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Serial section analysis of the lesions in diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is clinically and pathologically an independent entity and should be discriminated from the usual bronchiolitis obliterans. The lesions of 20 cases of DPB were serially sectioned and reconstruction was made focusing on the region from the terminal to the respiratory bronchioles. Morphological changes in the region of the respiratory bronchioles were clearly understood and were classified into three types by the presence and the size of the intraluminal granulation tissue. The walls of the respiratory bronchioles were thickened with cell infiltration and granulation tissue in all foci (28 in total), and 26 foci showed intraluminal granulation tissue whereas only 2 foci did not exhibit intraluminal plugs. Xanthoma cells were mostly observed in the interstitial tissue of the alveolar ducts, sacs, and septal walls distal to the stenotic sites as well as in the alveolar spaces in the marked cases.

Adult↗

A child with laryngo-onychocutaneous syndrome partially responsive to treatment with thalidomide.

Laryngo-onychocutaneous syndrome (LOCS) is a condition characterized by erosive or ulcerative skin lesions associated with excessive granulation tissue, at sites of trauma such as the digits, elbows and knees. Similar lesions can occur within the conjunctival mucosa, leading to corneal scarring and blindness. The main complications, however, occur in the respiratory tract, where a similar process of erosions and subsequent formation of granulation tissue causes airway obstruction which may lead to premature death. LOCS is now believed to be a nonblistering variant of junctional epidermolysis bullosa and to date there are no efficacious treatments available. We report a 16-year-old girl with LOCS who failed to respond to methylprednisolone and cyclophosphamide, but had a partial response to oral thalidomide with marked decrease in granulation tissue and tracheal secretions. Interruption of treatment resulted in prompt resurgence of the granulation tissue which was again controlled by reintroduction of thalidomide. We propose that in the absence of effective therapies for LOCS, a trial of thalidomide in these patients should be considered.

Adolescent↗

Topical phenytoin treatment of stage II decubitus ulcers in the elderly.

OBJECTIVE: To compare the healing of stage II decubitus ulcers with topically applied phenytoin sodium with two other standard topical treatment procedures in a long-term care setting; and to assess the extent of systemic absorption after topical application in the phenytoin group. METHODS: Forty-seven nursing home patients with stage II decubitus ulcers were chosen for this study. The patients were matched for age, gender, and size and severity of wounds, and randomly assigned to each treatment group. Clinical assessment of decubitus ulcers was performed at the beginning of treatment and at each dressing change. Ulcers were examined for the presence of healthy granulation tissue, reduction in surface dimensions, and time to healing. Two phenytoin sodium plasma concentrations were to be obtained on all patients in the phenytoin group. RESULTS: Topical phenytoin therapy resulted in a shorter time to complete healing and formation of granulation tissue when compared with DuoDerm dressings or triple antibiotic ointment applications (p < or = 0.05). The mean +/- SD time to healing in the phenytoin group was 35.3 +/- 14.3 days compared with 51.8 +/- 19.6 and 53.8 +/- 8.5 days for the DuoDerm and triple antibiotic ointment groups, respectively. Healthy granulation tissue in the phenytoin group appeared within two to seven days in all subjects. Patients in the standard treatment groups required six to 21 days to produce new granulation tissue. Serum phenytoin sodium concentrations were nondetectable. No patient withdrew from the study secondary to adverse treatment effects. CONCLUSIONS: Both the phenytoin and standard treatment groups showed progress over the study period. However, the phenytoin group demonstrated more rapid results in all aspects of ulcer healing.

Administration, Topical↗

The effect of gastroesophageal reflux on laryngotracheal reconstruction.

OBJECTIVES: To determine the need for preoperative evaluation for gastroesophageal reflux disease (GERD) in all children undergoing laryngotracheal reconstruction (LTR) and to assess the effect of GERD on the outcome of LTR. DESIGN: Prospective, single-blind observational study. SETTING: Tertiary care children's hospital. PATIENTS: Seventy-four pediatric patients with laryngotracheal stenosis who underwent LTR at the Children's National Medical Center, Washington, DC, from October 1, 1986, through August 31, 1994. INTERVENTION: Evaluation for and treatment of GERD, LTR, endoscopy, and removal of granulation tissue. MAIN OUTCOME MEASURES: Successful decannulation and number of endoscopies required to remove laryngeal and tracheal granulation tissue. RESULTS: Seventy-four patients underwent 82 LTRs. The senior surgeon was blinded to the status of GERD evaluation and treatment. Four groups were identified: 37 patients (40 LTRs) with no preoperative evaluation for GERD; 10 patients (11 LTRs) with normal findings on preoperative evaluation for GERD; seven patients (nine LTRs) with abnormal findings on preoperative evaluation for GERD but who failed to receive appropriate treatment; and 20 patients (22 LTRs) with abnormal findings on preoperative evaluation for GERD who received appropriate therapy. Severity and extent of stenosis as determined by multicentricity of stenosis, type of repair, and duration of stent were similar in the four groups. The effect of GERD and its treatment on the outcome of LTR was measured by the number of endoscopies necessary for removal of granulation tissue following reconstruction and successful decannulation. Statistical analyses indicate that (1) all children do not require preoperative evaluation for GERD; (2) neither the presence of GERD nor its treatment are major factors in determining the outcome of LTR. CONCLUSION: Preoperative evaluation for GERD and its treatment do not favorably affect the outcome of LTR.

Analysis of Variance↗

Topical vascular endothelial growth factor reverses delayed wound healing secondary to angiogenesis inhibitor administration.

The prevention of new blood vessel growth is an increasingly attractive strategy to limit tumor growth. However, it remains unclear whether anti-angiogenesis approaches will impair wound healing, a process thought to be angiogenesis dependent. Results of previous studies differ as to whether angiogenesis inhibitors delay wound healing. We evaluated whether endostatin at tumor-inhibiting doses delayed excisional wound closure. C57/BL6J mice were treated with endostatin or phosphate-buffered solution 3 days prior to the creation of two full-thickness wounds on the dorsum. Endostatin was administered daily until wound closure was complete. A third group received endostatin, but also had daily topical vascular endothelial growth factor applied locally to the wound. Wound area was measured daily and the wounds were analyzed for granulation tissue formation, epithelial gap, and wound vascularity. Endostatin-treated mice showed a significant delay in wound healing. Granulation tissue formation and wound vascularity were significantly decreased, but reepithelialization was not effected. Topical vascular endothelial growth factor application to wounds in endostatin-treated mice resulted in increased granulation tissue formation, increased wound vascularity, and wound closure approaching that of control mice. This study shows that the angiogenesis inhibitor endostatin delays wound healing and that topical vascular endothelial growth factor is effective in counteracting this effect.

Administration, Topical↗

Epithelial tissue-type plasminogen activator expression, unlike that of urokinase, its receptor, and plasminogen activator inhibitor-1, is increased in chronic venous ulcers.

BACKGROUND: The plasminogen activation system represents a potent mechanism of extracellular proteolysis and is an essential component of normal wound healing. It has also been implicated in the pathogenesis of chronic, nonhealing ulcers. Traditionally, urokinase-type plasminogen activator (uPA) has been associated with pericellular proteolytic activity involved in tissue remodelling processes, and tissue-type plasminogen activator (tPA) mainly with intravascular fibrinolysis. OBJECTIVES: The present study was conducted to characterize the spatial distribution of the various plasminogen activation system components in chronic ulcers and acute, well-granulating wounds. METHODS: The expression of uPA, tPA, urokinase receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and vitronectin was investigated by immunohistochemical staining, in addition to uPA, tPA and PAI-1 expression by in-situ hybridization, in samples from eight chronic venous ulcers, five decubitus ulcers, five well-granulating acute wounds and five normal skin samples. RESULTS: In chronic venous leg ulcers tPA mRNA was detected in basal and suprabasal keratinocytes at the leading wound edge, while in well-granulating wounds and in decubitus ulcers tPA mRNA was expressed only in a few keratinocytes. However, tPA was widely expressed in fibroblast- and macrophage-like cells in the stroma of well-granulating wounds, while less tPA was detected in the granulation tissue of chronic ulcers. tPA mRNA and protein were localized in the superficial granular layers in normal skin. Although no qualitative differences in expression of uPA, PAI-1 or uPAR in the wound edge keratinocytes in chronic ulcers vs. normally granulating wounds were found, their expressions were more pronounced in the granulation tissue of well-granulating wounds. CONCLUSIONS: These results suggest that in poorly healing venous leg ulcers, the pattern of tPA expression is altered in keratinocytes at the leading edge of the wound, and the patterns of tPA, uPA and PAI-1 expression are altered in the granulation tissue.

Acute Disease↗

Management of craniovertebral junction tuberculosis.

BACKGROUND: Tuberculosis of the craniovertebral junction (CVJ) is extremely rare. However, recent evidence suggests that the incidence of this condition may be increasing. The diagnosis is often difficult despite advances in imaging using magnetic resonance imaging. The transoral approach to the anterior CVJ provides excellent access to this region, has low mortality and morbidity, and enables biopsy of lesions and decompression of the neuraxis. Management of associated atlantoaxial instability, with regard to timing and method of stabilization, is controversial. METHODS: We report 24 cases of CVJ tuberculosis. Prominent manifestations of the disease included neck pain and stiffness, swelling of the retropharyngeal soft tissues, quadriparesis, osteolytic erosions, and atlantoaxial subluxation. Seven patients had acute presentation. All patients received antituberculous drug treatment for 18 months. Four patients were managed conservatively, 5 underwent only transoral biopsy, 9 patients underwent transoral decompression and posterior fusion, and 6 patients underwent only posterior fusion. RESULTS: Histopathologic analysis of biopsy material revealed abscess only in 5 cases, granulation tissue only in 6, abscess with granulation tissue in 4, granulation tissue with chronic osteomyelitis in 5, and chronic inflammation in 2. All patients improved, with mean improvement in Nurick grading of 1.71. Even patients with spinal cord signal intensity changes on magnetic resonance images showed improvement. CONCLUSIONS: Although CVJ tuberculosis is a rare disease, the outcome of treatment is good. Antituberculous drug therapy remains the mainstay of treatment after confirming the diagnosis. The surgical management options include transoral decompression with or without posterior fusion, depending upon the presence and persistence of atlantoaxial instability.

Adolescent↗

Evaluation of healing and external tunnel histology of silver-coated peritoneal catheters in rats.

A previous study showed that silver-coating peritoneal catheters tended to decrease the incidence of early exit-site infections in rats. This study was designed to further evaluate the healing, biocompatability, and external tunnel morphology of standard and silver-coated catheters. Catheters were coated with silver by an ion beam-assisted process. Fourteen male Sprague-Dawley rats underwent implantation of either a standard or silver-coated double-cuff peritoneal catheter. Weekly observation and photographs documented exit-site characteristics. Erythema, exudate, loose fit, and poor hair growth were evidence of an inflamed exit. Overt infection was indicated by the presence of three or more of the following: erythema, purulent exudate, exuberant granulation tissue, loose fit, and poor hair growth. Animals were sacrificed at six weeks, and catheters were removed and processed for histology of the external tunnel. Multiple measurements were taken using a Filar eyepiece, and data were expressed as a mean of several readings. Inflammation, vascularity, and fibrosis were judged semiquantitatively. At the end of six weeks, six of the seven exits of the silver catheters showed excellent healing, while one exit site had signs of excessive inflammation. Four of the exit sites of the standard catheters healed well, two were inflamed, and one was overtly infected. The sinus tract of the standard and silver catheters had similar characteristics: keratinized and nonkeratinized epithelium lined the external part of the sinus tract and merged into granulation tissue. A fibrous sheath was noted in some sinus tracts between the granulation tissue and the cuff. The cuff evoked a foreign body reaction, with fibrosis, multiple giant cells, and vascularization. Poorly healing or infected sinus tracts had highly vascular granulation tissue with overlying exudate. The cuff of these catheters had marked inflammation and scanty giant cells, although collagen bundle thickness was similar to the well-healing catheters. In conclusion, silver-coating potentially enhances healing of the exit sites of peritoneal catheters. Additionally, the similarity of the tunnel histomorphology of standard and silver catheters confirms the favorable biocompatibility of silver.

Animals↗

The opposite effect of morning or afternoon application of melatonin on collagen accumulation in the sponge-induced granuloma.

OBJECTIVES: Collagen accumulation in the sponge-induced granuloma is under inhibitory influence of melatonin. This effect was observed when the pineal hormone was injected late in the afternoon. DESIGN: The present study was conducted to compare the afternoon and morning melatonin application and to answer the question whether melatonin effect on the collagen accumulation in wounds is dependent on tissue circadian sensitivity to the pineal hormone. METHODS: In order to induce granulation tissue development, the Ivalon sponge was implanted subcutaneously in the Wistar rats. Then the animals were divided into 5 groups: intact controls, rats injected with vehicle in the morning or in the late afternoon, as well as animals receiving melatonin (30 &mgr;g/100g body wt) in the morning or late afternoon. After 4 weeks, the sponges were removed for the analysis of both soluble and total collagen content. Collagen was analyzed as hydroxyproline content in the tissue. Insoluble collagen was calculated. RESULTS: The afternoon application of melatonin was seen to decrease the total and insoluble collagen content in the sponge-induced granuloma (p<0.05). However, morning administration of the pineal hormone increased collagen capacity in the granulation tissue (p<0.01). CONCLUSION: Therefore, contradictory effect of morning or afternoon melatonin application on the collagen content in the granulation tissue has been shown. This phenomenon is supposed to be due to various circadian sensitivity of tissues to melatonin and may suggest that the mechanism of melatonin regulatory action on collagen accumulation in wounds is complex.

Journal Article↗

Acceleration of wound healing with topically applied deoxyribonucleosides.

HYPOTHESIS: We hypothesized that a topical mixture of purified deoxyribonucleosides would accelerate wound healing in an open wound model. DESIGN: Full-thickness 6-mm wounds were made on the ears of young adult rabbits. In some experiments, 2 of the 3 arteries in each ear were divided to induce wound ischemia. INTERVENTIONS: An equiweight mixture containing all 4 of the major deoxyribonucleosides (deoxyadenosine, deoxycytidine, deoxyguanosine, and thymidine), designated PN105, or other subgroups of deoxyribonucleosides, or vehicle (saline) was applied to wounds on 1 ear every 2 days, with the other ear serving as a control. MAIN OUTCOME MEASURES: Wound tissue was processed for histological examination 7 days after the initial wounding. Granulation tissue formation and epithelialization were measured in histological cross sections of wounds. RESULTS: Treatment of wounds with PN105 resulted in a 191% increase in total new granulation tissue (P<.05) and a higher incidence of complete wound reepithelialization (67% vs 37%; P<.05) when compared with controls, and a similar increase under ischemic conditions on day 7. Wound ischemia markedly impairs healing; PN 105 treatment resulted in a 242% increase in the amount of new granulation tissue formed by day 7 in ischemic wounds, relative to the appropriate controls (P<.05). All 4 of the major deoxyribonucleosides were required for optimum activity; mixtures with 3 or 2 were less active or inactive. CONCLUSIONS: Topically applied deoxyribonucleosides reproducibly accelerate wound healing in normal and ischemic wounds, and to a magnitude equivalent to that of recombinant growth factors such as platelet-derived growth factor, previously studied in this model. In view of their safety, availability, and efficacy, deoxyribonucleosides hold considerable promise for improving healing of chronic wounds.

Acrylic Resins↗

Localization and regulation of pregnancy-associated plasma protein a expression in healing human skin.

Pregnancy-associated plasma protein A (PAPP-A) is an IGF-binding protein-4 (IGFBP-4) metalloproteinase that cleaves inhibitory IGFBP-4 to amplify local IGF-I bioavailability in vitro. Thus it has functional implications in injury/repair responses. In this study we determined PAPP-A expression in healing human skin. Wounds were induced with a scalpel on the forearms of three normal subjects and were allowed to heal by first intention. Biopsies obtained on d 0, 2, 8, and 14 were processed for immunohistochemical detection of PAPP-A, IGF-I, and IGFBP-4. In uninjured skin (d 0), strong staining for PAPP-A was present in the epidermis, sweat and sebaceous gland epithelial cells, hair follicles, and blood vessels; no PAPP-A was detected in dermal fibroblasts or with mature collagen bundles. IGF-I localized strongly to epithelial cells of skin glands was weak to moderate in epidermis and blood vessels, and was absent in dermal cells. Weak focal staining for IGFBP-4 was found within uninjured epidermis. During wound healing, PAPP-A expression was induced in dermal granulation tissue within and adjacent to the injury. PAPP-A was present in dermis on d 2 and was increased in intensity and extent on d 8 and 14. PAPP-A expression also increased in the epidermis. PAPP-A expression in cells of granulation tissue colocalized with alpha-smooth actin staining of myofibroblasts and new blood vessels as well as with CD68 staining of macrophages and was associated with the compact, newly synthesized collagen of the healing wound. IGF-I staining was enhanced in the epidermis localized to the area of the incision and in granulation tissue associated with lymphoid cells. IGFBP-4 staining of the epidermis remained unchanged during wound healing, but was induced in the fibroblastic cells of granulation tissue over time. These data demonstrate localized and regulated expression of PAPP-A in human skin and suggest that PAPP-A may play an important role in an integrated IGF system in wound healing and tissue remodeling in vivo.

Actins↗

[Neoangiogenesis and human amniotic membrane. A clinico-instrumental study in phlebostatic ulcer of the lower extremities].

The present study was made in order to determine if granulation tissue development after treatment with Human Amniotic Membrane (HAM) is related with instrumental photoplethysmographically evidenced changes of the "ulcus layer". Daily, HAM fragments were disposed along the continuity solution of external patients with opened postthrombotic ulcus cruris. Instrumental examinations were made before, a week after and two weeks after treatment, and after the complete ulcus healing. Ulcus with a slight granulous or fibrogranulous layer developed a granulation tissue within the first week of treatment. On the contrary, in continuity solutions with necrotic layer, treatment with HAM failed. After the first week of treatment, a 84% of ulcus with slight granulation and fibrinogranulation, presented some sphygmic variations respect to baseline levels, like: raising in the amplitude and dicrotism appearing. Within the first week, all of the continuity solutions showed significant sphygmograms with a regular vascularization on the layer, this period of time concurred with the complete granulation phase of the ulcus. Long-preserved HAM stimulates in a significant way the appearing of the granulation tissue, within the first week of treatment. Sphygmic raisings are directly proportional with the amount of granulated tissue evidenced on the layer of the continuity solution.

Adult↗

[Effect of caffeine or NaCl on wound healing of the rat gingiva. Light and electron microscopic studies].

The present study was carried out to investigate histological and ultrastructural changes, particularly changes of the epithelium-connective tissue junction, in rat gingival wounds treated with Caffeine or NaCl. Light Microscopy The animal had an incision in the lingual gingiva of lower incisors. Immediately after incision, the wounds of Groups A, B and C were treated with distilled water, caffeine (2.5%) and NaCl (25%), respectively. The gingivae were examined histologically at 1, 2, 4, 6, 8, 12 and 28 days after treatment. Electron Microscopy Groups a, b and c received the same treatment as those of Groups A, B and C, respectively. The gingivae were examined ultrastructurally at 4 and 28 days after treatment. 1. Light Microscopic Observations (1) Group A. On all experimental days, the wounds were covered by the epithelium. At 1 and 2 days, the connective tissues exhibited depositions of fibrin, but, at 4, 6 and 8 days, they showed the granulation tissues. At 12 and 28 days, the connective tissues appeared normal. (2) Group B. On all experimental days, the wounds were covered by the epithelium. At 1 and 2 days, the connective tissues exhibited depositions of fibrin. At 4, 6 and 8 days, they displayed granulation tissues. At 12 and 28 days, the connective tissues appeared normal. (3) Group C. On all experimental days, the wounds were covered by the epithelium. At 1 and 2 days, the connective tissues exhibited depositions of fibrin. At 4, 6, 8 and 12 days, they displayed granulation tissues. At 28 days, the connective tissue was normal. (4) Histometrically, at 6 days, Groups A, B and C exhibited the highest, intermediate and lowest number of fibroblasts per unit area, respectively. There were no differences in the number of inflammatory cells between all three groups. 2. Electron Microscopic Observations (1) Group a. At 4 days, the normally-formed gingival basal lamina was observed rather frequently just beneath the basal surfaces of basal cells. On occasions, the basal lamina exhibited various changes such as detachments, breaks, thickenings and duplications. Moreover, absence of the basal lamina was observed. At 28 days, the irregular types of basal laminae decreased in number, and most of the basal laminae appeared normal in structure. (2) Group b. At 4 days, the normally-formed gingival basal lamina was observed less frequently as compared with those of Group a. The above-mentioned various changes of the basal lamina were found rather frequently.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

TGF-beta1 influences early gingival wound healing in rats: an immunohistochemical evaluation of stromal remodelling by extracellular matrix molecules and PCNA.

The effect of topically applied transforming growth factor beta1 (TGF-beta1) on the rat gingival wound healing process after flap surgery was evaluated by immunohistochemistry for extracellular matrix molecules (ECM), such as tenascin, heparan sulfate proteoglycan (HSPG) and type IV collagen, and for proliferating cell nuclear antigen (PCNA) in fibroblasts. TGF-beta1 solution was applied to the surgical wound experimental sites. Two microg/microl were applied at the time of the operation, and 1 microg/microl at days 1 and 2 after surgery, with contralateral control sites receiving the vehicle alone. Periodontal tissues were histologically examined at 3 and 7 days post-surgery. Tenascin was found to be more strongly stained in the granulation tissue from experimental sites at 3 days post-surgery. At 7 days postsurgery, HSPG-positive areas in granulation tissue had become smaller and there was a prominent proliferation of PCNA-positive fibroblast-like cells and type IV collagen-positive blood vessels. These results suggest that TGF-beta1 applied to surgical wounds influences early proliferation of gingival fibroblast-like cells, the formation of blood vessels, and ECM remodelling. In conclusion, TGF-beta1 application appears to promote granulation tissue formation in periodontal wound healing.

Animals↗

[Spontaneous osteonecrosis of the knee joint: MRT compared to CT, scintigraphy and histology].

PURPOSE: We compared MR imaging with scintigraphy and CT in eight patients with spontaneous osteonecrosis of the knee. The histological changes accounting for the MR signal abnormalities were evaluated. METHODS: Eight patients with spontaneous osteonecrosis of the knee joint underwent MR imaging before and after i.v. administration of Gd-DTPA. Nuclear scintigraphy was performed in all 8 patients, three patients also had CT scans of the knee area. Histologic correlation was available in three patients. RESULTS: Increased radionuclide uptake was observed in all patients. In one patient, however, scintigraphy showed increased radionuclide uptake consistent with osteonecrosis only in the medial femoral condyle, while MR imaging demonstrated osteonecrosis both in the medial as well as the lateral femoral condyles. MR demonstrated areas of low signal intensity on precontrast T1-weighted images in the femoral condyle in all patients. All these areas showed high signal intensity on T2-weighted images. On postcontrast T1-weighted images, signal intensity increase was either homogeneous throughout the lesion or it was seen at the periphery of the lesion in a band-like pattern. Histologically, the areas of high signal intensity on T2-weighted and on postcontrast T1-weighted images corresponded to granulation tissue. CONCLUSION: MR imaging detects granulation tissue adjacent to the necrotic zone. Using morphological and signal intensity criteria, MR imaging can be utilised to differentiate spontaneous osteonecrosis of the knee from osteochondritis dissecans, degenerative osteoarthritis, and other conditions affecting the knee joint.

Aged↗

Mitomycin-C in the postsurgical ear canal.

OBJECTIVE: Our goal was to evaluate the use of topical mitomycin-C (MMC) in the prevention of scar tissue formation in the postsurgical external auditory canal (EAC). Study design and setting We conducted a prospective pilot study at a tertiary care institution. METHODS: Six patients with recurrent postoperative granulation tissue after canaloplasty, tympanomastoidectomy, or lateral temporal bone resection were included. MMC (0.5 mg/mL) was applied topically for 5 minutes to the EAC/mastoid cavity. RESULTS: Outcomes were measured at initial MMC application and 1 and 3 months thereafter using a visual analog scale score based on the degree of EAC occlusion by granulation tissue. Need for debridement of recurrent granulation tissue on follow-up was noted. Three (50%) patients had improved VAS 1 month after treatment. Two (33%) had improved visual analog scale score at 3 months. Five (83%) required at least one debridement procedure. Repeat MMC application was performed in 2 patients. CONCLUSION: Topical MMC was ineffective in preventing scar formation in the postsurgical EAC.

Adult↗

Integrin expression in the dermis during scar formation in humans.

To evaluate changes leading to human wound reorganization we examined by immunohistochemistry the expression of several extracellular matrix (ECM) receptors (alpha2 chain of VLA-2, alpha3 chain of VLA-3, alpha6 chain of VLA-6, alphav, and beta1/beta3 chains of integrins) in a series of biopsies of human skin wounds healing by primary intention. The first time point investigated in this study was day 6 after injury, i.e. when a fibrin clot has been almost completely replaced by the granulation tissue. Gradual changes in integrin expression in granulation tissue and in the dermal scar were observed from the first time point investigated and were characterized by an up-regulation of alpha2beta1 complex, alphav integrin subunit, and beta1 integrin subunit. At day 27, the expression of the alpha2 chain of VLA-2 in the scar decreased. The expression of alphav and beta1 integrin subunits decreased but was still detectable by day 35. Vitronectin expression from day 7 onwards was also increased and colocalized to the area of the wounded dermis, and decreased by day 27. Our data suggests that, during the remodelling of the provisional matrix of the wound, dermal fibroblasts express transiently mainly alpha2 and alphav subunits of integrins associated with up-regulation of the beta1 subunit. It seems that up-regulation of some chains of integrins may be involved in the control of deposition of ECM components associated with wound healing.

Cicatrix↗

Fibroblast-collagen sponge interactions and the spatial deposition of newly synthesized collagen fibers in vitro and in vivo.

Fibroblast-collagen sponge interactions were studied in cell culture and dermal wound systems. In both models fibroblasts appear to adhere, attach and orient in the presence of type I collagen fibrils. In the presence of fibronectin, purified from bovine blood, adhesion and alignment of fibroblasts appeared to be enhanced as well as the deposition of thick collagen fibers. When collagen sponges were grafted onto full thickness dermal wounds the granulation tissue that was laid down within the collagen sponge appeared to differ from granulation tissue laid down below the collagen sponge or on similar wounds in the absence of a sponge. In the absence of a collagen sponge the granulation tissue is characterized by wavy collagen fibers that exhibit an extinction pattern characteristic of crimped fibers found in tendon when examined under polarized light. In contrast, collagen fibers laid down within the sponge appear to be highly oriented and lack evidence of crimp. These results suggest that the presence of a collagen matrix acts as a template that allows for the organized spatial deposition of newly synthesized collagen fibers. The enhanced biosynthesis of thick collagen fibers in the presence of a collagen sponge containing fibronectin may decrease the remodeling phase that is associated with dermal scarring.

Animals↗