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 (Mg) and lanthanum ions (La) were selected as biosignal molecules because Mgcan promote angiogenesis and both of them can enhance bone formation. Microspheres made of poly(lactide-co-glycolide) were applied to load La(CO), which was embedded into a MgO/MgCO-loaded cryogel made of photocrosslinkable gelatin methacryloyl to enable co-delivery of Mgand La. Evaluations of angiogenesis and osteogenesis were conducted via bothcell culture using human bone marrow mesenchymal stromal cells andimplantation using a rat model with calvarial defect (5 mm in diameter). Compared to systems releasing only Mgor La, 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.