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A Novel Biodegradable Delivery System for Bone Morphogenetic Protein-2

Engstrand, Thomas M.D.; Veltheim, Riikka M.D.; Arnander, Claes M.D.; Docherty-Skogh, Ann-Charlott M.D.; Westermark, Anders D.D.S.; Ohlsson, Claes M.D., Ph.D.; Adolfsson, Lars Ph.D.; Larm, Olle Ph.D.

Plastic and Reconstructive Surgery: June 2008 - Volume 121 - Issue 6 - p 1920-1928
doi: 10.1097/PRS.0b013e31817151b0
Experimental: Original Articles

Background: The efficacy of recombinant growth factors in vivo is highly dependent on the delivery vehicle. The authors investigated the osteoinductive effects of recombinant human bone morphogenetic proteins (BMP)-2 implanted together with a complex of heparin and chitosan.

Methods: Sixty rats were used. Three different carriers in gel formulation (type I collagen, heparin/type I collagen, and heparin/chitosan) were mixed with either 0, 10, or 50 μg of BMP-2, making the number of groups nine. The gels were injected into the quadriceps muscles of both legs in 45 rats (n = 10 per group). Freeze-dried formulations of the carriers were also tested with the same amounts of BMP-2 using 15 rats (n = 5 per group). Four weeks after implantation, the quality and amount of newly formed bone were assessed.

Results: Chitosan was shown to protect the heparinase-mediated degradation of heparin in vitro. The osteoinductive effects of BMP-2 in combination with heparin/chitosan were superior as compared with BMP-2 implanted together with type I collagen. Interestingly, the heparin/chitosan complex induced a small amount of bone also without BMP-2 added. The heparin/chitosan was completely absorbed after 4 weeks as determined by histologic evaluation, and a normal active bone formation was present. The freeze-dried formulations of the carriers demonstrated similar osteoinductive effects as the gels.

Conclusions: An osteoinductive formula for clinical use is needed for general bone reconstruction. Heparin in complex with chitosan has the ability to stabilize or activate the growth factor in vivo and induce the generation of new bone in good yields.

Stockholm and Gothenburg, Sweden

From the Stockholm Craniofacial Centre, Department of Reconstructive Plastic Surgery, Karolinska University Hospital and Karolinska Institute; Center for Bone Research, Sahlgrenska Academy; and ExThera, Karolinska Institute.

Received for publication April 20, 2007; accepted October 2, 2007.

Presented in part at the Sixth International Conference on Bone Morphogenetic Proteins, in Cavtat, Croatia, October 11 through 15, 2006.

Disclosure: The authors declare that they have no competing financial interests.

Thomas Engstrand, M.D., Craniofacial Center, Department of Reconstructive Plastic Surgery, Karolinska University Hospital, SE-171 76 Stockholm, Sweden,

©2008American Society of Plastic Surgeons