Fabricating oxygen self-supplying 3D printed bioactive hydrogel scaffold for augmented vascularized bone regeneration
Yang Yang, Wanmeng Wang, Qianrui Zeng, Ning Wang, Wenbo Li, Wenbo Li, Bo Chen, Qingxin Guan, Changyi Li, Wei Li, Wei Li
Abstract
Limited cells and factors, inadequate mechanical properties, and necrosis of defects center have hindered the wide clinical application of bone-tissue engineering scaffolds. Herein, we construct a self-oxygenated 3D printed bioactive hydrogel scaffold by integrating oxygen-generating nanoparticles and hybrid double network hydrogel structure. The hydrogel scaffold possesses the characteristics of extracellular matrix; Meanwhile, the fabricated hybrid double network structure by polyacrylamide and CaCl 2 -crosslinked sodium carboxymethylcellulose endows the hydrogel favorable compressive strength and 3D printability. Furthermore, the O 2 generated by CaO 2 nanoparticles encapsulated in ZIF-8 releases steadily and sustainably because of the well-developed microporous structure of ZIF-8, which can significantly promote cell viability and proliferation in vitro , as well as angiogenesis and osteogenic differentiation with the assistance of Zn 2+ . More significantly, the synergy of O 2 and 3D printed pore structure can prevent necrosis of defects center and facilitate cell infiltration by providing cells the nutrients and space they need, which can further induce vascular network ingrowth and accelerate bone regeneration in all areas of the defect in vivo . Overall, this work provides a new avenue for preparing cell/factor-free bone-tissue engineered scaffolds that possess great potential for tissue regeneration and clinical alternative. We have successfully constructed a self-oxygenated 3D printed bioactive hydrogel scaffold by integrating oxygen-generating nanoparticles with hybrid double network hydrogel, which achieved long-term O 2 generation, structural customization, and excellent mechanical properties to significantly enhance vascularized bone regeneration without the aid of cells or growth factors. • MOFs encapsulated CaO 2 nanoparticles were fabricated to achieve long-term O 2 release. • The hybrid double network hydrogel was designed to obtain high compressive strength. • Multi-level pore sizes were constructed by 3D printing to achieve osteoconductive. • The O 2 and 3D printed pore exhibited enhanced synergetic effects for vascularization. • The cell/factor-free composite scaffold significantly facilitated bone regeneration.