Biodegradable Poly-D,L-Lactic Acid-Polyethylene Glycol Block Copolymers as a BMP Delivery System for Inducing Bone

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

doi:10.2106/00004623-200100002-00003

Cited by 50 publications

(42 citation statements)

References 26 publications

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“…We synthesized PLA-PEG block copolymers of various molecular sizes with various PLA/PEG ratios (Fig. 1A) [53,54]. Results were assessed in vivo by mixing each polymer with rhBMP-2 and implanting the mixture into the back muscles of mice for 3 weeks to determine its capacity to induce ectopic bone formation.…”

Section: Synthetic Polymers For Bmp Delivery Systemmentioning

confidence: 99%

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Synthetic biodegradable polymers as drug delivery systems for bone morphogenetic proteins

Saito

Murakami

Takahashi

et al. 2005

Advanced Drug Delivery Reviews

111

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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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Section: Synthetic Polymers For Bmp Delivery Systemmentioning

confidence: 99%

“…To test this property, a combination of the rhBMP-2/PLA-DX-PEG composite with porous hydroxyapatite (HA) was used [54]. The rhBMP-2/PLA-DX-PEG composite was placed in the pores of an HA block, which then was inserted into the back muscle of mice.…”

Section: Combination Of the Rhbmp-2/polymer Composites With Other Matmentioning

confidence: 99%

Synthetic biodegradable polymers as drug delivery systems for bone morphogenetic proteins

Saito

Murakami

Takahashi

et al. 2005

Advanced Drug Delivery Reviews

111

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“…A previous study [24] reported that BMC of the ectopic bone induced by PLA-PEG/BMP-2 composite is about 6 mg higher than that by atelocollagen/BMP-2 composite. In our study, the BMC of DC alginate/OP-1 (3 lg) composite was about 6 mg higher than that of the atelocollagen/OP-1 (3 lg) composite and even much higher than that of CB alginate and PLA-PEG.…”

Section: Discussionmentioning

confidence: 90%

“…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]. For the experiment to detect the difference at the 5% significance level with 90% power in the one-way analysis of variance, the necessary number of mice per group was six.…”

Section: Methodsmentioning

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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“…12 Therefore, an effective carrier must be used to achieve a localized effect at the desired bone healing site. BMP carriers can be classified as naturally occurring polymers, 13,14 synthetic polymers, 15 composites of synthetic and naturally occurring polymers, 8 and inorganic salts. 16 Bovine bonederived type I collagen is used as a carrier to bind rhBMP-7 in the clinical setting.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of recombinant human BMP‐7 bone formation with bmp binding peptide in a rodent femoral defect model

Liao

Tzeng

Keorochana

et al. 2010

Journal Orthopaedic Research

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Bone morphogenetic binding peptide (BBP) is an 18.5 kDa fragment of a bone matrix protein peptide. A rat femoral defect model was used to test the effect of BBP combined with recombinant human bone morphogenetic protein-7 (rhBMP-7) to induced bone healing. Two doses of BBP (500 and 1000 mg) were tested with two doses of rhBMP-7 (2 and 5 mg), and the results were compared with a positive control (10 mg rhBMP-7). Bone healing was evaluated by radiology, manual palpation, microcomputed tomography, and histology. The high dose of 10 mg of rhBMP-7 resulted in a consistent 100% bone union rate and a mature histological appearance on histology, and was used as a positive control. When 1000 mg of BBP was combined with lower doses of BMP-7 (2 mg rhBMP-7 or 5 mg rhBMP-7) significant differences were seen in radiographic scores, manual palpation, and bone volume, when compared to 2 mg rhBMP-7 or 5 mg rhBMP-7 alone. The combination of 1000 mg of BBP and 5 mg rhBMP-7 also achieved 100% fusion rate, induced a larger amount of bone formation, and yielded similar maturity of bone marrow when compared with the high dosage 10 mg rhBMP-7 group. This study demonstrated that when combined together, BBP can enhance the bone healing of rhBMP-7. Improved healing imparted by the addition of BBP may result in lesser amounts of rhBMP-7 needed to achieve union in the clinical setting. ß

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Biodegradable Poly-D,L-Lactic Acid-Polyethylene Glycol Block Copolymers as a BMP Delivery System for Inducing Bone

Cited by 50 publications

References 26 publications

Synthetic biodegradable polymers as drug delivery systems for bone morphogenetic proteins

Synthetic biodegradable polymers as drug delivery systems for bone morphogenetic proteins

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

Enhancement of recombinant human BMP‐7 bone formation with bmp binding peptide in a rodent femoral defect model

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