Nitric Oxide-Releasing Bioinspired Scaffold for Exquisite Regeneration of Osteoporotic Bone via Regulation of Homeostasis

Osteoporotic bone regeneration is a challenging process which involves the occurrence of sophisticated interactions. Although various polymeric scaffolds have been proposed for bone repair, research on osteoporotic bone regeneration remains practically limited. In particular, achieving satisfactory bone regeneration when using osteoporotic drugs is challenging including bisphosphonates. Here, a novel nitric oxide-releasing bioinspired scaffold with bioactive agents for the exquisite regeneration of osteoporotic bone is proposed. The bone-like biomimetic poly(lactic-co-glycolic acid) scaffold is first prepared in combination with organic/inorganic ECM and magnesium hydroxide as the base implant material. Nanoparticles containing bioactive agents of zinc oxide (ZO), alendronate, and BMP2 are incorporated to the biomimetic scaffold to impart multifunctionality such as anti-inflammation, angiogenesis, anti-osteoclastogenesis, and bone regeneration. Especially, nitric oxide (NO) generated from ZO stimulates the activity of cGMP and protein kinase G; in addition, ZO downregulates the RANKL/osteoprotegerin ratio by suppressing the Wnt/beta-catenin signaling pathway. The new bone is formed much better in the osteoporotic rat model than in the normal model through the regulation of bone homeostasis via the scaffold. These synergistic effects suggest that such a bioinspired scaffold could be a comprehensive way to regenerate exceptionally osteoporotic bones.

Automated summary

In this study, a novel nitric oxide-releasing bioinspired scaffold with bioactive agents was proposed for the regeneration of osteoporotic bone. The scaffold, made of bone-like biomimetic poly(lactic-co-glycolic acid), organic/inorganic ECM, and magnesium hydroxide, incorporated nanoparticles containing zinc oxide (ZO), alendronate, and BMP2. The scaffold exhibited multifunctionality, such as anti-inflammation, angiogenesis, anti-osteoclastogenesis, and bone regeneration, mainly attributed to the nitric oxide generated from ZO. The new bone formation was significantly enhanced in the osteoporotic rat model, suggesting the potential of this bioinspired scaffold for regenerating osteoporotic bones.