Fig. 9.

Scaffolds for angiogenesis a) The category of angiogenesis scaffolds for BTE. 1) Scaffolds that can deliver osteoinductive and angioinductive molecules; 2) Scaffolds that deliver molecules with both osteoinductive and angioinductive abilities; 3) Scaffolds conducive for osteogenesis to deliver angioinductive molecules; 4) Scaffolds conductive for osteogenesis and angiogenesis without delivering inductive molecules. b) The approach for constructing scaffolds that support vascularization. The top-down approach represents the use of naturally derived polymer, which has inherent cell binding and degradation motif to construct scaffolds, while the bottom-up approach refers to the modification of synthetic polymer with growth factors, binding, and degrading protein sequences to form biodegradable angiogenesis scaffolds. c) Kolesky et al. used 3D bioprinting to construct a hydrogel matrix with a pre-designed vascular network. The procedure is as follows. 1) 3D-print a vascular network containing thermoreversible polymer pluronic and thrombin. Introduce cell components via printing cell-laden inks that contain gelatin, fibrinogen, and cells. 2) Cover ECM material containing gelatin, fibrinogen, cells, thrombin, and transglutaminase. Thrombin can cause the polymerization of fibrinogen into fibrin outside the vascular network and inside the ECM. Besides, transglutaminase further diffuses to crosslink gelatin and fibrin; 3) After casting, lower the temperature to liquefy pluronic and evacuate the vascular network. 4) Perfuse vascular ECs into the network to achieve vascularization. This Fig. was adopted from Refs. [252,320,321].