Anisotropic Microspheres–Cryogel Composites Loaded with Magnesium l-Threonate Promote Osteogenesis, Angiogenesis, and Neurogenesis for Repairing Bone Defects

Abstract

To achieve osteogenesis, angiogenesis, and neurogenesis for repairing bone defects, we constructed an anisotropic microspheres–cryogel composite loaded with magnesium l-threonate (MgT). These composites were prepared by the photo-click reaction of norbornene-modified gelatin (GB) in the presence of MgT-loaded microspheres through the bidirectional freezing method. The composites possessed an anisotropic macroporous (around 100 μm) structure and sustained release of bioactive Mg2+, which facilitate vascular ingrowth. These composites could significantly promote osteogenic differentiation of bone marrow mesenchymal stem cells, tubular formation of human umbilical vein vessel endothelial cells, and neuronal differentiation in vitro. Additionally, these composites significantly promoted early vascularization and neurogenesis as well as bone regeneration in the rat femoral condyle defects. In conclusion, owing to the anisotropic macroporous microstructure and bioactive MgT, these composites could simultaneously promote bone, blood vessel, and nerve regeneration, showing great potential for bone tissue engineering.

A Biomimetic Fibrous Composite Scaffold with Nanotopography-Regulated Mineralization for Bone Defect Repair

“…Bone grafting intervention is of particular importance for the repair of critical-sized bone defects that cannot be regenerated on their own . As an alternative to autografts and allografts with unsatisfactory clinical limitations, bone tissue engineering offers an attractive therapeutic option for bone augmentation, − which effectively regulates immunity, vascularization, and neurogenesis. − A central hotspot is guided bone regeneration based on scaffolds that provide physicochemical and biological cues for facilitating cellular adhesion, proliferation, migration, and differentiation. − With the merits of good biocompatibility, biodegradability, and favorable mechanical properties, synthetic biomedical polymers, such as poly­(ε-caprolactone) (PCL), poly­(lactic acid), poly­(lactic- co -glycolic acid), and poly­(hydroxybutyrate) have become the biomaterials of choice for bone repair scaffolds. − However, biomedical polymer scaffolds suffer from shortcomings in terms of osteoconductivity, osteoinductivity, and osteoengineering, posing a critical unmet challenge.…”