Enhanced Proliferation and Differentiation of Human Mesenchymal Stem Cell-laden Recycled Fish Gelatin/Strontium Substitution Calcium Silicate 3D Scaffolds  
[PERSON]  
1 Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 10607, Taiwan; [EMAIL_ADDRESS] (C.-T.Y. ); [EMAIL_ADDRESS] (F.-M.W.) 2 School of Medicine, China Medical University, Taichung 40447, Taiwan; [EMAIL_ADDRESS] (Y.-T.L. ); [PERSON]] (A.K.-X.L.) 33D Printing Medical Research Center, China Medical University Hospital, Taichung 40447, Taiwan 34 Department of Orthopedics, China Medical University Hospital, Taichung 40447, Taiwan; [EMAIL_ADDRESS]  
5 Department of Sports Medicine, China Medical University, Taichung 40447, Taiwan 5  
6 Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40447, Taiwan 5  
73D Printing Medical Research Institute, Asia University, Taichung 41354, Taiwan 5  
7 Correspondence: [EMAIL_ADDRESS]; Tel. : +886-4-22052121; Fax: +886-4-247590657  
Furthermore, bone regeneration is a complex physiological process regulated by osteoclast resorption with osteoblast bone formation and the entire process includes inflammatory reactions, endochondral bone formation and bone remodeling. Currently, for clinical cases, the golden method to repair bone defects is to use autologous bone grafts as this method avoids disease spreading and immunological rejection. However, autografts have some major drawbacks such as limited availability and invasive harvesting that requires additional surgery to harvest healthy bones from another site. Furthermore, additional surgeries mean increased surgical risks and complications [2]. Allograft is an alternative to bone repair; however, it is highly limited due to rejection and lack of availability. To solve this problem, researchers had attempted to develop novel biomaterials including ceramics, polymers and composites as an alternative choice for bone regeneration [3, 4, 5]. In order to promote bone healing, the material must be biocompatible, biodegradable and able to promote bone regeneration which mimics the distinctive property of natural bone [6]. With the emergence of newer 3D printing techniques, we are now able to fabricate scaffolds with customized shape, pore sizes and architectures that are similar to native bone [7, 8]. For many years, bioceramics has emerged as promising biomaterial for bone regeneration [9, 10]. Calcium phosphate is one of the most popular bioceramics which had been repeatedly shown to provide good osteoconduction activities [9, 10]. However, it is lacking in terms of biodegradability and biocompatibility, thus limiting its potential in clinical applications. To solve this problem, researchers attempted to combine calcium phosphate with various types of osteogenesis-related growth factors in order to enhance bone regeneration [11]. Recently, a calcium silicate-based biomaterial was investigated as a bioactive material for bone substitutes and it was found that calcium silicate (CS) had far better biodegradation and osteoconduction characteristic than calcium phosphate-based materials, thus resulting in enhanced bone regeneration [6, 12]. There were several studies indicating that CS-based materials were able to release Si ions gradually immersion and Si ions were found to not only increase regeneration of surrounding cells and tissues, but also induce bone mineralization by activating osteoblasts [13, 14]. In addition, several studies had attempted to incorporate different ions (such as strontium and copper) into CS-based materials in order to fabricate CS scaffolds with varied and diverse functions [15, 16], of which strontium (Sr) is a promising ion constantly shown to have beneficial effects for bone regeneration [17]. Furthermore, Sr-contained CS cements fabricated via the sol-gel process was found to not only enhance mechanical properties but also promote cell behaviors [18].