Role of Molecular Chemistry of Degradable pHEMA Hydrogels in Three-Dimensional Biomimetic Mineralization

Three-dimensional (3D) biomimetic mineralization is highly desired for soft biomaterials such as collagen to create useful hybrid biomaterials for orthopedic tissue engineering. Here, we apply an approach of current-mediated ion diffusion, as a feasible means of 3D biomimetic mineralization, to a series of generic, hydrolytically degradable poly(2-hydroxyethyl methacrylate) hydrogels with various molecular structures, imparted by the introduction of the comonomers, acrylic acid and 2-hydroxyethyl methacrylamide. This approach enables us to create a wide range of nanoscale single crystals of calcium phosphate within the hydrogels as characterized by high-resolution transmission electron microscopy (TEM). Molecular chemistry of the hydrogels, coupled with pH and gel strength, plays a crucial role in formation of the minerals. Both brushite (CaHPO 4 ·2H 2 O) and octacalcium phosphate (Ca 8 H 2 (PO 4 ) 6 ·5H 2 O) are observed in pHEMA homo hydrogel. Both octacalcium phosphate and monetite (CaHPO 4 ) are seen in a copolymer hydrogel, poly(2-hydrogelethyl methacrylate-co-acrylic acid). In another copolymer hydrogel (poly(2-hydroxyethyl methacrylate-co-2-hydroxyethyl methacrylamide), both hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ) and monetite (CaHPO 4 ) are observed. All these nanocrystals are essential to bone regeneration. They organize themselves primarily as nanoscale fibers, sheets, needles, and clusters. These nanoarchitectures are important to bone-cell attachment, proliferation, migration, and differentiation, and dictate the ingrowth of new bone tissues.