Editors' ChoiceDrug Delivery

Scar Tactics

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Science Translational Medicine  08 Dec 2010:
Vol. 2, Issue 61, pp. 61ec192
DOI: 10.1126/scitranslmed.3001992

A Google search of the words "scar removal" returns more than 1 million hits in less than a 10th of a second. The thousands of products—creams, oils, lasers, injectables—designed to rid the world of scars supports the notion that for individuals who are suffering from traumatic injuries or prepping for surgery, scar formation is a focus. Finding an efficacious scar removal treatment can be frustrating. But what about blocking scar formation in the first place? Alas, attempts to prevent scars from arising by using topical formulations have met with limited success because these agents penetrate tissues poorly and are quickly destroyed by proteases in the wound. Now, Jarvinen et al. describe an innovative strategy for the targeted delivery of a scar-reducing agent, decorin, by fusion with a wound-homing peptide.

The body’s natural response to tissue injury involves a rapid proliferation of fibroblast cells, which enhance the production of extracellular matrix compounds and replace damaged tissue with a fibrous scar. Transforming growth factor–β1 (TGF-β1), a major driver of this process, can be inhibited by decorin, a protein that has been difficult to manufacture in large quantities. By adding a wound-homing peptide—CAR, which recognizes regenerating blood vessels—decorin was specifically directed into tissue at sites of injury. The CAR-decorin fusion protein, when given intravenously to mice on day 3 after wounding and continued for 7 to 11 days, accelerated wound closure and significantly reduced the size of the resultant scar. The expression of several TGF-β–induced genes implicated in scar formation was reduced by CAR-decorin treatment, suggesting that the antiscarring properties of the fusion protein can be attributed to inhibition of TGF-β1 activity.

This study by Jarvinen et al. demonstrates that scar-reducing agents such as decorin can be administered systemically and achieve targeted delivery. And, through the new delivery method, decorin blocks scar formation at lower doses than it does when applied topically. Systemic treatment offers the additional ability to reduce scar formation in internal organs and may be useful in the prevention of permanent scars that form after ischemic events, such as heart attacks and strokes. Because the CAR peptide also targets tumor vasculature and decorin has antitumor properties, the CAR-decorin protein may have potential as a treatment for malignant diseases.

T. A. H. Järvinen, E. Ruoslahti, Target-seeking antifibrotic compound enhances wound healing and suppresses scar formation in mice. Proc. Natl. Acad. Sci. U.S.A. 24 November 2010 (10.1073/pnas.1016233107). [Abstract]

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