Multifunctional magnesium-organic framework doped biodegradable bone cement for antibacterial growth, inflammatory regulation and osteogenic differentiation

Abstract

Degradable bone cement has superior osteoconductivity and plasticity and is commonly used to treat defects greater than the critical-size. Magnesium gallate metal–organic frameworks (MOFs) (Mg-MOF), with antibacterial and anti-inflammatory properties, are doped into a composite cement composed of calcium sulfate, calcium citrate, and dicalcium hydrogen phosphate anhydrous (CS/CC/DCPA). The doping of the Mg-MOF slightly influences the microstructure and curing properties of the composite cement, with the mechanical strength of the cement displaying a significant increase from 27 to 32 MPa. Antibacterial tests reveal that the Mg-MOF bone cement has excellent antibacterial characteristics and can effectively inhibit bacterial growth in 4 h (Staphyloccocus aureus survival rate <10%). Herein, lipopolysaccharide (LPS)-induced macrophage models are used to investigate the anti-inflammatory characteristics of composite cement. The Mg-MOF bone cement can regulate the inflammatory factors and polarization of macrophages (M1 and M2). In addition, the composite cement promotes cell proliferation and osteo-differentiation of mBMSCs, and the activity of alkaline phosphatase and calcium nodules are increased. The bone related transcription factor and specific proteins, such as runt-related transcription factor 2 (Runx2), bone morphogenetic protein 2, osteocalcin (OCN), osteopontin (OPN), and collagen type 1 (COL1), were highly expressed by the Mg-MOF bone cements. Therefore, Mg-MOF doped CS/CC/DCPA bone cement is multifunctional for bone repair, which will promote bone formation and avoid the infection of wounds, and it is suitable for use with non-load-bearing bone defects.