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

Abstract

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.

Controlled and Sequential Delivery of Stromal Derived Factor-1 α (SDF-1α) and Magnesium Ions from Bifunctional Hydrogel for Bone Regeneration

“…Angiogenesis and osteogenesis are highly correlated in the process of bone development and bone generation according to previous literature [ 45 ]. Our findings are in agreement with reports that SDF-1α or Mg 2+ encapsulated scaffolds have excellent angiogenesis function for bone reconstruction [ 46 , 47 , 48 ]. Furthermore, at six weeks postoperatively, a large number of osteoblasts were observed in the central area of the defect in the XPMS group as compared to XPS and XPM group, suggesting that the promotion of SDF-1α and Mg 2+ on the recruitment and proliferation of BMSCs around the defect site.…”

Polycaprolactone/Gelatin/Hydroxyapatite Electrospun Nanomembrane Materials Incorporated with Different Proportions of Attapulgite Synergistically Promote Bone Formation

“…34 Magnesium ions also have a certain osteoinductive effect. [54][55][56][57][58] In addition, ATP has a large specific surface area and strong adsorption capacity and can absorb growth factors and nutrients in the surrounding tissues, which is beneficial for promoting the regeneration of defective tissues. 33,[59][60][61] The physical and chemical properties and structural characteristics of ATP make it a potential material for bone tissue repair.…”

Strategies for Enhancing Vascularization of Biomaterial‐Based Scaffold in Bone Regeneration

“…Besides, Mg ion when co-embedded with lanthanum (La 2 + ) in cryogel composite or MnÀ Ca silicate scaffolds, also stimulates the vascularization cascade setting the foundation for bone regeneration. [112][113][114] Cobalt plays a pivotal role in the production of vitamin B 12 and as cofactors in allied reaction; stem cell adhesion forms better apatite layers. Tissue constructs of collagen-glycosaminoglycan coated with Co-doped bioactive glass and Ti-based implants are corroborated to express VEGF in EC and formation of stem cell tubule by imitating hypoxic conditions.…”

“…The tensile strength and Young′s modulusalso improved with the incorporation of Magnesium ions. Besides, Mg ion when co‐embedded with lanthanum (La 2+ ) in cryogel composite or Mn−Ca silicate scaffolds, also stimulates the vascularization cascade setting the foundation for bone regeneration [112–114] …”