Biodegradable Zn–Sr alloy for bone regeneration in rat femoral condyle defect model: In vitro and in vivo studies

Abstract

Bone defects are commonly caused by severe trauma, malignant tumors, or congenital diseases and remain among the toughest clinical problems faced by orthopedic surgeons, especially when of critical size. Biodegradable zinc-based metals have recently gained popularity for their desirable biocompatibility, suitable degradation rate, and favorable osteogenesis-promoting properties. The biphasic activity of Sr promotes osteogenesis and inhibits osteoclastogenesis, which imparts Zn–Sr alloys with the ideal theoretical osteogenic properties. Herein, a biodegradable Zn–Sr binary alloy system was fabricated. The cytocompatibility and osteogenesis of the Zn–Sr alloys were significantly better than those of pure Zn in MC3T3-E1 cells. RNA-sequencing illustrated that the Zn-0.8Sr alloy promoted osteogenesis by activating the wnt/β-catenin, PI3K/Akt, and MAPK/Erk signaling pathways. Furthermore, rat femoral condyle defects were repaired using Zn-0.8Sr alloy scaffolds, with pure Ti as a control. The scaffold-bone integration and bone ingrowth confirmed the favorable in vivo repair properties of the Zn–Sr alloy, which was verified to offer satisfactory biosafety based on the hematoxylin-eosin (H&E) staining and ion concentration testing of important organs. The Zn-0.8Sr alloy was identified as an ideal bone repair material candidate, especially for application in critical-sized defects on load-bearing sites due to its favorable biocompatibility and osteogenic properties in vitro and in vivo.

Zn–0.8Mg–0.2Sr (wt.%) Absorbable Screws—An In-Vivo Biocompatibility and Degradation Pilot Study on a Rabbit Model

“…Heart, liver, spleen, lung, and kidneys-no abnormalities in the Zn-0.8Sr alloy group in comparison with the pure Ti group. The concentration of Zn 2+ and Sr 2+ in the blood and organs of the Zn-0.8Sr group was not higher than the pure Ti implant group [22] 54 rats, From the aforementioned studies, which were analysed in detail and whose results are summarized in Table 1, magnesium can be characterized as having very good biocompatibility with the surrounding bone-expressed by good new-bone production, good osteoconductivity and osteoinductivity, and good mechanical properties [2,3,27,28,30]. In the case of pure magnesium, hydrogen pockets were often formed [2,28,29].…”

Biodegradable metals for bone defect repair: A systematic review and meta-analysis based on animal studies

“…In addition, Zn–Mg, Zn–Ca, Zn–Sr binary alloys also suggest their bone defect repair potential [ 129 ]. A recently published study demonstrated that Zn-0.8Sr alloy has potential to repair critical-size bone defects in load-bearing situations [ 130 ]. Furthermore, Zn–2Cu alloy implants have also proved their potential in the treatment of orthopedic infections [ 131 ].…”

Biodegradable ZnLiCa ternary alloys for critical-sized bone defect regeneration at load-bearing sites: In vitro and in vivo studies

“…The regeneration of bone defect is a complicated process, which involves intricate interactions between various cells, cytokines and signaling pathways [ 12 ]. The potential mechanism how Zn0.8Li0.1Ca alloy scaffold assisted the bone with regeneration might be explained in two aspects: providing structural supports and regulating physiological functions.…”

“…Their long-term existence would also increase the risks of inflammation and infections. Thus, an ideal material for bone tissue engineering should provide enough mechanical supports, be biodegradable, and have good biocompatibility as well as osteogenic activity [ 6 , 12 ]. Therefore, biodegradable metals, which could be biodegraded in vivo while assisting the tissue with healing, have been investigated as a promising candidate [ 13 , 14 ].…”

“…However, the mechanical properties of pure Zn is unsatisfactory [ 18 , 19 ]. To enhance the performance of Zn-based biodegradable metals, alloying elements, including Li [ 20 , 21 ], Mg [ [22] , [23] , [24] , [25] , [26] , [27] , [28] ], Ca [ 29 , 30 ], Sr [ 12 , 31 ], Cu [ [32] , [33] , [34] , [35] ], Ag [ [36] , [37] , [38] ], Mn [ [39] , [40] , [41] , [42] ] and Fe [ 43 , 44 ], were introduced into the system. Among these researches, element Li have brought the most significant improvement in mechanical strength [ 45 ].…”