ZIF-8-modified hydrogel sequentially delivers angiogenic and osteogenic growth factors to accelerate vascularized bone regeneration

Aug 10, 2024Journal of controlled release : official journal of the Controlled Release Society

Hydrogel with ZIF-8 releases blood vessel and bone growth factors in order to speed up bone healing with new blood supply

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

The multifunctional hydrogel SHPP-ZB may enhance vascularized bone regeneration through the sequential release of growth factors.

SHPP-ZB incorporates BMP-2@ZIF-8 nanoparticles, protecting BMP-2 from degradation and ensuring its bioactivity.
The hydrogel demonstrates improved mechanical strength and injectability, making it suitable for complex bone defects.
In vitro studies show that SHPP-ZB has superior angiogenic and osteogenic properties compared to alternatives.
In vivo results suggest that SHPP-ZB enhances vascularized bone regeneration through the sequential delivery of growth factors.
RNA sequencing indicates that SHPP-ZB hydrogel may regulate key signaling pathways related to bone regeneration.

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To realize high-quality vascularized bone regeneration, we developed a multifunctional hydrogel (SHPP-ZB) by incorporating BMP-2@ZIF-8/PEG-NHnanoparticles (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 Znand 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. 2 2+

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ZIF-8-modified hydrogel sequentially delivers angiogenic and osteogenic growth factors to accelerate vascularized bone regeneration

Abstract

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