title: Tunable staged release of therapeutics from layer-by-layer coatings with clay interlayer barrier.
abstract: In developing new generations of coatings for medical devices and tissue engineering scaffolds, there is a need for thin coatings that provide controlled sequential release of multiple therapeutics while providing a tunable approach to time dependence and the potential for sequential or staged release. Herein, we demonstrate the ability to develop a self-assembled, polymer-based conformal coating, built by using a water-based layer-by-layer (LbL) approach, as a dual-purpose biomimetic implant surface that provides staggered and/or sustained release of an antibiotic followed by active growth factor for orthopedic implant applications. This multilayered coating consists of two parts: a base osteoinductive component containing bone morphogenetic protein-2 (rhBMP-2) beneath an antibacterial component containing gentamicin (GS). For the fabrication of truly stratified composite films with the customized release behavior, we present a new strategy-implementation of laponite clay barriers-that allows for a physical separation of the two components by controlling interlayer diffusion. The clay barriers in a single-component GS system effectively block diffusion-based release, leading to approximately 50% reduction in bolus doses and 10-fold increase in the release timescale. In a dual-therapeutic composite coating, the top GS component itself was found to be an effective physical barrier for the underlying rhBMP-2, leading to an order of magnitude increase in the release timescale compared to the single-component rhBMP-2 system. The introduction of a laponite interlayer barrier further enhanced the temporal separation between release of the two drugs, resulting in a more physiologically appropriate dosing of rhBMP-2. Both therapeutics released from the composite coating retained their efficacy over their established release timeframes. This new platform for multi-drug localized delivery can be easily fabricated, tuned, and translated to a variety of implant applications where control over spatial and temporal release profiles of multiple drugs is desired.
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA.
authors.forename: Jouha
authors.initials: J
authors.lastname: Min
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Braatz
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA. Electronic address: hammond@mit.edu.
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D016475:3T3 Cells; D000538:Aluminum Silicates / Q000737:chemistry*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival; D000077215:Clay; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D024881:Drug Resistance, Bacterial; D005839:Gentamicins / Q000494:pharmacology; D051379:Mice; D011108:Polymers / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D000538:Aluminum Silicates; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005839:Gentamicins; D011108:Polymers; D000077215:Clay
keywords: Antibacterial; BMP (bone morphogenetic protein); Bone; Controlled drug release; Layer-by-layer; Silicate