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Stratified-structural hydrogel incorporated with magnesium-ion-modified black phosphorus nanosheets for promoting neuro-vascularized bone regeneration
Ist Teil von
Bioactive materials, 2022-10, Vol.16, p.271-284
Ort / Verlag
China: Elsevier B.V
Erscheinungsjahr
2022
Link zum Volltext
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
Angiogenesis and neurogenesis play irreplaceable roles in bone repair. Although biomaterial implantation that mimics native skeletal tissue is extensively studied, the nerve-vascular network reconstruction is neglected in the design of biomaterials. Our goal here is to establish a periosteum-simulating bilayer hydrogel and explore the efficiency of bone repair via enhancement of angiogenesis and neurogenesis. In this contribution, we designed a bilayer hydrogel platform incorporated with magnesium-ion-modified black phosphorus (BP) nanosheets for promoting neuro-vascularized bone regeneration. Specifically, we incorporated magnesium-ion-modified black phosphorus (BP@Mg) nanosheets into gelatin methacryloyl (GelMA) hydrogel to prepare the upper hydrogel, whereas the bottom hydrogel was designed as a double-network hydrogel system, consisting of two interpenetrating polymer networks composed of GelMA, PEGDA, and β-TCP nanocrystals. The magnesium ion modification process was developed to enhance BP nanosheet stability and provide a sustained release platform for bioactive ions. Our results demonstrated that the upper layer of hydrogel provided a bionic periosteal structure, which significantly facilitated angiogenesis via induction of endothelial cell migration and presented multiple advantages for the upregulation of nerve-related protein expression in neural stem cells (NSCs). Moreover, the bottom layer of the hydrogel significantly promoted bone marrow mesenchymal stem cells (BMSCs) activity and osteogenic differentiation. We next employed the bilayer hydrogel structure to correct rat skull defects. Based on our radiological and histological examinations, the bilayer hydrogel scaffolds markedly enhanced early vascularization and neurogenesis, which prompted eventual bone regeneration and remodeling. Our current strategy paves way for designing nerve-vascular network biomaterials for bone regeneration.
A schematic diagram of the bilayer hydrogel scaffold for vascularization, neurogenesis, and bone regeneration. The upper (GelMA-BP@Mg) hydrogel served as a periosteal repair layer, while the bottom layer (GelMA-PEG/β-TCP) hydrogel served as a bone repair layer. Together, they accelerated the formation of a periosteal nerve-vascular network that enhanced bone regeneration. [Display omitted]
•Developing a periosteum-simulating bilayer hydrogel to improve the efficiency of neuro-vascularized bone repair.•A magnesium-ion-modified black phosphorus (BP) nanosheets incorporated hydrogel platform was designed.•Designing nerve-vascular network biomaterials for bone regeneration.