Improved anchorage of Ti6Al4V orthopaedic bone implants through oligonucleotide mediated immobilization of BMP-2 in osteoporotic rats

• Published in: PloS one 2014-01, Vol.9 (1), p.e86151-e86151
• Main Authors: Wölfle, Julia V, Fiedler, Jörg, Dürselen, Lutz, Reichert, Judith, Scharnweber, Dieter, Förster, Anne, Schwenzer, Bernd, Reichel, Heiko, Ignatius, Anita, Brenner, Rolf E
• Format: Article
• Language: English
• Subjects: Aluminum oxide; Animals; Arthritis; Biochemistry; Biocompatibility; Biology; Biomechanical Phenomena - drug effects; Biomechanics; Biomedical materials; Bone density; Bone Density - drug effects; Bone implants; Bone mineral density; Bone morphogenetic protein 2; Bone Morphogenetic Protein 2 - metabolism; Bone surgery; Comparative analysis; Computed tomography; Female; Humans; Hybridization; Immobilization; Immobilized Proteins - metabolism; Implants, Experimental; In vivo methods and tests; Joint surgery; Materials Science; Medicine; Microscopy, Electron, Scanning; Modular systems; Oligonucleotides; Oligonucleotides - metabolism; Orthopedics; Osteoporosis; Osteoporosis - diagnostic imaging; Osteoporosis - physiopathology; Osteoporosis - therapy; Ovariectomy; Rats; Rats, Wistar; Recombinant Proteins - metabolism; Rodents; Stem cells; Strands; Surface Properties; Surgery; Surgical implants; Tibia; Tibia - diagnostic imaging; Tibia - drug effects; Tibia - pathology; Tibia - physiopathology; Titanium; Titanium - pharmacology; Titanium base alloys; Transforming Growth Factor beta - metabolism; Transplants & implants; Vascular endothelial growth factor; X-Ray Microtomography
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0086151

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.