A biodegradable polymer as a cytokine delivery system for inducing bone formation

Saito, Naoto; Okada, Takao; Horiuchi, Hiroshi; Murakami, Narumichi; Takahashi, J.; Nawata, Masashi; Ōta, Hiroshi; Nozaki, Kazutoshi; Takaoka, Kunio

doi:10.1038/86715

Cited by 240 publications

(153 citation statements)

References 25 publications

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“…To overcome these problems, synthetic biodegradable polymers have recently been tested as a delivery vehicle for osteoinductive agents. Earlier studies performed in our laboratory found that the PLA-PEG block copolymer with plastic properties works effectively as a BMP delivery system [33,34]. We then attempted to development a new biodegradable bone-inducing material by adding rhBMP-2 to porous b-TCP granules using a PLA-PEG polymer delivery system.…”

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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“…The importance of these scaffolds is shown by the fact that human tissue development is driven by surface adhesions and cellular contacts. [8][9][10][11][12] Therefore, we decided to perform this research with the aim to obtain a complete bone tissue formation. For this reason we studied the differentiation process leading to in vitro woven bone formation in order to better understand the mechanisms involved as well as bone tissue formation after transplantation in vivo.…”

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confidence: 99%

Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation

d’Aquino¹,

Graziano²,

et al. 2007

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Stromal stem cells from human dental pulp (SBP-DPSCs) were used to study osteogenic differentiation in vitro and in vivo. We previously reported that SBP-DPSCs are multipotent stem cells able to differentiate into osteoblasts, which synthesize threedimensional woven bone tissue chips in vitro. In this study, we followed the temporal expression pattern of specific markers in SBP-DPSCs and found that, when differentiating into osteoblasts, they express, besides osteocalcin, also flk-1 (VEGF-R2). In addition, 30% of them expressed specific antigens for endothelial cells, including CD54, von-Willebrand (domain 1 and 2), CD31 (PECAM-1) and angiotensin-converting enzyme. Interestingly, we found endotheliocytes forming vessel walls, observing that stem cells synergically differentiate into osteoblasts and endotheliocytes, and that flk-1 exerts a pivotal role in coupling osteoblast and endotheliocyte differentiation. When either SBP-DPSCs or bone chips obtained in vitro were transplanted into immunocompromised rats, they generated a tissue structure with an integral blood supply similar to that of human adult bone; in fact, a large number of HLA-1 þ vessels were observed either within the bone or surrounding it in a periosteal layer. This study provides direct evidence to suggest that osteogenesis and angiogenesis mediated by human SBP-DPSCs may be regulated by distinct mechanisms, leading to the organization of adult bone tissue after stem cell transplantion.

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“…To optimize degradation of the polymer used to deliver rhBMP-2, para-dioxanone molecules were randomly inserted into the PLA segments of the PLA-PEG polymer without changing the total molecular weight [55].…”

Section: Synthetic Polymers For Bmp Delivery Systemmentioning

confidence: 99%

Synthetic biodegradable polymers as drug delivery systems for bone morphogenetic proteins

Saito

Murakami

Takahashi

et al. 2005

Advanced Drug Delivery Reviews

112

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Bone morphogenetic proteins (BMP) induce bone formation in vivo, and clinical application in repair of bone fractures and defects is expected.However, appropriate systems to deliver BMP for clinical use need to be developed. We synthesized a new synthetic biodegradable polymer, poly-D,L-lactic acid-para-dioxanon-polyethylene glycol block copolymer (PLA-DX-PEG), to serve as a biocompatible, biodegradable polymer for recombinant human (rh) BMP-2 delivery systems. In animal experiments new bone was efficiently formed and a large bone defect was repaired using PLA-DX-PEG/rhBMP-2 composites. In addition, this new polymer could be used as an injectable delivery system for rhBMP-2. The rhBMP-2/PLA-DX-PEG composites also could be combined with other materials such as hydroxyapatite or titanium. This new synthetic polymer might be used for rhBMP-2 delivery in various clinical situations involving repair of bone, leading to great changes in orthopedic treatment.2

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A biodegradable polymer as a cytokine delivery system for inducing bone formation

Cited by 240 publications

References 25 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

Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation

Synthetic biodegradable polymers as drug delivery systems for bone morphogenetic proteins

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