Fig. 9.

Integrated hierarchical osteochondral scaffold was designed by buoyancy, magnetic attraction and electric attraction techniques. (a) Growth factor gradients for osteochondral tissue engineering: I) Osteochondral tissue, engineered using of hMSC-laden GelMA hydrogels, with buoyancy used to form a morphogen gradient of BMP-2 complexed with heparin methacrylate (HepMA); II) Alizarin Red S staining revealed localized mineral deposition at one end of the tissue; III) Alcian Blue staining revealed tissue-wide staining for glycosaminoglycans, a component of both cartilage and bone [116]. (b) Engineering osteochondral tissue using magnetically-aligned glycosylated SPIONs: (I) SPIONs were conjugated with heparin to produce a glycosylated corona that could efficiently sequester and release growth factors; (II) An external magnetic field was used to field-align glycosylated SPIONs in a hMSC-laden agarose hydrogel, which was thermally gelled and cultured for 28 days to generate robust osteochondral constructs comprising both bone and cartilage tissue; (III) Finite element modeling of the magnetic field strength and distribution; (VI) The key mineralization protein osteopontin (red), which were present specifically at the bone end of the tissue [117]. (c) Using electric field migration to fabricate silk nanofiber hydrogels with gradients and the control of cell differentiation [118]. Reproduced with permission: (a) [116], copyright 2019, Wiley; (b) [117], copyright 2018, Elsevier; (c) [118], copyright 2020, Springer.