Effect of Bone Morphogenetic Protein-2 (BMP-2)/Hydroxyapatite/In Situ-Formed Hyaluronan Hydrogel Composites on Bone Formation in a Murine Model of Posterolateral Lumbar Fusion

Abstract

Several types of calcium phosphate (CaP) biomaterial carriers have been designed to deliver bone morphogenetic protein-2 (BMP-2) to augment spinal fusion in spinal surgery. Here, we evaluated an in situ-formed hydrogel (IFH) constructed from hyaluronan (IFH-HA) combined with a BMP2/hydroxyapatite (HAP) composite in bone formation in a murine model of posterolateral lumbar fusion (PLF). HAP was submerged in HA-tyramine (TA) polymer solution containing horseradish peroxidase (HRP) and 2 µg BMP-2 (BMP2/HA-TA/HRP solution). H 2 O 2 was added to initiate the curing reaction (BMP-2/IFH-HA). phosphate-buffered saline (PBS) was added to the BMP2/HA-TA/HRP solution (BMP-2/HA-TA) instead of H 2 O 2 to evaluate the effectiveness of the curing reaction. HAP immersed in PBS was used as a control. PLF model mice were randomly assigned to receive one these composites (n = 10 each). X-ray images were taken to assess the bone fusion, and microcomputed tomography analysis was conducted to examine new bone formation at the graft site four weeks following surgery. No evidence of fusion was observed four weeks after surgery in the Control or BMP2/HA-TA group. In contrast, the BMP2/IFH-HA group exhibited newly formed bone between the transverse processes and bone union in coronal sections. Relative to the Control and BMP2/HA-TA groups, the BMP2/IFH-HA group showed significantly greater bone volume. The BMP2/IFH-HA group also showed significantly elevated bone mineral content relative to the BMP2/HA-TA group. A composite comprising BMP2/HAP and IFH-HA, thus, enhanced the new bone formation in a murine model of PLF, suggesting its promise for augmenting spinal fusion.

An osteoinductive surface by adhesive bone morphogenetic protein-2 prepared using the bioorthogonal approach for tight binding of titanium with bone

“…Generally, rodents exhibit rapid bone healing. Therefore, to evaluate differences in the effects of implant modifications, study periods of 4 weeks or less are typically used [54][55][56][57][58] Irish et al 59 assayed 4-, 8-, or 12-week follow-up times after implantation. They showed that implant placement significantly increased the mineralizing surface, mineral apposition rate, and bone formation rate in rats at the trabecular and endocortical surfaces mainly at 4 weeks.…”