Biocompatible polyhydroxyalkanoates/bacterial cellulose composites: Preparation, characterization, and in vitro evaluation Ioana Chiulan, 1 Denis Mihaela Panaitescu, 1 Adriana Nicoleta Frone, 1 Mircea Teodorescu, 2 Cristian Andi Nicolae, 1 Angela C as¸ aric a, 3 Vlad Tofan, 4 Aurora S al  ageanu 4 1 Department of Polymer, National Institute for R&D in Chemistry and Petrochemistry ICECHIM, Bucharest, Romania 2 Department of Bioresources and Polymer Science, Faculty of Applied Chemistry and Materials Science, Polytechnic University of Bucharest, Bucharest, Romania 3 Department of Pharmaceutical Biotechnologies, National Institute for Chemical Pharmaceutical R&D ICCF, Bucharest, Romania 4 Infection and Immunity Laboratory, Cantacuzino National Institute, Bucharest, Romania Received 29 March 2016; revised 22 April 2016; accepted 27 May 2016 Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.35800 Abstract: Biocompatible composites play a critical role as scaffolds in tissue engineering. Novel biocomposites made from poly(3-hydroxybutyrate) (PHB), polyhydroxyalkanoate (PHA) and bacterial cellulose (BC) in different concentrations were prepared by solution casting and their thermal and mechanical behavior as well as biocompatibility was charac- terized. BC addition increased the thermal stability of the polymer matrix as evidenced by thermogravimetric analysis. The crystallinity of PHB and the crystallization temperature decreased with the addition of BC and PHA, thus increasing the processing window. BC in small concentration deter- mined an increase in the mechanical properties due to a con- certed action of PHA and filler. Good cells attachment and proliferation were observed for all the biocomposites. By the addition of PHA (more hydrophobic than the matrix) and vari- ous amounts of BC (highly hydrophilic), surface properties and cell attachment can be controlled. Cytocompatibility studies using L929 cell line revealed that this material is suit- able for biomedical applications. V C 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 00B:000–000, 2016. Key Words: poly(3-hydroxybutyrate), polyhydroxyoctanoate, bacterial cellulose, thermal properties, cell viability How to cite this article: Chiulan I, Mihaela Panaitescu D, Nicoleta Frone A, Teodorescu M, Andi Nicolae C, C as¸ aric a A, Tofan V, S al ageanu A. 2016. Biocompatible polyhydroxyalkanoates/bacterial cellulose composites: Preparation, characterization, and in vitro evaluation. J Biomed Mater Res Part A 2016:00A:000–000. INTRODUCTION Polyhydroxyalkanoates (PHAs), a family of biodegradable polyesters synthesized by a wide range of microbial species, have recently gained considerable interest for biomedical field and as alternative to petroleum-based polymers. 1 Besides some valuable properties, similar to those of con- ventional plastics, such as polyethylene, polypropylene, and polyethylene terephthalate, 2 the lack of toxicity of PHAs and their degraded products confers them a great potential for drug delivery systems, artificial tendon and ligaments, scaf- folds, soft tissue repair, and food packaging. 3,4 Poly(3- hydroxybutyrate) (PHB) is a thermoplastic polymer with relatively high crystallinity, high hydrophobicity, and proved biodegradability and biocompatibility. 3 Industrial application of PHB is limited in extrusion or injection processing due to its brittleness and very narrow temperature window. 5 By the copolymerization of 3-hydroxybutyrate with 3-hydroxyvalerate, poly(3-hydroxybutyrate-co-3-hydroxyval- erate) (PHBV copolymers) with lower glass transition and melting temperature, improved flexibility and melt stability resulted. 6 Good mechanical properties, besides intrinsic biodegradability and biocompatibility are required for bio- medical field, such as implants and tissue engineering. For this purpose, composites or blends of PHB with other natu- ral polymers or minerals were prepared. 7,8 Bacterial cellulose (BC) is a promising biopolymer, syn- thesized by strains of gram-negative bacteria, usually Aceto- bacter xylinum. Although chemically identical to plant cellulose, BC shows higher crystallinity (70–80%), higher purity, higher water retention capacity (up to 98–99% water), superior mechanical properties, and better thermal stability. 9 BC has been intensively studied for surgical implants, membranes for substituting natural skin, artificial blood vessel, cartilage repair, and bone regeneration. 10 Several studies regarding the synthesis of BC composites with the most common PHAs members, PHB, and PHBV have been reported. 11,12 Bionanocomposites prepared by the impregnation of BC pellicle with PHB solution in chloro- form showed increased tensile strength and elongation at break compared to neat PHB, better transparency or increased thermal stability. 11,12 However, the possible appli- cation of these multilayered films in biomedicine is limited. Corresponding to: I. Chiulan; e-mail: ioana.chiulan@yahoo.com, and D.M. Panaitescu; e-mail: panaitescu@icf.ro V C 2016 WILEY PERIODICALS, INC. 1