Safe to the core: genetic study clears Mo-Based implants for vascular use

Molybdenum (Mo)-containing biomaterials offer great potential for treating cardiovascular and cerebrovascular conditions due to their mechanical strength and degradability. Yet, concerns have lingered about the possible toxic effects of elevated serum Mo levels after these materials break down in the body. A new study applied Mendelian randomization (MR)—a genetic causal inference technique—to test whether increased Mo concentrations in the blood contribute to diseases like heart attack, stroke, or aneurysm. The analysis revealed no significant causal links. These findings provide the first gene-level evidence supporting the systemic biosafety of Mo-based biomaterials and offer critical reassurance for their continued development in medical applications.

Molybdenum’s unique combination of strength, corrosion resistance, and radiopacity makes it an attractive material for stents, valves, and vascular scaffolds. However, when these devices degrade, they release molybdenum (Mo) ions into the bloodstream—raising safety concerns, particularly for the heart and brain, where tissue response to systemic changes can be acute. Previous clinical studies have painted a conflicting picture, with some suggesting protective cardiovascular effects from dietary Mo and others linking elevated Mo levels to stroke. These inconsistent findings, often confounded by environmental and lifestyle variables, have hindered definitive conclusions. Due to these uncertainties, a gene-based approach was needed to rigorously evaluate Mo’s systemic safety.

In a study published (DOI: 10.1016/j.gendis.2025.101516) January 5, 2025, in Genes & Diseases, researchers from Xuanwu Hospital and Peking University used Mendelian randomization (MR) to evaluate the potential health risks posed by Mo released from biomedical implants. Drawing on genome-wide association study data, the team investigated whether increased serum Mo levels have a genetic link to cardiovascular and cerebrovascular disorders. The results showed no evidence of causal harm, helping to clarify a long-standing safety question surrounding Mo-based biomaterials.

The researchers selected genetic variants known to influence serum Mo levels and applied them as instrumental variables in a two-sample MR analysis. This approach allowed them to isolate the effects of Mo from other confounding factors. The final dataset included high-quality single nucleotide polymorphisms (SNPs) that passed rigorous statistical filtering, including F-statistics and linkage analysis, and excluded SNPs associated with known confounders. The MR analysis covered a broad range of cardiovascular and cerebrovascular outcomes—coronary artery disease, atrial fibrillation, heart failure, multiple stroke subtypes, and aneurysms. None showed statistically significant associations with serum Mo levels after correcting for multiple comparisons. Even a minor signal observed for cardioembolic stroke did not pass the significance threshold. Robustness was confirmed through funnel plots, scatter plots, and sensitivity tests including MR-Egger and leave-one-out analysis.

These results suggest that elevated Mo levels from implant degradation do not increase disease risk in these systems. The study not only meets MR design criteria but also achieves high statistical power and reproducibility, positioning it as a model for genetic-level biomaterial safety evaluation.

“Our study leverages human genetic data to answer a fundamental safety question: Can Mo biomaterials harm the heart or brain?” said Dr. Ming Li, senior author of the study. “We found no genetic evidence suggesting such risks. This strengthens the case for Mo-based implants as both effective and safe. While in vitro and clinical data remain important, gene-based validation offers an invaluable layer of confidence in biomaterial development.”

These findings pave the way for broader clinical adoption of Mo-based biomaterials in cardiovascular and neurovascular interventions. The genetic safety data provides a strong foundation for regulatory review and device approval, supporting innovation in biodegradable implants, vascular scaffolds, and surgical tools. Future work should explore experimental validation and long-term clinical outcomes, especially for edge cases like cardioembolic stroke. Nonetheless, this research marks a significant step forward in biomaterial safety assessment, demonstrating how genomic tools can complement traditional toxicology to ensure the safe integration of new materials in precision medicine.

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References

DOI

10.1016/j.gendis.2025.101516

Original Source URL

https://doi.org/10.1016/j.gendis.2025.101516

Funding Information

This study was funded by the National Natural Science Foundation of China (No. 82027802, 82102220), Research Funding on Translational Medicine from Beijing Municipal Science and Technology Commission (China) (No. Z221100007422023), Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (No. YGLX202325), Non-profit Central Research Institute Fund of Chinese Academy of Medical (No. 2023-JKCS-09), Beijing Association for Science and Technology Youth Talent Support Program (China) (No. BYESS2022081), Beijing Municipal Natural Science Foundation of China (No. 7244510), Science and Technology Innovation Service Capacity Building Project of Beijing Municipal Education Commission (No. 11000023T000002157177), and Outstanding Young Talents Program of Capital Medical University (China) (No. B2305).

About Genes & Diseases

Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Emphasis will be placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases.