Periodic Reporting for period 1 - Active implants (Active implants: Engineering microstructures of functional ceramics for stimulated bone growth) Reporting period: 2015-09-01 to 2017-08-31 Summary of the context and overall objectives of the project Replacement surgeries for bone tissue are a normal part of clinical practices nowadays with constantly increasing numbers for e.g. hip and knee joint replacements. However, such procedures are still a substantial intervention and afflicted with long healing times reducing the patient’s quality of life and generating high costs for the health care system. Thus, it is very desirable to develop implant materials that accelerate the healing process and support the development of a long lasting functional interface between bone and implant. For load-bearing bone it is well known that the application of mechanical stress leads to the creation of electric potentials, which serve as electric stimuli to trigger bone and vascular cell growth. Thus, the creation of stress generated electric potentials by the implant material mimicking this electric trigger for cell growth has the potential to accelerate the healing process and to improve the bone-implant bonding.Piezoelectric materials are potential candidates for this purpose, as they develop electric surface charges under mechanical load similar to load-bearing bone. The quality of the final bone-implant interface is determined by thes biocompatibility of the replacement material, its surface morphology and electric surface states. Especially the porosity of the ceramic is of crucial importance as the pores have to be large enough and of open structure to allow ingrowth of both bone and vascular cells. However, increasing porosity is alters the piezoelectric behaviour and by this the surface charges responsible for cell growth stimulation. The main research objective was to clarify the relationship between microstructure and piezoelectric behaviour of different piezoelectric ceramics. The knowledge gained forms the basis for the development of a new class of implant materials exploiting the piezoelectric characteristics to improve the healing process.Three different types of piezoelectric ceramics were successfully made. The piezoelectric performance of all material systems decreased with increasing porosity, but remained higher than the natural response of cortical bone. This makes them promising as porous bone implant materials. Two of the base systems exhibit highly stable performance even after long submersion in salt solution – simulating the state within the body. The third base system disintegrates when placed in salt solution. However, this process can be controlled, which makes this class of material promising as bioresorbable implant option. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far The material systems investigated were BaTiO3 (BT), (Ba,Ca)(Zr,Ti)O3 (BCZT) and (K,Na)NbO3 (KNN). A wide range of microstructures were produced and their impact on crucial parameters such as piezoelectric performance was determined. Biocompatibility and long-term integrity in liquid environments were also investigated.The final microstructure and the performance of a piezoelectric ceramic depends on the grain size of the starting materials. Different processing routes were chosen to produce ceramic powders with varying grain sizes. Larger grains were achieved with solid state synthesis, while powders with small grains were produced using sol-gel synthesis and spray pyrolysis. To achieve samples with a dense ceramic matrix and controlled porosity, the sacrificial template method was chosen. Mixtures of ceramic powder and pore former were pressed into pellets. The starch was burned off, leaving a defined pore structure behind. The piezoelectric properties scaled with the degree of porosity showing minimum values for the most porous compositions. The absolute values depend on pore shape and size, which are determined by the pore former used. Small and irregular shaped grains of the pore former lead to lower piezoelectric coefficient, whereas larger, spherical grains lead to better performance. Even though the values of the piezoelectric coefficient decreased for all materials with increasing porosity, the obtained values always exceeded that of cortical bone.As the materials are intended to be used as implant components, their stability and reliability is important. To simulate in-vivo conditions, the ceramics were soaked in NaCl-solution. Distinct differences were found for the different material classes. While BT-based materials appeared to be very stable during the soaking, the KNN-samples tend to dissolve. This dissolution process varied from a few days up to several weeks. The mechanism leading to this controllable solubility of KNN most likely depends on the exact phase composition. To control the solubility and maintain the piezoelectric output, KNN was doped with calcium, titanium and zirconium, which was found to stabilize the piezoelectric output after soaking compared to undoped samples.To determine the biocompatibility of the ceramic materials, cell tests were conducted on BT-based materials in collaboration with the University clinic in Erlangen/Germany. Cell proliferation and viability was found to be higher on the ceramic materials compared to a standard. This makes this material very promising for the usage in biomedical applications. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) The exploitation of the piezoelectric behavior in load-bearing implants to stimulate bone growth, is an interdisciplinary task that has not received much attention so far. To develop a new material to a level that it can be used as biomedical material, many aspects have to be optimized. Within this project, we tackled some of these challenges.To facilitate the formation of a strong interface between living structure and artificial material, the implant has to be porous. Studies on porous piezoelectric ceramics are sparse, as for most applications highly dense components are required. Our studies strongly contribute to the understanding of the impact of porosity on the piezoelectric properties of different material classes and highlight limitations and possibilities regarding the production process.The stability of piezoelectric materials within a “liquid” environment, such as the body, was not tackled so far by the piezoelectric research community. Here, our studies revealed significant differences between the material classes investigated, with BT-based ceramics being very stable in salt solutions, whereas KNN ceramics can dissolve within a few days or last up to a few weeks. These findings are not only important for biomedical applications, but highlight in general the sensitivity of KNN-based materials to humid environments. This has implications for general processing routines, esp. in terms of upscaling from laboratory to industrial amounts, as well as for other applications, where the materials are exposed to humidity or different kinds of vapor.The investigation of biocompatibility aspects are crucial for every material that is intended to be used within the body. As piezoelectric materials have not been in the focus as biomedical materials, only limited research exist in this field. The present project contributes an extensive study, highlighting the great potential of BCZT ceramics as biocompatible material. Besides the exploitation of the stress generated potentials in load-bearing implants, many other biomedical applications could benefit from the usage of piezoelectric materials. As such, our promising cell tests have implications far beyond the present project and might inspire to further research on piezoelectric materials within the biomedical context. Porous BT ceramics made with the same weight fraction but different kinds of pore former
