Magnetic Bioactive Glass-Based 3D Systems for Bone Cancer Therapy and Regeneration ^†

Several diseases, such as osteoporosis and bone cancer, are causing an increasing need for advanced bone repair materials suitable for skeletal reconstruction. Indeed, bone is the second most replaced organ in the body after blood. Approximately 2.2 million bone graft procedures are performed worldwide each year at an estimated cost of USD 2.5 billion per year [1]. Malignant bone tumors are one of the main non-trauma factors resulting in critical size bone loss/defects. The treatment of such bone defects is still a considerable challenge, and it is currently recognized that the increasing request for bone substitute materials cannot be tackled solely by autogenous or allogenic bone grafts [2]. On the other hand, surgical resection often fails to completely remove the tumor, which is the main cause of postoperative recurrence and metastasis. Therefore, a polymeric scaffold for bone regeneration that simultaneously kills residual tumor cells is of much benefit. Magnetic hyperthermia using superparamagnetic iron oxide nanoparticles (SPIONs) has emerged as a potential cancer treatment option, since it is considered an effective treatment without adverse side effects [3]. These SPIONs will generate clinically relevant heat (41 °C–45 °C) under the application of an alternating magnetic field to kill or sensitize tumor cells. On the other hand, mesoporous bioactive glasses (MBGs) dissolution products have demonstrated their effect on osteoblast cell gene expression and the potential effect on angiogenesis and neovascularization, which in turn promotes bone healing. Moreover, when BGs are implanted in the human body, a hydroxyl-carbonate-apatite (HCA) layer can be formed on the surface, which chemically bonds with living bone. We therefore propose a new concept for the treatment of bone cancer and the regeneration of bone defects: a polymeric scaffold produced by electrospinning containing MBG that combines magnetic hyperthermia therapy through the incorporation of the SPIONs into the scaffold and local drug delivery [4]. Additionally, the use of MBG nanoparticles in a polymeric matrix closely mimics the structure of natural bone, which contains nanoscale hydroxyapatite crystallites combined with the polymeric phase of collagen type I.

The experimental work to produce the multifunctional scaffolds is divided into three parts: (1) production and characterization of SPIONs and MBGs individually; (2) incorporation of these individual materials into a polyvinylpyrrolidone (PVP) matrix produced by electrospinning; (3) characterization and selection of such composites based on its bioactivity, biodegradability, biocompatibility, drug encapsulation/releasing profile, and magnetic studies, to select the membranes with the most desirable properties. The composites have been produced by individually adding the MBG and SPIONs to the electrospinning solution. The SPIONs were also incorporated in the polymeric matrix by the adsorption method (still be under characterization). To assess whether the materials keep their individual properties after the final blending, the composites were produced and characterized in different stages: PVP/SPIONs composites; PVP/MBG composites; PVP/SPIONs/MBG composites. The PVP/MBG composites were already characterized in terms of bioactivity. Magnetic hyperthermia assays were performed to evaluate the heating ability of SPIONs incorporated into PVP nanofibers. The production of the final PVP/SPIONs/MBG was already achieved but still is under characterization in terms of bioactivity and the heating ability for further comparation with PVP/BG and PVP/SPIONs composites. All composites were revealed to be biocompatible what is a great indicator for biomedical applications. The composites are under optimization in terms of degradation ratio, which is directly related to anticancer drug encapsulation and subsequent drug-releasing profile and is also related to PVP/MBG bioactive behavior.