Tethered-TGF-beta increases extracellular matrix production of vascular smooth muscle cells

Biomaterials developed for tissue engineering and wound healing application s need to support robust cell adhesion, yet also need to be replaced by new tissue synthesized by those cells. In order to maintain mechanical integri ty of the tissue, the cells must generate sufficient extracellular matrix b efore the scaffold is degraded. We have previously shown that materials con taining cell adhesive ligands to promote or improve cell adhesion can decre ase extracellular matrix production (Mann et al.. Modification of surfaces with cell adhesion peptides alters extracellular matrix deposition. Biomate rials 1999:20:2281-6). Such decreased matrix production by cells in tissue engineering scaffolds may result in tissue failure. However. we have found that TGF-beta1 can be used in scaffolds to dramatically increase matrix pro duction. Matrix production by vascular smooth muscle cells grown on adhesiv e ligand-modified glass surfaces and in PEG hydrogels containing covalently bound adhesive ligands was increased in the presence of 0.04 pmol/ml (1 ng /ml) TGF-beta1, TGF-beta1 can counteract the effect of these adhesive ligan ds on matrix production; matrix production could be increased even above th at observed in the absence of adhesive peptides. Further, TGF-beta1 covalen tly immobilized to PEG retained its ability to increase matrix production. Tethering TGF-beta1 to the polymer scaffold resulted in a significant incre ase in matrix production over the same amount of soluble TGF-beta1. (C) 200 1 Elsevier Science Ltd. All rights reserved.