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 2days. 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 10days. 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.
Drinnan
Charles T
CT
Department of Biomedical Engineering, University of Texas, Austin, United States. c.drinnan@mail.utexas.edu
Zhang
Ge
G
Alexander
Marc A
MA
Pulido
Arlynn S
AS
Suggs
Laura J
LJ
D000818:Animals; D000077214:Becaplermin; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D004338:Drug Combinations; D004339:Drug Compounding; D004355:Drug Stability; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005337:Fibrin / Q000737:chemistry*; D005340:Fibrinogen / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry; D007700:Kinetics; D008907:Mink; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry*; D055550:Protein Stability; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry; D012995:Solubility; D023822:Tissue Engineering / Q000379:methods*; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004338:Drug Combinations; D020100:Hydrogels; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D000077214:Becaplermin; D011092:Polyethylene Glycols; D005337:Fibrin; D005340:Fibrinogen