###### Abstract  
Strontium is known for enhancing bone metabolism, osteoblast proliferation, and tissue regeneration. This systematic review aimed to investigate the biological effects of strontium-doped calcium phosphate biomaterials for bone therapy. A literature search up to May 2024 across Web of Science, PubMed, and Scopus retrieved 759 entries, with 42 articles meeting the selection criteria. The studies provided data on material types, strontium incorporation and release, and in vivo and in vitro evidence. Strontium-doped calcium phosphate biomaterials were produced via chemical synthesis and deposited on various substrates, with characterization techniques confirming successful strontium incorporation. Appropriate concentrations of strontium were non-cytotoxic, stimulating cell proliferation, adhesion, and osteogenic factor production through key signaling pathways like Wnt/\(\beta\)-catenin, BMP-2, Rurnx2, and ERK. In vivo studies identified novel bone formation, angiogenesis, and inhibition of bone resorption. These findings support the safety and efficacy of strontium-doped calcium phosphates, although the optimal strontium concentration for desired effects is still undetermined. Future research should focus on optimizing strontium release kinetics and elucidating molecular mechanisms to enhance clinical applications of these biomaterials in bone tissue engineering. strontium; hydroxyapatite; calcium phosphate; osteoblasts; bone tissue; systematic review 29 July 2024 14 August 2024 27 August 2024 27 August 2024 27 August 2024 27 August 2024 27 August 2024 27  
facilitate the attachment, proliferation, and differentiation of osteoblasts, thereby accelerating the healing process and improving clinical outcomes [2]. In addition to their use in bone grafts and dental implants, calcium phosphate bioceramics are also employed in drug delivery systems, as well as in advanced fabrication techniques, such as 3D printing and nanotechnology. These technologies enable the creation of customized implants with complex geometries and controlled porosity, tailored to meet the specific needs of individual patients [2]. However, due to its high crystallinity, hydroxyapatite remains in the body for long periods after implantation, which makes complete tissue regeneration more difficult [3]. Therefore, in the search for resorbable biomaterials that can stimulate bone recovery, the partial ionic substitution of the calcium in the HA by other ions that could stimulate the production of new bone may be an essential step to achieve regenerative medicine [4]. Many ions have been experimentally incorporated into calcium phosphate ceramics, such as magnesium (Mg\({}^{2+}\)), zinc (Zn\({}^{2+}\)) and strontium (Sr\({}^{2+}\)) [4,5]. The presence of these components usually decreases the crystallinity of the material, making it more soluble and, since they are trace elements typically found in healthy bone tissue, there is reduced risk of adverse effects [6,7]. Among such ions, strontium has been highlighted due to the successful use of strontium malate in the treatment of osteoporosis [8], which indicates stimulatory biological effects during bone formation. Even though the biochemical signaling involved in this process remains unclear, it is believed that the presence of this ion can inhibit the action of osteoclasts resorption, while stimulating the production of new bone by osteoblasts [9]. Hence, the association of strontium ions with ceramic biomaterials, more than affecting physicochemical properties, may imply the direct release of biologically active material directly at the implant site. Indeed, several studies have been conducted, either in vivo or in vitro, testing different biomaterials based on strontium-doped calcium phosphate.