Intrafibrillar Mineralization and Immunomodulatory for Synergetic Enhancement of Bone Regeneration via Calcium Phosphate Nanocluster Scaffold.

Inspired by the bionic mineralization theory, organic-inorganic composites with hydroxyapatite nanorods orderly arranged along collagen fibrils have attracted extensive attention. Planted with an ideal bone scaffold will contribute greatly to the osteogenic microenvironment; however, it remains challenging to develop a biomimetic scaffold with the ability to promote intrafibrillar mineralization and simultaneous regulation of immune microenvironment in situ. To overcome these challenges, a scaffold containing ultra-small particle size calcium phosphate nanocluster (UsCCP) is prepared, which can enhance bone regeneration through the synergetic effect of intrafibrillar mineralization and immunomodulatory. By efficient infiltration into collagen fibrils, the UsCCP released from the scaffold achieves intrafibrillar mineralization. It also promotes the M2-type polarization of macrophages, leading to an immune microenvironment with both osteogenic and angiogenic potential. The results confirm that the UsCCP scaffold has both intrafibrillar mineralization and immunomodulatory effects, making it a promising candidate for bone regeneration.

Dynamic footprint of sequestration in the molecular fluctuations of osteopontin.

The sequestration of calcium phosphate by unfolded proteins is fundamental to the stabilization of biofluids supersaturated with respect to hydroxyapatite, such as milk, blood or urine. The unfolded state of osteopontin (OPN) is thought to be a prerequisite for this activity, which leads to the formation of core-shell calcium phosphate nanoclusters. We report on the structures and dynamics of a native OPN peptide from bovine milk, studied by neutron spectroscopy and small-angle X-ray and neutron scattering. The effects of sequestration are quantified on the nanosecond- ångström resolution by elastic incoherent neutron scattering. The molecular fluctuations of the free phosphopeptide are in agreement with a highly flexible protein. An increased resilience to diffusive motions of OPN is corroborated by molecular fluctuations similar to those observed for globular proteins, yet retaining conformational flexibilities. The results bring insight into the modulation of the activity of OPN and phosphopeptides with a role in the control of biomineralization. The quantification of such effects provides an important handle for the future design of new peptides based on the dynamics-activity relationship.