Hanwei Li, PhD, and colleagues apply tissue-engineering strategies to investigate the role of matrix metalloproteinases (MMPs) in keloid pathophysiology. The authors created 3-dimensional models from fibroblasts derived from keloid tissue and different biocompatible matrices. Matrix metalloproteinases 9 and 13 were upregulated in keloid derived cells. The addition of decorin, a glycosaminoglycan, to keloid fibroblasts significantly decreased type I collagen and MMP 1, MMP 9, and MMP 13 gene expressions. Furthermore, higher MMP gene expressions were observed in fibroblasts isolated from the margins of the original keloid wound compared with the center. The study provides insight to improving the study of keloids and suggests potential targets for therapy.