Controlled co-delivery system of magnesium and lanthanum ions for vascularized bone regeneration

For craniofacial bone regeneration, how to promote vascularized bone regeneration is still a significant problem, and the controlled release of trace elements vital to osteogenesis has attracted attention. In this study, an ion co-delivery system was developed to promote angiogenesis and osteogenesis. Magnesium ions (Mg2+) and lanthanum ions (La3+) were selected as biosignal molecules because Mg2+ can promote angiogenesis and both of them can enhance bone formation. Microspheres made of poly(lactide-co-glycolide) were applied to load La2(CO3)3, which was embedded into a MgO/MgCO3-loaded cryogel made of photocrosslinkable gelatin methacryloyl to enable co-delivery of Mg2+ and La3+. Evaluations of angiogenesis and osteogenesis were conducted via both in vitro cell culture using human bone marrow mesenchymal stromal cells and in vivo implantation using a rat model with calvarial defect (5 mm in diameter). Compared to systems releasing only Mg2+ or La3+, the combination system demonstrated more significant effects on blood vessels formation, thereby promoting the regeneration of vascularized bone tissue. At 8 weeks post-implantation, the new bone volume/total bone volume ratio reached a value of 40.1 ± 0.9%. In summary, a properly designed scaffold system with the capacity to release ions of different bioactivities in a desired pattern can be a promising strategy to meet vascularized bone regeneration requirements.