Rational design and fabrication of monophasic bioceramic microspheres with enhanced mechanical and biological performances in reconstruction of segmental bone defect.

Over the past decades, there has been extensive study on the design of porous bioceramic scaffolds with controlled bioactivity and biodegradation in bone tissue repair. A variety of suggestive models and concepts have been proposed with regard to the role of microstructure and composition of biomaterials which affect new bone tissue growth. However, it is a challenge to fabricate functional scaffolds with the desired physiological properties and osteogenic potentials that is comparable to the bone's natural healing time scale. We demonstrate a one-step versatile fabrication of a single-phase and homogenously mixed bioactive load-bearing scaffolds (Sr-CS, CaSiO3/Ca2SiO4, and CaP) with superior biological properties in a critical size bone defect (Ø ~ 6.0 × 8.0 mm). In vivo study revealed the CaSiO3/Ca2SiO4 scaffold had the best amount of new bone growth and osteogenic repair. The Sr-CS exhibited an adequate pore network for rapid inorganic exchange and moderate mechanical stability; however, the CaSiO3/Ca2SiO4 saw over-fast resorption and mass loss compared to the Sr-CS and CaP. On the other hand, the CaP scaffold saw mechanically outstanding elastroplastine and stability but had limited biodegradation of its constructs which retarded new cancellous bone growth. The CaSiO3/Ca2SiO4 group saw superior acceleration and formation of mineralized new bone tissues in the defect. Moreover, the CaSiO3/Ca2SiO4 showed appreciable decay of the biomaterials beneficial for osteogenic cell activity. The dramatic stimulation of bone repair and angiogenesis with the CaSiO3/Ca2SiO4 suggests a promising application of this novel bioactive scaffold in the repair of skeletal defects. Systemic representation of the fabricated microspheres with in vivo and in vitro study analysis.

Yolk-porous shell biphasic bioceramic granules enhancing bone regeneration and repair beyond homogenous hybrid.

Bioactive stimulation and spatiotemporal evolution of porous scaffolds with time are crucial for bone regeneration rate in bone repair process. Granule-type bioceramic scaffolds have attracted significant interest in biomedical applications in recent years. However, the major limitation of such porous architecture is that the low initial porosity is disadvantageous for enhancing new bone tissue ingrowth. Here we reported that the yolk-shell-structured biphasic bioceramic granules with adjustable shell microstructures were favorable for controllable ion release in vitro, superior to the granules with the conventional homogenous hybrid structures. Also, we illustrated a significant difference in biodegradation of the granules in vivo, and especially the porous-shell granules exhibited appreciable new bone tissue ingrowth with time. The underlying fundamental mechanisms governing the new bone tissue ingrowth behavior of the yolk-shell granule scaffolds were elucidated based on microCT analyses and histological observation. It was underscored that during biodegradation in vivo, the highly bioactive ions in yolk layer were continuously released due to the porous structures of the sparingly dissolvable shell layer, thereby resulting in hollow shell and rapid new bone tissue ingrowth. Hence, these results demonstrate that the slight tailoring in microstructure and component distribution of biphasic composites is beneficial for adjusting the bone regeneration, and may help us to precisely control bone repair efficiency for a variety of clinical conditions.

Core-shell-structured nonstoichiometric bioceramic spheres for improving osteogenic capability.

A rational design of fully interconnected porous constructs of biomaterials with controlled pore-wall bioactivity and biodegradation is of importance in the advancement of bone regenerative medicine. We hypothesize that the layered structure of hybrid bioceramics produces time-dependent biological performances to tune osteogenic responses. We thereby developed core-shell-structured nonstoichiometric Ca silicate (nCSi) spheres and evaluated the effect of spatiotemporal distribution of bi-component nCSi on osteogenic capability. The alginate-based 4% Sr-, 6% Mg-, or 10% Mg-doped nCaSi (i.e. CSi-Sr4, CSi-Mg6, CSi-Mg10) slurries were extruded into a Ca2+-rich solution through the core or shell layer of a coaxial bilayer nozzle, and after drying and sintering treatments, the core-shell nCSi ceramic spheres were prepared. The improved sintering property and denser structure of CSi-Mg6 and CSi-Mg10 shells readily retarded bioactive ion release and biodegradation of CSi-Sr4@CSi-Mg6 and CSi-Sr4@CSi-Mg10 spheres compared with those of CSi-Sr4@CSi-Sr4. When the spheres were implanted into the femoral bone defect in rabbits, the differences in biodegradation and bone regeneration rate in relation to microsphere scaffolds were measured at 6-18 weeks post-implantation. CSi-Sr4@CSi-Mg10 showed slow biodegradation and new bone regeneration, whereas CaSi-Sr4@CSi-Sr4 showed a much faster degradation such that a low osteogenic capacity was observed with prolongation of time. However, CSi-Sr4@CSi-Mg6 spheres displayed expected biodegradation and osteogenic activity with time. These results confirmed the slight tailoring in both doping ions and that component distribution of nCSi is beneficial for adjusting osteogenesis of core-shell spheres. By rationally choosing foreign ion doping, this concept may represent a versatile strategy for the production of a variety of core-shell bioactive ceramics for bone regeneration and repair applications.