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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/?-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.

SUBMITTER: Jia B

PROVIDER: S-EPMC7691683 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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

Jia Bo B Yang Hongtao H Zhang Zechuan Z Qu Xinhua X Jia Xiufeng X Wu Qiang Q Han Yu Y Zheng Yufeng Y Dai Kerong K

Bioactive materials 20201121 6

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 ...[more]

PMID: 33294736

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Project description:Enhanced understanding of differential gene expression and biological pathways associated with distinct phases of intramembranous bone regeneration following femoral marrow ablation surgery will improve future advancements regarding osseointegration of joint replacement implants, biomaterials design, and bone tissue engineering. A rat femoral marrow ablation model was performed and genome-wide microarray data were obtained from samples at 1, 3, 5, 7, 10, 14, 28, and 56 days post-ablation, with intact bones serving as controls at Day 0. Bayesian model-based clustering produced eight distinct groups amongst 9,062 significant gene probe sets based on similar temporal expression profiles, which were further categorized into three major temporal classes of increased, variable, and decreased expression. Osteoblastic- and osteoclastic-associated genes were found to be significantly expressed within the increased expression groups. Chondrogenesis was not detected histologically. Adipogenic marker genes were found within variable/decreased expression groups, emphasizing that adipogenesis was inhibited during osteogenesis. Differential biological processes and pathways associated with each major temporal group were identified, and significantly expressed genes involved were visually represented by heat maps. It was determined that the increased expression group exclusively contains genes involved in pathways for matrix metalloproteinases (MMPs), Wnt signaling, TGF-? signaling, and inflammatory pathways. Only the variable expression group contains genes associated with glycolysis and gluconeogenesis, the notch signaling pathway, natural killer cell mediated cytotoxicity, and the B cell receptor signaling pathway. The decreased group exclusively consists of genes involved in heme biosynthesis, the p53 signaling pathway, and the hematopoietic cell lineage. Significant biological pathways and transcription factors expressed at each time point post-ablation were also identified. These data present the first temporal gene expression profiling analysis of the rat genome during intramembranous bone regeneration induced by femoral marrow ablation.

Dataset Information

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

Publications

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

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