Treatment of nonunions with nonglycosylated recombinant human bone morphogenetic protein-2 delivered from a fibrin matrix.
OBJECTIVE
To report the results of the treatment of nonunions with nonglycosylated recombinant human bone morphogenetic protein-2 (nglBMP-2) delivered from a designed fibrin matrix.


METHODS
Experimental trial in rodents and prospective clinical study in dogs and cats with nonunion fractures.


METHODS
Twenty adult female, albino, Sprague-Dawley rats; 8 client-owned cats and dogs.


METHODS
After development of a fibrin matrix and evaluation of nglBMP-2 in a rodent femoral defect model, 8 consecutive long bone nonunion fractures (no progression in healing in > or = 3 months), were treated using 300 microg nglBMP-2 in a liquid fibrin precursor, injected into the defect gap after fracture revision and stabilization, or through a stab incision into the fracture site. The fibrin matrix was designed to clot in the wound after 60 seconds and to release the nglBMP-2 continuously over several days.


RESULTS
Using only fibrin gel, 7% of the rat femoral defect was filled with new formed bone compared with 79% defect filling using 2 microg nglBMP-2 (P=.006). Five and 10 microg nglBMP in fibrin resulted in union of all femoral defects with complete filling of the gap with new bone. Bony bridging and clinical healing was achieved in 7 patients within 24 weeks of administration of nglBMP-2.


CONCLUSIONS
Application of nglBMP-2 in a functional matrix can induce bone healing. Controlled release of nglBMP-2 from a fibrin matrix mimics the natural fracture hematoma.


CONCLUSIONS
nglBMP-2/fibrin can successfully replace a cancellous bone autograft in fracture treatment with an associated reduction in graft donor site morbidity and surgical time.
Schmökel
Hugo G
HG
Department of Clinical Veterinary Medicine, University of Berne, Switzerland. hugo.schmoekel@kkh.unibe.ch
Weber
Franz E
FE
Seiler
Gabriela
G
von Rechenberg
Brigitte
B
Schense
Jason C
JC
Schawalder
Peter
P
Hubbell
Jeffrey
J
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D018786:Bone Substitutes; D002415:Cats / Q000293:injuries*; D004285:Dogs / Q000293:injuries*; D005260:Female; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000628:therapy / Q000662:veterinary; D005337:Fibrin; D005592:Fracture Fixation / Q000379:methods / Q000662:veterinary*; D017102:Fracture Healing; D005599:Fractures, Ununited / Q000000981:diagnostic imaging / Q000628:therapy / Q000662:veterinary*; D008297:Male; D008663:Metacarpus / Q000293:injuries; D011446:Prospective Studies; D011859:Radiography; D011885:Radius Fractures / Q000000981:diagnostic imaging / Q000628:therapy / Q000662:veterinary; D051381:Rats; D017207:Rats, Sprague-Dawley; D013978:Tibial Fractures / Q000000981:diagnostic imaging / Q000628:therapy / Q000662:veterinary; D016212:Transforming Growth Factor beta; D016896:Treatment Outcome
C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D016212:Transforming Growth Factor beta; D005337:Fibrin