Fabrication and evaluation of an inositol hexaphosphate-zinc hydrogel with dual capabilities of self-mineralization and osteoinduction

To fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials.

The hydrogel framework (designated DF₀) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF₁, while the co-loaded hydrogel was named DF₂. The self-mineralization efficacy of the DF₀, DF₁ and DF₂ hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF₀, DF₁ and DF₂ hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group.

The DF₀, DF₁, and DF₂ hydrogels were successfully synthesized. Notably, DF₁ and DF₂ exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF₁, and amorphous calciumzinc phosphate in group DF₂. Biocompatibility tests revealed that none of the hydrogels (DF₀, DF₁, and DF₂) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF₁ and DF₂ groups, with the most profound staining observed in the DF₂ group.

The developed inositol hexaphosphate-zinc hydrogel (DF₂) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.