title: Use of a collagen-hydroxyapatite matrix in spinal fusion. A rabbit model.
abstract: METHODS
  The efficacy of a specially designed mineralized bovine collagen matrix as a carrier for bone marrow stem cells was studied in a rabbit posterolateral spinal fusion model.
  
  
  OBJECTIVE
  To determine if bone marrow cells added to Healos matrix will lead to fusion rates, biomechanical properties, and histologic properties comparable with those of fusions using autologous iliac crest bone graft; and to determine if the addition of preservative-free heparin to anticoagulate the bone marrow during harvest will adversely affect the fusion rate.
  
  
  BACKGROUND
  Although the development of new preparations of osteoinductive agents has advanced rapidly in recent years, the carrier systems that have been used in their application have received less attention. The composition and structure of the matrix used are key components affecting the ability of the matrix to function as a scaffold on which cells can migrate, adhere, proliferate, and form bone. The composition and design of matrix components also determine the ability of osteoinductive agents to influence local and hematogenously derived osteogenic precursor cells, which migrate to or are brought into the fusion site. Thus, the properties of the carrier can affect the behavior and efficacy of the osteoinductive agent that is used. The authors studied the properties of a new mineralized collagen matrix called Healos, which has been engineered specifically for spinal fusion application.
  
  
  METHODS
  Forty-four adult female New Zealand white rabbits were divided into five groups. Groups 1-4 underwent bilateral intertransverse fusion between L5 and L6. The fusions were augmented with either autologous iliac crest bone graft, Healos matrix alone, Healos matrix mixed with autologous bone marrow, or Healos matrix combined with heparinized autologous bone marrow. At 8 weeks after surgery, the fusions were characterized radiographically, histologically, and biomechanically. The rate of fusion was determined by radiographic analysis. The fifth group consisted of two animals whose bone marrow was aspirated from their tibias and femurs and then sent for determination of total nucleated cell count.
  
  
  RESULTS
  At 8 weeks, the radiographically determined fusion rate for autologous bone graft was 75% (9/12 animals), compared with 100% (10/10 and 9/9 animals) for groups in which fusions were done by using Healos matrix augmented with bone marrow (P < or = 0.1). Matrix used alone yielded a fusion rate of 18% (2/11 animals, P < or = 0.006). Histologically, the most mature bone was seen in the group augmented with autologous iliac crest graft, followed in decreasing order by the groups augmented with Healos with heparinized bone marrow, Healos with unheparinized bone marrow, and Healos alone. Biomechanically, the group augmented with autologous graft had the highest mean stiffness, followed by the groups augmented with Healos with heparinized bone marrow, Healos with untreated bone marrow, and finally Healos matrix alone. However, the differences in stiffness between groups were not statistically significant with the number of spines tested.
  
  
  CONCLUSIONS
  These results show that Healos is an osteoconductive matrix that can be a useful carrier in the biologic and mechanical environment of a posterolateral intertransverse fusion site. In combination with bone marrow, it produces fusion rates that are comparable with those of autologous bone graft. However, it must be combined with an osteoinductive or osteogenic agent to ensure reliable fusion rates and alone cannot produce reliable osteogenesis. The Healos matrix was not compared with other commercially available matrices currently in use. Therefore, the efficacy of Healos relative to these other materials could not be determined.
authors.affiliation: Department of Orthopaedic Surgery, University of California at San Francisco, USA.
authors.forename: B K
authors.initials: BK
authors.lastname: Tay
authors.forename: A X
authors.initials: AX
authors.lastname: Le
authors.forename: M
authors.initials: M
authors.lastname: Heilman
authors.forename: J
authors.initials: J
authors.lastname: Lotz
authors.forename: D S
authors.initials: DS
authors.lastname: Bradford
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage; D001672:Biocompatible Materials / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D001857:Bone Matrix; D018786:Bone Substitutes / Q000627:therapeutic use*; D016025:Bone Transplantation; D002417:Cattle; D005260:Female; D006493:Heparin / Q000008:administration & dosage; D008159:Lumbar Vertebrae / Q000601:surgery*; D016348:Osseointegration; D011817:Rabbits; D013123:Spinal Fusion / Q000379:methods*; D013314:Stress, Mechanical; D014182:Transplantation, Autologous
chemical_list: D000925:Anticoagulants; D001672:Biocompatible Materials; D018786:Bone Substitutes; D006493:Heparin