Alendronate-functionalized poly(amido amine) cryogels of high-toughness for biomedical applications

Abstract

Novel bisphosphonic acid-functionalized poly(amido amine) (PAA) macromers were synthesized through aza-Michael addition of sodium alendronate (ALE) and 5-amino-1-pentanol (AP) to N,N'-methylene bisacrylamide at two different molar ratios, with macmmer only having AP as comparison control. The macromers were photopolymerized to cryogels whose swelling, biodegradation and mineralization properties were studied. Biodegradation was most strongly affected by the macromer molecular weight. In mineralization studies, the control cryogel nucleated HAP, the others another type of biological apatite; the extent of mineralization depending on ALE concentration. Cryogel-apatite composites were studied by SEM, FTIR, XRD and thermogravimetric analysis. Mechanical tests reveal compressions up to 97% for cryogels, showing their high toughness. Young's modulus and compressive fracture stress increase with ALE content to 10 kPa and 2.2 +/- 0.4 MPa, respectively. The modulus increased significantly in mineralization due Ca2+-ALE bindings forming physical cross-links. Degradation products of ALE-containing cryogels showed dose, composition and cell type dependent cytotoxicity when incubated with osteosarcoma cells lines, Saos-2 and U-2 OS, and healthy C2C12 muscle cells.