Mesoporous Implants for Localized Controlled Drug Delivery

Doktorsavhandling, 2014

The use of bone-anchored implants is today a routine treatment for patients with normal regenerative capacity. However, there is an ongoing development within implant research to improve the osseointegration of implants. Despite considerable progress, further improvements are needed to achieve a more rapid healing and to enable treatment of patients suffering from low bone amounts or poor bone quality. One approach to improve the clinical outcome of bone-anchored implants is to use drugs to promote bone tissue regeneration. When using therapeutic treatments, the delivery system is crucial to obtain high efficiency and avoid toxic side effects. The primary aim of this thesis was to investigate how mesoporous titania thin films can be used for local drug delivery to obtain enhanced osseointegration of implants. The well-defined pore structure of mesoporous materials makes them appropriate as drug delivery systems. Templates of different sizes were used, enabling the pore size to be varied from 3.4 to 7.2 nm. Moreover, the adsorption and release of different drugs from mesoporous titania were monitored using quartz crystal microbalance with dissipation. The results showed that the mesoporous titania thin films served for high drug loading and controlled release. The drug administration of the osteoporosis drug alendronate was also evaluated in vivo. The drug was radiolabelled, which enabled molecular specific detection; hence, the drug distribution into the surrounding bone and the distal diffusion could be analyzed. The results showed that most of the released drug remained within a few 100 micrometers from the implant surface. Biological evaluation demonstrated that local delivery of the osteoporosis drugs alendronate and raloxifene from mesoporous titania thin films improved the osseointegrating performance of implants and that local delivery of chemokines, for homing of stem cells, enhanced the bone tissue regeneration. Another aim was to apply novel ex vivo analytical techniques to yield knowledge about the implant-bone interface. Atom probe tomography is considered as one of the most powerful tools for microstructural characterization. This technique was used for the first time to characterize an interface between a biomedical device and tissue. The analysis provided a three-dimensional atomic reconstruction of the interface between the implant and formed bone mineral. Raman spectroscopy with mapping capability was utilized to characterize the molecular identity of the formed bone mineral at implant surfaces with and without delivery of alendronate. It was shown that it is crucial to control the drug concentration in order to promote biomineralization. The results presented and discussed in this thesis demonstrate that mesoporous titania thin films are highly suitable as a drug delivery platform for bone anchored implants. Furthermore, the novel analytical ex vivo techniques applied allowed for new insights about tissue response to biomedical implants.