Preparation and characterization of a Novel mesoporous bioactive glass/calcium sulfate cement for vertebroplasty application

Vertebral compression fractures (VCFs) are deformities of the vertebral body that usually do not require an open surgical approach and are often due to osteoporosis or low energy trauma. They may be healed by themselves with a conservative management: brace support and bed rest, combined with the administration of analgesics and bisphosphonates. When the non-surgical approach is not effective, VCFs usually lead to untreatable pain, spine deformity and disability with a proven increase of mortality, especially in patients with poor conditions. Vertebroplasty and kyphoplasty are known as alternative minimal invasive approaches to VCFs. They are two percutaneous spine interventions which are performed with the goal of back pain relief and, when possible, restoring of the vertebral height. Vertebroplasty involves the injection of a bone cement through the trabeculae of the fractured vertebral body. In this procedure, cement injection is performed under continuous radiological control through a needle inserted in the vertebra by a transpedicular percutaneous approach. In kyphoplasty, a balloon tamp is inserted through a vertebroplasty needle in the fractured vertebral body and then is inflated/deflated and the created cavity is filled with the bone cement injected through a needle. In randomized trials it was found that VP and KP are equally safe and significantly superior to conservative treatment. Injectable bone cements play a critical role in the effectiveness of vertebroplasty and kyphoplasty. Regarding the bone replacement, several investigations have been focused on the materials exhibiting good bioactivity, biodegradability and biocompatibility. Injectable bone cements can be divided into various categories. The first group is polymer based cements which show unique properties due to their flexibility of composition. However, their poor mechanical strength limits their applications. Metals are considered as the second group that has high wear resistance, strength and ductility. However, their high rate of corrosion and low biocompatibility make them undesirable for living tissue. In addition, allergic reactions can occur due to the high diffusion of metal ions. Another group of materials are ceramics which possess generally good biocompatibility. Although these materials have resistance to corrosion and compression, they are brittle with low fracture strength. Calcium phosphate and calcium sulphate cements could be applicable as biomaterials for vertebral stabilization and augmentation. Nevertheless, their clinical applications have been limited due to some shortcomings. Currently, the number of commercial calcium sulphate-based cements is limited. Therefore, in recent years, several approaches have been proposed to develop the synthetic calcium-based bone cements. The aim of the present research was the synthesis of a mesoporous bioactive glass (MBG) by spray-drying a mild acidic aqueous synthesis solution. These particles are able to chemically bond to the bone and can be also utilized for targeted drug delivery. In order to synthesis the MBG particles, the classical methods are time-consuming due to the additional steps to obtain the final powders. Moreover, these methods are usually performed with ethanol-based solution which is flammable and expensive. Spray-drying can be considered as a single step production technique to transform a fluid feed to a dried solid powder. In fact, the spray-drying approach can be used as an effective alternative to the standard routes with faster kinetics which allows to produce the particles with controlled size and morphology. It is reported that the spray-dried mesoporous bioactive glasses or functionalized silica have been already produced by spraying synthesis solutions based on flammable solvents (mostly ethanol) under an inert atmosphere. In general, the effective procedures involve both safety and economic constraints for a future manufacturing scale-up. In this study, MBG particles were produced by the combination of sol-gel synthesis in an aqueous medium and spray-drying technique, which can be a further improvement in terms of safety, cost and environment. The second aim of this study was to develop an innovative injectable and bioresorbable composite cements based on alpha calcium sulphate hemihydrate as a resorbable matrix, enriched with mesoporous glass particles (to impart bioactivity) and a glass-ceramic radiopaque phase. The present work was in the frame of the European Union Seventh Framework Program (FP7/2007- 2013) under grant agreement no. [280575]-Restoration. During this study, the developed injectable cements were characterized in terms of physical and mechanical properties such as setting time, injectability and compressive strength. Moreover, in vitro bioactivity and degradability of prepared composite cements were assessed in simulated body fluid (SBF). Biological tests using rat bone marrow stromal cells were also carried out in vitro. In addition, further investigations were carried out in vivo by using large animal model (sheep).