A comprehensive review of bioactive glass: synthesis, ion substitution, application, challenges, and future perspectives en en Bioactive glass (BG) and glass-ceramics (GC) have been employed for bone treatment tissue engineering applications. Bioactive glasses/bioglasses can be considered promising materials for bone-regenerative scaffolds fabrication, owing to the adaptable properties that make them appropriately be designed regarding their composition. The essential properties of bioactive glasses, enabling them to be applied in the engineering of bone tissue, can be explained as their potential to augment differentiation osteoprogenitor and cells of mesenchymal stem cells, enzyme activity, osteoblast adhesion, and revascularization. Much research is conducted for the development of phosphate glasses, borate/borosilicate BGs, and silicate. Accordingly, some metal-based glasses have also been surveyed for tissue engineering uses, technologically and biomedically. Many rare elements can also be incorporated in the network of the glass to achieve promising properties, possessing a positive influence on the associated angiogenesis and/or remodeling of bone. This review motivates for providing an overview toward bioactive glasses’ general requirements, composition, production, and impact of ion substitution on bioactive glass. Attention has also been given to developments of bioactive glass applications in bone grafting, bone regeneration, drug delivery, dental implant coatings, antibacterial agents, and soft tissue engineering as well as challenges and future perspectives. 247 261 Varinder Pal Singh Sidhu Department of Mechanical and Industrial Engineering Ryerson University Canada info@jourcc.com Roger Borges Center of Humanities and Natural Sciences Brazil info@jourcc.com Mohammad Yusuf Department of Chemical Engineering Universiti Teknologi PETRONAS Malaysia info@jourcc.com Shirin Mahmoudi semiconductor institute materials and energy research center Iran shirin2020mahmoudi@gmail.com Shamimeh Fallah Ghorbani Visveswarapura Institute of Pharmaceutical Science Rajiv Gandhi University of Health Science India info@jourcc.com Mahdi Hosseinikia Department of Inorganic Chemical Processing University of Science and Technology (IUST) Iran info@jourcc.com Peyman Salahshour School of Science and Technology The University of Georgia Georgia info@jourcc.com Farnaz Sadeghi Department of Biomedical Engineering Islamic Azad University Iran info@jourcc.com Mehrnoosh Arefian Department of Biochemistry Islamic Azad University, Falavarjan Branch Iran info@jourcc.com Tissue engineering Synthesis Bioglass Bioactive glass Article5.pdf [1] D.S. 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