Page | 397 Development of novel ZrO 2 -Gd 2 O 3 nanocomposite functionalized with hyaluronic acid and its application for repair of bone defects in experimental animals Olesya І. Hodovana 1 , Olga Yu. Klyuchivska 2 , Oleg V. Godovanyi 1 , Olesya S. Miahkota 3 , Nataliya Ye. Mitina 3 , Tetiana Ye. Konstantinova 4 , Halyna I. Kotsyumbas 5 , Alexander S. Zaichenko 3 , Rostyslav S Stoika 2,* 1 Danylo Halytsky Lviv National Medical University, Department of Therapeutic Dentistry, Post-Diploma Education. Pekarska Str. 69, 79010, Lviv, Ukraine 2 Institute of Cell Biology, NAS of Ukraine, Department of Regulation of Cell Proliferation and Apoptosis. Drahomanov Str. 14/16, 79005, Lviv, Ukraine 3 Lviv Polytechnic National University, Department of Organic Chemistry. S. Bandera Str. 12, 79013, Lviv, Ukraine 4 O.O. Galkin Physical-Technical Institute, NAS of Ukraine, Department of Physical Materials, R. Luxemburg str. 72, 83114, Donetsk, Ukraine 5 Department of Normal and Pathological Morphology and Judicial Veterinary, Pekarska Str. 50, 79010, Lviv, Ukraine *corresponding author e-mail address: stoika@cellbiol.lviv.ua ABSTRACT The aim of this work was developing novel polymer-mineral radiopaque composites based on the nanoparticles of ZrO 2 -Gd 2 O 3 and functionalized with the hyaluronic acid, as well as their use for repair of bone defects in the experimental rats, and conduction of roentgenologic, histological and histochemical studies of the reparative osteogenesis. Roentgenologic study: 18 white outbred female rats of 8-9 months age and 300-350 g body weight were used in the experiments. The animals were divided into 3 groups, each including 6 rats. Artificial defect was done in rat’s vertebra, and further regeneration of the osseous tissue was performed by using synthesized nanocomposites Z1 and Z2 of different consistency. Іn control group, bone defect was sutured below the blood clot. Radiological investigations have been carried out in different terms of bone regeneration (15 and 30 days after surgical intervention). Histological and histochemical study: Artificial bone defects were formed in the caudal vertebra of 24 female rats. Experimental groups: 1) novel ZrO 2 - Gd 2 O 3 nanocomposite with the hyaluronic acid in its coating; 2) synthetic «Easy-Graft тм » material (Switzerland) prepared on the basis of β-tricalcium phosphate; 3) «Stimulus-Oss» material based on animal collagen with addition of 2% chlorohexidine and hydroxyapatite (Russian Federation); 4) control (bone defects were filled with blood clot). Vertebrae with the regenerate were isolated in 30 days by surgical intervention. Vertebra preparations were studied macroscopically and histologically. New experimental model (regeneration of bone defects artificially formed in rat’s caudal vertebra) was proposed by the authors and it showed its advantages in the reparative osteogenesis. Created biomaterial demonstrated satisfactory bio-compatibility after surgery. Its application was not accompanied by inflammatory reaction and suppuration of the regenerate, opposite to formation of large areas of destruction of the osseous tissue during regeneration of bone defect in control group of rats in which regeneration of the defect was performed under blood clot. High density of Z1 material allows keeping it in centre of bone defect, opposite to Z2 material leaking from the defect area (15 and 30 days after surgical intervention). Among 3 different osteoplastic materials used in the study, novel ZrO 2 -Gd 2 O 3 nanocomposite with the hyaluronic acid in its coating showed the highest effectiveness in stimulating regeneration of the osseous tissue. That effect was confirmed by the morphological, as well as by histological study of wound repair. New material has demonstrated the bio-tolerance and high integration with the osseous tissue. Novel in vivo experimental model of caudal vertebra proved its efficiency in testing materials used for regeneration of the osseous tissue. Created polymer-mineral radiopaque nanocomposite with ZrO 2 –Gd 2 O 3 core and the hyaluronic acid in its shell effectively enhanced regeneration of bone defect. The clinical, roentgenologic, histological and histochemical studies testify to bio-tolerance, radiopacity, as well as high integration of the applied Z1 material with the osseous tissue of the recipient bed. Keywords: osseous defect, rat’s caudal vertebra, novel osteoplastic materials, ZrO 2 -Gd 2 O 3 , radiopaque polymer-mineral nanocomposite, hyaluronic acid. 1. INTRODUCTION Creation of new bioplastic materials that are effective at surgical intervention is a crucial task in the contemporary reconstructive medicine. This issue was considered in numerous publications dedicated to such new materials affecting the regeneration processes [1-5]. Development of materials for the replacement of bone defects of various etiology, the ways for improvement of their biocompatibility, osteogenous potential, as well as providing osteoinduction, osteoconduction and radiopacity are the most important aims in the orthopedic and surgical practice. They are of special significance in the maxillofacial surgery, periodontology and implantology, since they are time-consuming and highly technological, should follow special clinical safety requirements and possess evident efficacy of a “final product” [6]. Various nanomaterials proved their usefulness in a reparative medicine, since they possess mechanical strength, flexibility, and chemical stability [7, 8]. However, bio-safety and efficacy requirements at using nanocomposites in medicine provoke additional experimental studies aimed at proving their biocompatibility and functional activity in the body [9]. Many contemporary osteoplastic materials are based on bone collagen, hydroxyapatite, or alpha- and beta-tricalcium phosphate [10]. Besides, big attention was paid to the nanoparticles (5-60 nm) of iron oxide, copper, zinc, silver, gold and titanium [11]. In particular, the nanoparticles based on zinc oxide possess the Volume 5, Issue 3, 2016, 397 - 405 ISSN 2284-6808 Open Access Journal Received: 10.12.2015 / Revised: 15.06.2016 / Accepted: 20.08.2016 / Published: 30.09.2016 Research Article Letters in Applied NanoBioScience www.NanoBioLetters.com