protein, is the most abundant member of the highly conserved β-thymosin family and controls cell morphogenesis and motility by regulating the dynamics of the actin cytoskeleton...
2016: Vitamins and Hormones
Khlifi Latifa, Sahli Sondess, Graiet Hajer, Ben-Hadj-Mohamed Manel, Khelil Souhir, Bouzidi Nadia, Jaballah Abir, Ferchichi Salima, Miled Abdelhedi
Pressure ulcer (PU) remains a common worldwide problem in all health care settings, it is synonymous with suffering. PU is a complex disease that is dependent on a number of interrelated factors. It involves multiple mechanisms such as physiological risk factors, chronic inflammation, oxidant-antioxidant imbalance and proteolytic attack on extracellular matrix by matrix metalloproteinases (MMP). Therefore, we propose that these wounds lead to molecular variations that can be detected by assessing biomarkers...
2016: Scientific Reports
Mohammed Ashrafi, Anil Sebastian, Barbara Shih, Nicholas Greaves, Teresa Alonso-Rasgado, Mohamed Baguneid, Ardeshir Bayat
Clinical consensus is that debridement is necessary for successful application of dermal skin substitutes (DSS) to chronic wounds. The aim here was to identify commonly expressed genes associated with wound healing in untreated acute wounds and chronic wounds treated with wound debridement followed by DSS. Cutaneous biopsies were taken at two time points from untreated acute and chronic wounds and from chronic wounds treated with DSS following debridement. Microarray analysis identified significant differences (p < 0...
July 1, 2016: Wound Repair and Regeneration
C Michael DiPersio, Rui Zheng, James Kenney, Livingston Van De Water
During cutaneous wound healing, keratinocyte proliferation and migration are critical for re-epithelialization. In addition the epidermis secretes growth factors, cytokines, proteases, and matricellular proteins into the wound microenvironment that modify the extracellular matrix and stimulate other wound cells that control the inflammatory response, promote angiogenesis and facilitate tissue contraction and remodeling. Wound keratinocytes express at least seven different integrins-the major cell adhesion receptors for the extracellular matrix-that collectively control essential cell-autonomous functions to ensure proper re-epithelialization, including migration, proliferation, survival and basement membrane assembly...
September 2016: Cell and Tissue Research
Sandra Matabi Ayuk, Heidi Abrahamse, Nicolette Nadene Houreld
The integration of several cellular responses initiates the process of wound healing. Matrix Metalloproteinases (MMPs) play an integral role in wound healing. Their main function is degradation, by removal of damaged extracellular matrix (ECM) during the inflammatory phase, breakdown of the capillary basement membrane for angiogenesis and cell migration during the proliferation phase, and contraction and remodelling of tissue in the remodelling phase. For effective healing to occur, all wounds require a certain amount of these enzymes, which on the contrary could be very damaging at high concentrations causing excessive degradation and impaired wound healing...
2016: Journal of Diabetes Research
Philip A Klenotic, Chao Zhang, Zhiyong Lin
The CCN family of proteins consists of 6 members (CCN1-CCN6) that share conserved functional domains. These matricellular proteins interact with growth factors, extracellular matrix (ECM) proteins, cell surface integrins and other receptors to promote ECM-intracellular signaling. This signaling leads to propagation of a variety of cellular actions, including adhesion, invasion, migration and proliferation within several cell types, including epithelial, endothelial and smooth muscle cells. Though CCNs share significant homology, the function of each is unique due to distinct and cell specific expression patterns...
May 30, 2016: Journal of Cell Communication and Signaling
Daniel Metcalf, David Parsons, I Philip Bowler
Delayed wound healing due to infection is a burden on healthcare systems, and the patient and caregiver alike. An emerging factor in infection and delayed healing is the presence development of biofilm in wounds. Biofilm is communities of microorganisms, protected by an extracellular matrix of slime in the wound, which can tolerate host defences and applied antimicrobials such as antibiotics or antimicrobial dressings. A growing evidence base exists suggesting that biofilm exists in a majority of chronic wounds, and can be a precursor to infection while causing delayed healing itself...
March 2016: Acta Medica Croatica: C̆asopis Hravatske Akademije Medicinskih Znanosti
Nastja Kucisec-Tepes
Chronic wound does not heal within the expected time frame because it remains in the inflammation phase of healing. The reason for this is the presence of necrotic tissue and a large number of microorganisms, primarily bacteria that secrete the biofilm, along with ischemia, hypoxia and edema. Biofilm is present in 90% of chronic wounds and 6% of the acute ones. Biofilm is a corporative association of microbes which adhere to the surface of the wound, guided by quorum sensing molecules. The association is surrounded by a moisturizing matrix of extracellular polymeric substances (slime) which protect the microbes from the impact of antibiotics, antiseptics, macro-organism defense and stress...
March 2016: Acta Medica Croatica: C̆asopis Hravatske Akademije Medicinskih Znanosti
Qingping Yang, Christelle Larose, Alessandra C Della Porta, Gregory S Schultz, Daniel J Gibson
Bacterial biofilms have been found in many, if not all, chronic wounds. Their excessive extracellular matrix secretion and the metabolic changes that they undergo render them highly tolerant of many antibiotic and antimicrobial treatments. Physical removal and/or disruption are a common approach to treating wounds suspected of having bacterial biofilms. While many of these techniques use mechanical energy as the primary means of removal, we have begun to investigate if surfactants could facilitate the removal of bacterial biofilms, or if they might sensitise the biofilms to antimicrobial interventions...
May 22, 2016: International Wound Journal
S C Chew, B Kundukad, W K Teh, P Doyle, L Yang, S A Rice, S Kjelleberg
Biofilms are surface-attached communities of microorganisms embedded in an extracellular matrix and are essential for the cycling of organic matter in natural and engineered environments. They are also the leading cause of many infections, for example, those associated with chronic wounds and implanted medical devices. The extracellular matrix is a key biofilm component that determines its architecture and defines its physical properties. Herein, we used growth chambers embedded with micropillars to study the net mechanical forces (differential pressure) exerted during biofilm formation in situ...
June 21, 2016: Soft Matter
Rebecca A Hortensius, Brendan Ac Harley
Tissue regeneration strategies have traditionally relied on designing biomaterials that closely mimic features of the native extracellular matrix (ECM) as a means to potentially promote site-specific cellular behaviors. However, inflammation, while a necessary component of wound healing, can alter processes associated with successful tissue regeneration following an initial injury. These processes can be further magnified by the implantation of a biomaterial within the wound site. In addition to designing biomaterials to satisfy biocompatibility concerns as well as to replicate elements of the composition, structure, and mechanics of native tissue, we propose that ECM analogs should also include features that modulate the inflammatory response...
May 2016: Experimental Biology and Medicine
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