Better early osteogenesis of electroconductive hydroxyapatite–calcium titanate composites in a rabbit animal model Prafulla Kumar Mallik, 1 Bikramjit Basu 2 1 Department of Materials Science and Engineering, Laboratory for Biomaterials, Indian Institute of Technology, Kanpur 208016, Uttar Pradesh, India 2 Laboratory for Biomaterials, Materials Research Centre, Indian Institute of Science, Bangalore 560012, Karnataka, India Received 1 January 2013; revised 18 March 2013; accepted 5 April 2013 Published online 13 June 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.34752 Abstract: In view of the fact that bone healing can be enhanced due to external electric field application, it is im- portant to assess the influence of the implant conductivity on the bone regeneration in vivo. To address this issue, this study reports the in vivo biocompatibility property of multi- stage spark plasma sintered hydroxyapatite (HA)–80 wt % cal- cium titanate (CaTiO 3 ) composites and monolithic HA, which have widely different conductivity property (14 orders of magnitude difference). The ability of bone regeneration was assessed by implantation in cylindrical femoral bone defects of rabbit animal model for varying time period of 1, 4, and 12 weeks. The overall assessment of the histology results sug- gests that the progressive healing of bone defects around HA–80 wt % CaTiO 3 is associated with a better efficacy with respect to (w.r.t) early stage neobone formation, which is his- tomorphometrically around 140% higher than monolithic HA. Overall, this study demonstrates that the in vivo biocompati- bility property of HA–80 wt % CaTiO 3 with respect to local effects after 12 weeks of implantation is not compromised both qualitatively and quantitatively, and a comparison with control implant (HA) points toward the critical role of electri- cal conductivity on better early stage bone regeneration. V C 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 842– 851, 2014. Key Words: HA, calcium titanate, electrical conductivity, in vivo biocompatibility How to cite this article: Mallik PK, Basu B. 2014. Better early osteogenesis of electroconductive hydroxyapatite–calcium titanate composites in a rabbit animal model. J Biomed Mater Res Part A 2014:102A:842–851. INTRODUCTION In last two decades, electrical stimulation has been investi- gated as a treatment option to heal the damage of the frac- tured bone tissue. 1,2 A study with a range of animal models has provided evidence that electrical stimulation can enhance the bone healing. 3 In these models, electrical stimu- lation using direct current has been delivered locally to damaged bone through metal electrodes (stainless steel, platinum, and titanium). At the end of the treatment pro- cess, the implanted metal electrode was removed from the site of newly healed bone tissue via surgical procedure. The major disadvantages of this approach are the risk of compli- cation of surgery and damage to the newly formed bone tis- sue. On the other hand, direct current stimulation while adequate for in vivo application has shortcomings for in vitro culture. This arises from the accumulation of charged compound on the electrodes, and this leads to a decrease in the magnitude of the electrical stimulus. This concomitantly limits the effectiveness of bone healing. In this perspective, an alternative approach to the external electric field applica- tion is the use of electroconductive implants. However, the in vivo biocompatibility property of electroconductive implants vis-a-vis that of the implants with poor conductiv- ity are not widely investigated. The development of the electrically active hydroxyapatite (HA)-based materials (HA=BaTiO 3 and HA=CaTiO 3 ) as bone substitute implant materials has attracted the attention of many biologists and materials scientists. 4–8 The main idea to develop such a HA-based electroconductive composite has focused on the improvement of desirable mechanical and electrical properties, while retaining biocompatibility property. Such research is motivated from the fact that natu- ral bone has significant electrical properties. For example, piezoelectricity, pyroelectricity, 9,10 and such properties help in maintaining the bone structure and fracture healing. 11,12 The studies have shown that polarization of HA ceramics may modulate new bone formation and resorption. In addi- tion to polarization of HA, the electrical properties of HA can be enhanced by the addition of conductive phases, such as CaTiO 3 . According to published literature reports, CaTiO 3 has better biocompatibility, 13 increased osteoblast cell adhe- sion, 14 and enhanced osteointegration 15 compared with monolithic HA. For this purpose, the composites of HA and 80% CaTiO 3 have been developed as an electrically active Correspondence to: B. Basu; e-mail: bikram@mrc.iisc.ernet.in Contract grant sponsor: Department of Science and Technology, Government of India 842 V C 2013 WILEY PERIODICALS, INC.