Fabrication of alginate–gelatin crosslinked hydrogel microcapsules and evaluation of the microstructure and physico-chemical properties Bapi Sarker, a Dimitrios G. Papageorgiou, b Raquel Silva, a Tobias Zehnder, a Farhana Gul-E-Noor,† c Marko Bertmer, c Joachim Kaschta, d Konstantinos Chrissafis, b Rainer Detsch a and Aldo R. Boccaccini * a Microencapsulation of cells by using biodegradable hydrogels offers numerous attractive features for a variety of biomedical applications including tissue engineering. This study highlights the fabrication of microcapsules from an alginate–gelatin crosslinked hydrogel (ADA–GEL) and presents the evaluation of the physico-chemical properties of the new microcapsules which are relevant for designing suitable microcapsules for tissue engineering. Alginate di-aldehyde (ADA) was synthesized by periodate oxidation of alginate which facilitates crosslinking with gelatin through Schiff's base formation between the free amino groups of gelatin and the available aldehyde groups of ADA. Formation of Schiff's base in ADA– GEL and aldehyde groups in ADA was confirmed by FTIR and NMR spectroscopy, respectively. Thermal degradation behavior of films and microcapsules fabricated from alginate, ADA and ADA–GEL was dependent on the hydrogel composition. The gelation time of ADA–GEL was found to decrease with increasing gelatin content. The swelling ratio of ADA–GEL microcapsules of all compositions was significantly decreased, whereas the degradability was found to increase with the increase of gelatin ratio. The surface morphology of the ADA–GEL microcapsules was totally different from that of alginate and ADA microcapsules, observed by SEM. Two different buffer solutions (with and without calcium salt) have an influence on the stability of microcapsules which had a significant effect on the gelatin release profile of ADA–GEL microcapsules in these two buffer solutions. Introduction Hydrogels, from naturally occurring biopolymers, are an important class of biomaterials that are widely used in the pharmaceutical and biomedical sectors. 1,2 Among the naturally occurring biopolymers, alginate and gelatin are extensively used for many biomedical applications because of their biocompat- ibility and biodegradability. 2,3 Alginate is commercially available as a sodium salt of alginic acid which is a polysaccharide and composed of b-D-mannur- onic acid and a-L-guluronic acid units arranged in blocks of poly(mannuronate) and poly(guluronate). 1,4 Alginate is widely used in cell encapsulation 4–7 and biofabrication 8–12 because of its rapid ionic gelation with divalent cations which is achieved through the poly(guluronate) portion. 13,14 However, usually alginate does not promote efficient cell attachment leading to very poor cell–material interactions, in addition alginate possesses very slow degradability and uncontrolled degradation kinetics. 14–17 These limitations of alginate can be overcome by incorporation of gelatin through covalent crosslinking with alginate di-aldehyde (ADA). 18,19 ADA is a partially oxidized product of alginate which facilitates the covalent crosslinking with gelatin through Schiff's base formation due to the reaction of free amino groups of lysine or hydroxylysine amino acid residues of gelatin and available aldehyde groups of ADA. 3,18 Moreover, the biodegradability of the alginate–gelatin cross- linked hydrogel can be tuned by using ADA of different degrees of oxidation which can control the hydrolysis properties of alginate 20,21 and also by changing the composition of ADA and gelatin. Gelatin is a biodegradable protein, produced by acidic or basic hydrolysis of collagen, which involves breaking of the collagen's triple helix structure into random coils. 22 The sol state of gelatin transforms into the gel state upon cooling of aqueous solution of gelatin, which involves a partial a Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, Cauerstrasse 6, 91058 Erlangen, Germany. E-mail: aldo.boccaccini@ww.uni-erlangen.de b Solid State Physics Section, Physics Department, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece c Institute of Experimental Physics II, University of Leipzig, Linn´ estr. 5, D-04103 Leipzig, Germany d Institute of Polymer Materials, University of Erlangen-Nuremberg, Martensstrasse 7, D-91058 Erlangen, Germany † Current address: Department of Chemistry, University of Western Ontario, London, Ontario, N6A5B7, Canada. Cite this: J. Mater. Chem. B, 2014, 2, 1470 Received 25th October 2013 Accepted 9th December 2013 DOI: 10.1039/c3tb21509a www.rsc.org/MaterialsB 1470 | J. Mater. Chem. B, 2014, 2, 1470–1482 This journal is © The Royal Society of Chemistry 2014 Journal of Materials Chemistry B PAPER Published on 11 December 2013. Downloaded by The University of Manchester Library on 22/06/2015 23:48:46. View Article Online View Journal | View Issue