Polymer Networks Combining Controlled Drug Release, Biodegradation, and Shape Memory Capability By Axel T. Neffe, Bui D. Hanh, Susi Steuer, and Andreas Lendlein* Biomaterials need to fulfill complex requirements, which are determined by a specific application. As such requirements can differ significantly from case to case, materials were developed, for which various properties [1,2] can be adjusted almost independently from each other. The choice of a suitable material and processes in order to allow the addition of desired functions is crucial and will only be effective when the underlying fundamental principles can be attributed to different structural elements on the molecular level. Multifunctional polymers that combine two functions such as shape-memory effect and biodegradability [3] or biodegradability and drug release [4] have been realized. However, a material that combines the three functions shape-memory capability, controlled drug release, and biodegradability has not yet been demonstrated. This would allow to combine the shape-memory effect for enabling minimally invasive implantation of bulky devices, [5] biodegradability to avoid a second surgery for implant removal, [6] and controlled drug release for treating infections, [7] reducing inflammatory responses, [8] or, later, supporting regeneration processes. [9] Such a combination of functions is demanded by biomaterial-assisted therapies, e.g., for vascular [10] and urinary stents or as scaffold material for reconstructive or aesthetic surgery (e.g., breast remodelling) [11] and in tissue engineering applications (e.g., bone regeneration). [12] Multimaterial systems presently applied in drug eluting stents cannot fulfill the complex demands, but the high level of interest they receive(d), [13] despite shortcomings and contraindications, [14] points to the necessity of new materials. Therefore, we explored whether three functions can be combined in one polymeric material. Our research strategy for the development of such a multi- functional polymer system was based on several key require- ments that had to be met: i) the incorporation of hydrophilic and hydrophobic drugs shall not influence the shape-memory functionality, ii) a diffusion-controlled release that is independent from biodegradation must be enabled, and iii) the programming process and shape recovery, which a device experiences during minimally invasive implantation, shall not change the drug release kinetic. The rational design criteria that we derived from the results of our research for the molecular architecture of a suitable polymer system as well as synthesis and functionaliza- tion procedures are described in this paper. Shape-memory polymers consist of two key components: netpoints, determining the permanent form, and switching domains formed by switching segments, responsible for the fixation of the temporary shape. [15] Chemical netpoints (covalent crosslinks) have the advantage of ensuring high form stability of the permanent shape, while forming only a small mass fraction of the polymer networks. Fixation by switching domains has been realized by crystallization and vitrification. [16] The switching domains determine the switching temperature T sw , which needs to be exceeded to induce the shape change. Our research strategy aimed at the incorporation of drug molecules. As these might act as softener in amorphous switching domains and change T sw in an unwanted way, shape-memory polymer networks with crystallizable switching segments were envisioned. In such a material, the drug molecules are most likely localized in the amorphous domains of the noncrystalline parts of the switching segments, which are semicrystalline in their temporary shape. We explored whether a drug can be incorporated without changing the thermomechanical behavior and shape-memory properties. We wanted to reach this aim by the proper selection of crystallizable switching segments containing hydrolizable bonds (e.g., chemical composition and chain segment length) as well as the process for drug incorporation. Under consideration of these assumptions, we selected two hydrolytically degradable shape-memory polymer networks, which were prepared by UV-curing of Oligo[(e-caprolactone)- co-glycolide]-dimethacrylates as precursors [17] having 14 mol% glycolide content and a number average molecular weight M n of 4900 g  mol 1 (network 1) and 12800 g  mol 1 (network 2) (structure see Fig. 1A) forming the switching segments. In earlier works [18] we found that depending on M n of the precursor molecules and glycolide content, the T sw and hydrolytic degradation rate can be adjusted without effecting the shape fixity and shape recovery rate. The networks with the above specified compositions have been selected because network 1 has a T sw of 30 8C (below body temperature) and network 2 has a T sw of 38 8C (slightly above body temperature). The polymer networks showed bulk degradation, whereby incorporation of glycolide units considerably accelerated mass loss. Ethacridine lactate (EL) and Enoxacin (EN) were chosen to be incorporated as hydrophilic and hydrophobic test drugs into the polymer matrix by two different methods: drug loading by swelling and in situ incorporation. Swelling of the networks in COMMUNICATION www.advmat.de [*] Prof. A. Lendlein, Dr. A. T. Neffe, Dr. B. D. Hanh, Dr. S. Steuer [+] Center for Biomaterial Development, Institute of Polymer Research GKSS Research Centre Geesthacht GmbH Kantstrasse 55, 14513 Teltow (Germany) E-mail: andreas.lendlein@gkss.de Prof. A. Lendlein, Dr. A. T. Neffe Berlin-Brandenburg Center for Regenerative Therapies (BCRT) Charite ´-Universita ¨tsmedizin Berlin-BCRT, Campus Virchow-Klinikum Augustenburger Platz 1, 13353 Berlin (Germany) [ + ] Present address: Intervet Innovation GmbH, Zur Propstei, 55270 Schwabenheim, Germany DOI: 10.1002/adma.200802333 3394 ß 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Adv. Mater. 2009, 21, 3394–3398