Oppositely charged gelatin nanospheres as building blocks for injectable and biodegradable gels.

www.MaterialsViews.com C O M M Oppositely Charged Gelatin Nanospheres as Building Blocks for Injectable and Biodegradable Gels U N IC A T Huanan Wang , Morten B. Hansen , Dennis W. P. M. Lowik , Jan C. M. van Hest , Yubao Li , John A. Jansen , and Sander C. G. Leeuwenburgh * IO N The emergence of regenerative medicine has led to a paradigm shift in the design of novel biomaterials, which are now increasingly considered as (bio)active scaffolds that induce tissue regeneration as opposed to the more traditional concept of passively accepted implant materials. [ 1 ] In order to present biological stimuli to the physiological environment and to trigger tissue repair, optimal integration of synthetic biomaterials within the surrounding tissue is of paramount importance. In that respect, hydrogels made from biodegradable polymers are ideal candidates, since they are generally biocompatible, biodegradable, and, in some cases, injectable. [ 2–4 ] In addition, polymeric hydrogels can act as a reservoir for sustained release of therapeutic and signaling agents. [ 4 ] Nevertheless, current gelbased materials exhibit a rather poor ability to present multiple signaling molecules at programmed time-points and release rates. Colloidal gels, on the other hand, have recently been identifi ed as a promising “bottom-up” strategy for the design of highly functional scaffolds by employing microor nanometer-scale particles as building blocks to assemble into shape-specifi c bulk materials. [ 5–13 ] To this end, interparticle interactions such as electrostatic forces, [ 14 ] magnetic forces, [ 14 ] hydrophobic interactions [ 15 ] and steric hindrance [ 16 ] can be exploited to induce selfassembly of microor nanoparticles into integrated scaffolds. By incorporation of bioactive agents (e.g., enzymes, growth factors and/or biomineral nanocrystals) into these particulate building blocks of variable biodegradability, injectable gels with micrometer-scale resolution and complexity can be formed. This new class of materials would offer virtually unlimited degree of freedom with respect to their capacity for programmed drug release of multiple biomolecules at predetermined release rates. Charged polymeric microor nanospheres are the most obvious building blocks for the design of such injectable and