Metal-organic frameworks (MOFs) for bone treatment and mineralization

Metal-organic frameworks (MOFs) have emerged as a flexible class of porous materials with tunable physicochemical properties, making them well-suited for biomedical applications, particularly bone regeneration and biomineralization. This review analyzes recent advances in MOF-based methodologies for bone tissue engineering, highlighting various MOFs, particularly biologically-based metalorganic frameworks (BioMOFs) and bioactive MOFs, and their roles in mimicking natural mineralization processes. MOFs can be applied as carriers for biomineralizing multiple biological targets, such as proteins, enzymes, bacterial cells, and viruses, enabling controlled encapsulation, protection, and functional delivery. Considerable focus is placed on the mechanisms by which MOFs promote osteogenesis and angiogenesis, including the pH-responsive or enzyme-activated release of osteoinductive ions such as calcium (Ca2+), magnesium (Mg2+), zinc (Zn2+), and strontium (Sr2+) from frameworks composed of alkaline-earth and transition-metal ions. MOF-based materials can be used to treat various bone disorders, including osteoporosis, osteomyelitis, bone malignancies, and diabetic bone anomalies, through several proposed mechanisms, including drug delivery, immunomodulation, antibacterial effects, and neovascularization promotion. Integrating MOFs with hydrogels, electrospun membranes, and functionalized three-dimensional (3D) scaffolds yields synergistic effects that enhance bone tissue regeneration. Challenges were discussed, including biocompatibility, biodegradability, and ion toxicity. Hopefully, this review provides insights into prospective methodologies for the systematic design of multifunctional MOF platforms for clinical use in orthopedic and regenerative medicine.