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Co-delivery of rhBMP-2 and zoledronic acid using calcium sulfate/hydroxyapatite carrier as a bioactive bone substitute to enhance and accelerate spinal fusion.
Tian, Xinggui; Vater, Corina; Raina, Deepak Bushan; Findeisen, Lisa; Matuszewski, Lucas-Maximilian; Tägil, Magnus; Lidgren, Lars; Winkler, Anja; Gottwald, Robert; Modler, Niels; Schaser, Klaus-Dieter; Disch, Alexander C; Zwingenberger, Stefan.
Afiliación
  • Tian X; University Center of Orthopaedic, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany.
  • Vater C; Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany.
  • Raina DB; University Center of Orthopaedic, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany.
  • Findeisen L; Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany.
  • Matuszewski LM; Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund, 22185, Sweden.
  • Tägil M; University Center of Orthopaedic, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany.
  • Lidgren L; Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany.
  • Winkler A; University Center of Orthopaedic, Trauma and Plastic Surgery, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany.
  • Gottwald R; Center for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus at TUD Dresden University of Technology, 01307, Dresden, Germany.
  • Modler N; Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund, 22185, Sweden.
  • Schaser KD; Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Lund, 22185, Sweden.
  • Disch AC; Institute of Lightweight Engineering and Polymer Technology at TUD Dresden University of Technology, 01062, Dresden, Germany.
  • Zwingenberger S; Institute of Lightweight Engineering and Polymer Technology at TUD Dresden University of Technology, 01062, Dresden, Germany.
Bioact Mater ; 36: 256-271, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38487704
ABSTRACT
Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been FDA-approved for lumbar fusion, but supraphysiologic initial burst release due to suboptimal carrier and late excess bone resorption caused by osteoclast activation have limited its clinical usage. One strategy to mitigate the pro-osteoclast side effect of rhBMP-2 is to give systemic bisphosphonates, but it presents challenges with systemic side effects and low local bioavailability. The aim of this in vivo study was to analyze if posterolateral spinal fusion (PLF) could be improved by utilizing a calcium sulfate/hydroxyapatite (CaS/HA) carrier co-delivering rhBMP-2 and zoledronic acid (ZA). Six groups were allocated (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, and CaS/HA + BMP-2 + local ZA). 10-week-old male Wistar rats, were randomly assigned to undergo L4-L5 PLF with implantation of group-dependent scaffolds. At 3 and 6 weeks, the animals were euthanized for radiography, µCT, histological staining, or biomechanical testing to evaluate spinal fusion. The results demonstrated that the CaS/HA biomaterial alone or in combination with local or systemic ZA didn't support PLF. However, the delivery of rhBMP-2 significantly promoted PLF. Combining systemic ZA with BMP-2 didn't enhance spinal fusion. Notably, the co-delivery of rhBMP-2 and ZA using the CaS/HA carrier significantly enhanced and accelerated PLF, without inhibiting systemic bone turnover, and potentially reduced the dose of rhBMP-2. Together, the treatment regimen of CaS/HA biomaterial co-delivering rhBMP-2 and ZA could potentially be a safe and cost-effective off-the-shelf bioactive bone substitute to enhance spinal fusion.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Bioact Mater Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: China
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Bioact Mater Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: China