Electrospun, synthetic bone void filler promotes human MSC function and BMP-2 mediated spinal fusion
Autor: | Samuel Eberlein, Dmitriy Sheyn, Khosrowdad Salehi, Derek G Ju, Tina Stefanovic, Juliane D. Glaeser, Melodie F. Metzger, Yasaman Arabi, Hyun W. Bae, L.E.A. Kanim, Phillip H. Behrens, Jae Hyuk Yang |
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Rok vydání: | 2020 |
Předmět: |
medicine.medical_treatment
Biomedical Engineering Cell Culture Techniques Bone Morphogenetic Protein 2 02 engineering and technology Bone healing Bone morphogenetic protein 2 Article Biomaterials 03 medical and health sciences 0302 clinical medicine Bone Marrow Osteogenesis medicine Animals Humans Bone Transplantation Tissue Engineering Tissue Scaffolds Chemistry Mesenchymal stem cell Synthetic bone Cell Differentiation Mesenchymal Stem Cells X-Ray Microtomography 021001 nanoscience & nanotechnology Cell function Biomechanical Phenomena Body Fluids Rats Radiography Spinal Fusion Spinal fusion Female Collagen 0210 nano-technology 030217 neurology & neurosurgery Biomedical engineering |
Zdroj: | J Biomater Appl |
ISSN: | 1530-8022 |
Popis: | Introduction Synthetic bone grafts are often used to achieve a well-consolidated fusion mass in spinal fusion procedures. These bone grafts function as scaffolds, and ideally support cell function and facilitate protein binding. Objective The aim was to characterize an electrospun, synthetic bone void filler (Reb) for its bone morphogenetic protein (BMP)-2 release properties and support of human mesenchymal stem cell (hMSC) function in vitro, and its efficacy in promoting BMP-2-/bone marrow aspirate-(BMA)-mediated posterolateral spinal fusion (PLF) in vivo. Methods BMP-2 release kinetics from Reb versus standard absorbable collagen sponge (ACS) was determined. hMSC adhesion and proliferation on Reb was tested using cell counting, fluorescence microscopy and MTS. Cell osteogenic differentiation was quantified via cellular alkaline phosphatase (ALP) activity. For in vivo analysis, 18 Lewis rats were treated during PLF surgery with the following groups: (I) Reb + BMA, (II) Reb + BMA + BMP-2 and (III) BMA. A safe, minimally effective dose of BMP-2 was used. Fusion consolidation was followed for 3 months using radiography and micro-CT. After sacrifice, fusion rate and biomechanical stiffness was determined using manual palpation, biomechanical tests and histology. Results In vitro, BMP-2 release kinetics were similar between Reb versus ACS. MSC proliferation and differentiation were increased in the presence of Reb. At 3 months post-surgery, fusion rates were 29% (group I), 100% (group II), and 0% (group III). Biomechanical stiffness was higher in group II versus I. Micro-CT showed an increased bone volume and connectivity density in group II. Trabecular thickness was increased in group I versus II. H&E staining showed newly formed bone in group II only. Conclusions Reb possesses a high protein binding affinity and promotes hMSC function. Combination with BMA and minimal dose BMP-2 allowed for 100% bone fusion in vivo. This data suggests that a minimally effective dose of BMP-2 can be used when combined with Reb. |
Databáze: | OpenAIRE |
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