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Characterization of Wound Repair Effects after rAd‐p21 Treatment
Author(s) -
Looper D.,
Kang D.W.,
Gu DL.,
Maneval D.,
Zepeda M.
Publication year - 2004
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2004.0abstractas.x
Subject(s) - in vivo , wound healing , medicine , ultimate tensile strength , fibroblast , andrology , adverse effect , surgery , pharmacology , in vitro , chemistry , biology , materials science , biochemistry , microbiology and biotechnology , metallurgy
Excessive scarring is a significant clinical problem, resulting in both adverse tissue form and function and the goal of therapeutic interventions is to reduce and prevent excessive scarring. We have demonstrated that a recombinant adenovirus containing the cyclin‐dependent kinase inhibitor p21 (rAd‐p21), inhibited scar formation by blocking cell cycle progression and attenuated cell proliferation at the wound site ( Perkins et al 2002 ). Recently, we have shown rAd‐p21 specific antiproliferative effects on granulation tissue in vivo ( Gu , et al , manuscript submitted). Safety parameters using rAd‐p21 for anti‐scarring may include effects on wound strength and dehiscence of the wound. We tested effects of rAd‐p21 on wound strength in vivo using tensile strength as an endpoint and included comparisons with other clinically relevant antiproliferative agents. Specifically, rAd‐p21 at doses from 1 × 10 7 to 3.8 × 10 10 particle (PN) per incision was administered intradermally to linear rat incisions and assayed 14–28 days post treatment. rAd‐p21 mildly reduced tensile strength at high doses (≥3 × 10 10 PN), whereas low to moderate doses (1 × 10 7 to 1 × 10 10 PN) had no effect. Interestingly, all rAd‐p21 treated wounds regained tensile strength indistinguishable from vehicle control, 4 weeks after treatment, suggesting that rAd‐p21 wounds recover with time. An adenovirus control vector, not containing a gene (rAd‐Empty), showed subtle reduction of tensile strength that was only statistically significant at day 21. This suggests that delivery of rAd‐Empty alone in the wound has little effect on wound strength. Triamcinolone at 5 mg/mL/wound, 5‐FU at 10 mg/mL/wound, and low doses of MMC did not significantly reduce tensile strength, although high doses of MMC (0.2 mg/mL/wound) severely reduced tensile strength which failed to recover after 28 days. Morphological analysis of all groups revealed necrosis only in the MMC treatment. This data suggests that rAd‐p21 may reduce the hyperproliferative status in excessive scar formation with minimal effects on wound strength.