DOI: 10.1002/cvde.201307057 Full Paper Design Strategies for Reduced-scale Surface Composition Gradients via CVD Copolymerization** By Yaseen Elkasabi, Aftin M. Ross, Jonathan Oh, Michael P. Hoepfner, H. Scott Fogler, Joerg Lahann, and Paul H. Krebsbach* A new method for generating and modeling reduced-scale copolymer gradients by CVD is reported. By exploiting diffusion through confined channels, functionalized [2.2]paracyclophanes are copolymerized into their poly(p-xylylene) (PPX) analogues as a composition gradient. Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) are used to verify the gradient composition profiles. Gradients are deposited on both flat substrates and 3-dimensional cylinders. Both the thickness and compositional profiles are fitted to a diffusion-based model using realistic physical parameters. The derived equation can be generalized and optimized for any copolymerization gradient through a confined geometry, thus allowing for broad applicability to other copolymer systems. Keywords: Coatings, Gradients, Polymers, Surface engineering, Transport modeling 1. Introduction Technological advancements in engineering and medicine often rely on the formation and utilization of spatiotemporal cues. Many of these approaches mimic the naturally occurring gradients observed in biology. For example, cell migration relies on the presence of signaling gradients that facilitate many in-vivo regenerative processes. [1,2] In addi- tion, chemical surface gradients play a critical role in sensing, mammalian development, [3] tissue regeneration, [2] cell migration, [4] and combinatorial materials discovery. [5] Fabrication of a surface gradient on variable length scales would significantly lower the amount of time required to synthesize a range of surface-coating compositions in series, and place researchers in a position to more accurately replicate normal biological processes. Several methods of generating surface chemical gradients have been developed over the years. [6] For example, microfluidic methods [7,8] can deliver robust gradients on the micrometer-length scale needed for microbiological environments. Photolithography [9–11] can be used to fabri- cate reactive chemical and/or surface energy gradients on adjustable length scales; however, the former method can only generate gradients on a fixed length scale; if the gradient slope is to be varied, it is likely to be within a narrow range. Furthermore, three-dimensional gradients on com- plex objects (e.g., porous scaffolds) are needed for in-vivo applications (e.g., tissue regeneration constructs). This type of robust material complexity cannot be easily realized by currently available photolithographic and/or microfluidic methods. To fill these technological gaps, a surface modification method is needed to preserve the delicate nature of soft materials, as well as the spectrum of complex substrate geometries. The CVD polymerization process [12,13] conformally coats three-dimensional objects [14] with polymer films at room temperature in a relatively short timeframe, making it an effective system for bio-interfacial applications. [15] Several classes of polymers, [16] such as polynaphthalenes, [17] poly- acrylates, [18,19] and polythiophenes [20] can be deposited as thin films with the CVD process. While the CVD of inert PPX has long been used in the micro-fabrication indus- try, [21,22] the polymerization of their functionalized precur- sors has been less established. [12,23] The same process can now impart surface coatings with tailored reactivities and functional groups, [24–28] several of which support cell proliferation, growth, and differentiation. [27,29] Recently [*] Dr. Y. Elkasabi, Prof. P. H. Krebsbach Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, North Campus Research Complex, 010-A149 2800 Plymouth Ave., Ann Arbor, MI 48109 (USA) E-mail: paulk@umich.edu Dr. A. M. Ross, Dr. J. Lahann, Prof. P. H. Krebsbach Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 (USA) Dr. J. Oh, Dr. J. Lahann Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109 (USA) Dr. M. P. Hoepfner, Dr. H. S. Fogler, Dr. J. Lahann Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109 (USA) Dr. J. Lahann Department of Macromolecular Science and Engineering, University of Michigan, Ann Arbor, MI 48109 (USA) [**] The authors would like to acknowledge a NSF major instrumentation grant (DMR-0420785), as well as an NIH T-32 training grant (DE007057-36) and NIH grant (DE018890, PHK). J.L. acknowledges support from DTRA under project HDTRA1-12-1-0039. A.M.R. would also like to acknowledge support from the University of Michigan Rackham Predoctoral Fellowship. Chem. Vap. Deposition 2014, 20, 23–31 © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim wileyonlinelibrary.com 23