Intradermal Injection of Autologous Dermal Fibroblasts Improves Wound Healing in Irradiated Skin (original) (raw)
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A model of wound healing in chronically radiation-damaged rat skin
Cancer Letters, 1998
The aim of this investigation was to develop a model for studying the chronic effects of radiation on wound healing in the rat. Six months after rats received a single radiation exposure of 20 Gy, a random-pattern dorsal skin flap was elevated. Two weeks after the flap was elevated, irradiated animals showed diminished scar formation and wound breaking strength, as compared with controls (P Ͻ 0.05). The effect of hyperbaric oxygen treatment was investigated in some rats who received 20 sessions at 2.4 atmospheres absolute for 90 min daily, 5 days per week, prior to flap elevation and 10 sessions after creation of the flap. Treated animals showed a trend toward improvements in wound breaking strength and scar formation (P = 0.06). A reproducible model of chronic radiation damage in the rat was established. Further studies involving investigations at times more that 2 weeks post-wounding are needed.
Cutaneous tissue repair: Practical implications of current knowledge. II
Journal of the American Academy of Dermatology, 1985
This article reviews the scientific basis for the certain factors that delay wound repair in the clinical setting. A brief history of wound healing is given, followed by a discussion of endogenous local factors (bacterial infection, hypoxia, foreign body, and desiccation) and endogenous systemic factors (nutritional deficiencies, aging, coagulation disorders, and the Ehlers-Danlos syndromes) associated with poor wound repair. Also reviewed are the mechanisms by which exogenously administered agents (glucocorticoids, antineoplastic agents, and anticoagulants) may delay healing. Commonly used topical antimicrobials, their spectrum of activity, and evidence of effects on wound healing are examined. Finally, properties of commercially available wound coverings and wound care in the future are discussed. (J AM ACAD DERMATOL 13:919-941, 1985.) When, as children, we ripped open our foreheads, noses, chins, elbows, knees, or shins, our mothers comforted, nourished, cleansed, and bandaged us, thus providing the basic elements for optimal wound repair. Their emotional and nutritional support gave us endogenous psychologic and physiologic strength to overcome our injuries, and their cleansing and occlusion of the wounds afforded us with the proper exogenous wound environment for healing. Mothers did these things on the basis of tradition rather than scientific i'"AiJi'~1!1 The CME articles are made possible through an
The Effect of External Beam Irradiation Timing on Skin Graft Survival
European Surgical Research, 2010
Background: The purpose of this study was to evaluate skin graft integrity after external beam irradiation in a rat model. Methods: Forty-eight male Wistar rats were randomly assigned to 8 groups (A, B, C, D, Ac, Bc, Cc and Dc). A rectangular full-thickness skin graft was raised and reapplied to its original bed on the dorsum of each rat. Groups Ac, Bc, Cc and Dc were the control groups and were not given postoperative irradiation. After grafting, 25 Gy unfractioned cobalt60 irradiation was administered to groups A, B, C and D on postoperative days 10, 20, 30 and 40, respectively. Histological samples were obtained 8 weeks after grafting. Dermal and epidermal thickness were measured by the KS-400 image analysis program. Results: The difference in the epidermal and/or dermal thickness between the irradiated groups was not found to be significant. Furthermore, when histological features and the image analysis of the irradiated groups were compared with each other, there were no signif...
Radiation Oncology, 2012
Purpose To describe a pilot study for a novel preclinical model used to test human tissue-based therapies in the setting of cutaneous radiation injury. Methods A protocol was designed to irradiate the skin of athymic rats while sparing the body and internal organs by utilizing a non-occlusive skin clamp along with an x-ray image guided stereotactic irradiator. Each rat was irradiated both on the right and the left flank with a circular field at a 20 cm source-to-surface distance (SSD). Single fractions of 30.4 Gy, 41.5 Gy, 52.6 Gy, 65.5 Gy, and 76.5 Gy were applied in a dose-finding trial. Eight additional wounds were created using the 41.5 Gy dose level. Each wound was photographed and the percentage of the irradiated area ulcerated at given time points was analyzed using ImageJ software. Results No systemic or lethal sequelae occurred in any animals, and all irradiated skin areas in the multi-dose trial underwent ulceration. Greater than 60% of skin within each irradiated zone und...
PubMed, 2023
Background: Late-effect radiation-induced wounds represent a particularly difficult category of wounds to manage and treat. Fibrosis, impaired cellular activity, ischemia, and wound chronicity all work to impair healing, and this becomes more pronounced when defects are large or when avascular structures such as bone are exposed. Effective treatment options for this type of wound are limited. Thorough excision of irradiated tissue followed by distal pedicled or free flap closure is the most successful; however, this often requires multiple-stage surgeries and prolonged hospitalization and is associated with significant donor site morbidity. This is complicated further when wounds are large or in difficult locations, when surgery is not appropriate, or when there is limited access to surgeons with the appropriate experience/skill to perform such procedures. Methods: This case series describes the use of an autologous heterogenous skin construct (AHSC) made from a small full-thickness sample of the patient's healthy skin. Three patients with intractable late-effect radiation wounds were treated with AHSC. Case 1 describes an abdominal wound with tunneling of 7.5 cm to the pubic symphysis, which had been treated for known osteomyelitis, and a shallower full-thickness groin wound. Case 2 describes a right scapular wound with exposed bone, which had failed flap closure. Case 3 describes a right thigh wound in a patient who had been treated for sarcoma with extensive radiation therapy. This eventually resulted in an above-the-knee amputation, which failed to heal, and full exposure of the distal end of the resected femur. All wounds had been present for greater than 10 months. Results: Mean percent volume reduction was 83% (±2.7) at 3 weeks and 92.9% (±4.7) at 4 weeks. The tunneled abdominal wound decreased in depth from 7.5 cm to 1.2 cm in 3 weeks. Complete closure was achieved at 11 weeks for the abdominal and groin wounds (patient 1) and at 16 weeks for the thigh wound (patient 3). The scapular wound volume of patient 2 had decreased by 91.8% at week 4 but was not fully restored until week 21. Mean time to closure was 16.1 (±4.7) weeks. Conclusions: AHSC was effective in covering exposed bone, improving wound bed vascularity, filling in significant wound depth, and achieving complete wound closure with one application in patients with intractable late-effect radiation wounds.
Annals of Surgery, 1995
Comparison of cultured skin substitutes (CSSs) and split-thickness autograft (STAG) was performed to assess whether the requirement for autologous skin grafts may be reduced in the treatment of massive burns. Summary Background Data Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates populated with autologous fibroblasts and keratinocytes have been demonstrated to close full-thickness skin wounds in athymic mice and to express normal skin antigens after closure of excised wounds in burn patients. Methods Data were collected from 17 patients between days 2 and 14 to determine incidence of exudate, incidence of regrafting, coloration, keratinization, and percentage of site covered by graft (n = 17). Outcome was evaluated on an ordinal scale (0 = worst; 10 = best) beginning at day 14, with primary analyses at 28 days (n = 10) and 1 year (n = 4) for erythema, pigmentation, epithelial blistering, surface roughness, skin suppleness, and raised scar. Results Sites treated with CSSs had increased incidence of exudate (p = 0.06) and decreased percentage of engraftment (p < 0.05) compared with STAG. Outcome parameters during the first year showed no differences in erythema, blistering, or suppleness. Pigmentation was greater, scar was less raised, but regrafting was more frequent in CSS sites than STAG. No differences in qualitative outcomes were found after 1 year, and antibodies to bovine collagen were not detected in patient sera. Conclusions These results suggest that outcome of engrafted CSSs is not different from STAG and that increased incidence of regrafting is related to decreased percentage of initial engraftment. Increased rates of engraftment of CSSs may lead to improved outcome for closure of bum wounds, allow greater availability of materials for grafting, and reduce requirements for donor skin autograft.
Radiation responses in skin and connective tissues: effect on wound healing and surgical outcome
Hernia, 2006
Radiation therapy, either alone or in combination with other types of treatment, is responsible for 40% of cancer cures and 70% of all cancer patients receive radiation therapy at some point during the course of their disease. Radiation therapy has profound eVects, both acute and long-term, on skin and connective tissues. Radiation therapy also aVects the time course and end result of wound healing, and the risk of postoperative complications. For example, radiation therapy of tumors in the abdomen or in the abdominal wall inevitably aVects the integrity of abdominal wall structures and may adversely aVect the outcome of operations on the abdominal wall, for example hernia surgery. All surgeons will encounter patients who have undergone or will receive radiation therapy. In these situations, it is important to carefully consider the optimum timing of surgery relative to radiation therapy, to decide which perioperative precautions are needed to minimize the risk of complications, to estimate and inform the patient about the increased risk of complications, and, if surgery is done before a planned course of radiation therapy, to consider how soon after surgery it is safe to commence the radiation treatment. This review will (1) describe features of acute and long term radiation-induced changes in skin and connective tissues; (2) provide a brief overview of the biological mechanisms underlying these changes; and (3) discuss practical considerations that have direct relevance to surgical decision making and postoperative outcome.