A [polycation:heparin] complex releases growth factors with enhanced bioactivity.
Growth factors are potent molecules that regulate cell functions including survival, self renewal, differentiation and proliferation. High-efficacy delivery of growth factors will be a powerful tool for regenerative medicine. Decades of intense research have significantly advanced the field of controlled delivery. There is, however, still a great unmet need for new methods that can improve overall efficacy of growth factor delivery. Here, we report a new growth factor delivery vehicle formed by self assembly of heparin and a biocompatible polycation, poly(ethylene argininylaspartate diglyceride) (PEAD). Of the many heparin-binding growth factors, we chose FGF-2 and NGF to demonstrate the potential of the [PEAD:heparin] delivery vehicle. The delivery vehicle incorporates both growth factors with high efficiency, controls their release, maintains the bioactivity of FGF-2 and increases the bioactivity of NGF relative to bolus delivery. [PEAD:heparin] appears to be a promising delivery matrix for many heparin-binding growth factors and may lead to efficient growth factor delivery for a variety of diseases and disabilities.
Department of Bioengineering and the McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Hunghao
H
Chu
Noah Ray
NR
Johnson
Neale Scott
NS
Mason
Yadong
Y
Wang
D000818:Animals; D001120:Arginine / Q000737:chemistry; D001224:Aspartic Acid / Q000737:chemistry; D001391:Azo Compounds / Q000737:chemistry; D001557:Benzenesulfonates / Q000737:chemistry; D001682:Biological Availability; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D004853:Epoxy Resins / Q000737:chemistry; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008027:Light; D008751:Methylene Blue / Q000031:analogs & derivatives / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D009474:Neurons / Q000166:cytology; D016716:PC12 Cells; D010316:Particle Size; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry*; D000071228:Polyelectrolytes; D011095:Polyethylenes / Q000138:chemical synthesis / Q000737:chemistry; D051381:Rats; D012542:Scattering, Radiation; D055672:Static Electricity
D001120:Arginine; D001224:Aspartic Acid; D001391:Azo Compounds; D001557:Benzenesulfonates; D004853:Epoxy Resins; D016222:Fibroblast Growth Factor 2; D006493:Heparin; D036341:Intercellular Signaling Peptides and Proteins; D008751:Methylene Blue; D020932:Nerve Growth Factor; D011073:Polyamines; D000071228:Polyelectrolytes; D011095:Polyethylenes; C435946:dimethylmethylene blue; C035364:Quetol 651; C014722:2-naphthol orange