ORIGINAL ARTICLE Effects of micro/nano strontium-loaded surface implants on osseointegration in ovariectomized sheep Fuwei Liu DDS 1 | Yongfeng Li DDS 2 | Jianfei Liang DDS 1 | Wen Sui DDS 3 | Anuj Bellare DDS 4 | Liang Kong DDS 1 1 State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China 2 Department of Stomatology, PLA 301 Hospital, Beijing, People's Republic of China 3 Department of Stomatology, Shenzhen Hospital of Southern Medical University, Shenzhen, People's Republic of China 4 Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, Massachusetts Correspondence Liang Kong, State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, 145 West Changle Rd, Xi'an 710032, People's Republic of China. Email: dentistkong@163.com Funding information National Natural Science Foundation of China, Grant/Award Numbers: 81500901, 81670803; Entrepreneurial and Innovative Program of Shenzhen for Overseas High-Level Talents, Grant/Award Number: [2018]236; Military Health Care Project of China, Grant/Award Number: 17BJZ14 Abstract Background: Poor osseointegration of dental implants often occurs in osteoporotic patients and processed implant surfaces could help to improve the dilemma. Purpose: This study aimed to compare the effects of different titanium (Ti) surfaces on bone- implant osseointegration in ovariectomized (OVX) sheep. Materials and Methods: Four groups were included: smooth titanium (ST) was merely polished Ti; micro titanium (MT) was treated with hydrofluoric acid (HF) for 30 minutes; strontium-loaded nano titanium (NT-Sr) was formed by magnetron sputtering; strontium-loaded micro/nano titanium (MNT-Sr) was fabricated by HF etching combined with magnetron sputter- ing. The biological responses were evaluated by human bone marrow-derived mesenchymal stem cells (hBMMSCs) experiments in vitro. Osseointegration was evaluated in vivo after each surface implant was inserted into OVX sheepmandibles. Results: The numbers of adhered and mineralized hBMMSCs increased significantly in the MNT-Sr group. The bone-implant contact and the maximal pull-out force increased significantly with MNT-Sr surface. The bone volume ratio and trabecular number of the MNT-Sr group were significantly higher than others, whereas trabecular separation decreased. Conclusions: These results indicated that an MNT-Sr surface promotes the differentiation of hBMMSCs in vitro and enhances bone-implant osseointegration in vivo, which may be a promis- ing option for clinical implants in osteoporotic patients. KEYWORDS implant surface, micro/nano rough, osteoporosis, strontium 1 | INTRODUCTION Osseointegration is defined as a direct interface between the bone and implant, without the involvement of any non-bone tissue. Implant surface topographies and the biological activity of host bone are two important factors that influence osseointegration and long- term implant fixation. 1,2 One of the most important risk factors for poor osseointegration is a poor biological response of the host bone, including a reduction of bone mineral density and alteration of trabecular bone characteristics, as observed in osteoporotic patients. 3 Osteoporosis is frequent in postmenopausal women; this condition may lead to several complications during implant osseoin- tegration. 4 Although the best approach would be to avoid osteopo- rotic implantation through the prevention of osteoporosis, there is a great need to improve implant surfaces for use in osteoporotic patients. 5 Fuwei Liu, Yongfeng Li, and Jianfei Liang contributed equally to this work. Received: 5 December 2018 Accepted: 4 January 2019 DOI: 10.1111/cid.12719 Clin Implant Dent Relat Res. 2019;19. wileyonlinelibrary.com/journal/cid © 2019 Wiley Periodicals, Inc. 1