Posterolateral Intertransverse Process Spinal Arthrodesis with rhBMP-2 in a Nonhuman Primate

Martin, George J.; Boden, Scott D.; Morone, Michael A.; Moskovitz, Peter A.

doi:10.1097/00024720-199906000-00001

Cited by 24 publications

(26 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The safety and accuracy of these carriers, however, are questionable. 30,39,40 A fast and uncontrolled release of drugs from collagen sponges with potential undesired drug-or carrier system-induced tissue reactions has been described. 39 An accurate intraoperative placement of these carriers at the desired region appears difficult, and inaccurate positioning may lead to uncontrolled interactions with the surrounding tissue or growth factor inefficacy.…”

Section: Biodegradable Pdlla Carrier Systemmentioning

confidence: 99%

“…39 An accurate intraoperative placement of these carriers at the desired region appears difficult, and inaccurate positioning may lead to uncontrolled interactions with the surrounding tissue or growth factor inefficacy. 1,16,24,33 Martin, et al, 30 for example, demonstrated in an intertransverse spinal fusion model that soft-tissue compression of the collagen sponge carrier prevented bone induction at standard growth factor doses. Boden, et al, 3 reported that a resorbable collagen sponge carrier was a suitable vehicle in rabbits and dogs; however, it was found to be subjectable to compression in a lumbar intertransverse spinal fusion model in monkeys.…”

Section: Biodegradable Pdlla Carrier Systemmentioning

confidence: 99%

See 1 more Smart Citation

Bone morphogenetic protein—2 application by a poly(d,l-lactide)—coated interbody cage: in vivo results of a new carrier for growth factors

Kandziora¹,

Bail²,

Schmidmaier³

et al. 2002

Journal of Neurosurgery: Spine

View full text Add to dashboard Cite

Object. Growth factors such as bone morphogenetic protein—2 (BMP-2) have been proven to promote spine fusion and to overcome the disadvantages of an autologous bone graft. The optimum method to deliver such growth factors remains a matter of discussion. The purpose of this study was to determine the safety and efficacy of a new poly(d,l-lactide) (PDLLA) carrier system for BMP-2 and to compare this carrier system with a collagen sponge carrier in a sheep cervical spine interbody fusion model. Methods. Thirty-two sheep underwent C3–4 discectomy and fusion: Group 1, titanium cage (eight animals); Group 2, titanium cage coated with a PDLLA carrier (eight animals); Group 3, titanium cage coated with a PDLLA carrier including BMP-2 (150 µg) (eight animals); and Group 4, titanium cage combined with a collagen sponge carrier including BMP-2 (150 µg) (eight animals). Blood samples, body weight, and temperature were assessed. Radiographs were obtained pre- and postoperatively and after 1, 2, 4, 8, and 12 weeks. At the same time points, disc space height, intervertebral angle, and lordosis angle were measured. After the sheep were killed 12 weeks postoperatively, flexion—extension radiography was performed to evaluate fusion sites. Quantitative computerized tomography scans were obtained to assess bone mineral density (BMD), bone mineral content (BMC), and bone callus volume (BCV). Biomechanical testing was performed in flexion, extension, axial rotation, and lateral bending. Stiffness, range of motion, neutral, and elastic zone were determined. Histomorphological and -morphometrical analyses were performed, and polychrome sequential labeling was used to determine the timeframe of new bone formation. There were no differences among the groups concerning blood counts, body weight, and temperature. Compared with the noncoated cages, all PDLLA-coated cages showed significantly higher values for BMD of the callus, as well as slightly higher values for BMC, BCV, and the bone volume/total volume ratio. In comparison with the cage-alone group, the BMP-2 groups showed significantly higher values for BMD and biomechanical stiffness. Histomorphological, -morphometrical, and polychrome sequential labeling analyses demonstrated greater progression of callus formation in the BMP-2 groups than in any other group. Compared with BMP-2 delivered using a collagen sponge carrier, BMP-2 application with a PDLLA carrier resulted in a higher BCV and a greater progression of interbody callus formation in the histomorphometrical analysis. Conclusions. The use of cervical spine interbody fusion cages coated with PDLLA as a delivery system for growth factors was effective. In this 12-week follow-up study, the PDLLA coating showed no adverse effects. The slight but not significant positive effect of the PDLLA carrier on interbody fusion might be a result of the degradation process of the biodegradable carrier. Compared with collagen sponge delivery of BMP-2, the PDLLA-coated interbody cages significantly increased the results of interbody bone matrix formation. In this new combination (implant + PDLLA + growth factor) the cage represents a “real fusion” cage, because it not only serves as a mechanical device for spinal fixation but also as a local drug delivery system.

show abstract

Section: Biodegradable Pdlla Carrier Systemmentioning

confidence: 99%

Section: Biodegradable Pdlla Carrier Systemmentioning

confidence: 99%

Bone morphogenetic protein—2 application by a poly(d,l-lactide)—coated interbody cage: in vivo results of a new carrier for growth factors

Kandziora¹,

Bail²,

Schmidmaier³

et al. 2002

Journal of Neurosurgery: Spine

View full text Add to dashboard Cite

show abstract

“…Incremental positive effects of increasing dose of BMP-2 have been observed in a mouse calvarial defect model using heparin conjugated polylactic-co-glycolic acid (PLGA) nanospheres and fibrin gel [19], a rat calvarial defect model with PLGA scaffold [24], a rat femoral defect model with both ACS and a hybrid alginate-PCL mesh delivery system [11], a rabbit radial defect model using a PLA scaffold [25], and a canine radial defect model using an ACS scaffold [26]. Moreover, in general, higher doses have been necessary to effectively induce bone formation in non-human primate studies compared to small animal studies [27]. Higher doses of BMP-2 may thus be considered necessary for recruitment or differentiation of progenitor cells for mineralized bridging [28], especially in the absence of bone grafting or bulking agents [22].…”

Section: Introductionmentioning

confidence: 99%

Delivery vehicle effects on bone regeneration and heterotopic ossification induced by high dose BMP-2

et al. 2017

View full text Add to dashboard Cite

Bone morphogenetic protein-2 (BMP-2), delivered on absorbable collagen sponge, is frequently used to treat bone defects. However, supraphysiological BMP-2 doses are common and often associated with complications such as heterotopic ossification and inflammation, causing pain and impaired mobility. This has prompted investigations into strategies to spatially control bone regeneration, for example growth factor delivery in appropriate scaffolds. Our objective was to investigate the spatiotemporal effects of high dose BMP-2 on bone regeneration as a function of the delivery vehicle. We hypothesized that an alginate delivery system would spatially restrict bone formation compared to a collagen sponge delivery system. In vitro, BMP-2 release was accelerated from collagen sponge compared to alginate constructs. In vivo, bone regeneration was evaluated over 12 weeks in critically sized rat femoral segmental defects treated with 30 μg rhBMP-2 in alginate hydrogel or collagen sponge, surrounded by perforated nanofiber meshes. Total bone volume, calculated from micro-CT reconstructions, was higher in the alginate group at 12 weeks. Though bone volume within the central defect region was greater in the alginate group at 8 and 12 weeks, heterotopic bone volume was similar between groups. Likewise, mechanical properties from ex vivo torsional testing were comparable between groups. Histology corroborated these findings and revealed heterotopic mineralization at 2 weeks post-surgery in both groups. Overall, this study recapitulated the heterotopic ossification associated with high dose BMP-2 delivery, and demonstrated that the amount and spatial pattern of bone formation was dependent on the delivery matrix.

show abstract

“…Gold standard rhBMP-2 delivery for lumbar arthrodesis is via an ACS. While the ACS carrier retains rhBMP-2 at the site of placement for 2 weeks [28], the ACS carrier is ineffective for PLF at clinically relevant doses due to soft tissue compression of the collagen [29]. A compression-resistant collagen/ceramic (85/15 β-TCP/HA) matrix (CRM) augmented with 430 μg/mL rhBMP-2 resulted in successful fusion in a rabbit arthrodesis modal, as determined by manual palpation and radiography [30].…”

Section: Discussionmentioning

confidence: 99%

Injectable and compression-resistant low-viscosity polymer/ceramic composite carriers for rhBMP-2 in a rabbit model of posterolateral fusion: a pilot study

et al. 2017

View full text Add to dashboard Cite

BackgroundThe 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.MethodsLV 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.ResultsThese 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.ConclusionThis study highlights the potential of LV grafts as injectable and compression-resistant rhBMP-2 carriers for posterolateral spinal fusion.

show abstract

Posterolateral Intertransverse Process Spinal Arthrodesis with rhBMP-2 in a Nonhuman Primate

Cited by 24 publications

References 0 publications

Bone morphogenetic protein—2 application by a poly(d,l-lactide)—coated interbody cage: in vivo results of a new carrier for growth factors

Bone morphogenetic protein—2 application by a poly(d,l-lactide)—coated interbody cage: in vivo results of a new carrier for growth factors

Delivery vehicle effects on bone regeneration and heterotopic ossification induced by high dose BMP-2

Injectable and compression-resistant low-viscosity polymer/ceramic composite carriers for rhBMP-2 in a rabbit model of posterolateral fusion: a pilot study

Contact Info

Product

Resources

About