title: BMP-2 delivered from a self-crosslinkable CaP/hydrogel construct promotes bone regeneration in a critical-size segmental defect model of non-union in dogs.
abstract: OBJECTIVE
  To determine whether the addition of recombinant human bone morphogenetic protein (rhBMP-2) to a self-crosslinkable cellulosic hydrogel/biphasic calcium phosphate (BCP) granules construct promotes bone healing in critical-size ulnar defects in dogs.
  
  
  METHODS
  A standardized 2 cm long ulnar ostectomy was performed bilaterally in five dogs to compare bone healing with hydrogel/BCP constructs associated with or without rhBMP-2. Cancellous-bone autografts were used as positive controls in unilateral ulnar defects in five additional dogs. Radiographically, bone healing was evaluated at four, eight, 12, 16 and 20 weeks postoperatively. Histological qualitative analysis with microCT imaging and light and scanning electron microscopy were performed 20 weeks after implantation.
  
  
  RESULTS
  All rhBMP-2-loaded constructs induced the formation of well-differentiated mineralized lamellar bone surrounding the BCP granules and bridging bone/implant interfaces as early as eight weeks after surgery. Bone regeneration appeared to develop earlier with the rhBMP-2 constructs than with the cancellous-bone autografts while similar results were obtained at 20 weeks. Constructs without any rhBMP-2 showed osteoconductive properties limited to the bone junctions and a lack of osteoinduction without bone ingrowth within the implantation site. In one dog, the leakage of the hydrogel loaded with rhBMP-2 induced an extensive heterotopic bone formation.
  
  
  CONCLUSIONS
  The addition of rhBMP-2 to a self-crosslinkable hydrogel/BCP construct could promote bone regeneration in a critical-size-defect model with similar performance to autologous bone grafts.
authors.affiliation: Minier Kévin, 12, Rue de L'Abbé Lemire, 59110 La Madeleine, France, Phone: +33 6 84 04 95 72, E-mail: kevminier@gmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Minier
authors.forename: A
authors.initials: A
authors.lastname: Touré
authors.forename: M
authors.initials: M
authors.lastname: Fusellier
authors.forename: B
authors.initials: B
authors.lastname: Fellah
authors.forename: B
authors.initials: B
authors.lastname: Bouvy
authors.forename: P
authors.initials: P
authors.lastname: Weiss
authors.forename: O
authors.initials: O
authors.lastname: Gauthier
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000627:therapeutic use*; D001861:Bone Regeneration / Q000187:drug effects*; D002130:Calcium Phosphates / Q000627:therapeutic use; D004285:Dogs / Q000293:injuries; D005260:Female; D005593:Fracture Fixation, Internal / Q000379:methods / Q000662:veterinary; D017102:Fracture Healing / Q000187:drug effects; D017759:Fractures, Malunited / Q000188:drug therapy* / Q000601:surgery; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D014458:Ulna Fractures / Q000188:drug therapy / Q000601:surgery / Q000662:veterinary
chemical_list: D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D011994:Recombinant Proteins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C020243:calcium phosphate
keywords: BMP-2; Recombinant human bone morphogenetic protein; bone union; calcium phosphate hydrogel; critical sized defect; dog