Behavior of plaster of Paris-calcium carbonate composite as bone substitute. A study in rats Anne Handrini Dewi, 1 Ika Dewi Ana, 1 Joop Wolke, 2 John Jansen 2 1 Department of Dental Biomedical Sciences, Faculty of Dentistry, Gadjah Mada University, Yogyakarta 55281, Indonesia 2 Department of Biomaterials, Radboud University Nijmegen Medical Center, 6500 HB Nijmegen, The Netherlands Received 26 September 2012; revised 1 November 2012; accepted 5 November 2012 Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.34513 Abstract: Calcium sulfate, also known as plaster of Paris (POP), is probably the oldest biomaterial used for bone grafting and considered to be a fast degradable material that allows complete resorption before the bone defect area is completely filled by new bone. The aim of this study was to investigate the possibil- ity to combine POP with calcium carbonate in order to increase the the osteoconductivity of this material. Twenty four male Sprague Dawley rats, 5-months-old and weighing 300–350 g, were used in the study. Various treatment groups were created by the implantation of cylindrical samples of POP-100, POP-075 and POP-050 into the femoral condyles. After 1 and 4 weeks of implantation, rats were sacrificed and the implanted areas and the surrounding tissue were retrieved for histological analysis. The study was completed by an in vitro experiment, which included the soaking of the experimental materials into simu- lated body fluid. The results indicated that the composites were appropriate to be used as bone grafting material. The incorpora- tion of CaCO 3 into POP did decrease the degradation rate of the cements and induced faster bone formation, thus provides promising properties to this material. V C 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 00A:000–000, 2012. Key Words: calcium sulfate, calcium carbonate, bone substi- tute, degradation, bone formation How to cite this article: Dewi AH, Ana ID, Wolke J, Jansen J. 2012. Behavior of plaster of Paris-calcium carbonate composite as bone substitute. A study in rats. J Biomed Mater Res Part A 2012:00A:000–000. INTRODUCTION Several alloplastic materials have been proposed to enhance the biologic repair of a skeletal defect. The requirements for an alloplastic bone grafting material are that the material has to be osteconductive, completely resorbable in a con- trolled manner without the release of toxic degradation products or elicit an inflammatory response, and sterilizable. Furthermore, the alloplastic graft must provide mechanical support to maintain space during bone regeneration. 1 In view of the aforementioned requirements, calcium sul- fate (CS), also known as plaster of Paris (POP), has been used in clinic for many years to treat skeletal defects, either alone or in combination with other bone graft materials. 2–5 The use of POP is based on its advantages, which include the ability to self-setting and a well-tolerated biological response without eliciting a severe inflammatory response. When hemihydrate is mixed with water, dihydrate is formed. This property makes it possible for POP to set in situ when it is applied into a bone defect. However, POP has a major setback as it is rapidly resorbed in vivo and consequently unable to provide a long term three-dimensional framework to support osteoconduc- tion. 4,6–8 To overcome this problem of fast degradation, medi- cal grade POP has been mixed with other bone graft materials such as b-Tricalcium Phosphate, 7 freeze dried demineralized bone graft, 5 and calcium phosphate. 9 Besides the aforementioned supplemental graft compo- nents, a wide variety of other bioceramics is available, which can be used in combination with POP, like, for example, coral which contains aragonite type of CaCO 3 . This material is al- ready used for bone grafting since 1970 because of its good osteoconduction, bioresorbability, biocompatibility, and bio- degradation. 10,11 The marine coral is made of aragonite type calcium carbonate (97%), shows morphologically a porous microstructure and is chemically quite similar to bone min- eral. Coral shows a good tissue response and is completely resorbed in the body. 12 Moreover, coral (aragonite or calcite forms of calcium carbonate or CaCO 3 ) is one of the limited number of materials that can form a chemical bond with bone and soft tissues in vivo. 13 In 2006, Combes et al. 14 demonstrated the application of 100% calcium carbonate as a good bone cement candidate due to the re-crystallization of the initial metastable phases of the cement, in which CaCO 3 reacts with water, forms a CaP layer in the presence of phosphate ions and acts as a template to facilitate apatite crystal formation and growth. Such a cement can be pre- pared by simply mixing water with CaCO 3 powder. After im- plantation, the cement will release calcium and carbonate ions, which subsequently can be incorporated into the apa- tite structure of the surrounding bone tissue. The released calcium ions inhibit the activity of osteclasts and shift the Correspondence to: John A. Jansen; e-mail: j.jansen@dent.umcn.nl Contract grant sponsors: DGHE of The Republic of Indonesia Scholarship V C 2012 WILEY PERIODICALS, INC. 1