Nanosized Silk–Magnesium Complexes for Promotion of Angiogenic and Osteogenic Activities

Injectable hydrogels with osteogenic and angiogenetic properties are of interest in bone tissue engineering. Since the bioactivity of ions is concentration-dependent, nanosized silk–magnesium (Mg) complexes were previously developed and assembled into hydrogels with angiogenic capabilities but failed to control both osteogenic and angiogenetic activities effectively. Here, nanosized silk particles with different sizes were obtained by using ultrasonic treatment to control silk–Mg coordination and particle formation, resulting in silk–Mg hydrogels with different types of bioactivity. Fourier transform infrared and X-ray diffraction results revealed that different coordination intensities were present in the different complexes as a basis for the differences in activities. Slow Mg ion release was controlled by these nanosized silk–Mg complexes through degradation. With the same amount of Mg ions, the different silk–Mg complexes exhibited different angiogenic and osteogenic capacities. Complexes with both angiogenic and osteogenic capacities were developed by optimizing the sizes of the silk particles, resulting in faster and improved quality of bone formed in vivo than complexes with the same composition of silk and Mg but only angiogenic or osteogenic capacities. The biological selectivity of silk–Mg complexes should facilitate applications in tissue regeneration.