Backbone-Degradable Polymers via Chemical Vapor Deposition

Polymers prepared by chemical vapor deposition (CVD) polymerization have found broad acceptance in research and industrial applications. However, their intrinsic lack of degradability has limited wider applicability in many areas, such as biomedical devices or regenerative medicine. In this study, we demonstrate, for the first time, a backbone-degradable polymer directly synthesized via chemical vapor deposition (CVD). The CVD co-polymerization of [2.2]paracyclophanes with cyclic ketene acetals, specifically 5,6benzo-2-methylene-1,3-dioxepane (BMDO), results in well-defined, hydrolytically degradable polymers, as confirmed by FTIR spectroscopy and ellipsometry. The degradation kinetics are dependent on the ratio of ketene acetals versus [2.2]paracyclophanes as well as the hydrophobicity of the films. These novel polymer coatings address a significant unmet need in the biomedical polymer field, as they provide access to a wide range of reactive polymer coatings that combine interfacial multifunctionality with degradability. The medical field has increasingly witnessed a shift from permanent implant materials to biodegradable materials that degrade after their intended use. For instance, surgical sutures, controlled drug delivery systems, drug-eluding stent coatings or tissue engineering scaffolds all benefit from degradable polymers. There exists numerous examples, where surface modification of biodegradable materials is required to introduce functional groups as anchor sites for biomolecule/drug conjugation. To date, substrate-independent and widely applicable chemical vapor deposition (CVD) coatings are well established for non-degradable substrates (e.g., metals), but functional, degradable coatings remain illusive. For example, CVD polymerization of [2.2]paracyclophanes can yield versatile poly(p-xylylene) coatings, which have been successfully applied for a wide range of permanently implanted devices (e.g., stents, pacemakers, or neural probes). Some of these polymers are commercially available and the most widely used member of the family, also know as Parylene C, is an ISO 10993 and United States Pharmacopeia (USP) Class VI (highest biocompatibility class) material. Because of their unique processing through vapor phase polymerization, these polymers feature a range of advantages, such as low-temperature deposition, substrateindependency, absence of process solvents, high conformity, and excellent mechanical properties. CVD-based poly(pxylylene)s have also been synthesized displaying a wide range of reactive side groups for efficient bioconjugation. While CVD polymers are widely used for functionalization of permanent implants and devices, they are intrinsically not degradable due to the absence of hydrolytically cleavable bonds in their backbone. Directly addressing this unmet need, we now report a novel class of functionalizable, and hydrolytically degradable polymer coatings made by chemical vapor deposition polymerization. Specifically, we use CVD co-polymerization to prepare degradable co-polymers displaying no functional group (co-polymer 2), hydroxyl groups (co-polymer 1) and alkyne groups (co-polymer 3) for further surface modification. Copolymerization of functionalized [2.2]paracyclophanes with cyclic ketene acetal (CKA) molecules results in degradable ester linkages inserted into the all-carbon-based poly-p-xylylene backbone. CKAs fulfill two critical criteria in this context: (i) CKAs polymerize following a radical polymerization mechanism compatible with the CVD polymerization process, while undergoing a rearrangement that can insert ester bonds in the polymer backbone. (ii) CKAs can sublime under the typical conditions required for CVD polymerization of [2.2]paracyclophanes. While a range of different CKAs preferentially undergo ring-opening polymerization, we focused on 5,6-benzo-2methylene-1,3-dioxepane (BDMO), which was synthesized following a slightly modified literature-known procedure. BMDO features a seven-membered cyclic ketene acetal ring, which has previously been shown to undergo quantitative rearrangement in solution-based reactions. 21] The radical that is generated after rearrangement of BMDO is stabilized by the adjacent benzene ring (Scheme 1), which makes it particularly suitable for CVD polymerization. For CVD co-polymerization, BMDO and [2.2]paracyclophanes, which act as the radical initiators, were sublimed at 0.07 Torr and temperatures above 100 °C and transferred in a stream of argon carrier gas into the pyrolysis zone, which was maintained at a temperature of 530 °C. After formation of the active intermediates (Scheme 1), the vapor was transferred into the deposition chamber, with the chamber wall temperature set to 120 °C and the holder cooled to 15 °C to optimize the deposition. Under these conditions, BMDO underwent molecular rearrangement followed by subsequent co-polymerization with the xylylene moieties. The co-polymerization proceeded with a growth rate of 0.1~0.2 Å/s and resulted in well-defined polymers displaying ester bonds in their polymer backbone. [a] Prof. Dr. Joerg Lahann* (J.L.), Dr. Xiaopei Deng (X.D.), Kenneth Chang (K.C.), Dr. Luis Solorio (L.S.), Fan Xie (F.X.) Biointerfaces Institute and Departments of Biomedical Engineering and Chemical Engineering, University of Michigan 2800 Plymouth Road, Ann Arbor, Michigan 48109, USA. E-mail: lahann@umich.edu [b] Dr. Shuhua Qi (S.Q.), Fan Xie (F.X) Department of Applied Chemistry, School of Science, Northwestern Polytechnical University, Xi’an 710072, China. [c] Prof. Dr. Joerg Lahann* (J.L.), Dr. Domenic Kratzer (D.K.), Dr. Christian Friedmann (C.F.) Institute of Functional Interfaces, Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz-Platz 1, 76344 EggensteinLeopoldsshafen, Germany. † F.X. and X.D. contributed equally to this work. Supporting information for this article is given via a link at the end of the document.