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Cell instructive scaffolding platforms displaying synergistic effects by virtue of their chemical and physical cues have tremendous scope in modulating cell phenotype and thus improving the success of any graft. In this regard, we report here the development of Si- and Zn-doped brushite cement composited with silk scaffolding that hierarchically emulated the cancellous bone. The composite scaffolds fabricated exhibited an open porous network capable of enhanced osteoblast survival as attested by increased alkaline phosphatase activity and also sustaining osteoclast activity affirmed by tartrate resistant acid phosphatase staining. Moreover, the chemical cues presented by dissolutions products from the composite scaffold enabled the osteoblasts to secrete proangiogenic factors which favored better endothelial cell survival, confirmed through in vitro experiments. Moreover, the efficacy of these composite biomimetic scaffolds was validated in vivo in volumetric femur defects in rabbits, which revealed that these matrices influenced vascular cell infiltration and favored the formation of matured bony plate. Fluorochrome labeling studies and microtomography analysis revealed that at the end of three months, the implanted composite scaffolds had completely resorbed, leaving behind neo-osseous tissue and vouching for clinical translation of these composite matrices as viable and affordable bone-graft substitutes.

In vitro and in vivo degradation behavior and biocompatibility of magnesium phosphate (MgP) bioceramics and the potential role of zinc (Zn) on degradation were compared. Samples were prepared by conventional solid-state sintering at 1200 °C for 2h. Zn-doped MgP (0.5 wt %) showed 50% less degradation than that of pure MgP after immersion into simulated body fluid (SBF) for 8 weeks. Osteoblast-like cell (MG-63) proliferation was evident in MgP ceramics, which was significantly enhanced upon Zn addition. Both Alamar Blue assay and Live/Dead imaging showed the highest cell attachment and proliferation for 0.5 wt % Zn-doped MgP. In vivo biocompatibility of these MgP ceramics were studied after implantation in the rabbit femur. The micro computed tomography (μ-CT) analysis showed that in vivo degradability increased with the increase in the Zn content which is in contradiction to in vitro degradability. Histological evaluation showed large influx of osteoclast cells to the implantation site for Zn-doped MgP samples compared to that of undoped MgP, which is the primary reason of increased degradability of these samples. After 90 days of implantation, large sections of 0.5 wt % Zn-doped MgP samples were replaced by newly formed bones. Fluorochrome labeling showed 78 ± 3% new bone formation for 0.5 wt % Zn-doped MgP ceramics compared to 56 ± 3% for pure MgP samples. Our findings suggest that the addition of Zn in MgP ceramics alters their sintering and degradation kinetics that leads to decreased in vitro degradation, however, when Zn-doped MgP ceramics were implanted in rabbits, higher degradability was observed due to lower Mg2+ ion concentration in the degradation media.

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