Alginate/bacterial cellulose/GelMA scaffolds with aligned nanopatterns and hollow channel networks for vascularized...

Designed macropores and nanopatterned surfaces are important architectural cues in three-dimensional (3D) scaffolds for promoting vascularization and bone regeneration. However, the fabrication of 3D scaffolds with both controlled nanopatterned surfaces and designed macropores remains a challenge, especially for hydrogel-based scaffolds. Herein, alginate (Alg)/bacterial cellulose (BC)/ Gelatin Methacryloyl (GelMA) composite scaffold with fully interconnected Hollow Channel Networks And An Aligned Nanopatterned Surface (HCAS) is fabricated using 3D printing, surface crosslinking, and prestretching/drying-induced orientation. The highly aligned nanofibrous structures significantly enhance the mechanical properties, as well as the structural stability of the hydrogel scaffold. In vitro experiments prove that the HCAS scaffold exhibits apparently enhanced angiogenic and osteogenic properties compared to the control groups since the aligned nanopatterns and hollow channels can activate the cyclic AMP-dependent Ras-related protein 1 (cAMP-RAP1) and mitogen-activated protein kinase (MAPK) pathways, respectively, and jointly promote the downstream phosphoinositide 3-kinase/hypoxia-inducible factor-1 (PI3K/HIF-1) pathway. In vivo experiments also show that HCAS scaffold significantly promotes vascularization and bone regeneration, further verifying the joint effect of the aligned nanopatterned surface and fully interconnected hollow channels in promoting vascularization and osteogenesis. Thus, the HCAS scaffold demonstrates that a cell- and growth factor-free approach can also promote satisfactory vascularization and bone regeneration, simply by creating nanopatterned surfaces and designed hollow channels within hydrogel scaffolds.