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Showing papers on "Wound healing published in 1981"


Journal Article
01 Aug 1981-Surgery
TL;DR: These experiments demonstrate that: (1) A hypoxic tissue gradient is mandatory for wound-healing angiogenesis, (2) when the hypoxic gradient is destroyed capillary growth cases, and (3) inspired oxygen concentrations affect the rate and density of capillary Growth.

654 citations


Journal ArticleDOI
TL;DR: The results indicate that fibronectin is a major component present during wound healing, and appears to be type I collagen in the reticular dermis adjacent to the wound area.

465 citations


Journal ArticleDOI
TL;DR: There may be a wavelength-selective influence of coherent light on the metabolic and proliferation processes in wound healing, with the associated problem of the possible carcinogenic effects of laser radiation.
Abstract: • We performed a study to determine whether laser radiation of low-power density would affect the healing of open skin wounds in rats. The wounds were irradiated daily with a helium-neon laser (wavelength, 632.8 nm) and an argon laser (wavelength, 514.5 nm) at a constant power density of 45 mW/sq cm. The rate of wound closure was followed by photographing the wounds in a standardized way. The collagen hydroxyproline concentration in the scar tissue was determined on the 18th postoperative day. Helium-neon laser radiation had a statistically significant stimulating effect on collagen synthesis in the wound, with a maximum effect at an energy density of 4 joules/sq cm. The rate of wound closure was enhanced significantly between the third and 12th postoperative days. The argon laser exposure produced a significant increase in collagen concentration both in irradiated and nonirradiated contralateral wounds. However, an acceleration of the healing rate was not registered in this case. The wound contraction up to the fourth day of the experiment was inhibited under helium-neon and argon laser exposure to 20 joules/sq cm. The described effects were not specific for the laser light. There may be a wavelength-selective influence of coherent light on the metabolic and proliferation processes in wound healing, with the associated problem of the possible carcinogenic effects of laser radiation. ( Arch Surg 1981;116:293-296)

374 citations


Journal Article
TL;DR: Findings are compatible with the hypothesis that fibronectin and fibrin play a role in epithelial migration and temporary adhesion to the surface during corneal wound healing, at a time when the normal anchoring mechanism is lost.

285 citations


Journal Article
TL;DR: Secretion of macrophage-derived growth factor may be relevant to the function of mononuclear phagocytes in several pathologic processes, including the neovascularization and fibroplasia of wound healing, smooth muscle hyperplasia in atherosclerosis, and proliferative glomerulonephritis.
Abstract: Cultured mouse peritoneal macrophages secrete a growth-promoting activity that stimulates 3 types of nonlymphoid mesenchymal cells in vitro: fibroblasts, vascular smooth muscle, and vascular endothelium. Production of this macrophage-derived growth factor (MDGF) is directly related to the number of viable macrophages and their time in culture, and is independent of platelet- or plasma-derived serum growth factors. Treatment of cultured macrophages with latex, bacterial lipopolysaccharide, or phorbol myristate acetate results in increased growth factor activity. Preliminary biochemical characterization of MDGF indicates that it is a heat labile (100 degrees C, 2 min), non-dialyzable protein, which contains at least 1 essential disulfide bond. Growth-promoting activity is not adsorbed by CM-Sephadex chromatography, under conditions that effectively remove platelet-derived growth factor(s). Serine protease activity is not required for the action of MDGF. Secretion of macrophage-derived growth factor may be relevant to the function of mononuclear phagocytes in several pathologic processes, including the neovascularization and fibroplasia of wound healing, smooth muscle hyperplasia in atherosclerosis, and proliferative glomerulonephritis.

267 citations


Journal ArticleDOI
TL;DR: A living skin equivalent is developed, which serves as a skin substitute in experimental animals and comes to resemble normal skin, although it lacks secondary derivatives, the cells for which may in time be available for incorporation into the fabricated tissue.
Abstract: We have developed a living skin equivalent, which serves as a skin substitute in experimental animals. On application it is rapidly vascularized, it inhibits wound contraction, and it is immunologically tolerated and persists for as long as it is allowed to remain in place. It comes to resemble normal skin, although it lacks secondary derivatives, the cells for which may in time be available for incorporation into the fabricated tissue.

224 citations



Journal ArticleDOI
TL;DR: Results suggest that in the re-epithelization of superficial wounds laminin and type IV collagen are not present in the initial epidermal-dermal interaction of the migrating epithelium but that BP antigen may be important in this early interaction.

145 citations


Journal ArticleDOI
TL;DR: Compared to immobilization, progressive exercise markedly enhanced the healing process by inducing a more rapid return of tissue DNA, collagen synthesis, and separation force to within "normal" limits.
Abstract: The purpose of this investigation was to determine whether alterations in physical activity would modify the repair process of ligaments as evaluated by tissue DNA, collagen synthesis, and tensile strength. Compared to immobilization, progressive exercise markedly enhanced the healing process by inducing a more rapid return of tissue DNA, collagen synthesis, and separation force to within "normal" limits. Exercise also significantly increased wet and dry weights of repaired ligaments whereas immobilization markedly decreased these measurements because of the change in total collagen content. However, it remains uncertain whether progressive exercise can cause a shift in the equilibrium rates between collagen synthesis and collagen degradation.

120 citations


Journal ArticleDOI
Tsuneji Suda1, Teruo Nishida1, Y Ohashi1, Shigenori Nakagawa1, Reizo Manabe1 
TL;DR: Investigation in the wounded rabbit cornea after corneal stroma was injured with a sharp knife or after lamellar keratoplasty was performed suggested that fibronectin plays an important role in the stromal wound healing.
Abstract: Fibronectin (FN) is present both in plasma and in extracellular matrix, and is postulated to be involved in wound healing. The appearance of FN was investigated in the wounded rabbit cornea after corneal stroma was injured with a sharp knife or after lamellar keratoplasty was performed. An indirect immunofluorescence technique was employed to detect the presence of FN. Normal, unwounded rabbit cornea showed an intensive fluorescence at Descemet's membrane. Strong specific fluorescence was observed at the edge of a stromal wound and beneath the sliding epithelial cells after non-perforating incisions. These could be detected as early as 3 hours after injury. The fluorescence became the strongest at 6 hours, and then gradually decreased in its intensity, disappearing by about 7 days when epithelial cells entirely filled the stromal wound. In case of lamellar keratoplasty, FN was detected at the interface of the graft and the recipient cornea. These results suggest that FN plays an important role in the stro...

113 citations


Journal ArticleDOI
TL;DR: It is suggested that the effect of mechanical tension alone may initiate formation of myofibroblasts in a tissue.
Abstract: Wound contraction results from the contractile activity of modified fibroblasts, termed myofibroblasts, which are present in the granulation tissue of the healing wound. This study examines the relative role of mechanical tension (stretching) and wound healing as events capable of stimulating the formation of myofibroblasts in mouse skin. The skin of hairless mice was subjected to mechanical stretching and to a small incisional wound either separately or in combination. Animals were killed at intervals between 1 and 6 days and the dermis examined with the electron microscope. Stretching alone produced little evidence of inflammation at any time interval but cells with the ultrastructural characteristics of myofibroblasts were present at 4 days and abundant at 6 days. Skin that had been both stretched and wounded showed a marked inflammatory response and also contained myofibroblasts, but they were less frequent than in the skin subjected to stretching alone. Very few myofibroblasts were evident in skin that had only been wounded. It is suggested that the effect of mechanical tension alone may initiate formation of myofibroblasts in a tissue.

Journal ArticleDOI
TL;DR: Transmission electron microscopy showed that the lamina densa was present across the wound hiatus and the development of desmosomes and hemidesmosomes during wound healing was demonstrated, which supports the hypothesis that the substances at the junctional zone are partly of epithelial origin.
Abstract: Epidermal repair was studied after the induction of a suction blister on human abdominal skin. The investigation was concerned with keratinocyte migration from the epidermal wound margins and changes at the dermo-epidermal junction.

Journal Article
TL;DR: Evidence that plasma proteins support tissue repair by metabolic as well as functional activity and neutralization of the potentially toxic products of the inflammatory response and the inhibition of microbial invasion and colonization is found.
Abstract: In response to injury, the concentrations of several plasma proteins are characteristically altered. In part, these changes reflect an essential contribution of many of these proteins, acting in concert, to the processes involved in wound healing. There is evidence that plasma proteins support tissue repair by metabolic as well as functional activity. Specifically, plasma proteins may directly facilitate wound healing by: provision of carbohydrates, lipids and amino acids in a usable form as biosynthetic precursors and energetic substrates; the transport of trace metal cofactors involved in various wound repair processes; adhesion of regenerating tissue; modulation of the rate of structural protein synthesis; alignment of collagen subunits; organization of cellular elements wound repair; prevention of autoimmune reactions; hormone transport and local modulation of hormonal effects; neutralization of the potentially toxic products of the inflammatory response and the inhibition of microbial invasion and colonization.

Journal ArticleDOI
H. D. Bruhn1, J. Pohl1
TL;DR: It is discussed that thrombin and factor XIII stimulate the proliferation of fibroblasts as growth hormones and regulate in combination with the inhibiting fibronectin the growth of fibROblasts in thrombus organization, would healing and in the arteriosclerotic vessel wall process.
Abstract: The stimulation of fibroblast proliferation by thrombin and factor XIII is accompanied by an intracellular increase of cGMP. In contrast fibronectin inhibits the3H-thymidine uptake of fibroblasts. Pre-treatment of fibroblasts with neuraminidase eliminates the stimulating effect of thrombin completely and induces a shift of the optimum stimulating effect of factor XIII to higher concentrations. It is discussed that thrombin and factor XIII stimulate the proliferation of fibroblasts as growth hormones and regulate in combination with the inhibiting fibronectin the growth of fibroblasts in thrombus organization, would healing and in the arteriosclerotic vessel wall process.

Journal ArticleDOI
TL;DR: The induced resistance response in carrot root slices to Botrytis cinerea, was accompanied by the enhanced accumulation of 6-methoxymellein, p -hydroxybenzoic acid and the polyacetylene falcarinol and the results are discussed in relation to the concentrations of these compounds found during wound healing.
Abstract: The induced resistance response in carrot root slices to Botrytis cinerea , was accompanied by the enhanced accumulation of 6-methoxymellein, p -hydroxybenzoic acid and the polyacetylene falcarinol. Falcarinol concentrations in the surface treated root tissues exceeded ED 50 values against B. cinerea within 12 h of the addition of live spores, reaching 280 μg/g fresh wt; 6-methoxymellein accumulated slowly at first but exceeded ED 50 values by 24 h. Infiltrated p -hydroxybenzoic acid was as effective as pretreatment of the slices with heat-killed conidia in an induction test. There was no evidence of any synergistic effect between the various inhibitors. The results are discussed in relation to the concentrations of these compounds found during wound healing and the possible mechanisms of enhanced accumulation detected in induced slices.

Journal Article
TL;DR: Rapid appearance of fibronectin, its abundance on the second day and gradual diminution upon the activation of type I collagen synthesis indicate its role as a biological guide for localization of cellular activity in wound repair.
Abstract: Fibronectin, an adhesive glycoprotein, was demonstrated with the Cellstic device in healing wounds of 13 children after routine surgery. An indirect immunofluorescent method was adapted to cytological and histological specimens made from the Cellstic sponges 1 to 92 hours after operation. As early as one hour after Cellstic implantation some bright fluorescent spots could be seen in the cytological specimens, although cell morphology still fully resembled to that of peripheral blood. The intensity of the fibronectin fluorescence increased rapidly until the maximum was reached 24-48 hours after surgery. Thereafter the fluorescence gradually decreased to the level of the first hours. Rapid appearance of fibronectin, its abundance on the second day and gradual diminution upon the activation of type I collagen synthesis indicate its role as a biological guide for localization of cellular activity in wound repair.

Journal ArticleDOI
TL;DR: Increased oedema with reduced vascular proliferation and cellular infiltration in the early healing period characterises the response to injury in the diabetic Chinese hamster.
Abstract: Wound healing was examined in normal and diabetic, non-ketotic Chinese hamsters by morphological and morphometric methods. Dermal, perforating wounds were made in the ears of the hamsters and the response to injury was evaluated in tissue biopsies. The response in normal hamsters was characterized by vascular and cellular migration and pronounced infiltration of polymorphonuclear leukocytes into the area closest to the wound (zone 1). The transition region (zone 2) between wounded and non-wounded tissue was infiltrated primarily by fibroblasts and capillaries. In wounds from diabetic hamsters, 8 h after injury, there was less cellular infiltration (fibroblasts 49%, polymorphonuclear leukoytes 48% of control) and vascular proliferation (47% of control). In the late phase of healing (16 h after injury) the vascular (87% of control) and polymorphonuclear leukocyte (103%) responses in diabetic wounds were not significantly different from control in zones 1 and 2. Wounds from diabetic hamsters also showed considerable oedema (143% of control) in zones 1 and 2, which was accompanied by vascular degeneration and necrosis. At 16 h the collagen content of diabetic wounds was also decreased (54% of control). Increased oedema with reduced vascular proliferation and cellular infiltration in the early healing period characterises the response to injury in the diabetic Chinese hamster.

Journal ArticleDOI
TL;DR: It is proposed that the homotypic contacts between cells of the columnar epithelium are involved in the intercellular interactions controlling pattern regulation in the imaginal wing disc.
Abstract: The normal elements of the cell surface and the cytoskeleton of imaginal wing disc cells in third-instar larvae of Drosophila melanogaster are described. This serves as a background for understanding the process of wound healing after experimentally cutting the two disc epithelia (columnar epithelium and peripodial membrane). The cells of both epithelial layers display microvilli at the apical surface, and there is a microvillar ridge at the periphery of each cell. The lateral cell surfaces display zonulae adhaerens, gap junctions, and septate junctions in characteristic patterns. A terminal web of 60–70-A microfilaments is located in the apical cell periphery, extends into the microvillar ridge, and is connected with the zonula adhaerens and probably also with the underlying belt of microtubules. Immediately after an incision is made in a normal disc, the two wound edges move apart to form a gape of about 45°. This fast wounding reaction is reversibly inhibited by treatment with cytochalasin B (0.5 μg/ml), suggesting that the wounding reaction is achieved by actinlike microfilaments. Initial wound closure results in an apposition of the columnar epithelium and the peripodial membrane (heterotypic contacts). Close (10–20 nm) heterotypic membrane contacts are found beginning at 12 hours after wounding, but cell junctions are not observed at such contact sites. Within 24 hours after wounding, the first focal cell membrane contacts are made between cells of corresponding epithelial types across the wound (homotypic contacts), at which time the heterotypic contacts are broken. At the time of epithelial healing, the wound surfaces shorten (“wound contraction”), and this is associated with cell-shape changes within the epithelial cells along the wound. Within 48 hours after wounding, homotypic cell junctions and nonjunctional membrane contacts are fully reestablished, and wound healing is completed. We propose that the homotypic contacts between cells of the columnar epithelium are involved in the intercellular interactions controlling pattern regulation in the imaginal wing disc.


Journal ArticleDOI
TL;DR: Control of collagen deposition and collagenolysis in the eye, lung, kidney, and around joints that are affected by rheumatoid arthritis will be possible in the next few years.
Abstract: • Research in wound-healing biology has reached the developmental or practical application stage in the following major areas: reduction of liver collagen, prevention of secondary remodeling of peritoneal fibrous adhesions to produce tendinous bands that cause mechanical intestinal obstruction, reduction in the amount of scar tissue on the surface of the skin, alteration of mechanical properties of restricting a scar on gliding surfaces, and prevention of conduit stenosis after a circumferential internal injury. Pharmacologic agents, such as β-aminopropionitrile, penicillamine, and colchicine, are being used as adjuvants to familiar surgical techniques. Control of collagen deposition and collagenolysis in the eye, lung, kidney, and around joints that are affected by rheumatoid arthritis will be possible in the next few years. ( Arch Surg 1981:116:1325-1329)

Journal ArticleDOI
TL;DR: It is the impression that, as traction membranes develop, there is not so much an increase in the contractile elements of the constituent cells as a rearrangement of the existing cytoplasmic microfilaments into compact highly organised bundles called stress cables.
Abstract: A combined ultrastructural and immunofluorescent study was conducted on experimentally induced fibrous membranes in the vitreous of adult rabbits. Autochthonous tissue cultured fibroblasts were injected into the mid-vitreous of one eye of each of 25 rabbits. The animals were monitored routinely with an ophthalmoscope and slit-lamp and were killed at various time periods between 5 minutes and 6 months. Appropriate tissue was taken for light microscopy, transmission electron microscopy, scanning electron microscopy, and indirect immunofluorescence. With this model we were able to show that the contractile elements in fibrous membranes are probably modified fibroblasts called myofibroblasts which are most abundant 3 to 6 weeks after injection. This is the time when retinal detachment usually occurs. It is our impression that, as traction membranes develop, there is not so much an increase in the contractile elements of the constituent cells as a rearrangement of the existing cytoplasmic microfilaments into compact highly organised bundles called stress cables. The behaviour and ultrastructural characteristics of intravitreal fibroblasts compare with the action of fibroblasts in the healing of wounds.

Journal ArticleDOI
TL;DR: Findings suggest that the biochemical changes in the wounds of jaundiced animals interfere with wound repair and the possible causes of this delay in healing and its clinical implications require further investigation.
Abstract: The effect of obstructive jaundice on wound healing was investigated in an experimental study of gastric and abdominal wounds in rats after ligation and division of the common bile duct. The healing of a parietal defect in these animals showed histologic evidence of delayed healing compared with controls. The bursting strength of the abdominal incision was also decreased, but not that of the stomach. These findings suggest that the biochemical changes in the wounds of jaundiced animals interfere with wound repair. The possible causes of this delay in healing and its clinical implications require further investigation.

Journal ArticleDOI
TL;DR: Compared the effects of equipotent anti-inflammatory doses of flurbiprofen and of prednisolone acetate on the inflammation and the healing (as measured by the wound bursting pressure) or 4-mm through-and-through incisions treated four times a day for ten postoperative days, the results suggest that flurbIProfen
Abstract: • Flurbiprofen is a nonsteroidal anti-inflammatory (NSAI) agent currently undergoing clinical investigation. Anti-inflammatory steroids have long been known to delay the healing of corneal stromal wounds. This study was designed to compare the effects of equipotent anti-inflammatory doses of flurbiprofen and of prednisolone acetate on the inflammation and the healing (as measured by the wound bursting pressure) of 4-mm through-and-through incisions treated four times a day for ten postoperative days. The results suggest that flurbiprofen and prednisolone are not different in their effect on both postoperative inflammation and postoperative wound healing. Since NSAI agents and steroids inhibit prostaglandin formation at different enzymatic steps, it is possible that prostaglandins not only are responsible for postoperative inflammation but also are required for postoperative wound healing.

Journal ArticleDOI
TL;DR: The reproduction of the Merkel cell in the regenerative epithelium seemed to be independent of the undifferentiated neuroectodermal tissue.
Abstract: Merkel cell development was studied in the regenerative labial mucous membrane of adult rabbits. Fullthick wounds were made on the inferior labial mucous membrane of the rabbits, then the regenerative mucous membrane was examined by electron and light microscopy at time intervals of 2, 7, 10, 14, 21 and 30 days after the injury. By 7 days, the regenerative area of the mucous membrane was replaced with a dense lamellar connective tissue, which was mainly composed of alternately arranged collagen fiber layers and fibroblasts, and an overlying stratified squamous epithelium. No Merkel cell was found 7 days after the injury. Ten days after the injury, a few very immature Merkel cells were identified in the regenerative epithelium. The Merkel cells increased in number and matured in structure during the course of the following regenerative period. Thirty days after the injury, the wounded area healed without forming a scar tissue, and the regenerated epithelial ridges usually included regular type Merkel cells. As adult animals were used in this experiment, the reproduction of the Merkel cell in the regenerative epithelium seemed to be independent of the undifferentiated neuroectodermal tissue.

Journal ArticleDOI
TL;DR: The author's methods for the treatment of rhinophyma are described, consisting of highly concentrated human fibrinogen which is clotted with a thrombin solution, and postoperative wound healing is accelerated and cosmetic results are excellent.
Abstract: The author's method for the treatment of rhino-phyma is described. Nasal lesions are removed in a three-step procedure. The resultant wound surfaces are sealed with fibrin sealant, consisting of highly concentrated human fibrinogen which is clotted with a thrombin solution. The resultant fibrin clot adheres firmly to the wound surface. Spot-bleeding from numerous small vessels is controlled by sealant application. Postoperative wound healing is accelerated and cosmetic results are excellent.

Journal ArticleDOI
TL;DR: Differences in vascular perfusion within and surrounding the site of burn and freeze injury are described and it is suspected that factors released from the burned matrix account for some of these differences in pattern of vascular perfusions.

Journal ArticleDOI
TL;DR: The healing mechanism following a small would produced by pricking the anterior center of a Swiss Webster mouse lens with a glass needle was studied histologically and showed a relatively slow wound healing.


Journal ArticleDOI
27 Aug 1981-Nature
TL;DR: Evidence is presented that infection of cultures of BALB/c 3T3 cells with mycoplasmas results in the accumulation of high levels of collagenase in the medium, indicating an important regulatory role in tissue remodelling, wound healing and ageing.
Abstract: The turnover of collagen, the major protein of the body, is controlled by the rate of collagen synthesis and the activity of collagenase, a highly specific protease which initiates collagen degradation Because collagen is largely resistant to other proteases, collagenase is believed to have an important regulatory role in such normal processes as tissue remodelling, wound healing and ageing In addition, the regulation of the activity of collagenase may be altered in diseases of connective tissue, particularly rheumatoid arthritis, and in malignant invasion and metastasis Collagenase is an extracellular enzyme, and thus it has been necessary to study its regulation in cells maintained in tissue culture, by measuring accumulation of the secreted protein in the culture medium In this way, collagenases have been isolated from many tissues and cells1–7 Little is known about the modulation of collagenase synthesis and secretion, but various treatments have been reported that induce its secretion in mammalian cells in monolayer culture8–17, possibly by a mechanism involving membrane perturbation We report here the production and secretion of collagenase by BALB/c 3T3 fibroblasts Their ability to synthesize collagen18,19 has been extensively studied, but there has been no previous report of their collagenolytic activity During studies of collagenase activity in BALB/c 3T3 cells, we noted that certain cultures had greatly increased enzyme activity corresponding to cultures in which contamination with mycoplasmas had been detected during routine assay Here we present evidence that infection of cultures of BALB/c 3T3 cells with mycoplasmas results in the accumulation of high levels of collagenase in the medium

Journal ArticleDOI
TL;DR: It is concluded that DPC wound have a higher blood-flow, especially in the initial wound healing phase, which supports the hypothesis that an increased blood-flowing during early wound healing is beneficial for the development of mechanical strength in the maturing normal scar.
Abstract: In an earlier study delayed primary closure (DPC) wounds were shown to develop higher biomechanical strength than primary closure (PC) wounds. In order to elucidate the underlying mechanism, local clearance of 133Xenon and thermography studies were undertaken. A paired comparison design with deposits of 133Xenon injected in the wound margins 3 and 4 days postoperatively, and directly into the wound tissue 10, 20 and 60 days postoperatively was used. Very pronounced differences, with higher blood-flows for DPC wounds, were found in the early measurements. In the later measurements there were significant but less obvious differences. With thermography no differences could be detected. It is concluded that DPC wound have a higher blood-flow, especially in the initial wound healing phase. This supports the hypothesis that an increased blood-flowing during early wound healing is beneficial for the development of mechanical strength in the maturing normal scar.