Integrative design of a poly(ethylene glycol)-poly(propylene glycol)-alginate hydrogel to control three dimensional biomineralization

A mineralized polymeric matrix has been extensively studied to understand biomineralization processes and to further regulate phenotypic functions of various cells involved in osteogenesis and physiological homeostasis. It has been often proposed that several matrix variables including charge density, hydrophobicity, and pore size play vital roles in modulating composition and morphology of minerals formed within a three dimensional (3D) matrix. However, the aspects have not yet been systematically examined because a tool enabling the independent control of the matrix variables is lacking. This study presents an advanced integrative strategy to control morphology and composition of biominerals with matrix properties, by using a hydrogel formulated to independently control charge density, hydrophobicity, and porosity. The hydrogel consists of poly(ethylene glycol) monomethacrylate (PEGmM), poly(propylene glycol) monomethacrylate (PPGmM), and methacrylic alginate (MA), so the charge density and hydrophobicity of the hydrogel can be separately controlled with mass fractions of MA and PPGmM. Also, hydrogels which present only nano-sized pores, termed nanoporous hydrogels, are lyophilized and rehydrated to prepare the hydrogels containing micro-sized pores, termed microporous hydrogels. We find that increasing the mass fractions of MA and PPGmM of the microporous hydrogel promotes the growth of apatite layers because of the increases in the charge density, hydrophobicity and pore size. In contrast, increasing mass fractions of MA and PPGmM of the nanoporous hydrogel enhances the formation of calcium carbonate minerals. The dependency of the mineralization on hydrogel variables is related to the change in supersaturation of mineral ions. Overall, the results of this study will be highly useful to better understand the interplay of matrix variables in biomineralization and to design a wide array of mineralized matrix potentially used in cell therapies and tissue engineering.