DOI: 10.1002/adma.200502640 Responsive Polymers at the Biology/Materials Science Interface By Cameron Alexander* and Kevin M. Shakesheff 1. Introduction The interface of materials science with biology is emerging as a major research focus and is integral to advances in medi- cine and biotechnology. New applications for materials in the life sciences are providing real challenges in terms of scope and complexity that cannot be met by existing systems. Clini- cal needs in particular are inspiring the design of materials that exhibit ‘bio-like’ behavior, such as a response to a stimu- lus or local environment, but with additional properties that derive from abiotic synthesis or design. In this brief article, we highlight some recent key advances in polymeric materials that draw inspiration from, or that will impact upon, biologi- cal phenomena, and consider some future directions that draw the biological and materials sciences ever closer together. We have chosen to focus primarily on new types of respon- sive polymers that can interconvert a stimulus into a function and their applications in biological environments. The ideal response is a reversible one, i.e., a polymer that can be switched repeatedly rather than triggered for a single event; however, both classes of behavior can be usefully exploited. We first consider some chemistries that impart responsive be- havior and subsequently consider how the novel materials properties of these polymers can be exploited. Responsive polymers can be used in solution, at surfaces or interfaces, and in complex 3D architectures, while biological applications include drug delivery, tissue engineering, and regenerative medicine. 2. Modes of Polymer Response 2.1. Light-Responsive Polymers Photochemical stimuli are potentially very useful in gener- ating responsive systems, with a variety of mechanisms by which polymers can be switched, including isomerization, elimination, photosensitization, and local heating. However, the wavelengths commonly employed in organic photochem- istry are not suitable for many biological systems, and thus the majority of work in this area has been confined to model sys- tems. Hoffmann, Stayton, and co-workers have prepared a temperature and photochemically switchable enzyme by con- jugating a switchable azopolymer (poly(N,N′-dimethylacryl- amide)-co-4-phenylazophenyl acrylate) to an engineered cys- teine-containing endoglucanase, which displayed varying and opposite activities depending on whether temperature or UV- vis illumination was used as the switch. [1] The polymer–endo- glucanase conjugate was active in glycoside hydrolase activity against o-nitrophenyl-D-cellobioside (ONPC) under UV irra- diation at 350 nm, but inactive for glycoside hydrolysis at higher wavelengths (420 nm). A related azopolymer–enzyme conjugate, poly((N,N′-dimethylacrylamide)-co-4-phenylazo- phenyl acrylamide)-graft-endoglucanase, was active under longer wavelength light but inactive under irradiation at 350 nm. The different responses of the two polymers were attributed to changes in polarity/dipole moments following the photoinduced trans–cis azobenzene isomerization. These RESEARCH NEWS Synthetic polymers can be prepared with features that combine many of the advantageous properties of natural materials, including environmental response. This Research News article considers the different types of response that can be ‘programmed in’ to polymers and the appli- cations that are developing as a consequence of the designed responses. In particular, we focus on two key applications at the biology/materials science interface: responsive drug delivery systems and ‘smart’ surfaces for cell culture and regenerative medicine. – [*] Dr. C. Alexander, Prof. K. M. Shakesheff Division of Advanced Drug Delivery and Tissue Engineering School of Pharmacy, Boots Science Building University of Nottingham University Park, Nottingham NG7 2RD (UK) E-mail: cameron.alexander@nottingham.ac.uk Adv. Mater. 2006, 18, 3321–3328 © 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 3321