A novel autologous bone graft substitute containing rhBMP6 in autologous blood coagulum with synthetic ceramics for reconstruction of a large humerus segmental gunshot defect in a dog: The first veterinary patient to receive a novel osteoinductive therapy

Abstract

Background: Management of large segmental defects is one of the most challenging issues in bone repair biology. Autologous bone graft substitute (ABGS) containing rhBMP6 within autologous blood coagulum (ABC) with synthetic ceramics is a novel biocompatible therapeutic solution for bone regeneration.

Case presentation: A 2-year old dog was brought to the veterinary clinics due to pain and bleeding from the right front leg after being unintendedly hit by a gunshot. Radiological examination revealed a large, 3 cm long multisegmental defect of the humerus on the right front leg with a loss of anatomical structure in the distal portion of the bone. The defect was treated surgically and an external fixator was inserted to ensure immobilization. Complete lack of bone formation 3 months following surgery required a full reconstruction of the defect site with a novel ABGS (rhBMP6 in ABC with ceramic particles) to avoid front leg amputation. The healing was then followed for the next 16 months. The callus formation was observed on x-ray images 2 months following ABGS implantation. The bone segments progressively fused together leading to the defect rebridgment allowing removal of the external fixator by 4 months after the reconstruction surgery. At the end of the observation period, the function of the leg was almost fully restored while analyses of the humeral CT sections revealed restoration and cortices rebridgment with a renewal of uniform medullary canal including structural reconstruction of the distal humerus.

Conclusion: This large humeral gunshot segmental defect of the front leg in a dog was saved from amputation via inducing bone regeneration using a novel ABGS osteoinductive device containing BMP6 in ABC.

Keywords: BMP; Bioceramics; Bone morphogenetic proteins; Segmental defect; TCP; Tissue engineering.

Fig. 1

(A) Timeline showing dates of gunshot injury, 1st and 2nd surgery, and monitoring including clinical examinations (CE), X-ray, and CT. (B) Implant preparation and implantation on the segmental defect site. (1) Blood was collected from the cephalic vein in a volume of 2,5 mL and mixed with rhBMP6 (250 μg), (2) whereupon it was withdrawn into a syringe containing CRM. (3) ABGS implant was left on the RT to coagulate. (4) Implantation into the gunshot injury area. The yellow arrow indicates gunshot pellet residuals, while the red arrow indicates a bone fragment. (C) (1) ABGS containing rhBMP6, ABC, and CRM. (2) Implantation of ABGS. (3) External fixator after surgery. (4) Restored full weight bearing of the leg on the last clinical examination.

Fig. 2

X-ray images showing the progress of humeral segmental bone defect healing. (A) X-ray image taken before 2nd surgery (Jun 2019); red arrow indicates a bone fragment, while yellow arrow indicates gunshot pellet residuals. (B) X-ray image taken after the 2nd reconstruction surgery (Jul 2019) showing bone fragment placed on the site of fracture. (C,D) The continuous progress of healing with fusion of bone fragments. (E,F,G,H) X-ray images showing the continuation of healing following external fixator removal and successful integration of the misplaced bone fragment (red arrow). The green arrow indicates the progressive decrease of the external fixator pinholes.

Fig. 3

(A) The X-ray image after the initial surgery using external fixator for the leg immobilization. The red arrow indicates a bone fragment, while the yellow arrow indicates gunshot pellet residuals. (B) X-ray image taken on the last clinical examination; red arrow indicates a bone fragment which was successfully integrated into the regenerated bone continuum, while green arrow indicates holes of removed external fixator pins. (C) CT section and (D) 3D reconstruction taken on the last visit confirming humeral segmental defect restoration.