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Low-dose BMP-2 is sufficient to enhance the bone formation induced by an injectable, PLGA fiber-reinforced, brushite-forming cement in a sheep defect model of lumbar osteopenia

  • BACKGROUND CONTEXT: Bioresorbable calcium phosphate cement (CPC) may be suitable for vertebroplasty/kyphoplasty of osteoporotic vertebral fractures. However, additional targeted de- livery of osteoinductive bone morphogenetic Proteins (BMPs) in the CPC may be required to counteract the augmented local bone catabolism and support complete bone regeneration. PURPOSE: This study aimed at testing an injectable, poly (l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming cement (CPC) containing low-dose bone morphogenetic Protein BMP-2 in a sheep lumbar osteopenia model. STUDY DESIGN/ SETTING: This is a prospective experimental animal study. METHODS: Bone defects (diameter 5 mm) were generated in aged, osteopenic female sheep and filled with fiber-reinforced CPC alone (L4; CPC+ fibers) or with CPC containing different dosages of BMP-2 (L5; CPC+ fibers + BMP-2; 1, 5, 100, and 500g BMP-2; n=5 or 6 each). The results were compared with those of untouched controlsBACKGROUND CONTEXT: Bioresorbable calcium phosphate cement (CPC) may be suitable for vertebroplasty/kyphoplasty of osteoporotic vertebral fractures. However, additional targeted de- livery of osteoinductive bone morphogenetic Proteins (BMPs) in the CPC may be required to counteract the augmented local bone catabolism and support complete bone regeneration. PURPOSE: This study aimed at testing an injectable, poly (l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming cement (CPC) containing low-dose bone morphogenetic Protein BMP-2 in a sheep lumbar osteopenia model. STUDY DESIGN/ SETTING: This is a prospective experimental animal study. METHODS: Bone defects (diameter 5 mm) were generated in aged, osteopenic female sheep and filled with fiber-reinforced CPC alone (L4; CPC+ fibers) or with CPC containing different dosages of BMP-2 (L5; CPC+ fibers + BMP-2; 1, 5, 100, and 500g BMP-2; n=5 or 6 each). The results were compared with those of untouched controls (L1). Three and 9 months after the operation, structural and functional effects of the CPC (±BMP-2) were analyzed ex vivo by measuring (1) bone Mineral density (BMD); (2) bone structure, that is, bone volume/total volume (assessed by micro-computed tomography [micro-CT] and histomorphometry), trabecular thickness, and trabecular number; (3) bone formation, that is, osteoid volume/bone volume, osteoid surface/bone surface, osteoid thickness, mineralizing surface/bone surface, mineral Apposition rate, and bone formation rate/bone surface; (4) bone resorption, that is, eroded surface/bone surface; and (5) compressive strength. RESULTS: Compared with untouched controls (L1), CPC+ fibers (L4) and/or CPC+ fibers + BMP-2(L5) significantly improved all parameters of bone formation, bone resorption, and bone structure. These effects were observed at 3 and 9 months, but were less pronounced for some parameters at 9 months. Compared with CPC without BMP-2, additional significant effects of BMP-2 were demonstrated for bone structure (bone volume/total volume, trabecular thickness, trabecular number) and formation (osteoid surface/bone surface and mineralizing surface/bone surface), as well as for the compressive strength. The BMP-2 effects on bone Formation at 3 and 9 months were dose-dependent, with 5–100g as the optimal dosage. CONCLUSIONS: BMP-2 significantly enhanced the bone formation induced by a PLGA fiber-reinforced CPC in sheep lumbar osteopenia. A single local dose as low as ≤100g BMP-2 was sufficient to augment middle to long-term bone formation. The novel CPC+ BMP-2 may thus represent an alternative to the bioinert, supraphysiologically stiff polymethylmethacrylate cement presently used to treat osteoporotic vertebral fractures by vertebroplasty/kyphoplasty.zeige mehrzeige weniger

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Metadaten
Autoren/innen:F. Gunella, E. Kunisch, M. Bungartz, S. Maenz, V. Horbert, L. Xin, J. Mika, J. Borowski, S. Bischoff, H. Schubert, P. Hortschansky, A. Sachse, Bernhard Illerhaus, Jens Günster, J. Bossert, K. D. Jandt, F. Plöger, R. W. Kinne, O. Brinkmann
Dokumenttyp:Zeitschriftenartikel
Veröffentlichungsform:Verlagsliteratur
Sprache:Englisch
Titel des übergeordneten Werkes (Englisch):The Spine Journal
Jahr der Erstveröffentlichung:2017
Organisationseinheit der BAM:8 Zerstörungsfreie Prüfung
8 Zerstörungsfreie Prüfung / 8.5 Mikro-ZfP
Verlag:Elsevier Inc.
Jahrgang/Band:17
Ausgabe/Heft:11
Erste Seite:1699
Letzte Seite:1711
DDC-Klassifikation:Naturwissenschaften und Mathematik / Chemie / Analytische Chemie
Freie Schlagwörter:Bone regeneration; Calcium phosphat cement; Computed tomography; Large animal model sheep; Osteoporotic vertebral fracture
Themenfelder/Aktivitätsfelder der BAM:Analytical Sciences
Analytical Sciences / Zerstörungsfreie Prüfung und Spektroskopie
DOI:https://doi.org/10.1016/j.spinee.2017.06.005
URL:http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS&DestLinkType=FullRecord;UT=WOS:000415312600014
ISSN:1529-9430
ISSN:1878-1632
Verfügbarkeit des Dokuments:Datei im Netzwerk der BAM verfügbar ("Closed Access")
Datum der Freischaltung:01.12.2017
Referierte Publikation:Ja
Datum der Eintragung als referierte Publikation:01.12.2017