Testing the critical size in calvarial bone defects: revisiting the concept of a critical-size defect.
BACKGROUND
There is a clinical need for bone replacement strategies because of the shortfalls endemic to autologous bone grafting, especially in the pediatric patient population. For the past 25 years, the animal model that has been used to test bone replacement strategies has been the calvarial critical-size defect, based on the initial size of the bone defect. This study was undertaken to test the concept of the critical size in several different models. A review of the theoretical and scientific bases for the critical-size defect was also undertaken.


METHODS
Two different rodent species (including 28 adult mice and six adult rats) were used to assess bone healing by means of two-dimensional radiographic analysis after creating small bone defects using different surgical techniques.


RESULTS
Defects in mice that were smaller than critical-size defects (1.8-mm diameter) were shown to heal a maximum of 50 percent 1 year postoperatively. Small defects (2.3-mm diameter) in the rat skull showed approximately 35 percent healing after 6 weeks. Neither the choice of rodent species nor the maintenance of the dura mater significantly affected calvarial bone healing.


CONCLUSIONS
These results suggest that calvarial bone healing is not well described and much more data need to be collected. Also, after a review of the existing literature and a critique of the clinical applicability of the model, it is suggested that the use of the term "critical-size defect" be discontinued.
Pittsburgh, Pa.; and Cleveland, Ohio From the Department of Surgery, Division of Plastic Surgery, the Departments of Oral Biology, Bioengineering, Anthropology, Orthodontics, Orthopaedic Surgery, and Molecular Genetics and Biochemistry, University of Pittsburgh; the Department of Plastic Surgery, Case Western Reserve University School of Medicine; and the Institute of Complex Engineered Systems and Molecular Biosensor and Imaging Center and Departments of Biomedical Engineering, Material Science and Engineering, and Biology, Carnegie Mellon University.
Gregory M
GM
Cooper
Mark P
MP
Mooney
Arun K
AK
Gosain
Phil G
PG
Campbell
Joseph E
JE
Losee
Johnny
J
Huard
D000818:Animals; D016025:Bone Transplantation; D004195:Disease Models, Animal; D004388:Dura Mater / Q000000981:diagnostic imaging / Q000473:pathology; D017102:Fracture Healing; D051379:Mice; D008810:Mice, Inbred C57BL; D019637:Orthopedic Procedures; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000000981:diagnostic imaging* / Q000601:surgery*; D013045:Species Specificity; D023822:Tissue Engineering; D014207:Trephining