Multimodal release of transforming growth factor-β1 and the BB isoform of platelet derived growth factor from PEGylated fibrin gels

We designed a growth factor release system to potentially stabilize neovascularization in the treatment of ischemic tissue. In this study, the release of PDGF-BB and TGF-β1 was controlled with distinct kinetics from injectable PEGylated fibrin gels. Growth factors can be loaded into PEGylated fibrin gels via 3 mechanisms: entrapment, conjugation through a homobifunctional amine reactive PEG linker, and physical affinity with the fibrin matrix. PDGF-BB was entrapped during thrombin-mediated crosslinking leading to a diffusion-controlled release over 2 days. TGF-β1 was both conjugated through the PEG linker and bound to the matrix via physical affinity, delaying the release rate of TGF-β1 up to 10 days. Further, the release rate was highly correlated to gel degradation rate indicating that TGF-β1 release is degradation-controlled. Therefore, by modulating the molar ratio of PEG to fibrinogen, we were able to control the release rate of TGF-β1 without altering the release kinetics of PDGF-BB. The bioactivity of loaded TGF-β1 was maintained upon release as evidenced by the inhibition of cell proliferation. This system could be expanded to incorporate growth factors loaded via 3 schemes with differing release rates from an injectable system allowing for a high degree of flexibility in other combinational drug delivery and tissue engineering systems.

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