DOI: 10.1002/chem.200800088 Novel Biodegradable Adaptive Hydrogels: Controlled Synthesis and Full Characterization of the Amphiphilic Co-Networks Laetitia Mespouille, [a] Olivier Coulembier, [a] Dilyana Paneva, [b] Philippe DegØe, [a] Iliya Rashkov, [b] and Philippe Dubois* [a] Introduction Since the pioneering work of Wichterle and Lim in 1960 on cross-linked poly(2-hydroxyethyl) methacrylate (PHEMA), [1] hydrogels have become a topic of great inter- est for biomedical [2] and pharmaceutical [3] applications, mainly due to their enhanced hydrophilic character and po- tential to be biocompatible. More recently, stimuli-respon- sive hydrogels, also called “intelligent” hydrogels, have at- tracted much attention because of their capability to under- go relatively large and abrupt physical or chemical changes in response to small, external stimuli in their environmental media (e.g., pH, temperature, ionic strength, osmotic pres- sure), [4,5] allowing their use in drug-delivery [6] and tissue-en- gineering systems. [7,8] To date, the most commonly used method to prepare cross-linked polymer networks is the free-radical polymerization (FRP) of vinyl and divinyl mon- omers. [9–11] FRP has many advantages over other mecha- nisms, such as mild reaction conditions, tolerance to protic impurities such as water, and it is applicable to a wide range of monomers. Unfortunately, traditional FRP proceeds in a highly nonideal fashion with a large discrepancy with respect to the mean-field theory of Flory and Stockmayer (FS theory). [12–16] As a consequence, there is no control over the network architecture and molecular parameters such as the molecular weight and polydispersity of chains between two cross-linking points, the cross-linker density, and volume dis- tribution. This lack of control results in poorly defined ma- Abstract: Adaptive and amphiphilic poly(N,N-dimethylamino-2-ethyl meth- acrylate-graft-poly[e-caprolactone]) co- networks (netP(DMAEMA-g-PCL)) were synthesized from a combination of controlled polymerization tech- niques. Firstly, PCL cross-linkers were produced by ring-opening polymeri- zation (ROP) of e-CL initiated by 1,4- butane-diol and catalyzed by tin(II) 2- ethylhexanoate ([SnACHTUNGTRENNUNG(Oct) 2 ]), followed by the quantitative esterification reac- tion of terminal hydroxyl end-groups with methacrylic anhydride. Then, PCL cross-linkers were copolymerized to DMAEMA monomers by atom-trans- fer radical polymerization (ATRP) in THF at 60 8C using CuBr complexed by 1,1,4,7,10,10-hexamethyltriethylenetet- ACHTUNGTRENNUNGramine (HMTETA) and 2-ethyl isobu- tyrylbromide (EiBBr) as catalytic com- plex and initiator, respectively. A com- prehensive study of gel formation was carried out by employing dynamic light scattering (DLS) to determine the gel point as a function of several parame- ters and to characterize the viscous sol- utions obtained before the gel point was reached. The evolution of the mean diameters was compared to a model previously developed by Fukuda and these attest to the living formation of the polymer co-network. Further- more, we also demonstrated the relia- bility of ATRP for producing well-de- fined and homogeneous polymer co- networks by the smaller deviation from Flory)s theory in terms of cross-linking density. For sake of clarity, the impact of polymerization techniques over the final structure and, therefore, proper- ties was highlighted by comparing two samples of similar composition, but that were produced by either ATRP or thermal-initiated free-radical polymeri- zation (FRP). Keywords: atom-transfer radical polymerization (ATRP) · caprolac- tone · co-network · ring-opening polymerization [a] Dr. L. Mespouille, Dr. O. Coulembier, Dr. P. DegØe, Prof. P. Dubois Center of Innovation and Research in Materials and Polymers (CIRMAP) Laboratory of Polymeric and Composite Materials University of Mons-Hainaut 20, Place du Parc 7000 Mons (Belgium) Fax:(+ 32)653-73-482 E-mail: philippe.dubois@umh.ac.be [b] Dr. D. Paneva, Prof. I. Rashkov Laboratory of Bioactive Polymers, Institute of Polymers Bulgarian Academy of Sciences, 1113 Sofia (Bulgaria) Chem. Eur. J. 2008, 14,6369–6378 # 2008 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim 6369 FULL PAPER