Transforming growth factor (TGF)-beta is a prototypic multifunctional cytokine whose broad modulatory mechanisms affect numerous biological functions both at the cell and organism levels. These include, but are not limited to, control of immune functions, embryogenesis, carcinogenesis, tissue responses to injury, cell proliferation, extracellular matrix (ECM) synthesis and degradation, and ...

New generations of synthetic biomaterials are being developed at a rapid pace for use as three-dimensional extracellular microenvironments to mimic the regulatory characteristics of natural extracellular matrices (ECMs) and ECM-bound growth factors, both for therapeutic applications and basic biological studies. Recent advances include nanofibrillar networks formed by self-assembly of small ...

The host response to injury or infection is a complex interplay of endocrine, metabolic, and immunological alterations designed to promote wound healing and restore the system to a state of homeostasis. Cytokines are the primary mediators of the inflammatory response to injury. This article serves as an introduction to this ...

The directed migration of cells (chemotaxis) occurs not only during wound healing and inflammatory responses but also during embryonic development. However, the intracellular signaling pathways that enable a cell to detect a chemoattractant and subsequently migrate toward the source are not clearly defined. The Dunn chemotaxis chamber in conjunction with ...

The developing fetus has the remarkable ability to heal dermal skin wounds by regenerating normal epidermis and dermis with restoration of the extracellular matrix architecture, strength, and function. The biology responsible for scarless wound healing in skin is a paradigm for ideal tissue repair. This regenerative capacity is lost in ...

Tissue repair is a dynamic compensatory cell proliferation and tissue regeneration response stimulated in order to overcome acute toxicity and recover organ/tissue structure and function. Extensive evidence in rodent models using structurally and mechanistically diverse hepatotoxicants such as acetaminophen (APAP), carbon tetrachloride (CCl4), chloroform (CHCl3), thioacetamide (TA), trichloroethylene (TCE), and ...

Localization of plasminogen and plasminogen activators on cell surfaces promotes plasminogen activation and serves to arm cells with the broad spectrum proteolytic activity of plasmin. Cell surface proteolysis by plasmin is an essential feature of physiological and pathological processes requiring extracellular matrix degradation for cell migration including macrophage recruitment during ...

Chymases, serine proteases exclusively expressed by mast cells, have been implicated in various pathological conditions. However, the basis for these activities is not known, i.e. the in vivo substrate(s) for mast cell chymase has not been identified. In this study we show that mice lacking the chymase mouse mast cell ...

Recent studies have revealed that sex hormones manifest a variety of biological and immunological effects in the skin. Pregnancy, menstruation and the menopause modulate the natural course of psoriasis, indicating a female hormone-induced regulation of skin inflammation. Estrogen in vitro down-regulates the production of the neutrophil, type 1 T cell ...

Both aging and diabetes are characterized by the formation of advanced glycation end products (AGEs). Both exhibit other similarities including deficits in wound healing that are associated with higher rates of fibroblast apoptosis. In order to investigate a potential mechanism for enhanced fibroblast apoptosis in diabetes and aged individuals, experiments ...

Normal orchestration of wound healing, the protective immune response and inflammation, involve a bewildering array of cells that communicate to each other locally by means of cell-surface receptors and their ligands. For local and middle- to long-distance coordination, some of these same cells make and export soluble messengers that communicate ...

Fibroblast proliferation and procollagen production are central features of tissue repair and fibrosis. In addition to its role in blood clotting, the coagulation cascade proteinase thrombin can contribute to tissue repair by stimulating fibroblasts via proteolytic activation of proteinase-activated receptor-1 (PAR1). During hemostasis, the coagulation cascade proteinase factor X is ...

The oral mucosa is susceptible to tissue injury from many causes, including infection, autoimmune disorders, surgical and accidental trauma, and gingival and periodontal inflammation; however, little is known about the events that influence wound healing in the mouth. Recent studies in non-oral tissues have implicated immune system-derived factors, in particular ...

The alpha1beta1 integrin, also known as "very late antigen" (VLA)-1, is normally expressed on mesenchymal cells, some epithelial cells, activated T cells, and macrophages, and interacts, via the I-domain of the extracellular domain of the alpha1 subunit, with collagen molecules in the extracellular matrix (ECM). By "outside-in" transmembranal signaling to ...

Imbalance in the expression of matrix metalloproteinases and their inhibitors contribute considerably to abnormal connective tissue degradation prevalent in various orthopaedic joint diseases such as rheumatoid arthritis and osteoarthritis. Matrix metalloproteinase expression has been detected in ligament, tendon, and cartilage tissues in the joint. They are known to contribute to ...

Matrix metalloproteinase-2 (MMP-2; gelatinase A) is known to degrade a broad range of extracellular matrix components and chemokines, and has important roles in the processes of cell migration, invasion, and involution during development, as well as during tumor growth and metastasis and in inflammation and repair. To better elucidate the ...

Local injury induces a complex orchestrated response to stimulate healing of injured tissues, cellular regeneration and phagocytosis. Practically, inflammation is defined as a defense process whereby fluid and white blood cells accumulate at a site of injury. The balance of cytokines, chemokines, and growth factors is likely to play a ...

Embryonic skeletal development involves the recruitment, commitment, differentiation, and maturation of mesenchymal cells into those in the skeletal tissue lineage, specifically cartilage and bone along the intramembranous and endochondral ossification pathways. The exquisite control of skeletal development is regulated at the level of gene transcription, cellular signaling, cell-cell and cell-matrix ...

AIM: Leukaemia inhibitory factor (LIF) is a pleotrophic cytokine expressed in a variety of cell types, and have shown to regulate stem cell proliferation, vascular genesis, inflammation, and immunity in various locations. Expression of LIF and its role in the cornea have not been studied previously. In this study, we ...

PURPOSE: We report the progression of bilateral central perforating ulceration in the cornea of a patient with familial amyloidotic polyneuropathy (FAP), also known as hereditary Portuguese amyloidosis, who received two corneal grafts in an interval of 6 years. The pathology of the original host and the grafted cornea is described. ...

The term "wound" describes the morphologic-functional disruption of the continuity of a tissue structure. A wound can be inflicted during life--when the cardiovascular and respiratory system is still intact--or after death, i.e. after cardiac and respiratory arrest. Traumatization during life triggers vital reactions that do not occur in postmortem wounds. ...

Activated protein C (APC) is a physiological serine protease that regulates blood clotting and inflammation. Keratinocytes are a major cell type of human skin and play a fundamental role in normal skin metabolism and cutaneous wound healing. In this study, we investigated the regulatory role of APC on the function ...

Although innate T lymphocytes such as gamma delta T cells have been extensively studied, their biological role has remained an enigma to researchers for many years. However, recent advances have begun to explain their complex role in the immune system. Gamma delta T cells are often the major T cell ...

In response to injury, tissues adjacent to the damaged area initiate a cascade of inflammatory and matrix remodeling events that are necessary to restore tissue integrity and function. The typical features of such healing effects in adult mammals are deposition of matrix proteins, which mature to scar tissues. In general, ...

Wound repair involves a complex interaction of various cell types, extracellular matrix molecules and soluble mediators. Details on signals controlling wound cell activities are beginning to emerge. In recent years this knowledge has been applied to a number of therapeutic strategies in soft tissue repair. Key challenges include re-adjusting the ...

The pathogenesis of pulmonary fibrosis is thought to involve alveolar epithelial injury that, when successfully repaired, can limit subsequent scarring. The plasminogen system participates in this process with the balance between urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) being a critical determinant of the extent of collagen accumulation ...

Cells of the innate immune system, including neutrophils and macrophages, are a highly visible component of normal wound healing in adult mammals. The role of inflammatory cells in the healing wound has been widely investigated, and evidence for both positive and negative influences exists. Several recent investigations support the emerging ...

During wound healing, the transition from granulation to scar tissue shows a decrease in myofibroblast cellularity. Previous results have correlated the disappearance of these cells with the induction of apoptotic cell death by some unknown stimuli. In contrast, hypertrophic scar appearance after wound healing is thought to be linked to ...

Significant numbers of macrophages are present during all stages of dermal wound repair, but the functional significance of these macrophages, especially during the later contraction and remodelling stages of repair, remains unclear. We investigated the effect of macrophages on wound contraction using a novel in vitro model based upon the ...

Irregular dysfunctional bleeding of the endometrium (ie, metrorrhagia without organic lesion) is common in women, whether treated or not with ovarian hormones. Several matrix metalloproteinases (MMPs) become normally expressed and/or activated at menstruation and cause extracellular matrix breakdown. We therefore explored whether episodes of irregular dysfunctional bleeding could be associated ...

Epidemiological data suggest an association between smoking, respiratory infections, and impaired wound healing. Inflammation is critical in the body's defense against pathogens and in the wound-healing process. Although nicotine is used to treat some inflammatory conditions, the mechanism of this action is largely unknown. To determine how nicotine affects inflammation, ...

Inflammatory response and cytokine elaboration are particularly active after myocardial infarction and contribute to cardiac remodeling and eventual host outcome. The triggers of cytokine release in the acute postinfarction period include mechanical deformation, ischemic stimulus, reactive oxygen species (ROS), and cytokine self-amplification pathways. Acutely, the elaboration of tumor necrosis factor, ...

Angiogenesis is essential for the repair of wounds and tissues damaged by ischemia. The regenerative process is tightly regulated by master angiogenic factors, cytokines and the downstream mediator NO. In addition, modulators of vascular growth, such as COX-2-generated prostanoids, contribute to the process by stabilizing the hypoxia-inducible factor and stimulating ...

Recent studies have demonstrated important pro-inflammatory roles for two matrix metalloproteinases (MMPs)-MMP-3 (stromelysin-1) and MMP-9 (gelatinase B)-in acute lung injury [Am. J. Respir. Cell Mol. Biol. 24 (2001) 1]. A role for MMP-3 in skin inflammation has also been demonstrated [Proc. Natl. Acad. Sci. U. S. A. 96 (1999) 6885]. ...

Cell proliferation and apoptosis are both important mechanisms for the regulation of tissue homeostasis. For instance, proliferation is crucial in wound repair, whereas apoptosis is important for removal of damaged cells and resolution of inflammation. Imbalance between cell proliferation and apoptosis can therefore lead to pathological conditions and disease. In ...

Cytokines are thought to play an important role in cellular loss and apoptosis during the repair of granulation tissue. In order to investigate the role of apoptosis following the administration of basic fibroblast growth factor (bFGF) to a wound, the present study examined the relationship between the degree of granulation ...

The problem of regeneration is fundamentally a problem of tissue homeostasis involving the replacement of cells lost to normal 'wear and tear' (cell turnover), and/or injury. This attribute is of particular significance to organisms possessing relatively long lifespans, as maintenance of all body parts and their functional integration is essential ...

Reactive oxygen species (ROS) are released into the alveolar space and contribute to alveolar epithelial damage in patients with acute lung injury. However, the role of ROS in alveolar repair is not known. We studied the effect of ROS in our in vitro wound healing model using either human A549 ...

We have demonstrated previously that new blood vessel formation induced by angiogenic growth factors in onplants placed on the chorioallantoic membrane (CAM) of the chick embryos is critically dependent on the cleavage of fibrillar collagen by a previously unidentified interstitial collagenase. In the present study we have used a quantitative ...

C57BL/6 mice were subjected to hindlimb unloading (HU) for a period of 3 wk to determine the possible effects on epithelial wound healing. A standardized corneal epithelial wound was performed, and parameters of the inflammatory response and reepithelialization were analyzed over an observation period of 96 h. Wound closure was ...

AIM: Oncostatin-M, a member of the gp 130 family of cytokines, has been associated with inflammation, connective tissue production, and extracellular matrix turnover. Since the reperfused heart is associated with an intense inflammatory reaction followed by scar formation, we tested the hypothesis that oncostatin-M is upregulated in response to cardiac ...

An introductory overview of the use of microfluidic devices for tissue engineering is presented. After a brief description of the background of tissue engineering, different application areas of microfluidic devices are examined. Among these are methods for patterning cells, topographical control over cells and tissues, and bioreactors. Examples where microfluidic ...

Current research on the development of new medical treatments of erectile dysfunction (ED) fall essentially into two main types of approaches: (1) the traditional strategy based on compounds acting to induce an erection on demand, without modifying the underlying pathologic alterations that lead to ED; and (2) more novel agents ...

During wound healing, myofibroblasts play a central role in matrix formation and wound contraction. At the end of healing, there is evidence that myofibroblasts disappear via apoptotic pathways. Hypertrophic scars are a fibroproliferative disorder that leads to considerable morbidity. It has been postulated that a defect in myofibroblast apoptosis could ...

Wound healing is an integrated and complex process involving a large number of regulatory molecules, including proinflammatory cytokines and growth factors, and an orchestrated tissue response. Dysregulation in cytokine or growth factor expression dramatically alters the normal wound healing process, and blocking the inappropriate production of specific proinflammatory cytokines or ...

This article provides an overview of the role of oxygen in wound healing. The understanding of this role has undergone a major evolution from its long-recognized importance as an essential factor for oxidative metabolism, to its recognition as an important cell signal interacting with growth factors and other signals to ...

Ex vivo engineering of living tissues is a rapidly developing area with the potential to impact significantly on a wide-range of biomedical applications. Major obstacles to the generation of functional tissues and their widespread clinical use are related to a limited understanding of the regulatory role of specific physicochemical culture ...

HYPOTHESIS: Studies indicate that a depressed wound immune function contributes to an increased rate of wound complications and impaired wound healing following trauma-hemorrhage (T-H). Androgen, ie, 5 alpha-dihydrotestosterone, is responsible for producing the depressed systemic cell-mediated immune responses following T-H in males. The aim of the present study was to ...

A large proportion of congenital heart defects result from dysmorphogenesis of valvuloseptal precursors, the endocardial cushions. Intrinsic to formation and maturation of these tissues are developmental changes in cell-cell and cell-extracellular matrix interactions. Interactions between cells and the extracellular matrix play critical roles in modulating cellular processes including proliferation, migration, ...

Healing of cutaneous wounds, which is crucial for survival after an injury, proceeds via a well-tuned pattern of events including inflammation, re-epithelialisation, and matrix and tissue remodelling. These events are regulated spatio-temporally by a variety of growth factors and cytokines. The inflammation that immediately follows injury increases the expression of ...