title: Comparative performance of three ceramic bone graft substitutes.
abstract: BACKGROUND
  A number of different synthetic calcium-based bone graft substitutes (BGS) are currently available for clinical use. There is, however, a lack of comparative performance data regarding the relative efficacy of these materials when placed in an osseous defect site.
  
  
  OBJECTIVE
  To compare the rate, quality, and extent of osseous healing in a standard rabbit defect model for three commercially available BGS materials by measuring early bone formation and completion of defect healing and to identify whether rapid scaffold resorption stimulated or impaired bone healing.
  
  
  METHODS
  Osteochondral defects, 4.8 mm in diameter and 6 to 7 mm deep, were made through the articular surface into the subchondral bone of the femoral condyle of New Zealand White rabbits and filled with cylindrical pellets of one of three commercially available BGS materials: dense calcium sulfate (DCaS), ultraporous tricalcium phosphate (beta-TCP), and porous silicated calcium phosphate (Si-CaP). The repair response was examined at 1, 3, 6, and 12 weeks after surgery (n=4 per BGS per time point).
  
  
  METHODS
  Qualitative histological and quantitative histomorphometric (% new bone, % bone graft substitute, capillary index, and mineral apposition rates) analysis.
  
  
  RESULTS
  Rapid resorption of D-CaS, primarily through dissolution, elicited a mild inflammatory response that left the defect site empty before significant quantities of new bone were formed. Both beta-TCP and Si-CaP scaffolds supported early bone apposition (<1 week). However, beta-TCP degradation products subsequently provoked an inflammatory response that impaired and reversed bone apposition within the defect site. The Si-CaP scaffolds appeared to be more stable and supported further bone apposition, with the development of an adaptive bone-scaffold composite; cell-mediated resorption of scaffold and new bone were observed in response to local load and contributed to the production of a functional repair within the defect site.
  
  
  CONCLUSIONS
  Rapid BGS resorption impaired the regenerative ability of local bone via three pathways: 1) insufficient persistence of an osteoconductive scaffold to encourage bone apposition, 2) destabilization of early bony apposition through scaffold disintegration, and 3) stimulation of an inflammatory response by elevated levels of particulate degradation products. This had a significant impact on the ultimate rate of healing. D-CaS did not stimulate early bone apposition, but bone repair was more advanced in D-CaS-treated defects at 12 weeks as compared with those treated with beta-TCP, despite the beta-TCP supporting direct bone apposition at 1 week. Si-CaP appeared to provide a more stable osteoconductive scaffold, which supported faster angiogenesis and bone apposition throughout the defect site, with the development of a functionally adaptive trabecular structure through resorption/remodelling of both scaffold and new bone. There was rapid formation of mineralized tissue at week 1 within the center of the defect and complete infiltration with dense, predominantly mature bone by weeks 3 to 6. The progressive remodeling of bone ingrowth and scaffold to reflect the distribution of local host tissue, combined with histological evidence of targeted osteoclastic resorption of both scaffold and bone, suggest that bone adaptation within the scaffold could be in response to Wolff's law. Although this model may not directly translate to a spinal fusion model and the products may vary according to the environment, these results suggest that, in patients in whom bone regeneration may be compromised, the degradation observed with some resorbable bone grafts may contribute to the decoupling of bone regeneration and resorbtion within the graft site, which may ultimately lead to incomplete bone repair.
authors.affiliation: IRC in Biomedical Materials, Queen Mary University of London, London, United Kingdom. k.a.hing@qmul.ac.jp
authors.forename: Karin A
authors.initials: KA
authors.lastname: Hing
authors.forename: Lester F
authors.initials: LF
authors.lastname: Wilson
authors.forename: Thomas
authors.initials: T
authors.lastname: Buckland
mesh_terms: D000042:Absorption; D000818:Animals; D001672:Biocompatible Materials; D001847:Bone Diseases / Q000503:physiopathology / Q000601:surgery*; D018786:Bone Substitutes / Q000592:standards; D001842:Bone and Bones / Q000098:blood supply; D002113:Calcification, Physiologic; D002130:Calcium Phosphates / Q000009:adverse effects / Q000378:metabolism; D002133:Calcium Sulfate / Q000009:adverse effects / Q000493:pharmacokinetics; D002516:Ceramics; D018919:Neovascularization, Physiologic; D016062:Porosity; D011817:Rabbits; D017640:Silicates; D013997:Time Factors; D014945:Wound Healing
chemical_list: D001672:Biocompatible Materials; D018786:Bone Substitutes; D002130:Calcium Phosphates; D017640:Silicates; C485817:beta-tricalcium phosphate; C020243:calcium phosphate; D002133:Calcium Sulfate