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GDF5 significantly augments the bone formation induced by an injectable, PLGA fiber-reinforced, brushite-forming cement in a sheep defect model of lumbar osteopenia

  • BACKGROUND CONTEXT: Biodegradable calcium phosphate cement (CPC) represents a promising option for the surgical treatment of osteoporotic vertebral fractures. Because of augmented local bone catabolism, however, additional targeted delivery of bone morphogenetic proteins with the CPC may be needed to promote rapid and complete bone regeneration. PURPOSE: In the present study, an injectable, poly(l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming cement (CPC) containing the bone morphogenetic Protein GDF5 was tested in a sheep lumbar osteopenia model. STUDY DESIGN/SETTING: This is a prospective experimental animal study METHODS: Defined bone defects (diameter 5 mm) were placed in aged, osteopenic female sheep. Defects were treated with fiber-reinforced CPC alone (L4; CPC+ fibers) or with CPC containing different dosages of GDF5 (L5; CPC+ fibers + GDF5; 1, 5, 100, and 500g GDF5; n = 5 or 6 each). The results were compared with those of untouched controlsBACKGROUND CONTEXT: Biodegradable calcium phosphate cement (CPC) represents a promising option for the surgical treatment of osteoporotic vertebral fractures. Because of augmented local bone catabolism, however, additional targeted delivery of bone morphogenetic proteins with the CPC may be needed to promote rapid and complete bone regeneration. PURPOSE: In the present study, an injectable, poly(l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming cement (CPC) containing the bone morphogenetic Protein GDF5 was tested in a sheep lumbar osteopenia model. STUDY DESIGN/SETTING: This is a prospective experimental animal study METHODS: Defined bone defects (diameter 5 mm) were placed in aged, osteopenic female sheep. Defects were treated with fiber-reinforced CPC alone (L4; CPC+ fibers) or with CPC containing different dosages of GDF5 (L5; CPC+ fibers + GDF5; 1, 5, 100, and 500g GDF5; n = 5 or 6 each). The results were compared with those of untouched controls (L1). Three and 9 months postoperation, structural and functional effects of the CPC (±GDF5) were assessed ex vivo by measuring (1) bone mineral density (BMD); (2) bone structure, that is, bone volume/total volume (assessed by micro-computed tomography and histomorphometry), trabecular thickness, and trabecular number; (3) bone formation, that is, osteoid volume/bone volume, osteoid surface/bone surface, osteoid thickness, mineralized 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), both CPC+ fibers (L4) and CPC+ fibers + GDF5 (L5) numerically or significantly improved all parameters of bone formation, bone resorption, and bone structure. These significant effects were observed both at 3 and 9 months, but for some parameters they were less pronounced at 9 months. Compared with CPC without GDF5, additional significant effects of CPC with GDF5 were demonstrated for BMD and parameters of bone formation and structure (bone volume/total volume, trabecular thickness, and trabecular number, as well as mineralized surface/bone surface). The GDF5 effects were dose-dependent (predominantly in the 5–100g range) at 3 and 9 months. CONCLUSIONS: GDF5 significantly enhanced the bone formation induced by a PLGA fiber-reinforced CPC in sheep lumbar osteopenia. The results indicated that a local dose as low as ≤100g GDF5 may be sufficient to augment middle to long-term bone formation. The novel CPC+ GDF5 combination may thus qualify as an alternative to the bioinert, supraphysiologically stiff poly-(methyl methacrylate) cement currently applied for vertebroplasty/kyphoplasty of osteoporotic vertebral fractures.zeige mehrzeige weniger

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Metadaten
Autoren/innen:M. Bungartz, E. Kunisch, S. Maenz, V. Horbert, L. Xin, F. Gunella, J. Mika, J. Borowski, S. Bischoff, H. Schubert, 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:1685
Letzte Seite:1698
DDC-Klassifikation:Naturwissenschaften und Mathematik / Chemie / Analytische Chemie
Freie Schlagwörter:Bone regeneration; 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.2017.06.007
URL:http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS&DestLinkType=FullRecord;UT=WOS:000415312600013
ISSN:1529-9430
ISSN:1878-1632
Verfügbarkeit des Volltexts:Volltext-PDF 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