Osteoblastic bone formation is induced by using nanogel‐crosslinking hydrogel as novel scaffold for bone growth factor

Abstract

Bone regeneration for the defects in revision surgery of joint replacement is an increasingly important issue. To repair bone defects, bone cell activation by growth factors using synthetic resorbable scaffold is a useful and safe option. We examine the efficiency of nanogel-crosslinking hydrogel as a novel synthetic scaffold for BMP to stimulate osteoblasts and to induce bone formation. Cholesterol-bearing pullulan nanogel-crosslinking hydrogel (CHPA/Hydrogel) was used to deliver BMP. The CHPA hydrogel pellets were implanted in vivo. Single implantation of CHPA/hydrogel containing low amounts of BMP induced osteoblastic activation and new bone formation in vivo. Furthermore, nanogel in a disc shape established recruitment of osteoblastic cells that vigorously formed bone to heal the calvarial defects, which did not heal spontaneously without it. In conclusion, CHPA/hydrogel serves as an efficient and versatile scaffold for the stimulation of osteoblasts to form bone and to repair defects via delivery of BMP.

Nanogel‐based scaffold delivery of prostaglandin E2 receptor–specific agonist in combination with a low dose of growth factor heals critical‐size bone defects in mice

“…Acrylate group-modified cholesterolbearing pullulan (CHPA)/PEG hydrogel was synthesized as previously described (14,18,22). EP4A (ONO-AE1-437) was provided by Dr. Toshiya Kanaji, Ono Pharmaceutical, and BMP-2 was a gift from Yamanouchi Pharmaceutical.…”

“…Thirty-six male ICR mice (8 weeks old; 6 mice in each of 6 groups) were used. Mice were housed under control conditions, as previously described (14,15,22). All experiments were approved by the animal welfare committee of Tokyo Medical and Dental University.…”

“…Therefore, it would be useful for the delivery of BMP-2 proteins (22). Our group previously demonstrated that nanogel can deliver PGE 2 alone or BMP-2 alone (14,15,22).…”

“…Therefore, it would be useful for the delivery of BMP-2 proteins (22). Our group previously demonstrated that nanogel can deliver PGE 2 alone or BMP-2 alone (14,15,22). However, a high dose (Ͼ2 g per defect) of BMP-2 in nanogel is still required when BMP-2 is used alone to repair large bone defects that otherwise would not heal spontaneously, and a single application of low-dose (0.5 g) BMP-2 alone cannot heal bone defects, even when it is delivered in nanogel (14,22).…”

“…Our group previously demonstrated that nanogel can deliver PGE 2 alone or BMP-2 alone (14,15,22). However, a high dose (Ͼ2 g per defect) of BMP-2 in nanogel is still required when BMP-2 is used alone to repair large bone defects that otherwise would not heal spontaneously, and a single application of low-dose (0.5 g) BMP-2 alone cannot heal bone defects, even when it is delivered in nanogel (14,22). Furthermore, administration of prostaglandin in nanogel alone still requires daily injections, and a single injection cannot induce bone formation (14).…”