Zeolite imidazolate framework-8 in bone regeneration: A systematic review

Abstract

Zeolite imidazolate framework-8 (ZIF-8) is a biomaterial that has been increasingly studied in recent years. It has several applications such as bone regeneration, promotion of angiogenesis, drug loading, and antibacterial activity, and exerts multiple effects to deal with various problems in the process of bone regeneration. This systematic review aims to provide an overview of the applications and effectiveness of ZIF-8 in bone regeneration. A search of papers published in the PubMed, Web of Science, Embase, and Cochrane Library databases revealed 532 relevant studies. Title, abstract, and full-text screening resulted in 39 papers being included in the review, including 39 in vitro and 22 animal studies. Appropriate concentrations of nano ZIF-8 can promote cell proliferation and osteogenic differentiation by releasing Zn²⁺ and entering the cell, whereas high doses of ZIF-8 are cytotoxic and inhibit osteogenic differentiation. In addition, five studies confirmed that ZIF-8 exhibits good vasogenic activity. In all in vivo experiments, nano ZIF-8 promoted bone formation. These results indicate that, at appropriate concentrations, materials containing ZIF-8 promote bone regeneration more than materials without ZIF-8, and with characteristics such as promoting angiogenesis, drug loading, and antibacterial activity, it is expected to show promising applications in the field of bone regeneration. STATEMENT OF SIGNIFICANCE: This manuscript reviewed the use of ZIF-8 in bone regeneration, clarified the biocompatibility and effectiveness in promoting bone regeneration of ZIF-8 materials, and discussed the possible mechanisms and factors affecting its promotion of bone regeneration. Overall, this study provides a better understanding of the latest advances in the field of bone regeneration of ZIF-8, serves as a design guide, and contributes to the design of future experimental studies.

Keywords: Bone regeneration; Metal-organic frameworks; Stem cells; Zeolitic imidazolate framework-8; Zinc.