Bisphosphonate-functionalized poly(amido amine) crosslinked 2-hydroxyethyl methacrylate hydrogel as tissue engineering scaffold

Abstract

• Bisphosphonate-functionalized poly(amido amine) macromer (PAA-BP) was synthesized. • Crosslinking with PAA-BP adds excellent mineralization ability to 2-hydroxyethyl methacrylate (HEMA) hydrogel. • This hydrogel is biocompatible and facilitates cell adhesion after mineralization. • PAA-BP improves swelling and degradation properties of the hydrogel. • This hydrogel can be used for tissue engineering scaffolds. The first water soluble, bisphosphonate (BP, not bisphosphonic acid)-functionalized poly(amido amine) macromer (PAA-BP) is synthesized and used as a crosslinker for synthesis of a biodegradable and biocompatible hydrogel for tissue engineering scaffolds. The synthesis of PAA-BP is performed in three steps, the first two giving the control macromers (PAA-NHBoc and PAA-NH 2 ): i) Michael addition reaction of N,N’ -methylene bisacrylamide and N -Boc-1,6-hexanediamine (acrylamide/amine ratios of 1.2), ii) deprotection of Boc-protected amine groups, iii) Michael addition reaction of the amine groups with tetraethyl vinylidene bisphosphonate. The degree of BP substitution is 50% and molecular weight of the PAA-BP macromer is found to be 4800 g/mol. These macromers are incorporated into hydrogels by copolymerization with 2-hydroxyethyl methacrylate and the influence of bisphosphonate functionality on hydrogel properties; degradation, swelling, mechanical and mineralization, is investigated. The mineralization abilities, hence the mechanical properties of the hydrogels are strongly influenced by the BP functionality; PAA-BP forming strong (E = 83 ± 1 kPa) hydrogel-apatite composites, PAA-NH 2 also working to a lesser degree (E = 54 ± 3 kPa). Cytocompatibility of the hydrogels is observed on Saos-2 human osteosarcoma, U-2 OS human bone osteosarcoma epithelial, C2C12 mouse myoblast muscle and NIH mouse embryonic fibroblast 3T3 cells. PAA-BP crosslinked hydrogels facilitate adhesion of C2C12 cells after mineralization. In summary, BP-functionalized hydrogel may have a potential impact on bone tissue engineering.