Injectable and compression-resistant low-viscosity polymer/ceramic composite carriers for rhBMP-2 in a rabbit model of p

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RESEARCH ARTICLE

Open Access

Injectable and compression-resistant lowviscosity polymer/ceramic composite carriers for rhBMP-2 in a rabbit model of posterolateral fusion: a pilot study Stefanie M. Shiels1*, Anne D. Talley2, Madison A. P. McGough3, Katarzyna J. Zienkiewicz2, Kerem Kalpakci4, Daniel Shimko4, Scott A. Guelcher2,4,5 and Joseph C. Wenke1

Abstract Background: The challenging biological and mechanical environment of posterolateral fusion (PLF) requires a carrier that spans the transverse processes and resists the compressive forces of the posterior musculature. The less traumatic posterolateral approach enabled by minimally invasive surgical techniques has prompted investigations into alternative rhBMP-2 carriers that are injectable, settable, and compression-resistant. In this pilot study, we investigated injectable low-viscosity (LV) polymer/composite bone grafts as compression-resistant carriers for rhBMP-2 in a single-level rabbit PLF model. Methods: LV grafts were augmented with ceramic microparticles: (1) hydrolytically degradable bioactive glass (BG), or (2) cell-degradable 85% β-tricalcium phosphate/15% hydroxyapatite (CM). Material properties, such as pore size, viscosity, working time, and bulk modulus upon curing, were measured for each LV polymer/ceramic material. An in vivo model of posterolateral fusion in a rabbit was used to assess the grafts’ capability to encourage spinal fusion. Results: These materials maintained a working time between 9.6 and 10.3 min, with a final bulk modulus between 1.2 and 3.1 MPa. The LV polymer/composite bone grafts released 55% of their rhBMP-2 over a 14-day period. As assessed by manual palpation in vivo, fusion was achieved in all (n = 3) animals treated with LV/BG or LV/CM carriers incorporating 430 μg rhBMP-2/ml. Images of μCT and histological sections revealed evidence of bone fusion near the transverse processes. Conclusion: This study highlights the potential of LV grafts as injectable and compression-resistant rhBMP-2 carriers for posterolateral spinal fusion. Keywords: Posterolateral fusion, Rabbit, Bone morphogenetic protein, Polyurethane, Injectable, Compression resistant

Background Spinal fusion surgeries are performed for a variety of ailments, such as disc degeneration, spinal stenosis, and degenerative spondylolisthesis, as well as traumatic injuries [1]. Autograft bone is the current gold standard due to its osteoconductive, osteoinductive, and osteogenic properties. Traditional harvesting sights include the iliac crest and local bone following spinal decompression; however, * Correspondence: [email protected] 1 US Army Institute of Surgical Research, Fort Sam Houston, TX, USA Full list of author information is available at the end of the article

these involve risk of donor site morbidity or inadequate bone supply. Synthetic bone grafts have been investigated as alternatives to autograft. The growth factor recombinant human bone morphogenetic protein-2 (rhBMP-2) promotes differentiation, maturation, and proliferation of multipot