Collagen and heparin matrices for growth factor delivery

Transforming growth factor-beta 2 (TGF-beta 2) loses biological activity under physiological conditions as measured by its loss of activity in phosphate buffered saline (PBS), pH 7.4 at 37 degrees C. Studies were carried out to determine if TGF-beta 2 could be stabilized by the production of a heparin/TGF-beta 2 (Hep/TGF-beta 2) complex. In vitro studies showed that Hep/TGF-beta 2 remained active and TGF-beta 2 alone lost activity, when stored for:2 months in PBS at 37 degrees C, as measured by a Mink lung bioassay. These findings show the utility of using a heparin/TGF-beta 2 complex to stabilize the TGF-beta 2. Stable Hep/TGF-beta 2 complex was mixed with injectable fibrillar collagen for use as a tissue scaffold material. Collagen and TGF-beta 2 formulations were tested for in vivo activity in a rat subcutaneous model. Forty-five animals were implanted with two injections of fibrillar collagen (FC), fibrillar collagen with heparin and guinea pig serum albumin (FC/Hep/GSA), fibrillar collagen with TGF-beta 2 (FC + TGF-beta 2), or fibrillar collagen with heparin/TGF-beta 2 complex (FC + Hep/TGF-beta). Five animals were explanted at day 7, 21 and 42. The FC + Hep/TGF-beta 2 formulation and FC + TGF-beta 2, admired formulation both produced increased extracellular matrix deposition and activation of cells in vivo. The ability of the FC + Hep/TGF-beta 2 complex to recruit fibroblasts and produce new connective tissue locally, demonstrates the TGF-beta 2 activity of the FC + Hep/TGF-beta 2 complex in vivo. (C) 1997 Elsevier Science B.V.