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Spine (Phila Pa 1976). 2021, 46:E234-E242. 10.1097\/BRS.0000000000003770","journal-title":"Spine (Phila Pa 1976)"},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2018.03.006","article-title":"The local cytokine and growth factor response to recombinant human bone morphogenetic protein-2 (rhBMP-2) after spinal fusion","volume":"18","author":"Koerner JD","year":"2018","unstructured":"Koerner JD, Markova DZ, Schroeder GD, et al.. The local cytokine and growth factor response to recombinant human bone morphogenetic protein-2 (rhBMP-2) after spinal fusion. Spine J. 2018, 18:1424-1433. 10.1016\/j.spinee.2018.03.006","journal-title":"Spine J"},{"key":"ref51","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000002044","article-title":"Dose-dependent nerve inflammatory response to rhBMP-2 in a rodent spinal nerve model","volume":"42","author":"Liau ZQG","year":"2017","unstructured":"Liau ZQG, Lam RWM, Hu T, Wong HK. 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