Skip to main content
Erschienen in: European Spine Journal 7/2012

01.07.2012 | Original Article

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

verfasst von: Tomiya Matsumoto, Hiromitsu Toyoda, Sho Dohzono, Hiroyuki Yasuda, Shigeyuki Wakitani, Hiroaki Nakamura, Kunio Takaoka

Erschienen in: European Spine Journal | Ausgabe 7/2012

Einloggen, um Zugang zu erhalten

Abstract

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), β-tricalcium phosphate powder (400 mg), and rhBMP-2 (0, 30, 60 or 120 μg) 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.

Conclusion

Solid 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.
Literatur
1.
Zurück zum Zitat Akamaru T, Suh D, Boden SD, Kim HS, Minamide A, Louis-Ugbo J (2003) Simple carrier matrix modifications can enhance delivery of recombinant human bone morphogenetic protein-2 for posterolateral spine fusion. Spine 28:429–434PubMed Akamaru T, Suh D, Boden SD, Kim HS, Minamide A, Louis-Ugbo J (2003) Simple carrier matrix modifications can enhance delivery of recombinant human bone morphogenetic protein-2 for posterolateral spine fusion. Spine 28:429–434PubMed
2.
Zurück zum Zitat Albee FH (1913) An experimental study of bone growth and the spinal bone transplant. JAMA 60:1044–1049CrossRef Albee FH (1913) An experimental study of bone growth and the spinal bone transplant. JAMA 60:1044–1049CrossRef
3.
Zurück zum Zitat Bach FH, Fishman JA, Daniels N, Proimos J, Anderson B, Carpenter CB, Forrow L, Robson SC, Fineberg HV (1998) Uncertainty in xenotransplantation: individual benefit versus collective risk. Nat Med 4:141–144PubMedCrossRef Bach FH, Fishman JA, Daniels N, Proimos J, Anderson B, Carpenter CB, Forrow L, Robson SC, Fineberg HV (1998) Uncertainty in xenotransplantation: individual benefit versus collective risk. Nat Med 4:141–144PubMedCrossRef
4.
Zurück zum Zitat Boden S, Schimandle J, Hutton W (1995) An experimental lumbar intertransverse process spinal fusion model. Radiographic, histologic, and biomechanical healing characteristics. Spine (Phila Pa 1976) 20:412–420CrossRef Boden S, Schimandle J, Hutton W (1995) An experimental lumbar intertransverse process spinal fusion model. Radiographic, histologic, and biomechanical healing characteristics. Spine (Phila Pa 1976) 20:412–420CrossRef
5.
Zurück zum Zitat Boden SD, Kang J, Sandhu H, Heller JG (2002) Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans: a prospective, randomized clinical pilot trial: 2002 Volvo Award in clinical studies. Spine 27:2662–2673PubMedCrossRef Boden SD, Kang J, Sandhu H, Heller JG (2002) Use of recombinant human bone morphogenetic protein-2 to achieve posterolateral lumbar spine fusion in humans: a prospective, randomized clinical pilot trial: 2002 Volvo Award in clinical studies. Spine 27:2662–2673PubMedCrossRef
6.
Zurück zum Zitat Bono CM, Vaccaro AR (2007) Interspinous process devices in the lumbar spine. J Spinal Disord Techn 20:255–261CrossRef Bono CM, Vaccaro AR (2007) Interspinous process devices in the lumbar spine. J Spinal Disord Techn 20:255–261CrossRef
7.
Zurück zum Zitat Bostman O, Myllynen P, Riska EB (1984) Posterior spinal fusion using internal fixation with the Daab plate. Acta Orthopaedica Scandinavica 55:310–314PubMedCrossRef Bostman O, Myllynen P, Riska EB (1984) Posterior spinal fusion using internal fixation with the Daab plate. Acta Orthopaedica Scandinavica 55:310–314PubMedCrossRef
8.
Zurück zum Zitat Butler D (1998) Last chance to stop and think on risks of xenotransplants. Nature 391:320–324PubMedCrossRef Butler D (1998) Last chance to stop and think on risks of xenotransplants. Nature 391:320–324PubMedCrossRef
9.
Zurück zum Zitat Cobey MC (1971) The value of the Wilson plate in spinal fusion. Clinical Orthop Relat Res 76:138–140CrossRef Cobey MC (1971) The value of the Wilson plate in spinal fusion. Clinical Orthop Relat Res 76:138–140CrossRef
10.
Zurück zum Zitat DeLustro F, Dasch J, Keefe J, Ellingsworth L (1990) Immune responses to allogeneic and xenogeneic implants of collagen and collagen derivatives. Clinical Orthop Relat Res 260:263–279 DeLustro F, Dasch J, Keefe J, Ellingsworth L (1990) Immune responses to allogeneic and xenogeneic implants of collagen and collagen derivatives. Clinical Orthop Relat Res 260:263–279
11.
Zurück zum Zitat DePalma AF, Rothman RH (1968) The nature of pseudarthrosis. Clinical Orthop Relat Res 59:113–118 DePalma AF, Rothman RH (1968) The nature of pseudarthrosis. Clinical Orthop Relat Res 59:113–118
12.
Zurück zum Zitat Dohzono S, Imai Y, Nakamura H, Wakitani S, Takaoka K (2009) Successful spinal fusion by E. coli-derived BMP-2-adsorbed porous beta-TCP granules: a pilot study. Clinical Orthop Relat Res 467:3206–3212CrossRef Dohzono S, Imai Y, Nakamura H, Wakitani S, Takaoka K (2009) Successful spinal fusion by E. coli-derived BMP-2-adsorbed porous beta-TCP granules: a pilot study. Clinical Orthop Relat Res 467:3206–3212CrossRef
13.
Zurück zum Zitat Drummond D, Guadagni J, Keene JS, Breed A, Narechania R (1984) Interspinous process segmental spinal instrumentation. J Pediatr Orthop 4:397–404PubMedCrossRef Drummond D, Guadagni J, Keene JS, Breed A, Narechania R (1984) Interspinous process segmental spinal instrumentation. J Pediatr Orthop 4:397–404PubMedCrossRef
14.
Zurück zum Zitat Heller KD, Prescher A, Schneider T, Block FR, Forst R (1998) Stability of different wiring techniques in segmental spinal instrumentation. An experimental study. Arch Orthop Trauma Surg 117:96–99PubMedCrossRef Heller KD, Prescher A, Schneider T, Block FR, Forst R (1998) Stability of different wiring techniques in segmental spinal instrumentation. An experimental study. Arch Orthop Trauma Surg 117:96–99PubMedCrossRef
15.
Zurück zum Zitat Hoshino M, Egi T, Terai H, Namikawa T, Takaoka K (2007) Regenerative repair of long intercalated rib defects using porous cylinders of beta-tricalcium phosphate: an experimental study in a canine model. Plast Reconstr Surg 119:1431–1439PubMedCrossRef Hoshino M, Egi T, Terai H, Namikawa T, Takaoka K (2007) Regenerative repair of long intercalated rib defects using porous cylinders of beta-tricalcium phosphate: an experimental study in a canine model. Plast Reconstr Surg 119:1431–1439PubMedCrossRef
16.
Zurück zum Zitat Israel DI, Nove J, Kerns KM, Kaufman RJ, Rosen V, Cox KA, Wozney JM (1996) Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo. Growth factors (Chur, Switzerland) 13:291–300CrossRef Israel DI, Nove J, Kerns KM, Kaufman RJ, Rosen V, Cox KA, Wozney JM (1996) Heterodimeric bone morphogenetic proteins show enhanced activity in vitro and in vivo. Growth factors (Chur, Switzerland) 13:291–300CrossRef
17.
Zurück zum Zitat Johnsson R, Stromqvist B, Aspenberg P (2002) Randomized radiostereometric study comparing osteogenic protein-1 (BMP-7) and autograft bone in human noninstrumented posterolateral lumbar fusion: 2002 Volvo Award in clinical studies. Spine 27:2654–2661PubMedCrossRef Johnsson R, Stromqvist B, Aspenberg P (2002) Randomized radiostereometric study comparing osteogenic protein-1 (BMP-7) and autograft bone in human noninstrumented posterolateral lumbar fusion: 2002 Volvo Award in clinical studies. Spine 27:2654–2661PubMedCrossRef
18.
Zurück zum Zitat Jutte PC, Castelein RM (2002) Complications of pedicle screws in lumbar and lumbosacral fusions in 105 consecutive primary operations. Eur Spine J 11:594–598PubMedCrossRef Jutte PC, Castelein RM (2002) Complications of pedicle screws in lumbar and lumbosacral fusions in 105 consecutive primary operations. Eur Spine J 11:594–598PubMedCrossRef
19.
Zurück zum Zitat Kasai Y, Inaba T, Akeda K, Uchida A (2008) Tadpole system as new lumbar spinal instrumentation. J Orthop Surg Res 3:41PubMedCrossRef Kasai Y, Inaba T, Akeda K, Uchida A (2008) Tadpole system as new lumbar spinal instrumentation. J Orthop Surg Res 3:41PubMedCrossRef
20.
Zurück zum Zitat Kato M, Namikawa T, Terai H, Hoshino M, Miyamoto S, Takaoka K (2006) Ectopic bone formation in mice associated with a lactic acid/dioxanone/ethylene glycol copolymer-tricalcium phosphate composite with added recombinant human bone morphogenetic protein-2. Biomaterials 27:3927–3933PubMedCrossRef Kato M, Namikawa T, Terai H, Hoshino M, Miyamoto S, Takaoka K (2006) Ectopic bone formation in mice associated with a lactic acid/dioxanone/ethylene glycol copolymer-tricalcium phosphate composite with added recombinant human bone morphogenetic protein-2. Biomaterials 27:3927–3933PubMedCrossRef
21.
Zurück zum Zitat Kato M, Toyoda H, Namikawa T, Hoshino M, Terai H, Miyamoto S, Takaoka K (2006) Optimized use of a biodegradable polymer as a carrier material for the local delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2). Biomaterials 27:2035–2041PubMedCrossRef Kato M, Toyoda H, Namikawa T, Hoshino M, Terai H, Miyamoto S, Takaoka K (2006) Optimized use of a biodegradable polymer as a carrier material for the local delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2). Biomaterials 27:2035–2041PubMedCrossRef
22.
Zurück zum Zitat Kubler NR, Reuther JF, Faller G, Kirchner T, Ruppert R, Sebald W (1998) Inductive properties of recombinant human BMP-2 produced in a bacterial expression system. Int J Oral Maxillofac Surg 27:305–309PubMedCrossRef Kubler NR, Reuther JF, Faller G, Kirchner T, Ruppert R, Sebald W (1998) Inductive properties of recombinant human BMP-2 produced in a bacterial expression system. Int J Oral Maxillofac Surg 27:305–309PubMedCrossRef
23.
Zurück zum Zitat Lindholm TS, Nilsson OS, Lindholm TC (1982) Extraskeletal and intraskeletal new bone formation induced by demineralized bone matrix combined with bone marrow cells. Clin Orthop Relat Res 171:251–255 Lindholm TS, Nilsson OS, Lindholm TC (1982) Extraskeletal and intraskeletal new bone formation induced by demineralized bone matrix combined with bone marrow cells. Clin Orthop Relat Res 171:251–255
24.
Zurück zum Zitat Matsushita N, Terai H, Okada T, Nozaki K, Inoue H, Miyamoto S, Takaoka K (2004) A new bone-inducing biodegradable porous beta-tricalcium phosphate. J Biomed Mater Res 70:450–458CrossRef Matsushita N, Terai H, Okada T, Nozaki K, Inoue H, Miyamoto S, Takaoka K (2004) A new bone-inducing biodegradable porous beta-tricalcium phosphate. J Biomed Mater Res 70:450–458CrossRef
25.
Zurück zum Zitat Minamide A, Kawakami M, Hashizume H, Sakata R, Tamaki T (2001) Evaluation of carriers of bone morphogenetic protein for spinal fusion. Spine 26:933–939PubMedCrossRef Minamide A, Kawakami M, Hashizume H, Sakata R, Tamaki T (2001) Evaluation of carriers of bone morphogenetic protein for spinal fusion. Spine 26:933–939PubMedCrossRef
26.
Zurück zum Zitat Namikawa T, Terai H, Suzuki E, Hoshino M, Toyoda H, Nakamura H, Miyamoto S, Takahashi N, Ninomiya T, Takaoka K (2005) Experimental spinal fusion with recombinant human bone morphogenetic protein-2 delivered by a synthetic polymer and beta-tricalcium phosphate in a rabbit model. Spine 30:1717–1722PubMedCrossRef Namikawa T, Terai H, Suzuki E, Hoshino M, Toyoda H, Nakamura H, Miyamoto S, Takahashi N, Ninomiya T, Takaoka K (2005) Experimental spinal fusion with recombinant human bone morphogenetic protein-2 delivered by a synthetic polymer and beta-tricalcium phosphate in a rabbit model. Spine 30:1717–1722PubMedCrossRef
27.
Zurück zum Zitat Oikarinen J (1982) Experimental spinal fusion with decalcified bone matrix and deep-frozen allogeneic bone in rabbits. Clin Orthop Relat Res 162:210–218 Oikarinen J (1982) Experimental spinal fusion with decalcified bone matrix and deep-frozen allogeneic bone in rabbits. Clin Orthop Relat Res 162:210–218
29.
Zurück zum Zitat Park P, Garton HJ, Gala VC, Hoff JT, McGillicuddy JE (2004) Adjacent segment disease after lumbar or lumbosacral fusion: review of the literature. Spine 29:1938–1944PubMedCrossRef Park P, Garton HJ, Gala VC, Hoff JT, McGillicuddy JE (2004) Adjacent segment disease after lumbar or lumbosacral fusion: review of the literature. Spine 29:1938–1944PubMedCrossRef
30.
Zurück zum Zitat Reeg SE (2001) A review of comorbidities and spinal surgery. Clin Orthop Relat Res 384:101–109 Reeg SE (2001) A review of comorbidities and spinal surgery. Clin Orthop Relat Res 384:101–109
31.
Zurück zum Zitat Rolander SD (1966) Motion of the lumbar spine with special reference to the stabilizing effect of posterior fusion. An experimental study on autopsy specimens. Acta orthopaedica Scandinavica 90(Suppl):91–144 Rolander SD (1966) Motion of the lumbar spine with special reference to the stabilizing effect of posterior fusion. An experimental study on autopsy specimens. Acta orthopaedica Scandinavica 90(Suppl):91–144
32.
Zurück zum Zitat Ruppert R, Hoffmann E, Sebald W (1996) Human bone morphogenetic protein 2 contains a heparin-binding site which modifies its biological activity. Eur J Biochem/FEBS 237:295–302CrossRef Ruppert R, Hoffmann E, Sebald W (1996) Human bone morphogenetic protein 2 contains a heparin-binding site which modifies its biological activity. Eur J Biochem/FEBS 237:295–302CrossRef
33.
Zurück zum Zitat Saito N, Okada T, Horiuchi H, Murakami N, Takahashi J, Nawata M, Ota H, Nozaki K, Takaoka K (2001) A biodegradable polymer as a cytokine delivery system for inducing bone formation. Nat Biotechnol 19:332–335PubMedCrossRef Saito N, Okada T, Horiuchi H, Murakami N, Takahashi J, Nawata M, Ota H, Nozaki K, Takaoka K (2001) A biodegradable polymer as a cytokine delivery system for inducing bone formation. Nat Biotechnol 19:332–335PubMedCrossRef
34.
Zurück zum Zitat Saito N, Takaoka K (2003) New synthetic biodegradable polymers as BMP carriers for bone tissue engineering. Biomaterials 24:2287–2293PubMedCrossRef Saito N, Takaoka K (2003) New synthetic biodegradable polymers as BMP carriers for bone tissue engineering. Biomaterials 24:2287–2293PubMedCrossRef
35.
Zurück zum Zitat Sandhu HS, Kanim LE, Kabo JM, Toth JM, Zeegen EN, Liu D, Delamarter RB, Dawson EG (1996) Effective doses of recombinant human bone morphogenetic protein-2 in experimental spinal fusion. Spine 21:2115–2122PubMedCrossRef Sandhu HS, Kanim LE, Kabo JM, Toth JM, Zeegen EN, Liu D, Delamarter RB, Dawson EG (1996) Effective doses of recombinant human bone morphogenetic protein-2 in experimental spinal fusion. Spine 21:2115–2122PubMedCrossRef
36.
Zurück zum Zitat Schimandle J, Boden S, Hutton W (1995) Experimental spinal fusion with recombinant human bone morphogenetic protein-2. Spine (Phila Pa 1976) 20:1326–1337 Schimandle J, Boden S, Hutton W (1995) Experimental spinal fusion with recombinant human bone morphogenetic protein-2. Spine (Phila Pa 1976) 20:1326–1337
37.
Zurück zum Zitat Steinmann JC, Herkowitz HN (1992) Pseudarthrosis of the spine. Clin Orthop Relat Res 284:80–90 Steinmann JC, Herkowitz HN (1992) Pseudarthrosis of the spine. Clin Orthop Relat Res 284:80–90
38.
Zurück zum Zitat Swanson KE, Lindsey DP, Hsu KY, Zucherman JF, Yerby SA (2003) The effects of an interspinous implant on intervertebral disc pressures. Spine 28:26–32PubMedCrossRef Swanson KE, Lindsey DP, Hsu KY, Zucherman JF, Yerby SA (2003) The effects of an interspinous implant on intervertebral disc pressures. Spine 28:26–32PubMedCrossRef
39.
Zurück zum Zitat Valentin-Opran A, Wozney J, Csimma C, Lilly L, Riedel GE (2002) Clinical evaluation of recombinant human bone morphogenetic protein-2. Clin Orthop Relat Res 395:110–120 Valentin-Opran A, Wozney J, Csimma C, Lilly L, Riedel GE (2002) Clinical evaluation of recombinant human bone morphogenetic protein-2. Clin Orthop Relat Res 395:110–120
40.
Zurück zum Zitat Wang EA, Rosen V, D’Alessandro JS, Bauduy M, Cordes P, Harada T, Israel DI, Hewick RM, Kerns KM, LaPan P et al (1990) Recombinant human bone morphogenetic protein induces bone formation. Proc Natl Acad Sci USA 87:2220–2224PubMedCrossRef Wang EA, Rosen V, D’Alessandro JS, Bauduy M, Cordes P, Harada T, Israel DI, Hewick RM, Kerns KM, LaPan P et al (1990) Recombinant human bone morphogenetic protein induces bone formation. Proc Natl Acad Sci USA 87:2220–2224PubMedCrossRef
41.
Zurück zum Zitat Wang JC, Haid RW Jr, Miller JS, Robinson JC (2006) Comparison of CD HORIZON SPIRE spinous process plate stabilization and pedicle screw fixation after anterior lumbar interbody fusion. Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2005. J Neurosurg 4:132–136 Wang JC, Haid RW Jr, Miller JS, Robinson JC (2006) Comparison of CD HORIZON SPIRE spinous process plate stabilization and pedicle screw fixation after anterior lumbar interbody fusion. Invited submission from the Joint Section Meeting on Disorders of the Spine and Peripheral Nerves, March 2005. J Neurosurg 4:132–136
42.
Zurück zum Zitat Weigel U, Meyer M, Sebald W (1989) Mutant proteins of human interleukin 2. Renaturation yield, proliferative activity and receptor binding. Eur J Biochem/FEBS 180:295–300CrossRef Weigel U, Meyer M, Sebald W (1989) Mutant proteins of human interleukin 2. Renaturation yield, proliferative activity and receptor binding. Eur J Biochem/FEBS 180:295–300CrossRef
43.
Zurück zum Zitat Yano K, Hoshino M, Ohta Y, Manaka T, Naka Y, Imai Y, Sebald W, Takaoka K (2009) Osteoinductive capacity and heat stability of recombinant human bone morphogenetic protein-2 produced by Escherichia coli and dimerized by biochemical processing. J Bone Mineral Metab 27:355–363CrossRef Yano K, Hoshino M, Ohta Y, Manaka T, Naka Y, Imai Y, Sebald W, Takaoka K (2009) Osteoinductive capacity and heat stability of recombinant human bone morphogenetic protein-2 produced by Escherichia coli and dimerized by biochemical processing. J Bone Mineral Metab 27:355–363CrossRef
Metadaten
Titel
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
verfasst von
Tomiya Matsumoto
Hiromitsu Toyoda
Sho Dohzono
Hiroyuki Yasuda
Shigeyuki Wakitani
Hiroaki Nakamura
Kunio Takaoka
Publikationsdatum
01.07.2012
Verlag
Springer-Verlag
Erschienen in
European Spine Journal / Ausgabe 7/2012
Print ISSN: 0940-6719
Elektronische ISSN: 1432-0932
DOI
https://doi.org/10.1007/s00586-011-2130-x

Weitere Artikel der Ausgabe 7/2012

European Spine Journal 7/2012 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.