Stimulation of bone healing by sustained bone morphogenetic protein 2 (BMP-2) delivery.
The aim of the study was to investigate the effect of a sustained release of bone morphogenetic protein2 (BMP-2) incorporated in a polymeric implant coating on bone healing. In vitro analysis revealed a sustained, but incomplete BMP-2 release until Day 42. For the in vivo study, the rat tibia osteotomy was stabilized either with control or BMP-2 coated wires, and the healing progress was followed by micro computed tomography (µCT), biomechanical testing and histology at Days 10, 28, 42 and 84. MicroCT showed an accelerated formation of mineralized callus, as well as remodeling and an increase of mineralized/total callus volume (p=0.021) at Day 42 in the BMP-2 group compared to the control. Histology revealed an increased callus mineralization at Days 42 and 84 (p=0.006) with reduced cartilage at Day 84 (p=0.004) in the BMP-2 group. Biomechanical stiffness was significantly higher in the BMP-2 group (p=0.045) at Day 42. In summary, bone healing was enhanced after sustained BMP-2 application compared to the control. Using the same drug delivery system, but a burst release of BMP-2, a previous published study showed a similar positive effect on bone healing. Distinct differences in the healing outcome might be explained due to the different BMP release kinetics and dosages. However, further studies are necessary to adapt the optimal release profiles to physiological mechanisms.
Julius Wolff Institute, Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin 13353, Germany. mirjafassbender@web.de.
Mirja
M
Faßbender
Julius Wolff Institute, Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin 13353, Germany. susann.minkwitz@charite.de.
Susann
S
Minkwitz
Julius Wolff Institute, Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin 13353, Germany. post@catrinstrobel.de.
Catrin
C
Strobel
Department of Orthopedics, Orthopedics and Traumatology, Heidelberg University Hospital, Schlierbacher Landstraße 200a, Heidelberg 69118, Germany. gerhard.schmidmaier@med.uni-heidelberg.de.
Gerhard
G
Schmidmaier
Julius Wolff Institute, Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin 13353, Germany. britt.wildemann@charite.de.
Britt
B
Wildemann
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000737:chemistry / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000601:surgery; D002356:Cartilage / Q000502:physiology; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D019344:Lactic Acid / Q000737:chemistry; D023421:Models, Animal; D011091:Polyesters; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014945:Wound Healing / Q000187:drug effects
D055396:Bone Morphogenetic Protein 2; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide)