We would like to inform you about a new study by scientists from the Department of Tissue Engineering, namely Věra Hedvičáková, Radmila Žižková, Eva Šebová, Eva Filová and Michala Rampichová, published in the prestigious International Journal of Nanomedicine (IF 7.033). The study entitled “The Gradual Release of Alendronate for the Treatment of Critical Bone Defects in Osteoporotic and Control Rats” was created in collaboration with the partner institutions of the IEM CAS, namely:
- Technical University in Liberec (open in a new window),
- Faculty of Medicine in Pilsen – Charles University (LFP UK) (open in a new window),
- Biomedical Centre of LFP UK (open in a new window),
- First Faculty of Medicine of the UK (open in a new window),
- Biofabics (open in a new window).
The research focuses on the treatment and development of new therapeutic agents to regenerate bone defects in osteoporotic patients. The standard treatment consists of the systemic administration of drugs such as bisphosphonates (BPs), with alendronate (ALN) being one of the most common. ALN is a type of BPs that has been investigated in clinical trials in recent decades. Oral administration of ALN increases bone mineral density and decreases the risk of clinical fractures. However, over the years, associated problems such as jaw osteonecrosis appeared. Therefore new directions, such as the local administration of ALN, are being investigated.
In this study, a nanofibrous polycaprolactone scaffold with incorporated hydroxyapatite (HA), prepared by the electrospinning technique, served as a drug delivery system for ALN. The designed scaffold was first tested in vitro to verify its biocompatibility. Moreover, the co-cultures of primary osteoblasts and induced osteoclasts isolated from control or osteoporotic animals were used for complex examination of the scaffold properties. Subsequently, a comprehensive in vivo study was performed. The effect of the scaffold releasing the ALN on the healing capacity of the bone was examined in control and osteoporotic rats with or without systemic ALN administration.
Scientists successfully prepared emulsion/dispersion scaffolds based on the emulsion of polycaprolactone, hydroxyapatite, and Pluronic F68 with ALN, containing HA nanoparticles as the dispersion phase. The HA and poloxamers enabled the control of ALN release kinetics without affecting the overall scaffold morphology. The ALN was gradually released from the scaffolds for more than 22 days. In the case of emulsion scaffolds without the dispersion phase, the release was slower, with sequestration of 40% of ALN in the fibers after 22 days. Alternatively, scaffolds with the emulsion/dispersion concept showed faster release and resulted in a 90% ALN release in 22 days. The scaffolds demonstrated the ALN effect on bone cells in vitro. Despite the slow degradation rate of the scaffold in vivo, the released ALN supported the bone formation surrounding the implant residues and stimulated denser bone formation in the paracrine of the defect.
The complete study can be found on the International Journal of Nanomedicine (open in a new window) website.