FIG. 1.

(a) Schematic representation of the fetal-mimetic approach to articular cartilage regeneration. Fetal or adult cartilage was decellularized, digested, and functionalized to produce an injectable, in situ cross-linkable, fetal (f-) or adult (a-) CarMa macromer for cell encapsulation. hMSCs were suspended in CarMa hydrogel precursor solution and cross-linked by UV irradiation. Next, the encapsulated hMSCs were cultured in chondrogenic medium/TGF-β1 supplemented with BMP-7 for differentiation to the superficial zone phenotype of chondrocytes or IHH for differentiation to the calcified zone phenotype; (b) hMSCs were encapsulated in f-CarMa hydrogel and cultured in chondrogenic medium/TGF-β1 supplemented with BMP-7 to generate a superficial zone-like cellular construct. Next, the hMSCs in the superficial zone construct were incubated in chondrogenic medium/TGF-β1 with sequential addition of IGF-1 and IHH to induce differentiation of the encapsulated cells to the middle and calcified zone phenotypes, respectively. SEM images of the lyophilized f-CarMa (c) and a-CarMa (d) hydrogels. (e) Effect of macromer concentration in the precursor solution on the elastic modulus of f-CarMa and a-CarMa hydrogels after UV cross-linking. The scale bars in (c) an (d) are 10 μm. BMP, bone morphogenetic protein; hMSC, human mesenchymal stem cell; IHH, Indian hedgehog; IGF, insulin-like growth factor; SEM, scanning electron microscope; TGF, transforming growth factor; UV, ultraviolet.