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PubMed1984

Excess granulation tissue responses associated with isotretinoin therapy.

Multiple polypoid projections of granulation tissue developed in two patients receiving isotretinoin for acne. Histological study of the lesions revealed increased amounts of non-sulphated acid mucopolysaccharides in the ground substance of the granulation tissue stroma. Complete resolution occurred following curettage with or without chemical cautery. The role of isotretinoin in the development of these lesions is discussed.

Acne Vulgaris↗

PubMed2003

Regular tracheostomy tube changes to prevent formation of granulation tissue.

OBJECTIVES/HYPOTHESIS: Tracheostomy is a commonly performed operative procedure that has been described since 2000 B.C. The early indications for tracheostomy were for upper airway obstruction, usually occurring in young people as a result of an infectious process. Recently, tracheostomies are more commonly performed in the critically ill patient to assist in long-term ventilatory support. Granulation tissue at the stoma and the trachea has been described as a late complication resulting in bleeding, drainage, and difficulty with maintaining mechanical ventilatory support. STUDY DESIGN: The present report is of an observational study of a newly implemented policy that required regular changing of tracheostomy tubes. Comparable groups of patients were compared before and after this procedural change to document complications. Data collection consisted of chart reviews of all admissions for 1 year before the policy change and the subsequent 2 years. Complication rates were compared using standard statistical techniques. METHODS: A policy change was instituted that required all tracheostomy tubes to be changed every 2 weeks in conjunction with a detailed evaluation of the tracheostomy stoma. Charts were reviewed the year before the change in policy and in the subsequent 2 years to determine the incidence of granulation tissue requiring operative intervention. RESULTS: The number of patients requiring surgical intervention secondary to granulation tissue showed a statistically significant decrease (P =.02). A review of policies and procedures from the six largest hospitals in southeastern Michigan had no recommendations for routine tracheostomy tube changes. CONCLUSIONS: A policy requiring a routine change of tracheostomy tubes results in fewer complications from granulation tissue. Tracheostomy tube changes to prevent granulation tissue and its complications.

Adult↗

PubMed1993

Dose responsive effects of PDGF-BB, PDGF-AA, EGF, and bFGF on granulation tissue in a guinea pig partial thickness skin excision model.

A guinea pig partial thickness skin excision model was used to evaluate the effects of recombinant human PDGF-BB, PDGF-AA, EGF, and bFGF on granulation tissue (neodermis) formation. These growth factors tended to increase the thickness of the granulation tissue bed when assessed histologically at day 7. Using only four animals per group, PDGF-BB at 30 and 100 micrograms/ml consistently and significantly increased the thickness of the granulation bed 2-3 times that of control. Except for the increased thickness, the granulation tissue appeared normal. PDGF-AA and EGF also significantly increased the granulation tissue thickness, and bFGF gave indications of an effect. There was no evidence of synergistic effects between PDGF-BB, EGF, and/or bFGF.

Animals↗

PubMed1992

Epidermal growth factor receptor at endothelial cell and pericyte interdigitation in human granulation tissue.

Angiogenic immature capillaries in human granulation tissue possess many cytoplasmic interdigitations between endothelial cells and pericytes (CIDEP). Epidermal growth factor (EGF) is a potent mitogenic polypeptide which accelerates angiogenesis in vivo and in vitro. We have recently demonstrated in immature capillaries that EGF is present at the CIDEP and proposed that the CIDEP may be involved in a signaling pathway for EGF (Wakui et al., 1990c. Microvasc. Res. 40, 285-291). This study follows that previous report. In the present study, I have investigated the ultrastructural localization of the EGF receptor (EGF-r) at CIDEP. Immunoreactivity for the EGF-r in immature capillaries was located strictly at the CIDEP in large numbers, at the coated pits and vesicles of endothelial cells, and at some lysosome-like structures of the endothelial cells and the pericytes. On the other hand, immunoreactivity for EGF-r was absent in mature capillaries. At the CIDEP, EGF-r immunoreactivity was present at the cell membrane and a few cytoplasmic elements at the tip of pericyte cytoplasmic projections, but it was completely absent at the corresponding endothelial membrane indentation. The present results support our proposed hypothesis that the CIDEP in immature capillaries act as a pathway for EGF transportation from the endothelial cell to the pericyte by a receptor-mediated process.

Biological Transport↗

PubMed1975

Granulation tissue formation in oophorectomized rats treated with female sex hormones. II. Studies on the amount of collagen and on tensile strength.

The content of hydroxyproline and tensile strength of granulation tissue was studied in oophorectomized rats treated with female sex hormones. Estrogen alone caused a slight decrease of hydroxyproline, but had no effect on the tensile strength of the granulation tissue at one week. Progesterone alone or in combination with estrogen decreased the content of hydroxyproline and the tensile strength of the granulation tissue up to one week in the case of progesterone-treated animals and up to two weeks in the case of animals treated with the combination of the hormones. At one week no direct correlation was found between the amount of hydroxyproline and the tensile strength of granulation tissue in oophorectomized rats treated with estrogen and progesterone in combination.

Animals↗

PubMed1991

Differential expression of markers for endothelial cells, pericytes, and basal lamina in the microvasculature of tumors and granulation tissue.

The structure and function of the tumor microvasculature is of great interest for cancer biology, diagnosis, and therapy. The distribution of endothelial cells, pericytes, and basal lamina in tumors is not well documented. In this study, the authors investigated the distribution of markers for these different components in a series of malignant human tumors and in human granulation tissue, both situations with extensive angiogenesis. Their results show a striking heterogeneity in the expression of markers for pericytes and endothelial cells between different tumors, but also within a single tumor lesion. To be able to distinguish between these two adjacent cell types decisively, all marker studies were carried out both on the light and the electron microscopical level and compared with staining results in granulation tissue of cutaneous wounds in healthy volunteers and of decubitus lesions. In granulation tissue of decubitus lesions, well-defined zones with increasing levels of maturation can be delineated. It was found that antibodies recognizing von Willebrand factor often failed to stain the tumor capillaries. Of the pericyte markers, alpha-smooth muscle actin was only locally expressed by pericytes in the tumor vasculature, whereas the high-molecular-weight melanoma-associated antigen, a chondroitin sulfate proteoglycan, stained the microvasculature broadly. Staining of the basal lamina components collagen type IV and laminin was, within the tumor, not restricted to the microvasculature. From their findings the authors conclude that 1) for the visualization of the tumor vasculature, antibodies recognizing endothelial markers, especially monoclonal antibodies PAL-E and BMA 120, are preferable to those recognizing pericytes or basal lamina; 2) within the microvasculature of tumors and granulation tissue, a heterogeneity of expression of endothelial and pericyte markers is observed; 3) during the formation of granulation tissue, all three microvascular components can be demonstrated already in the histologically earliest stage, suggesting not only an involvement of endothelial cells but also of pericytes and basal lamina in the initial steps of angiogenesis in wound healing.

Adult↗

PubMed2004

[Effects of substance P on granulation tissue fibroblasts proliferation and expression of basic fibroblast growth factor mRNA].

OBJECTIVE: To explore the proliferation-promoting effect of sensory neuropeptide substance P (SP) on the cultured granulation tissue fibroblasts in vitro and its regulative effect on the gene expression of basic fibroblast growth factor (bFGF) mRNA. METHODS: The proliferation-promoting effect of cultured granulation tissue fibroblasts was observed by means of MTT; the regulative effect of SP on gene expression of fibroblast bFGF by RT-PCR. The time and dose-efficiency relations were also observed. RESULTS: There was a significant proliferation-promoting effect of SP on the cultured granulation tissue fibroblasts in vitro in a remarkable dose-dependent fashion. However, bFGF antibody only partly exerted its inhibitive effect. SP could induce the bFGF mRNA expression of the fibroblasts at the 3rd and 6th hour (P < 0.01). SP could promote the bFGF mRNA expression of the fibroblasts in the concentration of 10(-9) - 10(-5) mol/L and peaked in the concentration of 10(-7) mol/L. CONCLUSIONS: SP has a significant proliferation-promoting effect on the granulation tissue fibroblasts, which is correlated with SP inducing bFGF mRNA expression of fibroblasts.

Animals↗

PubMed2005

Second-intention repair in the horse and pony and management of exuberant granulation tissue.

Second-intention repair is faster in ponies than in horses and faster in body wounds than in limb wounds. To a large extent, the differences between horses and ponies can be explained by differences in the local inflammatory response, which are a result of the functional capacity of leukocytes. In ponies, leukocytes produce more inflammatory mediators,resulting in better local defense, faster cellular debridement, and a faster transition to the repair phases, with more wound contraction. In horses,leukocytes produce fewer mediators, initiating a weak inflammatory response, which becomes chronic. This inhibits wound contraction and gives rise to the formation of exuberant granulation tissue. The anatomic environment that influences the inflammatory response and wound contraction most probably determines the differences between body and limb wounds. In body wounds, better perfusion results in faster initiation of the inflammatory phase. The weaker local resistance results in a greater degree of contraction. In limb wounds, particularly of horses, the initial inflammatory response is weak and wound contraction is restricted. Both factors give rise to chronic inflammation, which further inhibits wound contraction and promotes exuberant granulation tissue. The high incidence of exuberant granulation tissue in limb wounds of horses can thus be explained by the chronicity of the inflammatory response as well as by the common use of bandages during treatment. Chronic inflammation is often not recognized as a cause of exuberant granulation tissue. It must be prevented and treated to promote the healing process. Bandages and casts stimulate the formation of exuberant granulation tissue; however, they are advantageous in many respects and play an important role in support of the overall healing process.

Animals↗

PubMedDate not supplied

Cranio-caudal differences in granulation tissue formation: an experimental study in the rat.

This study examined potential regional differences in the deposition of granulation tissue in cellulose sponges placed in the dorsum of rats. Four cellulose sponge implants, 10 x 10 x 5 mm in size, two in cranial and two in caudal positions, were used to induce granulation tissue formation in the back of the rat. A cranio-caudal difference in connective tissue formation was assessed from 1 to 24 weeks after implantation. Granulation tissue ingrowth, measured histomorphometrically, was enhanced at 2 weeks and the surrounding capsule was thinner from 1 to 3 weeks in implants located in the cranial part of the back. In the cranial position, the number of fibroblasts, assessed semiquantitatively, was higher and the ratio of inflammatory cells to fibroblasts lower at 2-3 weeks. Also, the ratio of hydroxyproline content to total nitrogen content was higher after the first week in cranial specimens. Thus, a distinct cranio-caudal difference in the proliferative phase was observed. These results show the obvious practical considerations underlying the need for randomization or comparison between implants from exactly corresponding cranio-caudal locations.

Absorbable Implants↗

PubMed2005

Peripheral blood mononuclear cells acquire myofibroblast characteristics in granulation tissue.

BACKGROUND: Bone marrow-derived cell populations possess progenitor cell capacities. Emerging evidence also suggests significant plasticity of differentiated mononuclear cell lineages. We therefore assessed the distribution of transplanted peripheral blood mononuclear cells (PBMCs) in granulation tissue formation, and evaluated their possible transdifferentiation into myofibroblasts. METHODS: Silastic tubes were inserted into the peritoneal cavity of rats, followed by injection of PKH26-labelled PBMCs isolated from donor animals. At 3, 14 and 21 days, the distribution of PKH26(+) cells as well as their colocalization with myofibroblast/smooth muscle cell [alpha-smooth muscle (alpha-SM) actin] or macrophage markers (ED1/ED2) were determined. RESULTS: Round-shaped PKH26(+) cells accumulated around the implants at 3 days, while myofibroblasts were rare. Later, peritoneal granulation tissue constituted an inner, multilayered capsule primarily comprising alpha-SM actin(+) cells that was surrounded by more loosely organized inflammatory connective tissue. PKH26-labelled, spindle-shaped cells were abundantly found in tissue capsules. As a key finding, granulation tissue at 14 and 21 days contained cells with both PKH26 and alpha-SM actin labelling. Accordingly, a subpopulation of cells staining positive for macrophage markers showed a spindle-shaped morphology and alpha-SM actin expression. CONCLUSIONS: Transplanted PBMCs contribute to granulation tissue, and acquire myofibroblast characteristics during de novo tissue formation. Mononuclear cells may transdifferentiate into myofibroblast-like cells within an inflammatory environment.

Actins↗

PubMed1983

Wound fluids mediate granulation tissue growth phases.

The effects of exudates (wound fluids) from experimental granulation tissue on the synthesis of connective tissue components in fibroblast cultures were tested. The exudate from the early phase of granulation tissue (4 days after implantation) stimulated fibroblast proliferation and also the production of hyaluronic acid comparable to rat serum. On the contrary, the two later exudates (10 and 14 days after implantation) strongly inhibited fibroblast proliferation. These exudates also turned fibroblast glycosaminoglycan synthesis to more sulphate containing molecules. Collagen and protein synthesis were only slightly affected, the maximal collagen synthesis being obtained with the early phase wound fluid. The analysis of exudates and rat serum in sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed the clear similarity the exudates from the later growth stages produced some new proteins, which may regulate the altered metabolism of cultured fibroblasts.

Animals↗

PubMed1976

Fibroblast DNA synthesis activation in sponge induced granulation tissue. The effect of antineutrophil serum and cyclophosphamide.

DNA synthesis in rat and rabbit polyvinyl sponge induced granulation tissue has been studied using thymidine (methyl-3H). Synthesis was determined by measurement of thymidine incorporation into cold trichloroacetic acid insoluble material and by autoradiography. Granulation tissue was removed and immediately incubated in vitro in the presence of thymidine (methyl-3H) for three hours. The label was incorporated into the nuclei of fibroblasts and, to a lesser extent, of endothelial cells. The labeled material was 93% lysable by DNase and its synthesis was inhibited by hydroxyurea and bleomycin. In this system synthesis was linear for two hours and then ceased. A marked increase in DNA synthesis occurred in tissue harvested at 44 hours after sponge implantation. This rise was confirmed by autoradiographic studies which showed an increase in nuclear labeling at two days after implantation. Neutropenia produced by injections of antineutrophil serum or cyclophosphamide failed to inhibit activation of DNA synthesis in fibroblasts or endothelial cells. Amonocytosis also had no effect on this process. Rates of thymidine incorporation into DNA and thymidine phosphates in vivo were similar to those found during in vitro incubations of granulation tissue.

Animals↗

PubMed2000

Successful use of argon plasma coagulation and tranilast to treat granulation tissue obstructing the airway after tracheal anastomosis.

We successfully used argon plasma coagulation (APC) and tranilast to treat granulation tissue that had formed on an end-to-end tracheal anastomosis. APC had several advantages over laser in the management of exuberant granulation tissue, and we considered tranilast to be effective in our patient. To our knowledge, this is the first description of the use of APC in the management of anastomotic granulation tissue in the trachea or bronchus.

Adult↗

PubMed1988

Granulation tissue formation and metabolism of zinc and copper in alloxan-diabetic rats.

The early wound healing phases, and zinc and copper metabolism were assessed in traumatized insulin dependent diabetic rats. Granulation tissue was obtained by implanting Ivalon sponges subcutaneously and analysed on the fourth and seventh postoperative days by applying quantitative biochemical methods. The DNA content on day 4 and the amounts of RNA, hydroxyproline and hemoglobin on day 7 were significantly lower in granulation tissue from diabetic rats. The alkaline phosphatase activity, a marker for polymorphonuclear leukocytes (PMNs), was raised in the diabetic granulation tissue. The concentrations of zinc and copper were found to be increased in the kidney of diabetic rats compared with operated, non-diabetic controls. Our data suggest that the early granulation tissue formation is disturbed, with a prolonged inflammatory phase, decreased collagen formation and reduced vascularization. Zinc and copper are accumulated in the kidney of rats with uncontrolled, insulin dependent diabetes mellitus.

Acid Phosphatase↗

PubMed1985

Granulation tissue formation in experimental wounds inoculated with Staphylococcus aureus.

The effects of inoculated Staphylococcus aureus microorganisms on developing granulation tissue were studied in rats. Hollow cylindrical viscose cellulose sponges were implanted subcutaneously as an inductive matrix for the growth of granulation tissue. The control implants were injected immediately after implantation with 1 ml of physiological saline while the experimental implants were injected with a corresponding volume of saline solution containing live staphylococci in the following concentrations: 10(2), 10(3), 10(4) or 10(5) microorganisms per milliliter. Analyses of wound fluid and granulation tissue were carried out two weeks after implantation. Implants inoculated with 10(3) or more organisms reproducibly developed infection which delayed healing while implants inoculated with 10(2) bacteria showed no infection and were usually able to clear themselves from the organisms. In the latter implants the number of wound fluid monocytes and macrophages was markedly elevated and the mean amount of collagen hydroxyproline exceeded the control level by 55%. This demonstrates that wound healing can be accelerated to a certain extent by inoculation of live staphylococci. The acceleration concerns only such bacterial concentrations which are able to promote a local inflammatory response but which can be governed by wound defence mechanisms.

Animals↗

PubMed1976

Effects of sialoadenectomy and parotin hormone on the development of rat sponge-induced granulation tissue.

A study was made concerning the effects of sialoadenectomy and parotin hormone administration upon sponge-induced granulation tissue of young adult rats. The effects of sialoadenectomy alone and sialoadenectomy plus a single subcutaneous injection of parotin hormone, in two different doses (0.15 and 0.30 mg), on the development of 15-day-old granulation tissue were observed. The action of parotin hormone administration without sialoadenectomy was also investigated. The results have shown that sialoadenectomy produces a retardation effect upon the development of the tissue. This effect was partially inhibited by 0.15 mg and totally eliminated by the administration of 0.30 mg of the hormone. When administered in rats which were not sialoadenectomized, the dose of 0.30 mg caused increased fibroplasia and vascularization of granulation tissue, while a dose of 0.15 mg did not cause any significant difference when compared to the control tissue.

Animals↗

PubMed2000

Role of multinuclear cells in granulation tissue in osteomyelitis: immunohistochemistry in 66 patients.

We investigated the origin of multinuclear cells (MNCs) in the granulation tissue in osteomyelitis by immunohistochemical techniques in 66 patients. 12 samples were analyzed for the presence of CD68, cathepsin K, CD11b and tartrate-resistant acid phosphatase (TRAP) activity. Many MNCs were present in the granulation tissue adjacent to a sequestrum. MNCs in contact with the sequestrum were also noted, however, no osteoblasts were found. Immunohistochemically, CD68, cathepsin K and TRAP were strongly expressed in most of the MNCs, while CD11b positive cells were not found. MNCs remote from and in contact with the sequestrum showed the same immunohistochemical features which are characteristic of osteoclasts. Further, MNCs in contact with the sequestrum had originally developed in the granulation tissue and directly infiltrated towards the sequestrum without cell-to-cell interaction with osteoblasts.

Acid Phosphatase↗

PubMed2000

Granulation tissue flap technique in extensive wounds for covering exposed bone after tumor excision.

BACKGROUND: Second intention partial wound healing followed by skin grafting is a well-established method in dermatosurgery. In wide tumor excision, where periosteum is removed, growth of granulation tissue in the central areas of bare bone can be prolonged. OBJECTIVE: We describe a new technique for a faster, reliable closure of large defects utilizing granulation tissue flaps. METHODS: Postoperative wounds were treated with wet dressings until granulation tissue had developed on the wound edges. The central defects were then covered with lateral granulation tissue flaps. Subsequently split skin grafting was performed. RESULTS: Thirty-eight patients (37-99 years old) were treated between 1991 and 1999. Skin defects were located primarily on the scalp and forehead, and ranged from 3 to 13 cm in diameter. Wound bed preparation for skin grafting was achieved in all patients. Only minor complications, such as partial granulation flap necrosis in 5 of 38 patients or delayed skin graft healing in 4 of 38 patients, were seen. CONCLUSIONS: This technique for the closure of extensive skin defects is safe and effective.

Adult↗