Trans. Nonferrous Met. Soc. China 28(2018) 17631773 Osteogenic composite nanocoating based on nanohydroxyapatite, strontium ranelate and polycaprolactone for titanium implants Murat Taner VURAT 1,2 , Ayşe Eser ELÇIN 1 , Yaşar Murat ELÇIN 1,2 1. Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory, Faculty of Science and Stem Cell Institute, Ankara University, Ankara 06100, Turkey; 2. Biovalda Health Technologies, Inc., Ankara 06830, Turkey Received 16 October 2017; accepted 3 April 2018 Abstract: Titanium and its alloys are commonly used as dental and bone implant materials. Biomimetic coating of titanium surfaces could improve their osteoinductive properties. In this work, we have developed a novel osteogenic composite nanocoating for titanium surfaces, which provides a natural environment for facilitating adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs). Electrospinning was used to produce composite nanofiber coatings based on polycaprolactone (PCL), nano-hydroxyapatite (nHAp) and strontium ranelate (SrRan). Thus, four types of coatings, i.e., PCL, PCL/nHAp, PCL/SrRan, and PCL/nHAp/SrRan, were applied on titanium surfaces. To assess chemical, morphological and biological properties of the developed coatings, EDS, FTIR, XRD, XRF, SEM, AFM, in-vitro cytotoxicity and in-vitro hemocompatibility analyses were performed. Our findings have revealed that the composite nanocoatings were both cytocompatible and hemocompatible; thus PCL/HAp/SrRan composite nanofiber coating led to the highest cell viability. Osteogenic culture of MSCs on the nanocoatings led to the osteogenic differentiation of stem cells, confirmed by alkaline phosphatase activity and mineralization measurements. The findings support the notion that the proposed composite nanocoatings have the potential to promote new bone formation and enhance bone-implant integration. Key words: osteogenic nanocoating; composite nanofiber; titanium implant; nanohydroxyapatite; strontium ranelate; polycaprolactone; electrospinning; mesenchymal stem cells 1 Introduction Bone is a highly vascularized and dynamic organ that has a number of functions such as protection, mineral storage and source of hematopoietic and mesenchymal stem cells (MSCs). Chemically, bone tissue consists of 1% sodium chloride, 1%2% magnesium phosphate, 1%2% calcium fluoride, 7% calcium carbonate and 58% calcium phosphate. Bone tissue, known as osseous, is made of cancellous and cortical bone. Living bone is mainly composed of collagen (70%), bone mineral and water. In addition, organic materials such as polysaccharides, proteins and lipids are present in less amounts [1,2]. Bone healing is a complex process with three distinct overlapping steps: early inflammatory stage, repair stage and the late remodeling stage [3,4]. Initially, within few days a local hematoma develops at the fracture site. Cellular inflammatory elements such as lymphocytes, monocytes, macrophages, and polymorphonuclear cells infiltrate the hematoma to secrete cytokines and growth factors. In the repair stage, fibroblasts facilitate vascular ingrowth and there is high osteoblast activity. At this stage, the newly formed bone needs to be remodeled. The last stage of bone tissue healing is the remodeling stage where bone is restored to its healthy condition [5,6]. The coating of orthopaedic implants or bone fixator surfaces aims to improve the implant-bone integration, restore tissue functions and accelerate bone healing. An ideal implant surface coating should mimic the bone tissue by being biocompatible, osteoinductive, and mechanically stable [6]. Due to their high corrosion resistance, unique mechanical properties, osseointegration capacity and high biocompatibility with the tissue, titanium and its alloys are widely preferred in the dental and orthopaedic implant applications [7,8]. Owing to their lack of direct Corresponding author: Yaşar Murat ELÇIN; E-mail: elcinmurat@gmail.com; elcin@ankara.edu.tr DOI: 10.1016/S1003-6326(18)64820-4