Synthesis of bioactive class II poly(gamma-glutamic acid)/silica hybrids for bone regeneration

Bone grafts are commonly used to regenerate bone in defect sites resulting from disease or trauma but there is clinical need for artificial materials that will be readily available and reduce pain and recovery time for the patient. Current artificial bone graft materials include bioactive ceramics and glasses, which are too brittle for bone defects that experience cyclic load. The synthesis of a new nanocomposite material is described that has the potential of being a tough off-the-shelf artificial bone graft that can regenerate a bone defect and have enough flexibility to press-fit into place. The poly(gamma-glutamic acid)/bioactive silica hybrid material with composition 40 wt% organic and 60 wt% bioactive inorganic (composition 70 mol% SiO2 and 30 mol% CaO) was synthesised using a sol-gel route. The potential advantage of a hybrid material over conventional composites is the molecular scale interactions between the bioactive inorganic and the tough degradable organic. The organic and inorganic chains were covalently cross-linked using an organosilane that has an organic functionality to bond to poly( g-glutamic acid) (gamma-PGA) and an alkoxysilane group that condenses with the inorganic phase. The covalent cross-linking (class II hybrid) is required to control the dissolution and improve mechanical properties of the material. The two key variables, the concentration of cross-linking agent and the addition of calcium, were investigated by Si-29 solid-state NMR and electron microscopy. The hybrid materials were bioactive in simulated body fluid (SBF) with a hydroxy carbonate apatite (HCA) layer detected after immersion for 72 h. The hybrid material favours cell attachment and is not cytotoxic as demonstrated by culture of the osteosarcoma cell line SaOs-2 on the material for 4 days