The synergy of metal-organic frameworks and biomaterials for bone tissue engineering: recent advances, challenges, and future recommendations.

There has recently been a noticeable increase in the prevalence of bone-related conditions, including osteoarthritis, arthritis, fractures, bone cancer, and infections, thereby creating an urgent demand for advanced biomaterials in regenerative medicine. Among emerging candidates, metal-organic frameworks (MOFs), with their large surface area, tunable porosity, and inherent bioactivity, have demonstrated considerable potential in bone tissue engineering. Initially, research focused on pristine MOFs as bioactive scaffolds or drug delivery vehicles due to their capacity for controlled encapsulation and release of therapeutic agents. However, issues such as poor stability, potential toxicity, and limited mechanical strength have driven the development of MOF-based composites. By incorporating MOFs into hydrogels, electrospun fibers, biocements, and three-dimensional scaffolds, researchers have improved biocompatibility, enhanced structural integrity, and achieved synergistic effects on bone regeneration. Consequently, these composites offer multifunctional platforms that simultaneously provide mechanical support, local drug delivery, and osteoinductive cues. This review highlights recent advances in the field, analyzes key limitations, and emphasizes the need for systematic strategies in design, synthesis, and evaluation. Furthermore, the integration of computational modeling and machine learning is proposed as a promising direction for optimizing material performance and accelerating clinical translation. Ultimately, interdisciplinary collaboration will be essential to realize the full potential of next-generation MOF-based composites in bone repair and regenerative therapies.