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  • 1
    Electronic Resource
    Electronic Resource
    Randomized trial of topically applied repifermin (recombinant human keratinocyte growth factor-2) to accelerate wound healing in venous ulcers (2001)
    Oxford, UK : Blackwell Science, Ltd.
    Wound repair and regeneration 9 (2001), S. 0 
    Details
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: About 600,000 people in the United States are estimated to be affected by venous ulcers. The cornerstone of care of chronic venous ulcers involves the application of compression bandages. Other therapies include treatment of associated infection, treatment for edema and inflammation, and debridement when necessary. Repifermin, a recombinant human KGF-2 (fibroblast growth factor-10), exerts a proliferative effect on epithelial cells, in vitro and in vivo, and has been shown to accelerate wound healing in several experimental animal models. A randomized, double-blind, parallel-group, placebo-controlled, multicenter study was conducted to evaluate the safety and efficacy of topical repifermin treatment, for 12 weeks, in the healing of chronic venous ulcers in 94 patients. Repifermin was shown to accelerate wound healing, with significantly more patients achieving 75% wound closure with repifermin than with placebo. The treatment effect appeared more marked for a subgroup of patients with initial wound areas ≤ 15 cm2 and wound ages of ≤ 18 months. A longer duration of treatment (e.g., 26 weeks) may allow better differentiation of the benefit of repifermin compared with placebo, particularly with respect to complete wound closure. The safety assessment showed that repifermin was well tolerated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1524-475x.2001.00347.x
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  • 2
    Electronic Resource
    Electronic Resource
    Fascial fibroblast kinetic activity is increased during abdominal wall repair compared to dermal fibroblasts (2004)
    Oxford, UK; Malden, USA : Blackwell Science Inc
    Wound repair and regeneration 12 (2004), S. 0 
    Details
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abdominal wall fascial wound healing failure is a common clinical problem for general surgeons, manifesting in early postoperative fascial dehiscence as well as delayed development of incisional hernias. We previously reported that abdominal wall fascial incisions normally recover breaking strength faster than simultaneous dermal incisions in a rodent model. The accelerated fascial repair was associated with greater fibroblast cellularity within fascial wounds and increased wound collagen deposition. The current study was designed to determine whether accelerated fascial healing is the result of increased fascial fibroblast kinetic activity as measured by a more efficient fibroblast phenotype for binding to and remodeling a collagen matrix. Using a new model of abdominal wall repair, fibroblast cell cultures were developed from uninjured and wounded fascia and compared to dermal fibroblasts in order to define the fibroproliferative kinetic properties of abdominal wall fibroblasts. Fascial wound fibroblasts produced a more efficient and greater overall collagen lattice compaction compared to dermal fibroblasts. Acute fascial wound fibroblasts also showed enhanced cell proliferation compared to dermal fibroblasts but no significant differences in collagen production when normalized to cell number. These results suggest that fascial fibroblasts express distinct acute repair phenotypes and therefore a specific mechanism for fascial repair following injury.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1067-1927.2004.012506.x
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  • 3
    Electronic Resource
    Electronic Resource
    Effect of cytokine growth factors on the prevention of acute wound failure (2004)
    Oxford, UK; Malden , USA : Blackwell Science Inc
    Wound repair and regeneration 12 (2004), S. 0 
    Details
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Cytokine growth factor treatment of chronic wounds has met with mixed results. The chronic wound presents a hostile environment to peptides such as growth factors. Cytokine growth factors have not been studied extensively in acute wounds. However, incisional hernias are a major example of acute wound failure that has not been solved by various mechanical approaches. A biological approach to acute wound failure by use of cytokine growth factors may offer a new strategy. A rodent incisional hernia model was used. Seventy-six rats underwent 3-cm midline celiotomies and were closed with fine, fast-absorbing sutures to induce intentional acute wound failure. Group 1 received no other treatment. The midline fascia in Groups 2–10 was infiltrated with 100 µl of vehicle alone or vehicle containing various test cytokine growth factors. Necropsy was performed on postoperative day 28 and the wounds were examined for herniation. Incisional hernias developed in 83 percent (13/16) of untreated incisional and 88 percent (7/8) and 83 percent (5/6) of the two vehicle-treated incisions (PBS and carboxymethylcellulose). Hernia incidences were decreased by priming of the fascial incision with transforming growth factor-β2 (12%, 1/8), basic fibroblast growth factor (25%, 2/8) and interleukin-1β (50%, 3/6) (p 〈 0.05). Aqueous platelet-derived growth factor, becaplermin, insulin-like growth factor, and granulocyte macrophage-colony stimulating factor did not significantly decrease the incidence of acute wound failure (p 〉 0.05). A biological approach to acute wound failure as measured by incisional hernia formation can be useful in reducing the incidence of this complication. Transforming growth factor-β2, basic fibroblast growth factor, and interleukin 1β all eliminated or significantly reduced the development of incisional hernias in the rat model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1067-1927.2004.012109.x
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  • 4
    Electronic Resource
    Electronic Resource
    Negatively charged beads and transforming growth factor-β1 stimulate bone repair in rabbits (1996)
    Oxford, UK : Blackwell Science
    Wound repair and regeneration 4 (1996), S. 0 
    Details
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previous studies have shown the osteogenic potential of negatively charged Sephadex beads when used to heal osseous defects in an animal model. The present study examined the effect of adding the growth factors transforming growth factor-β1 and basic fibroblast growth factor to negatively charged Sephadex beads and neutral (non-osteogenic) Sephadex beads in a critical size calvarial defect in rabbits. New Zealand White rabbits were divided into six groups of five rabbits; 15 mm parietal defects were created and filled with either negatively charged Sephadex beads (three groups) or neutral Sephadex beads (three groups). Each group received either 2 µg of transforming growth factor-β1, 1 µg of basic fibroblast growth factor, or buffer (control). Animals were killed at 5 weeks, and their calvaria were submitted to plain radiographic and histomorphometric analyses. Defects treated with negatively charged Sephadex beads produced significantly more new trabecular bone than neutral Sephadex beads (p 〈 0.01), whereas the neutral beads treated with transforming growth factor-β1 formed significantly more bone than controls. The addition of transforming growth factor-β1 to negatively charged beads resulted in near closure of the craniotomy defect. The application of transforming growth factor-β1 to this model resulted in significantly more ectopic bone (p 〈 0.01) outside the defect on the dural and periosteal surfaces. Basic fibroblast growth factor, in the dose used, appeared to have an inhibitory effect on new bone formation fostered by negatively charged Sephadex beads. This study suggests that the addition of transforming growth factor-β1 to the known osteoconductive matrix of negatively charged Sephadex beads may be therapeutically useful in nonhealing bony defects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1524-475X.1996.40314.x
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  • 5
    Electronic Resource
    Electronic Resource
    A time to integrate the complete wound team: from bench to bedside and beyond (1996)
    Oxford, UK : Blackwell Science
    Wound repair and regeneration 4 (1996), S. 0 
    Details
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1524-475X.1996.40203.x
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  • 6
    Electronic Resource
    Electronic Resource
    Becaplermin gel in the treatment of pressure ulcers: a phase II randomized, double-blind, placebo-controlled study (1999)
    Oxford, UK : Blackwell Science Inc
    Wound repair and regeneration 7 (1999), S. 0 
    Details
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Pressure ulcers are associated with significant rates of morbidity and mortality, particularly in the geriatric and spinal cord–injured populations. Newer pharmacologically active therapies include the use of topically applied recombinant human platelet-derived growth factor-BB (becaplermin), the active ingredient in REGRANEX® (becaplermin) Gel 0.01%, which has been approved in the United States for treatment of lower extremity diabetic neuropathic ulcers that extend into the subcutaneous tissue or beyond and have an adequate blood supply. In this study, the efficacy of becaplermin gel in the treatment of chronic full thickness pressure ulcers was compared with that of placebo gel. A total of 124 adults (≥ 18 years of age) with pressure ulcers were assigned randomly to receive topical treatment with becaplermin gel 100 μg/g (n = 31) or 300 μg/g (n = 32) once daily alternated with placebo gel every 12 hours, becaplermin gel 100 μg/g twice daily (n = 30), or placebo (sodium carboxymethylcellulose) gel (n = 31) twice daily until complete healing was achieved or for 16 weeks. All treatment groups received a standardized regimen of good wound care throughout the study period. Study endpoints were the incidence of complete healing, the incidence of ≥ 90% healing, and the relative ulcer volume at endpoint (endpoint/baseline). Once-daily treatment of chronic pressure ulcers with becaplermin gel 100 μg/g or 300 μg/g significantly increased the incidences of complete and ≥ 90% healing and significantly reduced the median relative ulcer volume at endpoint compared with that of placebo gel (p 〈 0.025 for all comparisons). Becaplermin gel 300 μg/g did not result in a significantly greater incidence of healing than that observed with 100 μg/g. Treatment with becaplermin gel was generally well tolerated and the incidence of adverse events was similar among treatment groups. In conclusion, once-daily application of becaplermin gel is efficacious in the treatment of chronic full thickness pressure ulcers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1524-475X.1999.00141.x
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  • 7
    Electronic Resource
    Electronic Resource
    In vivo characterization of keratinocyte growth factor-2 as a potential wound healing agent (1999)
    Oxford, UK : Blackwell Science Inc
    Wound repair and regeneration 7 (1999), S. 0 
    Details
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Human keratinocyte growth factor-2 exerts a proliferative effect on epithelial cells and mediates keratinocyte migration. It has also been shown to increase both deposition of granulation tissue and collagen and maturation of collagen. Because these properties should affect the healing trajectory of wounds, this study set out to investigate the effects of keratinocyte growth factor-2 on the healing of three different types of wounds. Human meshed skin grafts explanted to athymic “nude” rats, surgical incisions in Sprague-Dawley rats, and acute excisional rat wounds inoculated with Escherichia coli were used. Two concentrations of recombinant human keratinocyte growth factor-2 were compared to a vehicle control and keratinocyte growth factor-1. Keratinocyte growth factor-2 significantly accelerated the rate of epithelialization in the meshed skin graft model and effected a modestly more rapid gain in breaking strength of surgical incisions than keratinocyte growth factor-1 or the vehicle control treatment. Neither keratinocyte growth factors accelerated wound closure by contraction of the excisional wounds. Based on these data, keratinocyte growth factor-2 may be useful in accelerating healing in wounds healing mainly by the process of epithelialization such as venous stasis ulcers, partial thickness burn wounds, and skin graft donor sites. It might also accelerate the gain in incisional wound strength in acute surgical or traumatic wounds.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1524-475X.1999.00172.x
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  • 8
    Electronic Resource
    Electronic Resource
    Significance of cell cycle for wound stratification in clinical trials: analysis of a pressure ulcer clinical trial utilizing cyclin D/cdk4 (2003)
    Malden, USA : Blackwell Science Inc
    Wound repair and regeneration 11 (2003), S. 0 
    Details
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: During the past 5 years, progress in the treatment of pressure ulcers appears to have reached a plateau. Several factors in the design of recent clinical studies may have contributed to this situation. These factors include the criteria chosen for patient selection, small sample size, and lack of a concisely defined final clinical outcome. Hunt noted that wound stratification according to a patient's physiological characteristics may be a key to quantifying differences among clinical treatments.1To address this issue, we examined the expression of cyclin D/cdk4 in pressure ulcer fibroblasts taken from tissues during a recent clinical trial. The treatment groups included patients treated with the following regimens: placebo, granulocyte macrophage-colony stimulating factor alone, basic fibroblast growth factor alone, or granulocyte macrophage-colony stimulating factor and basic fibroblast growth factor given in sequence.2 Immunocytochemical colocalization of cyclin D and cdk4 showed that, before the initial treatment began, patients were distributed disproportionately among treatment subgroups in regards to the initial expression of these markers. For example, we found that compared with other subgroups, ulcer fibroblasts in the basic fibroblast growth factor treatment group showed a much lower expression of cyclin D/cdk4 at day 0. However, this group exhibited higher levels of expression of this complex after 35 days of treatment. This study shows that measurement of cyclin D/cdk4 expression permits more accurate stratification of patients within treatment subgroups, measurement of a cell's ability to detect the presence of functional cytokines, identification of area(s) of failure within the G1 of the cell cycle, and a basis for critical evaluation of various treatments. (WOUND REP REG 2003;11:11–18)
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1524-475X.2003.11104.x
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  • 9
    Electronic Resource
    Electronic Resource
    Ratios of activated matrix metalloproteinase-9 to tissue inhibitor of matrix metalloproteinase-1 in wound fluids are inversely correlated with healing of pressure ulcers (2002)
    Malden, USA : Blackwell Science Inc
    Wound repair and regeneration 10 (2002), S. 0 
    Details
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previous analyses of fluids collected from chronic, nonhealing wounds found elevated levels of inflammatory cytokines, elevated levels of proteinases, and low levels of growth factor activity compared with fluids collected from acute, healing wounds. This led to the general hypothesis that chronic inflammation in acute wounds produces elevated levels of proteinases that destroy essential growth factors, receptors, and extracellular matrix proteins, which ultimately prevent wounds from healing. To test this hypothesis further, pro- and activated matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), and the ratios of MMPs/TIMPs were assayed in fluids and biopsies collected from 56 patients with chronic pressure ulcers. Specimens included ulcers treated for 0, 10, and 36 days with conventional therapy or with exogenous cytokine therapies. Quantitative assay data were correlated with the amount of healing. The average MMP-9/TIMP-1 ratio in fluids from 56 ulcers decreased significantly as the chronic pressure ulcers healed. Furthermore, the average MMP-9/TIMP-1 ratio was significantly lower for fluids collected on day 0 from wounds that ultimately healed well (≥85% reduction in initial wound volume) compared with wounds that healed poorly (〈50% wound volume reduction). These data show that the ratio of MMP-9/TIMP-1 levels is a predictor of healing in pressure ulcers and they provide additional support for the hypothesis that high levels of MMP activity and low levels of MMP inhibitor impair wound healing in chronic pressure ulcers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1524-475X.2002.10903.x
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  • 10
    Electronic Resource
    Electronic Resource
    Dynamic forces in the cell cycle affecting fibroblasts in pressure ulcers (2001)
    Oxford, UK : Blackwell Science Inc
    Wound repair and regeneration 9 (2001), S. 0 
    Details
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Utilizing specific cell cycle markers of gene activity, temporal changes in the equilibrium of proliferating and non proliferating fibroblasts were shown in pressure ulcers after 36 days of quality care. Average cell counts from multiple tissue sections showed that fibroblast nuclei were stained in decreasing order by antibodies to p21, p21/proliferating cell nuclear antigen (PCNA) and PCNA. P21 labeling suggested that the majority of ulcer fibroblasts were senescent. Fibroblast nuclei showing PCNA staining identified those fibroblasts that were capable of synthesizing DNA and contributing to pressure ulcer repair. Increased rates of wound closure were correlated with a decreasing number of p21 positive cells and an increasing portion of PCNA labeled cells. While the proportion of antigens appeared to correlate with the status of wound closure after 36 days of quality care, they did not always appear to reflect the final outcome of the pressure ulcer. No significant differences were observed in ulcer fibroblasts labeled with p21 at 0 and 10 days, however, the differences were significant after 36 days of quality care (p= 0.05, analysis of variance, post hoc Tukey test). The cellular contribution to pressure ulcer repair appeared to occur from ulcer fibroblasts that were ca-pable of division, of emerging from quiescence, and that were successful in repairing their DNA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1524-475x.2001.00019.x
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