title: Controlled delivery of platelet-rich plasma-derived growth factors for bone formation.
abstract: Platelet-rich plasma (PRP) represents an autologous source of growth factors essential for bone regeneration. The clinical efficacy of PRP is, however, unpredictable, and this is likely due to the inefficient and inconsistent delivery of PRP-derived growth factors. Previous investigations have shown that current methods of PRP preparation result in a premature release of the relevant bone stimulatory factors. As successful bone regeneration requires multiple factors presented in a physiologic temporal and spatial cascade, the objective of this study is to control the bioavailability of PRP-derived growth factors using a hydrogel carrier system. Specifically, the release of platelet-derived growth factor, transforming growth factor beta-1, and insulin-like growth factor from two types of alginate carriers was compared over time. The effects of the released factors on the growth and alkaline phosphatase (ALP) activity of human osteoblast-like cells were also evaluated. It was found that factor release profiles varied as function of carrier type, and binding of growth factors to the alginate matrix also modulated their release. The bioactivity of released factors was maintained in vitro and they promoted cell proliferation and ALP activity. These results demonstrate the potential of this autologous multifactor delivery system for controlling the bioavailability of PRP-derived factors. Future studies will focus on optimizing this system to increase the clinical efficacy of PRP by matching the distribution and temporal sequencing of PRP-derived factors to the bone healing cascade.
authors.affiliation: Biomaterials and Interface Tissue Engineering Laboratory, Department of Biomedical Engineering, Columbia University, New York, New York 10027, USA. hl2052@columbia.edu
authors.forename: Helen H
authors.initials: HH
authors.lastname: Lu
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Vo
authors.forename: Hsin Sheila
authors.initials: HS
authors.lastname: Chin
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lin
authors.forename: Matthew
authors.initials: M
authors.lastname: Cozin
authors.forename: Rick
authors.initials: R
authors.lastname: Tsay
authors.forename: Sidney
authors.initials: S
authors.lastname: Eisig
authors.forename: Regina
authors.initials: R
authors.lastname: Landesberg
mesh_terms: D000464:Alginates / Q000378:metabolism; D001861:Bone Regeneration / Q000187:drug effects; D002214:Capsules; D002454:Cell Differentiation / Q000187:drug effects; D004337:Drug Carriers / Q000494:pharmacology; D016503:Drug Delivery Systems; D020723:Glucuronic Acid / Q000378:metabolism; D006603:Hexuronic Acids / Q000378:metabolism; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007700:Kinetics; D008863:Microspheres; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D053657:Platelet-Rich Plasma / Q000737:chemistry*; D013002:Somatomedins / Q000494:pharmacology; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D000464:Alginates; D002214:Capsules; D004337:Drug Carriers; D006603:Hexuronic Acids; D010982:Platelet-Derived Growth Factor; D013002:Somatomedins; D053773:Transforming Growth Factor beta1; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020723:Glucuronic Acid