Efficient regeneration of rat calvarial defect with gelatin-hydroxyapatite composite cryogel

Abstract

To induce bone regeneration efficiently, a properly designed organic-inorganic composite scaffold is necessary and important. Gelatin-hydroxyapatite (HA) composite is a suitable choice for the purpose because it can resemble the chemical composition of natural bone tissue. The gelatin-HA composite can be implanted into bone defects as a hydrogel or cryogel, however, it is interesting to know the effect of their different morphology on inducing osteogenesis in vivo. Herein, HA nanowire (HANW) reinforced photocrosslinkable methacrylated gelatin (GelMA) cryogel and hydrogel are prepared and comparatively investigated by being implanted into rat calvarial defects. The cryogel acts as a kind of sponge with interconnected macropores, allowing cell infiltration, as well as, displaying rapid shape recovery and excellent mechanical stability under cyclic compression loading. Conversely, the hydrogel is rigid and easily crushed during the first compression test, showing no shape recovery ability, instead inhibiting cell migration and spreading. Accordingly, the GelMA/HANW composite cryogel is able to promote osteogenesis significantly more in comparison with the corresponding hydrogel at six and 12 weeks post-implantation, as revealed by comprehensive evaluations using radiographic examination, histochemical and immunohistochemical staining methods. Neo-bone tissues have grown into the macroporous cryogel six and 12 weeks after the implantation, while the dense hydrogel prevents the tissue ingrowth, causing the newly formed sparse bone tissue to only elongate into the gaps between cracked hydrogel blocks. In summary, organic-inorganic macroporous cryogels demonstrate superiority for in vivo applications to induce bone regeneration.