The Matrix-Binding Domain of Microfibril-Associated Glycoprotein-1 Targets Active Connective Tissue Growth Factor to a Fibroblast-Produced Extracellular Matrix

It is advantageous to use biomaterials in tissue engineering that stimulate extracellular matrix (ECM) production by the cellular component. Connective tissue growth factor (CTGF) stimulates type I collagen (COL1A1) transcription, but is functionally limited as a free molecule. Using a matrix-binding domain (MBD) from microfibril-associated glycoprotein-1, the fusion protein MBD-CTGF was targeted to the ECM and tested for COL1A1 transcriptional activation. MBD-CTGF produced by the ECM-synthesizing fibroblasts, or provided exogenously, localized to the elastic fiber ECM. MBD-CTGF, but not CTGF alone, led to a two-fold enhancement of COL1A1 expression. This study introduces a targeting technology that can be used to elevate collagen transcription in engineered tissues and thereby improve tissue mechanics.Evolution of the elastic fiber protein MAGP-1 has produced an intriguing solution to a common tissue engineering problem: how can a fully biological scaffold be created that can stimulate extracellular matrix production de novo? By tethering connective tissue growth factor to a cell-derived scaffold using a peptide derived from MAGP-1, Weinbaum et al. have created a completely biological biomaterial endowed with the ability to stimulate collagen production by fibroblasts.