Optimized use of a biodegradable polymer as a carrier material for the local delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2)

Kato, Minori; Toyoda, Hiromitsu; Namikawa, Takashi; Hoshino, Minoru; Terai, Hidetomi; Miyamoto, Shimpei; Takaoka, Kunio

doi:10.1016/j.biomaterials.2005.10.007

Cited by 82 publications

(70 citation statements)

References 26 publications

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“…With the use of equivalent amounts of carrier material, the BMP-2-induced new bone mass at the interspinous process region appeared to depend on the BMP-2 dose, and the optimal dose for consistent, solid posterior fusion was 60-120 lg of BMP-2 in 600 mg of carrier for this rabbit model. However, responsiveness to BMP-2 is known to vary widely depending on the animal species, with high responsiveness in rodents and lower responsiveness in higher mammals [21,39]. Much higher doses of BMP-2 in addition to a larger amount of carrier material are thus likely to be essential in achieving solid posterior spinal fusion for nonhuman primates and humans.…”

Section: Discussionmentioning

confidence: 99%

“…The physicochemical characters and efficacy of the hydrogel polymer for local delivery of BMP-2 to elicit ectopic bone formation has been reported elsewhere [21].…”

Section: Rhbmp-2mentioning

confidence: 99%

“…To address these issues, we have introduced recombinant bone morphogenetic protein (BMP)-2 and have developed a delivery system [20,21,24,34] to enhance new bone formation temporospatially and avoid surgery to procure autograft material. The properties of the delivery system as a carrier material can be listed as follows: (1) no risk of disease transfer; (2) controlled biodegradability that can effectively regulate the release of recombinant human BMPs (rhBMPs); and (3) plasticity and ease of handling [21]. The present experimental study attempted a simple and less-invasive spinal fusion of posterior interspinous processes using rhBMP-2 in combination with synthetic carrier materials without bone grafting.…”

Section: Introductionmentioning

confidence: 99%

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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%

“…The physicochemical characters and efficacy of the hydrogel polymer for local delivery of BMP-2 to elicit ectopic bone formation has been reported elsewhere [21].…”

Section: Rhbmp-2mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…The mice were anesthetized by intraperitoneal injection of pentobarbital. As reported previously [14,15], carrier material/OP-1 composites were implanted beneath the fascia of the back muscles on the left side (one composite per animal). The experiment was designed under the assumption that the justifiable difference (effect size) between the atelocollagen group as a control and the other groups was 6 mg in BMC and the standard deviation within each group was 3 from the result of the previous study [24].…”

Section: Methodsmentioning

confidence: 99%

“…For cytokine therapy, an appropriate carrier material is needed that retains BMP and releases it slowly, while serving as a scaffold for new bone formation [28,29]. Several materials have already been evaluated as BMP carriers, including collagen obtained from animal sources [3,11,13,31], synthetic polymers [14,15,19], tricalcium phosphate [17], and other inorganic materials [16]. Atelocollagen is a well-established BMP carrier, and has already been used clinically.…”

Section: Introductionmentioning

confidence: 99%

Synthetic Alginate is a Carrier of OP-1 for Bone Induction

Nanno

Sugiyasu

Daimon

et al. 2009

Clin Orthop Relat Res

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Bone morphogenetic proteins (BMPs) can induce bone formation in vivo when combined with appropriate carriers. Several materials, including animal collagens and synthetic polymers, have been evaluated as carriers for BMPs. We examined alginate, an approved biomaterial for human use, as a carrier for BMP-7. In a mouse model of ectopic bone formation, the following four carriers for recombinant human OP-1 (BMP-7) were tested: alginate crosslinked by divalent cations (DC alginate), alginate crosslinked by covalent bonds (CB alginate), Type I atelocollagen, and poly-D,L-lactic acid-polyethyleneglycol block copolymer (PLA-PEG). Discs of carrier materials (5-mm diameter) containing OP-1 (3-30 lg) were implanted beneath the fascia of the back muscles in six mice per group. These discs were recovered 3 weeks after implantation and subjected to radiographic and histologic studies. Ectopic bone formation occurred in a dosedependent manner after the implantation of DC alginate, atelocollagen, and PLA-PEG, but occurred only at the highest dose implanted with CB alginate. Bone formation with DC alginate/OP-1 composites was equivalent to that with atelocollagen/OP-1 composites. Our data suggest DC alginate, a material free of animal products that is already approved by the FDA and other authorities, is a safe and potent carrier for OP-1. This carrier may also be applicable to various other situations in the orthopaedic field.

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Implantable Materials for Local Drug Delivery in Bone Regeneration

Díaz‐Rodríguez

Landín

2016

Advanced Materials Interfaces

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Optimized use of a biodegradable polymer as a carrier material for the local delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2)

Cited by 82 publications

References 26 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

Synthetic Alginate is a Carrier of OP-1 for Bone Induction

Implantable Materials for Local Drug Delivery in Bone Regeneration

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