BMP2 Delivered from a CaP/hydrogel Construct Can Promote Bone Regeneration in a Critical Sized Segmental Defect Model of Non-union in Dogs

Introduction
The purpose of this study was to determine whether the addition of BMP2 to a biphasic calcium phosphate (BCP) granule/cellulosic hydrogel construct could improve bone healing in critical-sized ulnar defects in dogs compared to the same construct without any BMP2. Cancellous bone autografts were used as positive controls.

Materials and Methods
This study was conducted on 10 adult spayed female beagle dogs after Animal Welfare and Ethical committee approval. A bilateral standardized 2-cm long diaphyseal ulnar ostectomy was performed. Osteosynthesis was achieved with a 2.4 LCP plate. The lyophilisate rhBMP2 was solubilised with te aqueous phase of the polymer. Each ostectomy site was radiographically evaluated immediately after surgery and at 4, 8, 12, 16 and 20 weeks postoperatively. Bone healing was evaluated at both the proximal and distal interfaces with the host bone. Twenty weeks after implantation, constructs were explanted, preserving both proximal and distal bone interfaces. Postoperative histological analysis included microCT imaging and light and scanning electron microscopy.

Results
Clinical outcome was considered excellent in all cases. Radiographically, all proximal interfaces and 4 out 5 distal interfaces appeared healed as early as 2 months after implantation with the BMP2 loaded constructs. Only one proximal interface and no distal interface appeared healed with the unloaded constructs. Constructs without BMP2 showed limited osteconductive properties and only 50% of the bone-biomaterial interfaces appeared healed after 20 weeks. Results obtained with the autografts were similar to those from the BMP2 constructs at 20 weeks but bone regeneration appeared to develop earlier with the BMP2 constructs than with cancellous bone autografts. In one dog, the hydrogel was not adequately set at the time of implantation and eight weeks later extensive heterotopic bone formation was observed within the soft tissue surrounding the defect area, from the implantation site to the distal ulna.  [...]