Improved anchorage of Ti6Al4V orthopaedic bone implants through oligonucleotide mediated immobilization of BMP-2 in osteoporotic rats.
The aim of the present study was to test the biocompatibility and functionality of orthopaedic bone implants with immobilized oligonucleotides serving as anchor stands for rhBMP-2 and rhVEGF-A conjugated with complementary oligonucleotides in an osteoporotic rat model. Al2O3-blasted acid etched Ti6Al4V implants, carrying oligonucleotide anchor strands and hybridized with rhBMP-2 or rhVEGF-A through complementary 31-mer oligonucleotide stands were inserted into the proximal tibia of ovariectomized rats. At the time of surgery (15 weeks after ovariectomy) microCT analysis showed significantly lower bone mineral density compared to non-ovariectomized animals. Bone-implant contact (BIC) and pullout-force were not negatively affected by non-hybridized anchor strands. Twelve weeks after surgery, a significantly higher pullout force was found for BMP-2 hybridized to the anchor strands compared to non-hybridized anchor strands or native samples, and on histomorphometric analysis BIC was highest in the BMP group. Thus, we could show the biocompatibility and in vivo functionality of this modular, self-organizing system for immobilization and subsequent release of BMP-2 in vivo.
Department of Orthopaedic Surgery, Centre of Musculoskeletal Research, University of Ulm, Ulm, Germany.
Julia V
JV
Wölfle
Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopaedic Surgery, Centre of Musculoskeletal Research, University of Ulm, Ulm, Germany.
Jörg
J
Fiedler
Institute of Orthopaedic Research and Biomechanics, Centre of Musculoskeletal Research, University of Ulm, Ulm, Germany.
Lutz
L
Dürselen
Max Bergmann Center of Biomaterials, TU Dresden, Dresden, Germany.
Judith
J
Reichert
Max Bergmann Center of Biomaterials, TU Dresden, Dresden, Germany.
Dieter
D
Scharnweber
Institute of Biochemistry, TU Dresden, Dresden, Germany.
Anne
A
Förster
Institute of Biochemistry, TU Dresden, Dresden, Germany.
Bernd
B
Schwenzer
Department of Orthopaedic Surgery, Centre of Musculoskeletal Research, University of Ulm, Ulm, Germany.
Heiko
H
Reichel
Institute of Orthopaedic Research and Biomechanics, Centre of Musculoskeletal Research, University of Ulm, Ulm, Germany.
Anita
A
Ignatius
Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopaedic Surgery, Centre of Musculoskeletal Research, University of Ulm, Ulm, Germany.
Rolf E
RE
Brenner
D000497:Alloys; D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D055767:Immobilized Proteins / Q000378:metabolism*; D020007:Implants, Experimental; D008855:Microscopy, Electron, Scanning; D009841:Oligonucleotides / Q000378:metabolism*; D009985:Orthopedics; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D013499:Surface Properties; D013977:Tibia / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D014025:Titanium / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D055114:X-Ray Microtomography
D000497:Alloys; D055396:Bone Morphogenetic Protein 2; D055767:Immobilized Proteins; D009841:Oligonucleotides; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; C031462:titanium alloy (TiAl6V4); D014025:Titanium