Strontium Calcium Phosphate Nanotubes as Bioinspired Building Blocks for Bone Regeneration.

Calcium phosphate (CaP)-based ceramics are the most investigated materials for bone repairing and regeneration. However, the clinical performance of commercial ceramics is still far from that of the native tissue, which remains as the gold standard. Thus, reproducing the structural architecture and composition of bone matrix should trigger biomimetic response in synthetic materials. Here, we propose an innovative strategy based on the use of track-etched membranes as physical confinement to produce collagen-free strontium-substituted CaP nanotubes that tend to mimic the building block of bone, i.e., the mineralized collagen fibrils. A combination of high-resolution microscopic and spectroscopic techniques revealed the underlying mechanisms driving the nanotube formation. Under confinement, poorly crystalline apatite platelets assembled into tubes that resembled the mineralized collagen fibrils in terms of diameter and structure of bioapatite. Furthermore, the synergetic effect of Sr2+ and confinement gave rise to the stabilization of amorphous strontium CaP nanotubes. The nanotubes were tested in long-term culture of osteoblasts, supporting their maturation and mineralization without eliciting any cytotoxicity. Sr2+ released from the particles reduced the differentiation and activity of osteoclasts in a Sr2+ concentration-dependent manner. Their bioactivity was evaluated in a serum-like solution, showing that the particles spatially guided the biomimetic remineralization. Further, these effects were achieved at strikingly low concentrations of Sr2+ that is crucial to avoid side effects. Overall, these results open simple and promising pathways to develop a new generation of CaP multifunctional ceramics that are active in tissue regeneration and able to simultaneously induce biomimetic remineralization and control the imbalanced osteoclast activity responsible for bone density loss.

Synthesis of Sr-morin complex and its in vitro response: decrease in osteoclast differentiation while sustaining osteoblast mineralization ability.

Strontium ranelate (SrR) has been used as the ultimate choice for osteoporosis treatment. However, the development of more tolerable and bioactive Sr2+ carriers is still a need. The design of Sr2+-based platforms has moved towards the obtention of anion carriers that can also exhibit a positive effect on bone metabolism. In this sense, we used morin, a natural flavonoid, as a new arrangement for Sr2+ carriage in the synthesis of an Sr2+ complex. It has been claimed that phenolic compounds promote bone health. Therefore, we hypothesized that the association of Sr2+ with morin could improve its anabolic effects. Complexes with the general formula [(C15H9O7)Sr(H2O)2]Cl·3H2O were synthesized and characterized by elemental analysis, thermogravimetry, UV-Vis and infrared absorption spectroscopies and 1H-nuclear magnetic resonance. We showed that the complexation between morin and Sr2+ occurred among the 3-OH and 4C[double bond, length as m-dash]O groups of morin. Preosteoclasts cultures with the Sr-morin complex exhibited a reduced osteoclast differentiation rate and sustained osteoblast mineralization ability. The response of Sr-morin was higher than that observed for SrR at the same concentration range. Considering the above-mentioned observations, the Sr-morin complex could be an interesting approach to be further exploited not only as an alternative treatment for osteoporosis but also in the design of materials for faster osteointegration.