1. ZIF-8-modified hydrogel sequentially delivers angiogenic and osteogenic growth factors to accelerate vascularized bone regeneration.
- Author
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Niu X, Xiao S, Huang R, Huang D, Aifantis KE, Yu H, Xue C, Yin L, Dunne N, and Li X
- Subjects
- Animals, Nanoparticles chemistry, Durapatite chemistry, Durapatite administration & dosage, Angiogenesis Inducing Agents administration & dosage, Angiogenesis Inducing Agents pharmacology, Angiogenesis Inducing Agents chemistry, Male, Polyvinyl Alcohol chemistry, Polyethylene Glycols chemistry, Tannins chemistry, Tannins administration & dosage, Tannins pharmacology, Neovascularization, Physiologic drug effects, Humans, Rats, Sprague-Dawley, Mice, Bone Regeneration drug effects, Hydrogels chemistry, Hydrogels administration & dosage, Osteogenesis drug effects, Bone Morphogenetic Protein 2 administration & dosage, Alginates chemistry, Becaplermin administration & dosage
- Abstract
To realize high-quality vascularized bone regeneration, we developed a multifunctional hydrogel (SHPP-ZB) by incorporating BMP-2@ZIF-8/PEG-NH
2 nanoparticles (NPs) into a sodium alginate/hydroxyapatite/polyvinyl alcohol hydrogel loaded with PDGF-BB, allowing for the sequential release of angiogenic and osteogenic growth factors (GFs) during bone repair. ZIF-8 served as a protective host for BMP-2 from degradation, ensuring high encapsulation efficiency and long-term bioactivity. The SHPP-ZB hydrogel exhibited enhanced mechanical strength and injectability, making it suitable for complex bone defects. It provided a swelling interface for tissue interlocking and the early release of Zn2+ and tannin acid (TA) to exert antioxidant and antibacterial effects, followed by the sequential release of angiogenic and osteogenic GFs to promote high-quality vascularized bone regeneration. In vitro experiments demonstrated the superior angiogenic and osteogenic properties of SHPP-ZB compared to other groups. In vivo experiments indicated that the sequential delivery of GFs via SHPP-ZB hydrogel could improve vascularized bone regeneration. Further, RNA sequencing analysis of regenerative bone tissue revealed that SHPP-ZB hydrogel promoted vascularized bone regeneration by regulating JUN, MAPK, Wnt, and calcium signaling pathways in vivo. This study presented a promising approach for efficient vascularized bone regeneration in large-scale bone defects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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