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PubMed1984

Regeneration-induced lengthening of the cut ends of the rat colon.

The transected colon was studied in rats in an attempt to determine whether the regenerating cut ends could be induced to lengthen by delaying or preventing their spontaneous reattachment. When the two cut ends of the defunctionalized colon were separated by a 2-3-cm length of silastic tubing mucosal, luminal and serosal continuity across the gap was restored in 8-10 weeks. Cannulation of one cut end with silastic tubing so placed as to extend 2-3 cm beyond the cut end led to lengthening of the intestine over the exposed end of the tubing by 20 weeks. The area subadjacent to regenerated mucosa filled initially with granulation tissue which was gradually replaced by loose connective tissue containing at times a thin layer of smooth muscle.

Animals↗
PubMed1991

Power drills to fenestrate exposed bone to stimulate wound healing.

Power drills can be used to stimulate the formation of granulation tissue over exposed cortical bone. These tools allow for the rapid fenestration and selective abrasion of large areas of exposed bone; fenestration and abrasion create the multiple bleeding points essential for the production of granulation tissue. The granulation tissue thus produced is allowed to grow out through the holes to cover bone. This procedure can be performed in an outpatient setting, usually without the need for either local or general anesthesia; it is particularly useful for patients considered to be poor risks for general anesthesia. Healing by granulation tissue is a somewhat slow process, but it has a high success rate, causes few complications, and produces very good cosmetic results. Two cases illustrate the method of fenestration of exposed cranial bone to stimulate granulation tissue. Specific instructions describe the needed care of exposed bone.

Aged↗
PubMed2001

Microcirculation is similar in ischemic and venous ulcers.

Microcirculation of 15 ischemic and 15 venous ulcers, their scars, and intact surrounding skin were examined in order to demonstrate their similarities in the development and healing process. Subpapillary and nutritive perfusion of four areas were investigated by a laser Doppler perfusion imager (arbitrary units) and capillary microscopy (capillaries/mm2): one ulcer area without granulation tissue (no wound healing) and one with granulation tissue (ulcer healing); one skin area adjacent to the ulcer (1-8 mm) (scar developed from ulcer areas) and one distant (12-25 mm; intact skin). Areas without granulation tissue in ischemic and venous ulcers were similar, demonstrating a lack of capillaries (0.13 +/- 0.52; 0.93 +/- 2.09) and low laser Doppler flux (0.81 +/- 0.69; 1.47 +/- 1.17; P > 0.05 for each). In granulation tissue of both ulcers there was a tendency to a higher capillary density (0.67 +/- 1.40; 5.60 +/- 2.32; P < 0.0001 for venous ulcers) and a higher laser Doppler flux (1.15 +/- 0.67; 4.04 +/- 1.62; P < 0.0001 for venous ulcers) than in areas without granulation tissue. In scars of ischemic and venous ulcers capillary density (8.18 +/- 8.84; 13.60 +/- 5.45) and laser Doppler flux (1.72 +/- 1.00; 1.94 +/- 1.45) were similar (P > 0.05). In skin distant from ischemic ulcers very high capillary density (24.63 +/- 1.89) was associated with low laser Doppler flux (0.99 +/- 0.59); distant from venous ulcer capillary density was moderate (10.47 +/- 3.42) while laser Doppler flux was high (3.77 +/- 1.62; P < 0.0001 between both groups). The development and healing process of ischemic and venous ulcers is similar. Nutritive and subpapillary perfusion are involved in ulcer healing. In intact skin surrounding ischemic and venous ulcers, microcirculation is different due to the underlying pathophysiology.

Aged↗
PubMed1996

The effect of tumor necrosis factor-alpha on wound healing. An experimental study.

The inflammatory phase in wound healing is considered to be a preparatory process for the formation of new tissue. A monocyte-derived cytokine, tumor necrosis factor-alpha (TNF-alpha), is a highly conserved molecule known to play a major role in the pathogenesis of gram-negative shock. Besides this, previous experimental studies show that TNF-alpha may have either a beneficial or detrimental role in wound healing. The purpose of the present study was to examine the effects of TNF-alpha on developing granulation tissue in rats as well as on rat and human granulation tissue cells in culture. Subcutaneously implanted cylindrical hollow sponges were used for studying the effects of locally applied TNF-alpha on granulation tissue in rats. These implants were treated either on the day of implantation or for the first 4 or 7 days after implantation with a solution containing various amounts of TNF-alpha while the control implants were treated correspondingly with the carrier solution only. The analyses of the granulation tissue were carried out 4, 7, 14 and 21 days after implantation. In the histological specimen these sponges were cut into small pieces and stained with Weigert van Gieson to visualize collagen. The amount of granulation tissue grown into the sponge was calculated from the cross section of every sponge. For the cell culture studies fibroblasts were released from human and rat granulation tissue which was cut into small pieces and digested by collagenase and DNase in Hank's balanced salt solution. The cells were exposed to 1, 10, or 100 ng/ml of TNF-alpha and the rate of collagen synthesis was measured as synthesis of protein-bound 3H-hydroxyproline. The number of cells in the culture dishes was counted with Bürger's hemocytometer after detaching the cells with trypsin treatment. As interleukin-1 (IL-1) and TNF-alpha overlap in many of their functions, the effects of lipopolysaccharide (LPS), human interleukin 1 beta (IL-1) and prostaglandin E2 (PGE2) on experimental granulation tissue in rats as well as on rat granulation tissue cells in culture were studied with the same method. After a single application of TNF-alpha into the sponge, no essential differences between the groups were detected. However, after daily applications of TNF-alpha for 4 days, an inhibitory effect on tissue repair was observed after 4 and 7 days. Collagen formation, indicated by the hydroxyproline content of the sponge, was significantly lower in the group treated with TNF-alpha than in the controls. This effect was not observed after 14 or 21 days. These findings were confirmed in the histological samples. In the cultures of rat granulation tissue fibroblasts TNF-alpha decreased 3H-hydroxyproline production to about 75% of that in the controls and it had also a decreasing effect on pro alpha 1(I) and pro alpha 1(III) collagen mRNA levels maximally by 67% and 77% of the control level, respectively. In the cultures of human granulation tissue fibroblasts a similar inhibiting effect on the production of collagen was seen. TNF-alpha decreased the production of 3H-hydroxyproline to 56% of the control value with a dose of 100 ng/ml. Similarly, IL-1 beta decreased hydroxyproline content of granulation tissue seven days postoperatively and PGE2 decreased nonsignificantly the amounts of hydroxyproline but the steady-state levels of pro alpha 1(I) and pro alpha 1(III) collagen chain mRNAs were slightly elevated. In the IL-1 beta-treated fibroblast cultures collagen production decreased by 15% compared with that of the controls. PGE2 decreased collagen production by 34% of that in the controls. This effect could be abolished with indomethacin. Indomethacin alone stimulated collagen production by 40%. In vivo IL-1 decreases the formation of normal granulation tissue. This effect may be partly due to IL-1 stimulated secretion of PGE2.

Animals↗
PubMed2005

[Experimental-clinical grounds for the treatment of granulating soft tissue wounds by the wound edge approximating stapler].

Factors of risk of the appearance of wound complications were studied in experiment on a model of granulating wounds in 18 mongrel dogs. A traditional method (control group) and an apparatus method (main group) were used for suturing the wounds. In the main group of animals suturing the wounds was performed after bringing together the wound edges by specially designed devices. Morphological and microbiological investigations have shown that the leading role in the appearance of complications belongs to the morphological substrate of the wound with the main component including the degree of traumatizing the paravulnerable tissue with a suture thread when connecting the wound edges by a traditional method, ischemia of the paravulnerable tissues under conditions of microbial dissemination. The introduction of the developed method of closing the soft tissue granulating wounds into clinical practice resulted in a statistically significant reduction of pyo-inflammatory complications in the main group of patients. A conclusion is made on a more favorable course of the wound process when using the apparatus method of closing the wounds.

Animals↗
PubMed2001

Interferon-gamma-induced inhibition of wound healing in vivo and in vitro.

This work was undertaken to study the effects of various doses of interferon-gamma (IFN-gamma) on developing granulation tissue in rats and on granulation tissue-derived fibroblasts in culture. For in vivo studies cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In the test groups the implants were injected daily for four days with a solution containing 160, 800, 4000, or 20000 units of IFN-gamma while the implants of the control group were treated correspondingly with the carrier solution only. Analyses of granulation tissue in the sponge cylinders, carried out 7 days after implantation, showed an IFN-gamma-related decrease in the formation of new granulation tissue. The largest, dose-dependent effect was seen in the accumulation of collagen. For in vitro studies, cultures of rat granulation tissue fibroblasts were treated with 100, 500, 1000, or 5000 units/ml of IFN-gamma. IFN-gamma decreased collagen synthesis to about 50 per cent of that in controls. IFN-gamma treatment also decreased type I procollagen mRNA levels maximally by 41 per cent from the control level. It is concluded that IFN-gamma inhibits the formation of new granulation tissue by decreasing collagen synthesis.

Animals↗
PubMed2001

Interferon-gamma-induced inhibition of wound healing in vivo and in vitro.

This work was undertaken to study the effects of various doses of interferon-gamma (IFN-gamma) on developing granulation tissue in rats and on granulation tissue-derived fibroblasts in culture. For in vivo studies cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In the test groups the implants were injected daily for four days with a solution containing 160, 800, 4000, or 20000 units of IFN-gamma while the implants of the control group were treated correspondingly with the carrier solution only. Analyses of granulation tissue in the sponge cylinders, carried out 7 days after implantation, showed an IFN-gamma-related decrease in the formation of new granulation tissue. The largest, dose-dependent effect was seen in the accumulation of collagen. For in vitro studies, cultures of rat granulation tissue fibroblasts were treated with 100, 500, 1000, or 5000 units/ml of IFN-gamma. IFN-gamma decreased collagen synthesis to about 50 per cent of that in controls. IFN-gamma treatment also decreased type I procollagen mRNA levels maximally by 41 per cent from the control level. It is concluded that IFN-gamma inhibits the formation of new granulation tissue by decreasing collagen synthesis.

Analysis of Variance↗
PubMed1998

The 9E3/CEF4 gene product is a chemotactic and angiogenic factor that can initiate the wound-healing cascade in vivo.

The chicken gene 9E3/CEF4 codes for a 9-kDa protein that belongs to the C-X-C family of chemokines. This gene is stimulated to high levels by thrombin, and is overexpressed in the granulation tissue of wounds, especially in areas of neovascularization, suggesting that it is importantly involved in wound healing. The authors used the Chorioallantoic Membrane (CAM) assay to examine experimentally the functions of the 9E3 chemokine in vivo. It was shown that at lower doses this protein is chemotactic for monocyte/macrophages and lymphocytes (but not heterophils), and directly or indirectly stimulates the growth of blood vessels towards the pellet containing the protein, causes hyperproliferation of the ectoderm of the CAM, and formation of a tissue that resembles the granulation tissue of wounds. At higher doses, however, it does not stimulate chemotaxis of leukocytes but instead causes the blood vessels of the CAM to undergo sprouting. It was also shown that this protein is found in the endothelial cells of developing blood vessels but not in those of mature blood vessels and that, in the latter, expression can be stimulated by application of agents that cause inflammation or are known to be angiogenic. Because the product of the 9E3 gene has chemotactic and angiogenic properties, it is proposed that it be called the chicken Chemotactic and Angiogenic Factor (cCAF). These observations show that in the absence of wounding, cCAF, by itself, can initiate a complex series of events that strongly resemble those involved in the immune response and granulation tissue formation, suggesting an important role for this and related chemokines in wound healing. Although this chemokine belongs to the C-X-C family it can perform functions of both the C-C (chemotaxis for monocyte/macrophages and lymphocytes) and C-X-C (angiogenesis) families, suggesting that this could be the first of a functionally broader family of chemokines which would be generated as a response to emergency situations.

Allantois↗
PubMed1986

The evolution of lesions in erythema elevatum diutinum.

We obtained biopsies from early, fully developed, and late lesions of erythema elevatum diutinum (EED) in a 49-year-old man. The histologic and electron-microscopic findings were compared with those reported in the literature and three other cases from our files. Early lesions show leukocytoclastic vasculitis with capillary proliferation. Later lesions show vasculitis, dermal aggregates of neutrophils, fibrosis, and areas of granulation tissue. Newly formed vessels in granulation tissue may be more susceptible to damage by immune complexes, and the early formation of granulation tissue in EED may prevent an early resolution of vasculitis. Damage to dermal connective tissue in EED incites either scarring or, rarely, a fibrohistiocytic proliferation. Ultrastructural examination of one case showed histiocytes with myelin figures and intracellular lipid and cholesterol.

Erythema↗
PubMed2001

Ocular surface reconstruction in LOGIC syndrome by amniotic membrane transplantation.

PURPOSE: To determine whether preserved amniotic membrane can be used to reconstruct the ocular surface after excision of the invading granulation material typical of LOGIC syndrome (laryngeal and ocular granulation tissue in children from the Indian subcontinent). METHODS: Granulation tissue was dissected and excised from both eyes of a 10-year-old boy with LOGIC syndrome. This procedure was followed by coverage of the corneal, scleral, and subtarsal regions of each eye with amniotic membrane, which had been stored for 6 months at -70 degrees C. RESULTS: Initial 2.5-month follow up demonstrated complete disappearance of granulation tissue. The fornices were patent, there was no recurrence of symblepharon, ocular inflammation was suppressed, and the patient reported markedly increased comfort. Both eyelids remained ptotic because of levator muscle atrophy secondary to many years of inability to open either eye. No residual scarring or evidence of granulation tissue was observed in that period. The 10-month follow up demonstrated limited recurrence, particularly where there was an intraoperative break in the amniotic membrane. CONCLUSIONS: After 24 operations to treat the ocular complications induced by LOGIC syndrome, amniotic membrane transplantation was the first effective treatment. In the early follow up period (2-3 months), there was complete cessation of the proliferation of granulation tissue and reepithelialization of the corneal surface. Longer follow up (10 months) demonstrated limited recurrence, which will require retreatment.

Amnion↗
PubMedDate not supplied

Interactions between tissues engaged in wound repair and skeletal muscle regeneration.

Enhanced accumulation of granulation tissue in a wound healing model was observed in the presence of regenerating skeletal muscle. This study characterized the tissue accumulated in the normal wound healing and regeneration-adapted models. DNA, RNA, total protein, collagen, and noncollagen protein content, and protein:DNA and noncollagen protein:collagen ratios were determined using standard methods. DNA did not differ; but RNA increased and total protein decreased compared to early granulation tissue. Mean protein: DNA ratio was lower in regeneration-associated granulation tissue compared to age-matched normal and early granulation tissue. Collagen was reduced and noncollagen protein was increased in tissue surrounding regenerating muscle, yielding an elevated noncollagen:collagen ratio. The relative cellularity of granulation tissue was enhanced and collagen deposition potentially reduced, when accompanied by regeneration. Factors from a regeneration environment can interact with cells engaged in wound repair and potentially alter their behavior.

Animals↗
PubMed2003

The systemic immune response is more prominent than the mucosal immune response in the pathogenesis of periodontal disease.

BACKGROUND/AIM: The diseased periodontium appears to express features of a systemic and a mucosal immune response. Our aims were to determine differences in immunoglobulin expression between gingivitis and periodontitis lesions and to ascertain whether immune and inflammatory cells were recruited into the diseased periodontium by the mucosal addressin adhesion molecule (MAdCAM-1). METHODS: In situ hybridization and immunohistochemistry were used to detect the expression of chemokines, adhesion molecules and immunoglobulins in tissue sections of gingival and granulation tissues excised from periodontitis-affected sites and of healthy tissue and gingivitis-affected tissue excised during crown-lengthening procedures. RESULTS: Greater numbers of plasma cells were observed in periodontitis gingival/granulation tissue lesions compared with gingivitis lesions. While IgA1 were predominant in all lesions, IgA2 and J-chain expressing plasma cells were present in increased proportions in gingival tissues compared with granulation tissue. Intracellular adhesion molecule-1 (ICAM-1) was higher in periodontitis than in gingivitis and interleukin-8 mRNA was higher in lesions with a pronounced neutrophil infiltrate. Vascular cell adhesion molecule-1 (VCAM-1) localized to the deep connective tissue and indicated the presence of a systemic type of immune response in this region. Periodontal tissues (n=71 biopsies) did not appear to express MAdCAM-1, in positive control sections of small intestine where it was detected. CONCLUSION: Overall, the systemic-type immune response is predominant, and although the mucosal immune response is minor and limited to the superficial tissues it may have an important role in the host defense to periodontal pathogens.

Adult↗
PubMedDate not supplied

Effect of sharp debridement using curette on recalcitrant nonhealing venous leg ulcers: a concurrently controlled, prospective cohort study.

The objective of this study was to evaluate the effect of sharp debridement on the progression of recalcitrant chronic venous leg ulcers (CVLU) and to assess the feasibility of performing this procedure in an outpatient setting. We performed a prospective study of 55 CVLU (53 patients) over a 12-month period. The study group, which underwent debridement, contained 28 CVLU whose wound beds had slough, nonviable tissue, and no granulation tissue. The control group was 27 CVLU with minimal (15-20%) granulation tissue, but no slough or nonviable tissue. Treatments were otherwise similar. Age, body mass index, mean ulcer surface area (MSA) and mean ulcer duration were comparable in both groups. Ulcer measurements were taken at 4 weeks before debridement, at the time of debridement, and 4 and 20 weeks post-debridement. There was no change in the MSA from 4 weeks before to the time of debridement in either group. At 4 weeks post-debridement, the study ulcers showed a 6 cm(2) reduction in the MSA vs. a 1 cm(2) reduction in controls (P = 0.02). By week 20 post-debridement, the study ulcers achieved a 7.4 cm(2) reduction in the MSA vs. an increase of 1.3 cm(2) in controls (P = 0.008). Between weeks 8 and 20 post-debridement, 16% of study ulcers vs. 4.3% of control ulcers achieved complete healing. Infection rates and antimicrobial usage were similar. We conclude that sharp debridement is effective in stimulating healing of recalcitrant CVLU. It is safe, well tolerated, and can be performed in an outpatient setting.

Aged↗
PubMed1988

[Temporary skin replacement with lyophilized swine skin and foam substances--comparative experimental studies].

Using the skin replacement materials Corethium 2, Coldex, Epigard and SYSpur-derm, both fresh wound and wounds up to 6 days old were covered in rats. The histological work-up 1-7 days later showed material-dependent differences in the wound reaction. Under Corethium 2, a heavy layer of wound exudate formed on the first day both on fresh and granulating wound surfaces. Beneath this layer granulation tissue formed that was of regular thickness and well vascularized, filling the defect. Reepithelialization of the wound surface was not hindered by the material. In contrast, a strong connection was established between the wound base and the covering material when using the three foam substances Coldex, Epigard and SYSpur-derm, through the formation of granulation tissue. This process was dependent on the age of the wound. Thickening of the granulation tissue under the covering material was suppressed by the foam substances. Reepithelialization of the surface of the wound was disturbed by the growth of granulation tissue. The netlike structure of Epigard and the properties of the cover layer (fluid-resistant and protective against bacteria) make it possible for the granulation tissue to infiltrate evenly in the whole area of the wound covering and permit growth within the material right up to the surface. In addition to granulation tissue, epithelium also grows into the foam and spreads evenly. Epigard is suitable for long-term covering of large wounds. SYSpur-derm has a different fine structure than Epigard, which hinders the growth of granulation tissue, so that there are only cone-shaped connections between the wound base and the covering material. Rapid desiccation of the wound exudate cannot be prevented. Leukocytes and granulation tissue cannot spread in the foam. With SYSpur-derm an intermediate layer of wound exudate was observed more frequently than with Epigard. SYSpur-derm should be changed regularly in order to remove the detritus and exsudate from the wound. In comparison with polyurethane foam material the polyvinyl-alcohol foam (Coldex) was more complicated to handle, did not adapt as well to the wound, and dried up within a few hours. Between the base of the wound and Coldex, an intermediate layer often formed and, because of the rapid drying-out process, there was appreciably less infiltration with leukocytes and granulation tissue than with SYSpur-derm. With Coldex, as a rule the granulation tissue was more generously vascularized than in the other three materials.

Animals↗
PubMed2002

Inhibition by acharan sulphate of angiogenesis in experimental inflammation models.

1. The effects of acharan sulphate, a glycosaminoglycan isolated from the giant African snail Achatina fulica, on angiogenesis in the granulation tissue were analysed using an air pouch-type carrageenin-induced inflammation model in rats and a cotton thread-induced inflammation model in mice. 2. In the carrageenin-induced inflammation model in rats, intra-pouch injections of acharan sulphate (5 and 50 micro g) inhibited the pouch fluid accumulation and the granulation tissue formation as well as the angiogenesis in the granulation tissue at day 6 in a dose-dependent manner. 3. The inhibitory effects of acharan sulphate at 50 micro g on the pouch fluid accumulation and the leucocyte infiltration into the pouch fluid was not so effective as that of the cyclo-oxygenase inhibitor indomethacin at 100 micro g, but the inhibitory effects of acharan sulphate at 50 micro g on the granulation tissue formation and angiogenesis in the granulation tissue were almost the same as those of indomethacin at 100 micro g. 4. Acharan sulphate did not affect levels of vascular endothelial growth factor (VEGF) in the granulation tissue and in the pouch fluid at day 6, but indomethacin significantly lowered them. 5. In the cotton thread-induced inflammation model in mice, injections of acharan sulphate (10 micro g) at the site of the cotton thread implantation inhibited the granulation tissue formation and angiogenesis as indomethacin (20 micro g) did. Acharan sulphate (10 micro g) did not affect levels of VEGF in the cotton thread-induced granulation tissue at day 5, but indomethacin (20 micro g) significantly lowered them. 6. In culture of human vascular endothelial cells, acharan sulphate at 10 and 100 micro g ml(-1) inhibited VEGF-induced capillary tube formation. 7. These findings suggest that the inhibitory effect of acharan sulphate on angiogenesis in carrageenin- and cotton thread-induced granulation tissues is not due to the inhibition of VEGF protein induction, but is due to the inhibition of VEGF-induced vascular tube formation.

Animals↗
PubMedDate not supplied

Delayed wound healing in aged rats is associated with increased collagen gel remodeling and contraction by skin fibroblasts, not with differences in apoptotic or myofibroblast cell populations.

Aging has been anecdotally reported to result in prolonged wound healing. Measurement of punch biopsy wound closure in young (4 month old) and old (36 month old) rats indicated there was a significant delay in wound closure by old rats during the early phase of repair, after which closure rates were equivalent. The delay in granulation tissue accumulation in older animals could involve premature programmed cell death (apoptosis); however, apoptotic fibroblasts in sponge granulation tissue and tissue culture were less abundant in samples from old rats relative to young rats. Myofibroblasts express alpha-smooth muscle actin, and they are believed to be important in wound contraction. There were no significant differences in overall abundance or distribution of alpha-smooth muscle actin containing myofibroblasts in granulation tissue and in cultured granulation tissue fibroblasts regardless of the age of the donor rat. The spatial distribution of myofibroblasts and apoptotic cells was distinct. Fibroblasts from granulation tissue and skin explants were placed in a collagen gel contraction assay prior to the 5th passage to determine their in vitro contractility. While granulation tissue fibroblasts from young and old rats showed similar collagen gel contractility, skin fibroblasts from old rats displayed greater collagen gel contractile behavior than young skin fibroblasts. Greater gel contractility of fibroblasts from old rats appeared to result, in large part, from the ability of those cells to cause generalized gel degradation. Gelatin zymography indicated a greater abundance of matrix metalloproteinase-2 in supernatants from gels containing skin fibroblasts from old rats. Taken together, these results suggest that the age-associated healing delay in the rat may not be related to the appearance or abundance of distinct myofibroblast or apoptotic cell populations. Proteolysis may have a significant role in delayed wound healing in aged animals.

Age Factors↗
PubMed2003

Effect of substance P on gene expression of transforming growth factor beta-1 and its receptors in rat's fibroblasts.

OBJECTIVE: To investigate the effect of substance P (SP) on gene expression of transforming growth factor beta-1 (TGFbeta-1), transforming growth factor receptor-1 (TGFR-1) and transforming growth factor receptor-2 (TGFR-2) in fibroblasts cultured in vitro from rat's granulation tissues. METHODS: The fibroblasts from the granulation tissues in the skeletal muscle of rat's hind limbs injured by formaldehyde were cultured in vitro. When different concentrations (10(-9)-10(-5) mol/L) of SP were added into the culture medium, the changes of gene expression of TGFbeta-1, TGFR-1 and TGFR-2 in the cultured fibroblasts were observed with reverse transcription polymerase chain reaction at different intervals (0, 3, 6, 12 and 24 hours after incubation). RESULTS: The gene expression of TGFbeta-1, TGFR-1 and TGFR-2 in the fibroblasts cultured from rat's granulation tissues was up-regulated by SP. The peak level of the mRNA expression was found at 10(-8) mol/L SP and the up-regulation effect was not found at 10(-5) mol/L and 10(-6) mol/L. The peak levels of gene expression of TGFbeta-1, TGFR-1 and TGFR-2 in the fibroblasts treated with SP were achieved at 6 and 12 hours, respectively. CONCLUSIONS: SP has up-regulation effect on the gene expression of TGFbeta-1, TGFR-1 and TGFR-2 in fibroblasts from rat's granulation tissues in vitro, and the effect is related to different stimulating concentrations of SP. It may be concerned with proliferation and differentiation of fibroblasts and formation of scar tissues during wound healing.

Analysis of Variance↗
PubMed2000

Angiogenesis in wound healing.

During wound healing, angiogenic capillary sprouts invade the fibrin/fibronectin-rich wound clot and within a few days organize into a microvascular network throughout the granulation tissue. As collagen accumulates in the granulation tissue to produce scar, the density of blood vessels diminishes. A dynamic interaction occurs among endothelial cells, angiogenic cytokines, such as FGF, VEGF, TGF-beta, angiopoietin, and mast cell tryptase, and the extracellular matrix (ECM) environment. Specific endothelial cell ECM receptors are critical for these morphogenetic changes in blood vessels during wound repair. In particular, alpha(v)beta3, the integrin receptor for fibrin and fibronectin, appears to be required for wound angiogenesis: alpha(v)beta3 is expressed on the tips of angiogenic capillary sprouts invading the wound clot, and functional inhibitors of alpha(v)beta3 transiently inhibit granulation tissue formation. Recent investigations have shown that the wound ECM can regulate angiogenesis in part by modulating integrin receptor expression. mRNA levels of alpha(v)beta3 in human dermal microvascular endothelial cells either plated on fibronectin or overlaid by fibrin gel were higher than in cells plated on collagen or overlaid by collagen gel. Wound angiogenesis also appears to be regulated by endothelial cell interaction with the specific three-dimensional ECM environment in the wound space. In an in vitro model of human sprout angiogenesis, three-dimensional fibrin gel, simulating early wound clot, but not collagen gel, simulating late granulation tissue, supported capillary sprout formation. Understanding the molecular mechanisms that regulate wound angiogenesis, particularly how ECM modulates ECM receptor and angiogenic factor requirements, may provide new approaches for treating chronic wounds.

Animals↗