Preoperative and Postoperative Topical Tretinoin on High-Tension Excisional Wounds and Full-Thickness Skin Grafts in a Porcine Model: A Pilot Study

Otley, Clark C.; Gayner, Scott M.; Ahmed, Iftikhar; Moore, Eric J.; Roenigk, Randall K.; Sherris, David A.

doi:10.1046/j.1524-4725.1999.99005.x

Cited by 19 publications

(14 citation statements)

References 11 publications

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“…Several past studies have, in fact, demonstrated beneficial effects of retinoid use in wound healing. Although most of these studies have focused on wounds in the skin, [11][12][13][14][15][16][17] retinoid efficacy has also been demonstrated in healing of wounds in other tissues-bone, cornea, respiratory tract, upper digestive system, and gut. [18][19][20][21][22][23][24][25] Although retinoids have beneficial activities, skin irritation is commonly seen following topical application of RA.…”

Section: Discussionmentioning

confidence: 99%

“…Although most studies have focused on wounds in the skin, [11][12][13][14][15][16][17] retinoid efficacy has also been demonstrated in healing of wounds in other tissues (bone, cornea, respiratory tract, upper digestive system, and gut). 27 Likewise, skin irritation is also a complication with synthetic retinoidal agents currently on the market.…”

Section: Introductionmentioning

confidence: 99%

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MDI 301, a nonirritating retinoid, improves abrasion wound healing in damaged/atrophic skin

Warner

Bhagavathula

Nerusu

et al. 2008

Wound Repair Regeneration

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MDI 301 is a picolinic acid-substituted ester of 9-cis retinoic acid. It has been shown in the past that MDI 301 increases epidermal thickness, decreases matrix metalloproteinase (MMP) activity, and increases procollagen synthesis in organ-cultured human skin. Unlike all-trans retinoic acid (RA), MDI 301 does not induce expression of proinflammatory cytokines or induce expression of leukocyte adhesion molecules in human skin. In the present study we examined topical MDI 301 treatment for ability to improve the structure and function of skin in three models of skin damage in rodents and for ability to improve abrasion wound healing in these models. MDI 301 was applied daily to the skin of rats treated with the potent corticosteroid, clobetasol propionate, to the skin of diabetic rats (8 weeks posttreatment with streptozotocin) and to the skin of aged (14-16-month-old) rats. In all three models, subsequently induced abrasion wounds healed more rapidly in the retinoid-treated animals than in vehicle-treated controls. Immediately after complete wound closure, tissue from the wound site (as well as from a control site) was put into organ culture and maintained for 3 days. At the end of the incubation period, culture fluids were assessed for soluble type I collagen and for MMPs-2 and -9. In all three models, the level of type I collagen was increased and MMP levels were decreased by MDI 301. In all three models, skin irritation during the retinoid-treatment phase was virtually nonexistent.Minor abrasions that occur in healthy skin are expected to heal without incident. Interventions are designed primarily to prevent infection and to provide support for the body's own regenerative mechanisms. In contrast, wounds in chronically damaged and atrophic skin often go on to form nonhealing ulcers with devastating consequences. Diabetes alone is a contributing factor in up to 70% of the > 55,000 amputations that occur annually. [1][2][3][4] Skin that has become atrophic as a consequence of the aging process also demonstrates impaired wound healing, 5-7 as does skin that has been damaged as a result of extended corticosteroid use. [8][9][10] The majority of wound-healing research is directed toward understanding the pathophysiology of impaired wound healing and identifying interventions that can mitigate the critical patho-physiological events.Several past studies have demonstrated the efficacy of all-trans retinoic acid (RA) and its parent compound all-trans retinol (ROL, vitamin A) in wound healing. Although most studies have focused on wounds in the skin, [11][12][13][14][15][16][17] retinoid efficacy has also been demonstrated in healing of wounds in other tissues (bone, cornea, respiratory tract, upper digestive system, and gut). 27 Likewise, skin irritation is also a complication with synthetic retinoidal agents currently on the market. 28 Irritation is a major cause of non-compliance among retinoid users. In addition, excessive irritation may counteract the beneficial effects of retinoid use or actually predispo...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MDI 301, a nonirritating retinoid, improves abrasion wound healing in damaged/atrophic skin

Warner

Bhagavathula

Nerusu

et al. 2008

Wound Repair Regeneration

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“…4 Application on already open wounds, however, has yielded varying results. In some animal models, tretinoin therapy has been found to enhance healing 4,15,16 ; in others, it has been shown to have no effect 17 or to cause inflammation and excessive granulation without reepithelialization. 5,18 It has been suggested that tretinoin may be too irritating when applied after wounding has occurred, especially to the surrounding skin.…”

Section: Commentmentioning

confidence: 99%

The Effect of Short-Contact Topical Tretinoin Therapy for Foot Ulcers in Patients With Diabetes

Tom¹,

Peng²,

Allaei³

et al. 2005

Arch Dermatol

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Interventions: Patients were randomized to 4 weeks of daily treatment with either topical 0.05% tretinoin solution (Retin-A) or placebo saline solution. Photographs and assessment of wound size and appearance were assessed every 2 weeks for a total of 16 weeks. Main Outcome Measures:The proportion of ulcers that healed in each group and the degree of change in ulcer size.Results: Twenty-two patients, with a total of 24 foot ulcers, completed the study. At the end of 16 weeks, 2 (18%) of 11 ulcers in the control group and 6 (46%) of 13 ulcers in the tretinoin treatment group healed completely. Topical tretinoin therapy significantly decreased ulcer area and depth compared with placebo treatment over the 16 weeks of the study (PϽ.01 for surface area; P = .02 for depth). Adverse effects mainly consisted of mild pain at the ulcer site.Conclusions: Short-contact application of topical tretinoin improved the healing of foot ulcers in patients with diabetes. The tretinoin therapy was generally well tolerated, without serious local or systemic adverse effects.

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“…Use of direct-current electrical field, hyperbaric oxygen therapy, and pharmacologic applications of phenytoin, tretinoin, and fibrin tissue adhesive glue have been reported. [3][4][5][6][7][8][9][10] Growth factors are members of a large functional group of polypeptide regulatory molecules, secreted by many different cell lines through autocrine and paracrine fashions, influencing the biologic activities of responsive cells. 14,15 Experimental studies have found that the levels of growth factors increased at the wound sites, which promoted nutrient flow, angiogenesis, and vascular remodeling necessary for skin graft survival.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, some efforts have been made to improve skin graft take in such wounds, including use of direct-current electrical field, hyperbaric oxygen therapy, and pharmacologic applications of phenytoin, tretinoin, and fibrin tissue adhesive glue. [3][4][5][6][7][8][9][10] The results from these methods were inconsistent.…”

mentioning

confidence: 99%

Improvement of Full-Thickness Skin Graft Survival by Application of Vascular Endothelial Growth Factor in Rats

Zhang

Oswald

Lin

et al. 2008

Annals of Plastic Surgery

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The effect of vascular endothelial growth factor (VEGF) on skin graft survival was studied in rats. Models of skin grafting on muscle and periosteum were designed. For the study of skin grafting on muscle model, 32 rats were divided into 4 groups. VEGF was administrated systemically after skin graft placement intrafascially injected into the recipient bed at the time of graft placement and topically applied to the recipient bed at the time of graft placement. Control groups consisted of grafts placed on sites without systemic or local VEGF treatment. With the study of skin grafting on periosteum, 40 rats were divided into 4 groups. VEGF was systemically, intraperiosteally, and topically applied to the recipient bed. The control animals received no treatment. On the fifth postoperative day, the survival area of each skin graft was measured and the graft was harvested for histology with CD31 immunohistochemical staining. The results showed that in skin grafting on muscle model, the mean viable percentage of the skin graft was 66.1% +/- 10.2% in the group receiving systemic application of VEGF and 56.1% +/- 9.8% in the group receiving VEGF intrafascia injection. The survival percentages were significantly higher than those found in the control group (22.5% +/- 7.7%) and the group with VEGF topical application (30.8% +/- 4.1%). In skin grafting on periosteum, the group receiving VEGF intraperiosteum injection reached a survival percentage of 50.5% +/- 4.3%, significantly higher than the groups with VEGF systemic application (28.7 +/- 5.5%), VEGF topical application (32.5% +/- 4.8%), and the control (25.8% +/- 6.0%). Histology showed that sections taken from grafts with VEGF intrafascia and intraperiosteum treatment revealed angiogenesis. The data demonstrated that administration of VEGF into the either muscular or periosteal recipient beds for skin grafting can improve the skin graft survival.

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Preoperative and Postoperative Topical Tretinoin on High-Tension Excisional Wounds and Full-Thickness Skin Grafts in a Porcine Model: A Pilot Study

Cited by 19 publications

References 11 publications

MDI 301, a nonirritating retinoid, improves abrasion wound healing in damaged/atrophic skin

MDI 301, a nonirritating retinoid, improves abrasion wound healing in damaged/atrophic skin

The Effect of Short-Contact Topical Tretinoin Therapy for Foot Ulcers in Patients With Diabetes

Improvement of Full-Thickness Skin Graft Survival by Application of Vascular Endothelial Growth Factor in Rats

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