Pretreatment of photoaged forearm skin with topical tretinoin accelerates healing of full-thickness wounds

Popp, Christina; Kligman, Albert M.; Stoudemayer, T.

doi:10.1111/j.1365-2133.1995.tb08623.x

Cited by 66 publications

(43 citation statements)

References 25 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%

See 1 more Smart Citation

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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“…[3][4][5] The effects of tretinoin therapy on open wounds are still unclear. A recent report by Paquette et al 6 found that short-contact daily application of topical tretinoin improved the healing of chronic leg ulcers in 5 patients who were taking immunosuppressive agents for systemic illnesses.…”

Section: Ower Extremity Ulcersmentioning

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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“…On the other hand, where skin cell proliferation has slowed (for example, in aged skin), retinoid stimulate growth and result in epidermal thickening [32]. Retinoid stimulatory effects also extend to the dermis, where suppression of the major collagen-degrading enzymes [7,8] and stimulation of procollagen synthesis [13,18,19] improve appearance [16,17,33] and improve the healing of wounds that subsequently occur [2,20,25,34]. In spite of the beneficial effects, the capacity of RA to irritate the skin makes it less than desirable for many users.…”

Section: Discussionmentioning

confidence: 99%

“…Given the ability of RA to reduce collagen damage and induce new collagen synthesis, it is not surprising that topical retinoid use not only improves the appearance of damaged skin but also results in better function. Specifically, a number of past studies have demonstrated that RA-pretreatment improves healing of wounds that subsequently occur in skin that has been damaged as a result of aging/photoaging or as a consequence of diabetes or chronic corticosteroid use [2,20,25,34,36].…”

Section: Introductionmentioning

confidence: 99%

MDI 301, a non-irritating retinoid, induces changes in human skin that underlie repair

2006

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Previous studies have demonstrated that all-trans retinoic acid (RA) increases collagen production and decreases matrix metalloproteinase (MMP) activity in organ-cultured human skin. Decreased MMP activity is associated with up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1). These changes are accompanied by a hyperplastic response in the epidermis. Here we show that a synthetic picolinic ester-substituted retinoid (designated as MDI 301) has comparable effects to those of RA in regard to these activities. What makes these findings of interest is that RA also stimulates elaboration of several pro-inflammatory cytokines and up-regulates leukocyte adhesion molecules in organ-cultured skin. MDI 301 does not induce such changes or is much less active. In a past study we showed that while RA was irritating to the skin of topically treated hairless mice, MDI 301 was essentially non-irritating under the same conditions [Varani et al. (2003) Arch. Dermatol Res 295:255-262]. Taken in conjunction with the findings from the past study, the present data suggest that MDI 301 will be similar to RA in capacity to repair damaged skin, but will be effective under conditions that are not irritating. These findings, thus, suggest that retinoid efficacy and clinically relevant irritancy are not inextricably linked. Potential for efficacy under conditions in which irritation is not observed is a strong rationale for further development of MDI 301 as a skin-repair agent.

show abstract

Pretreatment of photoaged forearm skin with topical tretinoin accelerates healing of full-thickness wounds

Cited by 66 publications

References 25 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

MDI 301, a non-irritating retinoid, induces changes in human skin that underlie repair

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