Prevention of arthrofibrosis by monoclonal antibody against vascular endothelial growth factor: a novel use of bevacizumab in rabbits.
BACKGROUND
Prevention of arthrofibrosis by different drugs and surgical techniques is an essential issue in modern orthopedics.


OBJECTIVE
Intra-articular injection of bevacizumab can reduce arthrofibrosis on the rabbit's stifle joint model.


METHODS
Arthrofibrosis was induced in the right stifle joint of thirty male New Zealand white rabbits by removing the cortical bone of the medial femoral condyle under general anesthesia. The rabbits were randomly divided into three equal groups. The control group received intra-articular injection of saline; the one-injection group received a single dose of bevacizumab (2.5mg/kg), and the two-injection group received two intra-articular injections; the operation day and 14 days later. Forty-five days after surgery, animals were sacrificed. The severity of fibrosis was assessed based on the range of motion of the joint, a macroscopic adhesion score, and histopathologic variables such as the number of fibroblasts and of inflammatory cells, collagenous matrix deposition, synovial hyperplasia, granulation tissue formation, vascular proliferation, and presence of giant cells.


RESULTS
Although no statistically significant differences were found between the range of motion (P=0.222) and the macroscopic evaluation (P=0.067) of the control group and the one-injection group, all microscopic variables regarding the prevention of arthrofibrosis were significantly superior in the one-injection group except granulation tissue (P=0.347). Compared to the one-injection group, the two-injection group had better results not only in terms of macroscopic evaluation (P=0.001 for range of motion and 0.012 for visual adhesion score) but also in most of the histopathologic variables especially the number of fibroblasts (P=0.002), vascularity (P=0.028) and collagenous matrix deposition (P=0.039).


CONCLUSIONS
A single intra-articular injection of bevacizumab was effective for prevention of microscopically detected arthrofibrosis in the rabbit. Compared to single injection, two injections of bevacizumab improved the clinical outcome.


METHODS
Level II.
Research Center for Bone and Joint Diseases, Department of Orthopedic Surgery, Chamran Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
M J
MJ
Emami
F M
FM
Jaberi
N
N
Azarpira
A R
AR
Vosoughi
N
N
Tanideh
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis / Q000188:drug therapy / Q000473:pathology; D006965:Hyperplasia / Q000188:drug therapy / Q000473:pathology; D007270:Injections, Intra-Articular; D007592:Joint Diseases / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D011817:Rabbits; D013264:Stifle / Q000473:pathology*
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab