Acid-responsive composite hydrogel platform with space-controllable stiffness and calcium supply for enhanced bone regeneration

Abstract Many hydrogel scaffolds for bone regeneration do not satisfy clinical needs due to uncontrollable mechanical properties and calcium supply and a lack of outstanding osteogenic functions. Herein, a novel acid-responsive composite hydrogel scaffold platform was developed to provide controllable stiffness and calcium supply for enhanced bone regeneration. For this purpose, pluronic F127 diacrylate (F127-DA) was selected as the model scaffold matrix material due to its good biocompatibility and easy formulation capability. Nano-CaCO3 was chosen as the composite material to provide an acid-responsive property and controlled calcium supply. The acid-responsive nano-CaCO3 may lead to space-controlled distribution of nano-CaCO3 in a hydrogel under acid treatment, leading to effective regulation of the mechanical properties of the hydrogel scaffold. Furthermore, the hydrogel may efficiently modulate the expression of Col1, BMP2 and OPN, which are beneficial for osteogenesis. In vivo studies in a rabbit skull bone defect model indicated that this F127-DA/nano-CaCO3 composite hydrogel platform performed better in bone regeneration than a pure F127-DA hydrogel. Therefore, this responsive composite hydrogel platform provides a simple and robust strategy for developing advanced composite hydrogel scaffolds for effective bone repair.