Core–Shell Biphasic Microspheres with Tunable Density of Shell Micropores Providing Tailorable Bone Regeneration

Abstract

Unlike the conventional porous scaffolds, which have continuous three-dimensional porous architecture and mechanical support, the macroscopic pore structures of bioceramic granules—that is, the void space among closely packed granules—are of very limited porosity. Furthermore, it is difficult to adjust the biodegradation and bioactive ion release sufficiently to stimulating new bone ingrowth during the early stage after implantation. In this study we demonstrate a new strategy for selectively tailoring the porous microstructures of specific component in the core–shell biphasic microspheres (∼2 mm in diameter) composed of 4% strontium-substituted calcium silicate (CSi-Sr4) and beta-tricalcium phosphate (CaP). Our method uses rapidly gelling microspheres derived from bi-flows of alginate-loaded CaP and CSi-Sr4 slurries through the coaxially aligned nozzles, and collected using chitosan solution. When 15 μm diameter polystyrene (PS) microspheres are premixed into the CaP slurry with a PS/CaP ratio (x; x% = 0%, 15%, 30%, and 45%), the micropores can be tailored in the CaP-shell layer after sintering, and as a result the biodegradation of both CSi core and CaP shell in CSi-Sr4@CaP-px microspheres could be adjusted simultaneously. The critical-sized bone defect model reveals that the bone regeneration rate is very slow in the CSi-Sr4@CaP-p0 group, and the bone ingrowth only occurred in the macropores; but in the CSi-Sr4@CaP-p15 and CSi-Sr4@CaP-p30 groups, the bone ingrowth increased significantly. The histological results show that, intriguingly, the hollow core after CSi biodissolution favors new bone ingrowth through the porous CaP shell. It is reasonable to consider that this new idea could provide insights toward designing biphasic composite scaffolds with precisely tuned, time-dependent spatiotemporally evolving porous microstructures that are beneficial for bone regeneration and repair in situ.

Impact Statement

We have developed the new core-shell bioceramic CSi-Sr4@CaP-px microspheres with tuning porous shell layer so that the biodegradation of both CSi-Sr4 core and CaP shell is readily adjusted synergistically. This is for the first time, to the best of our knowledge, that the bioceramic scaffolds concerning gradient distribution and microstructure-tailoring design is available for tailoring biodegradation and ion release (bioactivity) to optimizing osteogenesis. Furthermore, it is possibly helpful to develop new bioactive scaffold system for time-dependent tailoring bioactivity and microporous structure to significantly enhance bone regeneration and repair applications, especially in some non-load-bearing arbitrary 3D anatomical bone and teeth defects.