title: Multilayer thin film coatings capable of extended programmable drug release: application to human mesenchymal stem cell differentiation.
abstract: The promise of cellular therapy lies in healing damaged tissues and organs in vivo as well as generating tissue constructs in vitro for subsequent transplantation. Adult stem cells are ideally suited for cellular therapies due to their pulripotency and the ease with which they can be cultured on novel functionalized substrates. Creating environments to control and successively driving their differentiation toward a lineage of choice is one of the most important challenges of current cell-based engineering strategies. In recent years, a variety of biomedical platforms have been prepared for stem cell cultures, primarily to provide efficient delivery of growth or survival factors to cells and a conducive microenvironment for their growth. Here, we demonstrate that repeating tetralayer structures composed of biocompatible poly(methacrylic acid) (PMAA)/poly(acryl amide) (PAAm)/poly(methacrylic acid) (PMAA)/poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) micelles arrayed in layer-by-layer (LbL) films can serve as a payload region for dexamethasone (dex) delivery to human mesenchymal stem cells (MSCs). This architecture can induce MSC differentiation into osteoblasts in a dose-dependent manner. The amount of dex loaded in the films is controlled by varying the deposition conditions and the film thickness. Furthermore, release of dex is also controlled by changing the amount of covalent crosslinking of multilayers via thermal treatments. The multilayer architecture including payload and cell-adhesion region introduced here are well suited for extended cell culture thus affording the important and protective effect of both dex release and immobilization. These films may find applications in the local delivery of immobilized therapeutics for biomedical applications, as they can be deposited on a wide range of substrates with different shapes, sizes, and composition.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue Cambridge, Massachusetts 02139, USA ; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue Cambridge, Massachusetts 02139, USA ; School of Chemical and Biological Engineering, Intelligent Hybrids Research Center, Seoul National University, Seoul 151-744, Republic of Korea.
authors.forename: Jinkee
authors.initials: J
authors.lastname: Hong
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue Cambridge, Massachusetts 02139, USA ; Joint Program Executive Office for Chemical and Biological Defense, Ft Detrick, MD 21702, USA.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Alvarez
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue Cambridge, Massachusetts 02139, USA ; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue Cambridge, Massachusetts 02139, USA.
authors.forename: Nisarg J
authors.initials: NJ
authors.lastname: Shah
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue Cambridge, Massachusetts 02139, USA ; Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue Cambridge, Massachusetts 02139, USA.
authors.forename: Linda G
authors.initials: LG
authors.lastname: Griffith
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue Cambridge, Massachusetts 02139, USA.
authors.forename: Byeong-Su
authors.initials: BS
authors.lastname: Kim
authors.affiliation: School of Chemical and Biological Engineering, Intelligent Hybrids Research Center, Seoul National University, Seoul 151-744, Republic of Korea.
authors.forename: Kookheon
authors.initials: K
authors.lastname: Char
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue Cambridge, Massachusetts 02139, USA ; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue Cambridge, Massachusetts 02139, USA.
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
keywords: Human mesenchymal stem cells; Layer-by-layer; controlled release; dexamethasone; differentiation; multilayer