Specific effects of glycosaminoglycans in an analog of extracellular matrix that delays wound contraction and induces regeneration.
Previous studies have shown that a simple analog of extracellular matrix delays wound contraction and, if seeded with keratinocytes, inhibits scar synthesis by inducing partial regeneration of the dermis and the epidermis in full-thickness skin wounds in the guinea pig. The active extracellular matrix analog was selected from a large number of copolymers of type I collagen and chondroitin-6-sulfate differing in average pore diameter and degradation rate. However, these previous studies did not provide information on the potential role of the glycosaminoglycan component of this collagen-glycosaminoglycan matrix. The present study focuses on the effect of substitution of chondroitin-6-sulfate by other glycosaminoglycans or with the corresponding proteoglycans. The three substituents of chondroitin-6-sulfate studied were dermatan sulfate, decorin (a proteoglycan-containing dermatan sulfate chain), and aggrecan (a proteoglycan in which 90% of the glycosaminoglycan component was chondroitin-6-sulfate). Each test matrix was grafted on full-thickness skin wounds in the guinea pig, and the wound contraction kinetics were followed. Previous studies have strongly suggested that delay in onset of contraction is necessary for regeneration. Substitution of chondroitin-6-sulfate by either dermatan sulfate or decorin increased the delay in wound contraction by the greatest increment. However, the difference between substitution either by the dermatan sulfate chains or by the corresponding proteoglycan was not significant. Substitution of chondroitin-6-sulfate by aggrecan did not affect the activity of the extracellular matrix analog. These results suggest that the glycosaminoglycan component of the proteoglycan, rather than the protein core, is responsible for the increment of activity. It is speculated that the morphogenetic activity of the extracellular matrix analog resides in its putative ability to neutralize transforming growth factor-beta, leading thereby to downregulation of the inflammatory response in the wound bed.
Shafritz
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TA
Harvard Medical School/MIT Division of Health Sciences and Technology, Cambridge, Mass., USA.
Rosenberg
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LC
Yannas
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