Preparation of magnetic calcium phosphate microcarriers loaded with bisphosphate-modified GDF-5 for bottom-up bone tissue engineering

For bottom-up bone tissue engineering, microcarriers play crucial roles in serving as scaffolds that provide structural support and environmental cues for cell growth. Studies have demonstrated that the physicochemical properties of microcarriers, such as surface structure and chemistry, have significant effects on cell phenotype. However, current research on microcarriers has primarily focused on hydrogels or polymers, neglecting the exploration of hard materials that mimic the bone tissue environment. In this study, a new facile method to fabricate magnetic calcium phosphate (CaP)-based microcarriers were presented. By this method, magnetic calcium phosphate was obtained without changing the surface nanostructure of CaP microspheres. These magnetic CaP microspheres were utilized as cell-adhesive microcarriers, allowing for cell-guided assembly into spherical microtissue under a relatively low number of cells. However, when using CaP microspheres as microcarriers, only loose aggregates were observed. To enhance the biofunctionality of the magnetic CaP microcarriers, bisphosphonate-modified growth differentiation factor-5 (PGDF-5) were synthesized and selectively deposited onto the magnetic CaP surfaces. Coculture with preosteoblastic cells demonstrated that PGDF-5 modified microcarriers effectively improved cell osteogenic differentiation and angiogenesis, thereby facilitating the formation of highly stable cell spheroids. Collectively, all findings suggest that PGDF-5 modified magnetic CaP microcarriers hold great potential as tools for fabricating bottom-up tissue engineered bone-mimicking tissue.