Using growth factor conditioning to modify the properties of human cell derived extracellular matrix

We have recently reported on a bench-top approach for isolating extracellular matrix (ECM) from pure populations of cells grown in culture using sacrificial, open-celled foams to concentrate and capture the ECM. To increase both the accumulation and the strength of the ECM harvested, cell-seeded polyurethane (PU) foams were cultured in media supplemented with either transforming growth factor β-1 (TGFβ1) or hepatocyte growth factor (HGF). At the end of a 3-week culture period, ECM yield was significantly increased for samples conditioned in supplemented media. Control foams yielded 48 ± 12 mg of material for every gram of PU foam seeded. Yield values increased to 102 ± 21 and 243 ± 25 mg for HGF and TGFβ1-treated samples, respectively. HGF supplementation increased the modulus by 59%, while TGFβ1 treatment increased the elastic modulus by 204%. TGFβ1-stimulated material was organized into a network that was markedly denser than control material, with HGF-stimulated network density intermediate to TGFβ1 and controls. Our study showed that TGFβ1-treated samples were collagen enriched while HGF samples had an increased gylcosaminoglycan concentration. The results demonstrate that growth factor supplementation, particularly with TGFβ1, can significantly alter the biomechanical properties of cell-derived ECM that may be used for therapeutic applications.