Paper BI+AS+NS-FrM6
Novel Insights into Drug Release by a Functionalized Biomaterial and Dispersion into Bone using Surface Analytical Techniques

Friday, October 26, 2018, 10:00 am, Room 101B

Bone is a complex composite material with similarities to hierarchically structured functional materials. In the case of a fracture or the need for a replacement (e.g. hip prosthesis) filler or replacement materials are necessary. Next generation bone implants are functionalised with drugs to stimulate bone healing locally or to provoke antibiotic effects. Here we focus on the release and dispersion of the anti-osteoporotic agent Sr²⁺ from strontium enriched bone cement. The knowledge of the release and dispersion kinetics of the drug plays an eminent role for the performance optimisation of the biomaterial.

Due to practical and technical reasons it is almost impossible to track the drug release kinetics, drug dispersion and the degradation of the implant material in vivo. Here we apply time of flight secondary ion mass spectrometry (ToF-SIMS) depth profiling to obtain the diffusion coefficient of Sr²⁺ in the mineralised areas of healthy and osteoporotic rat bone in post mortem examinations. For data evaluation of the depth profiles in mineralised bone we applied a simple diffusion model. The obtained diffusion coefficient for trabecular osteoporotic bone is with 1.76×10^-10 cm²/s more than two decades higher than that for healthy bone (2.91×10^-12 cm²/s). In cortical bone no significant difference in the diffusion coefficient (healthy 1.33×10^-12 cm²/s, osteoporotic 4.17×10^-12 cm²/s) could be found. The varying diffusion coefficients can be explained by the different bone nanostructure, which was investigated by focused ion beam scanning electron microscopy (FIB-SEM) and high-resolution transmission electron microscopy (HR-TEM).

The data of cement dissolution experiments into water in combination with inductively coupled plasma mass spectrometry (ICP-MS) analysis account for dissolution kinetics following Noyes-Whitney rule. For dissolution in A-MEM cell culture media the process is kinetically hindered and can be described by Korsmeyer-Peppas kinetics. An adsorbed protein layer on top of the cement surface, which was detected by ToF-SIMS, is responsible for the kinetic inhibition. Based on the results of various analytical experiments we developed a two-phase model and performed a finite element calculation for the release and dispersion of Sr²⁺ in bone. The validity of the applied model is proven by animal experiments. We compared the calculated images to mass spectrometric images of bone cross sections and achieved good conformity. It appears that drug removal via the vascular system is negligible. This is a good basis for predictions of drug mobility in bone.