High biocompatibility and improved osteogenic potential of novel Ca–P/titania composite scaffolds designed for regeneration of load-bearing segmental bone defects Carla Cunha, 1,2 Simone Sprio, 1 Silvia Panseri, 1,2 Massimiliano Dapporto, 1 Maurilio Marcacci, 2 Anna Tampieri 1 1 Laboratory of Bioceramics and Bio-hybrid Composites, Institute of Science and Technology for Ceramics, National Research Council, Via Granarolo 64, Faenza 48018, Italy 2 Laboratory of Biomechanics and Technology Innovation, Rizzoli Orthopaedic Institute, Via di Barbiano 1/10, Bologna 40136, Italy Received 2 August 2012; revised 28 September 2012; accepted 4 October 2012 Published online 22 November 2012 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.34479 Abstract: Regeneration of load-bearing bone segments is still an open challenge due to the lack of biomaterials mimicking natural bone with a suitable chemicophysical and mechanical performance. This study proposes ceramic bone scaffolds made of b-tricalcium phosphate (b-TCP) and titania (TiO 2 ), developed from hydroxyapatite (HA) and TiO 2 starting nano- powders, which exhibit high and interconnected macroporos- ity (>70 vol %). The scaffold composition was designed to achieve a synergistic effect of bioactivity/resorbability and mechanical properties suitable for load-bearing regenerative applications. The analysis of the morphology, structure, and mechanical strength of the scaffolds resulted in compression strength nearly twice that of commercially available HA bone grafts with similar structure (Engipore V R ). Biological characteri- zation was carried out for human MG-63 osteoblast-like cells proliferation, activity, attachment, and viability. b-TCP/TiO 2 scaffolds show high proliferation rate, high viability, and high colonization rates. Moreover, an increased activity of the osteogenic marker alkaline phosphatase (ALP) was found. These results demonstrate that b-TCP/TiO 2 scaffolds have good potential as osteogenically active load-bearing scaffolds; moreover, given the high and interconnected macroporosity as well as the resorbability properties of b-TCP, these scaffolds may enhance in vivo osteointegration and promote the forma- tion of new organized bone, thus resulting in very promising biomimetic scaffolds for long bone regeneration. V C 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 1612–1619, 2013. Key Words: bioactivity, calcium phosphates, composites, long bone regeneration, titania How to cite this article: Cunha C, Sprio S, Panseri S, Dapporto M, Marcacci M, Tampieri A. 2013. High biocompatibility and improved osteogenic potential of novel Ca–P/titania composite scaffolds designed for regeneration of load-bearing segmental bone defects. J Biomed Mater Res Part A 2013:101A:1612–1619. INTRODUCTION Bone tissue engineering relies on scaffolds able to mimic the three-dimensional (3D) environment of the extracellular matrix, thus providing adequate chemical and biochemical signaling as well as a high surface area-to-volume ratio for cellular colonization; moreover, in the case of critical defects in load-bearing sites, 3D scaffolds should also provide struc- tural support and reduced stiffness, so as to be compliant with biomechanical stimuli and prevent stress shielding effects. 1,2 So far, regeneration of load-bearing bone parts is still an open challenge, due to the lack of biomaterials exhibiting both chemicophysical mimesis with natural bone and suitable mechanical performance that fully comply with the clinical standard. In this respect, bone-like ceramics have been stud- ied extensively during the last decades, particularly hydroxy- apatite (HA) and other calcium phosphate (Ca/P) ceramics, such as tricalcium phosphate (TCP), given the close similarity of these materials to the mineral phase of natural bone. 3,4 Compared with HA, TCP has a lower calcium-to-phosphorous ratio, which increases the degradation rate in a biological environment. 5 In fact, b-TCP has been shown to present accelerated degradation and an optimal reactivity with the surrounding bone tissue. 6 Different HA scaffolds have been developed so far 7,8 and several commercial products based on HA are now widely used in bone tissue replacement. However, calcium phosphates have intrinsic mechanical weak- ness and fragility, which prevents their use as load-bearing bone scaffolds. As an alternative to calcium phosphates, a wide range of bioactive materials has been investigated, including bio-glasses 9,10 and apatite–wollastonite glass– ceramics. 11,12 Still, in spite of their attractive features, the Correspondence to: C. Cunha; e-mail: carla.cunha@ineb.up.pt Contract grant sponsor: Italian Ministry of Education for financial support under the National Project ‘Bioprotesi’ RBIP068JL9 1612 V C 2012 WILEY PERIODICALS, INC.