Alendronate loaded graphene oxide functionalized collagen sponge for the dual effects of osteogenesis and anti-osteoclastogenesis in osteoporotic rats

Abstract

Graphene Oxide (GO)-related hydrogels have been extensively studied in hard tissue repair, because GO can not only enhance the mechanical properties of polymers but also promote osteogenic differentiation of mesenchymal stem cells. However, simple GO-related hydrogels are not ideal for the repair of osteoporotic bone defects as the overactive osteoclasts in osteoporosis. Alendronate (Aln) is known to inhibit osteoclasts and may bind to GO through covalent connection. Therefore, delivering Aln in GO-related hydrogels may be effective to repair osteoporotic bone defects. Here, we developed a control-released system which is constructed by collagen (Col)-GO sponges loaded with Aln (Col-GO-Aln) for osteoporotic bone defect repair. In vitro, Col-GO-Aln sponges prolonged the release period of Aln, and the sponge containing 0.05% (w/v) GO released Aln faster than sponge with 0.2% GO. Furthermore, tartrate-resistant acid phosphatase (TRAP) and F-actin staining demonstrated that Col-GO-Aln sponges effectively inhibited osteoclastogenesis of monocyte-macrophages. In vivo, micro-CT scan showed that the volume of newborn bone in defect site by 0.05% GO sponge was nearly three times larger than that of other groups. Moreover, the CT and histological examinations of rat femur proved that Col-GO-Aln sponges decreased the number of osteoclasts and suppressed the systemic bone loss in osteoporotic rats. These findings reveal that the application of GO as carriers of anti-osteoporosis drugs is a viable treatment for osteoporosis. The results also underscore the potential of GO-related hydrogels with Aln-releasing capacity for bone regeneration in osteoporosis.

Keywords

• Osteoporosis
• Osteoporotic bone defect
• Graphene oxide
• Osteoclast
• Alendronate