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  • 1
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    Journal of Biomedical Materials Research 39 (1998), S. 539-548 
    ISSN: 0021-9304
    Keywords: cytokine delivery via covalent binding ; tissue repair ; biomaterials ; collagen ; transforming growth factor β ; polyethylene glycol ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine , Technology
    Notes: To overcome rapid diffusion and clearance from the implant site and to increase stability, recombinant transforming growth factor β2 (TGF-β2) was covalently bound to injectable bovine dermal fibrillar collagen (FC) and its activity compared to admixed TGF-β2. Covalent binding was achieved in a two-step procedure: First, TGF-β2 was reacted with the difunctional polyethylene glycol (PEG) linker, and then the PEG-attached TGF-β2 (PEG-TGF-β2) was bound to the fibrillar collagen (FC-PEG-TGF-β2). Initial binding of TGF-β2 to difunctional succinimidyl glutarate (D-SG-PEG) or succinimidyl propionate polyethylene glycol (D-SE-PEG) linkers was completed after reacting for 8 or 10 min as monitored by reverse-phase high-performance liquid chromatography. After reaction with injectable fibrillar collagen, extraction of unbound PEG-TGF-β2 and Western blot analysis, using a TGF-β specific antibody, demonstrated that at least 85% of the TGF-β2 was bound to the fibrillar collagen. The activity of PEG-TGF-β2 was fully stable in phosphate-buffered saline at 4°C and 37°C for at least up to 4 weeks. Unmodified TGF-β2 mixed with fibrillar collagen was completely inactivated after 1 week of incubation, as measured by the mink lung epithelial cell (Mv1Lu) growth inhibition assay. Formulations of FC-PEG-TGF-β2 containing 40 μg/mL TGF-β2 were implanted subcutaneously into rats and analyzed after days 7, 21, and 42. All TGF-β2-containing formulations showed the TGF-β typical fibroblastic response at the day 7 time point. Covalent binding of TGF-β2 to collagen with both difunctional PEG crosslinkers resulted in a significantly stronger and longer-lasting TGF-β2 response than that observed with admixed formulations of collagen and TGF-β. The TGF-β response with FC-PEG-TGF-β2 lasted up to day 42 but was not seen after day 7 for TGF-β2 admixed to FC. These findings clearly demonstrate that TGF-β2 remains fully active after being covalently bound to collagen via difunctional PEG. In addition, covalent binding potentiates and prolongs in vivo TGF-β responses and stabilizes the TGF-β in vitro. Results suggest that this method of formulation could be useful to stabilize and deliver similar peptide growth factors or biologically active agents. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 539-548, 1998.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
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