title: Biomimetic calcium phosphate/polyelectrolyte multilayer coatings for sequential delivery of multiple biological factors.
abstract: Combinations of growth factors synergistically enhance tissue regeneration, but typically require sequential, rather than co-delivery from biomaterials for maximum efficacy. Polyelectrolyte multilayer (PEM) coatings can deliver multiple factors without loss of activity; however, sequential delivery from PEM has been limited due to interlayer diffusion that results in co-delivery of the factors. This study shows that addition of a biomimetic calcium phosphate (bCaP) barrier layer to a PEM coating effectively prevents interlayer diffusion and enables sequential delivery of two different biomolecules via direct cell access. A simulated body fluid method was used to deposit a layer of bCaP followed by 30 bilayers of PEM made with poly-l-Lysine (+) and poly l-Glutamic acid (-) (bCaP-PEM). Measurements of MC3T3-E1 proliferation and viability over time on bCaP-PEM were used to demonstrate the sequential delivery kinetics of a proliferative factor [fibroblast growth factor-2 (FGF-2)] followed by a cytotoxic factor (antimycin A, AntiA). FGF-2 and AntiA both retained their bioactivity within bCaP-PEM, yet no release of FGF-2 or AntiA from bCaP-PEM was observed when cells were absent indicating a cell-mediated, local delivery process. This coating technique is useful for a variety of applications that would benefit from highly localized, sequential delivery of multiple biomolecules governed by cell initiated degradation that avoids off-target effects associated with diffusion-based release. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1500-1509, 2017.
authors.affiliation: Reconstructive Sciences, University of Connecticut Health, Farmington, Connecticut.|Biomedical Engineering, University of Connecticut, Storrs, Connecticut.
authors.forename: E E
authors.initials: EE
authors.lastname: Jacobs
authors.affiliation: Department of Surgery, University of Connecticut Health, Farmington, Connecticut.
authors.forename: G
authors.initials: G
authors.lastname: Gronowicz
authors.affiliation: Department of Medicine, University of Connecticut Health, Farmington, Connecticut.
authors.forename: M M
authors.initials: MM
authors.lastname: Hurley
authors.affiliation: Reconstructive Sciences, University of Connecticut Health, Farmington, Connecticut.|Biomedical Engineering, University of Connecticut, Storrs, Connecticut.
authors.forename: L T
authors.initials: LT
authors.lastname: Kuhn
mesh_terms: D000818:Animals; D000968:Antimycin A / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D040761:Biomimetic Materials / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002130:Calcium Phosphates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D000071228:Polyelectrolytes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; D000071228:Polyelectrolytes; D016222:Fibroblast Growth Factor 2; D000968:Antimycin A; C020243:calcium phosphate
keywords: biomaterial; calcium phosphate; fibroblast growth factor-2; multifactor delivery; polyelectrolyte multilayer films