A Macroporous Cryogel with Enhanced Mechanical Properties for Osteochondral Regeneration In vivo

The dense networks of conventional hydrogel hinder the efficient cell penetration and thus tissue regeneration. In this study, a macroporous cryogel with excellent mechanical properties was designed and fabricated through cryogelation and crosslinking of methacrylated gelatin (Gel-MA) and gelatin grafted with 2-ureido-4[1 H ]-6-methyl-pyrimidinone (Gel-UPY). The successful modification of the two functional units on the side chain of gelatin was confirmed by 1 H-NMR and infrared spectroscopy. The macroporous structure of cryogel was verified by scanning electron microscopy and confocal microscopy. The compressive modulus of cryogel (110 kPa) was 2 magnitudes higher than that of the conventional hydrogel of the same chemical compositions (8 kPa). Both the hydrogel and cryogel exhibited excellent stress-recovery ability. The cryogel could well maintain the viability of chondrocytes and facilitated their migration into the scaffold interior. After being implanted into osteochondral defects in rabbits for 12 w, the Gel-MA/Gel-UPY cryogel better facilitated the regeneration of upper cartilage and subchondral bone compared to the conventional hydrogel.