Calcium Phosphate Biomaterials Composite Device: In-Vitro and In-Vivo Investigation

Low crystalline apatite (LCA) and calcium phosphate cements (CPC) based on amorphous calcium phosphate and dicalcium phosphate dihydrate (1 to 1 ratio) were combined with bioresorbable PLGA copolymer (0 to 20 wt.%) for preparation of solid-formed devices. A pilot manufacturing based on powder processing techniques using isostatic pressure (44,000 psig) was conducted. Processing parameters such as isostatic pressure, temperature, times and device dimension were varied to achieve appropriate mechanical properties comparable to that of allograft bone dowel used as a gold standard in clinical application. The solid-form devices were characterized for physico-chemical and mechanical performance, as well as subjected to an in-vitro wet environment incubation at body temperature (37°C). Fluid diffusion was investigated to evaluate the fluid absorption (through microporosity) and the compressive strength of wet devices vs. incubation time (up to 30 days) was also studied. The shear strength and compressive strength of pure LCA dowels was respectively 26 and 122 MPa, which corresponds to a process densification of about 30%. The compressive strength was dramatically improved with addition of various amounts of copolymer. The maximum compressive strength of 180 MPa was obtained for dowels containing 10 wt.% copolymer. Calcium phosphate composite also increased the shear strength to about 42 MPa. These mechanical performances were significantly higher than that of allograft bone dowel (MD-II™), reported about 10 MPa. A pilot sheep interbody fusion of lumbar spine (L3/L4 and L4/L5) demonstrates mechanical integrity and intervertebral fusion at 6 months. LCA was found to be the most suitable CaP material because of its biocompatibility, chemical composition, nano-structure and high specific surface area that exhibits in-vivo biointegrity and cell mediated process.