Simple Carrier Matrix Modifications Can Enhance Delivery of Recombinant Human Bone Morphogenetic Protein-2 for Posterolateral Spine Fusion

Akamaru, Tomoyuki; Suh, Dan; Boden, Scott D.; Kim, Hak-Sun; Minamide, Akihito; Louis-Ugbo, John

doi:10.1097/01.brs.0000048644.91330.14

Cited by 95 publications

(76 citation statements)

References 23 publications

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“…To manufacture an osteoinductive artificial bone graft substitute, cytokines retaining osteoinductive activity (e.g., BMPs) have been combined with collagen and used to obtain spinal fusion in experimental animals or in human cases [1,4,5,17,25,26,35,36]. This experimental study was designed to achieve solid posterior interspinous lumbar fusion more effectively and less invasively than before with proper use of rhBMP-2 in combination with synthetic carrier materials.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of interspinous process lumbar fusion with recombinant human bone morphogenetic protein-2 delivered with a synthetic polymer and β-tricalcium phosphate in a rabbit model

et al. 2011

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Introduction As a powerful bone-inducing cytokine, rhBMP-2 has been used as a bone graft substitute in combination with animal-derived collagen to achieve interbody or posterolateral spinal fusion. Successful interspinous process fusion using rhBMP-2 in combination with synthetic carrier materials would offer a safe, minimally invasive spinal fusion option for the treatment of spinal disorders. The aims of the present study were to achieve interspinous process fusion by implanting rhBMP-2-retaining degradable material instead of bone grafting and to evaluate efficacy for vertebral stabilization. Materials and methods A polymer gel (200 mg), btricalcium phosphate powder (400 mg), and rhBMP-2 (0, 30, 60 or 120 lg) were mixed to generate a plastic implant, which was then placed during surgery to bridge the L5-6 interspinous processes of 58 rabbits. Control animals received implants either without rhBMP-2 or with autogenous bone chips from the iliac crest. L5-6 vertebrae were recovered 8 weeks postoperatively. Interspinous process fusion was evaluated by radiography, biomechanical bending test, intradiscal pressure (IDP) measurement, and histology. Results In bending tests, strength of fusion was significantly greater in BMP60 and BMP120 groups than in sham, BMP0, BMP30 or autogenous bone groups. IDP at L5-6 was significantly reduced in BMP60 and BMP120 groups compared to sham, BMP0, BMP30, and autograft groups. Histologically, coronal sections of the fusion mass showed a bone mass bridging both spinous processes. ConclusionSolid interspinous process fusion was achieved in rabbit models by 8 weeks after implanting the biodegradable bone-inducing material. These results suggest a potential new less-invasive option without bone grafting for the treatment of lumbar disorders.

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Section: Discussionmentioning

confidence: 99%

Efficacy of interspinous process lumbar fusion with recombinant human bone morphogenetic protein-2 delivered with a synthetic polymer and β-tricalcium phosphate in a rabbit model

et al. 2011

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“…9,43 Pre-clinical studies have also suggested that because of its favorable binding properties to osteoinductive growth factors such as rhBMP-2, the dose required to achieve successful bony fusion is effectively reduced. 44,45 To this end, recent studies have demonstrated that a 10-15% hydroxyapatite composition in a ceramic carrier is ideal for stem cell adhesion and osteoblastic differentiation. 46,47 In comparison, Grafton 1 is a DBM processed from human tissue into bone fibers combined with glycerol (79-85% content) to achieve a putty-like consistency.…”

Section: Discussionmentioning

confidence: 99%

Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein‐2 in a rodent arthrodesis model

Hsu¹,

Polavarapu²,

Riaz³

et al. 2011

Journal Orthopaedic Research

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The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in spine fusion has led to concerns regarding a potential accompanying inflammatory response. This study evaluates a combination therapy (TrioMatrix 1 ; Pioneer Surgical, Inc., Marquette, MI) comprised of a demineralized bone matrix (DBM), hydroxyapatite, and a nanofiber-based collagen scaffold in a rodent spine fusion model. Thirty-six athymic rats that underwent a posterolateral intertransverse spinal fusion were randomly assigned to 1 of 5 treatment groups: absorbable collagen sponge alone (ACS, negative control), 10 mg rhBMP-2 on ACS (positive control), TrioMatrix 1 , Grafton 1 (Osteotech, Inc., Eatontown, NJ), and DBX 1 (Synthes, Inc., West Chester, PA). Both TrioMatrix 1 and rhBMP-2-treated animals demonstrated 100% fusion rates as graded by manual palpation scores 8 weeks after implantation. This rate was significantly greater than those of the ACS, Grafton 1 , and DBX 1 groups. Notably, the use of TrioMatrix 1 as evaluated by microCT quantification led to a greater fusion mass volume when compared to all other groups, including the rhBMP-2 group. T2-weighted axial MRI images of the fusion bed demonstrated a significant host response associated with a large fluid collection with the use of rhBMP-2; this response was significantly reduced with the use of TrioMatrix 1 . Our results therefore demonstrate that a nanocomposite therapy represents a promising, cost-effective bone graft substitute that could be useful in spine fusions where BMP-2 is contraindicated.

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“…Therefore, our results suggest that male rat BMSCs, which were xenogenically transplanted into the posterolateral lumbar spine of female rabbits, successfully survived without immune suppression. The CRM has been demonstrated to be an effective osteoconductive material in previous spine fusion study [1]. We therefore used CRM as a carrier of xenogenic BMSCs in this study.…”

Section: Discussionmentioning

confidence: 99%

“…A compression resistant matrix (CRM, Medtronic Sofamor Danek, USA) used in this study was chemically composed of 15% hydroxyapatite (HA) and 85% b-tricalcium phosphate (b-TCP) with 500 lm average pore size and 80% porosity [1]. Aliquots of BMSCs (1 9 10 6 cells) were incubated with 5 cc CRM matrix in 25 T culture flask for 2 h to allow attachment; 32 female New Zealand rabbits (3.5-4 kg) were divided into two groups in this study.…”

Section: Implantation Of Bmscs Loaded Onto Crmmentioning

confidence: 99%

Transplanted xenogenic bone marrow stem cells survive and generate new bone formation in the posterolateral lumbar spine of non-immunosuppressed rabbits

et al. 2008

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Simple Carrier Matrix Modifications Can Enhance Delivery of Recombinant Human Bone Morphogenetic Protein-2 for Posterolateral Spine Fusion

Cited by 95 publications

References 23 publications

Efficacy of interspinous process lumbar fusion with recombinant human bone morphogenetic protein-2 delivered with a synthetic polymer and β-tricalcium phosphate in a rabbit model

Efficacy of interspinous process lumbar fusion with recombinant human bone morphogenetic protein-2 delivered with a synthetic polymer and β-tricalcium phosphate in a rabbit model

Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein‐2 in a rodent arthrodesis model

Transplanted xenogenic bone marrow stem cells survive and generate new bone formation in the posterolateral lumbar spine of non-immunosuppressed rabbits

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