The role of recombinant human bone morphogenetic protein-2 in PLGA capsules at an extraskeletal site of the rat

Isobe, Masatsugu; Yamazaki, Yasuharu; Mori, Masahiro; Ishihara, Kazuhíko; Nakabayashi, Nobuo; Amagasa, Teruo

doi:10.1002/(sici)1097-4636(199904)45:1<36::aid-jbm5>3.0.co;2-i

Cited by 37 publications

(13 citation statements)

References 24 publications

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“…The profile shows a burst of protein (= 50%) on the first day with a total of 70% to 80% of the loaded protein released from the microspheres or devices in 5 to 7 days. This corresponds to the early release profiles reported for similar systems [24,26,28]. Duggirala et al had reported that unbound rhBMP-2 releases first, in 5 to 7 days, followed by slow release of bound protein starting at around 4 weeks.…”

Section: In Vitrosupporting

confidence: 84%

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Effect of a freeze-dried CMC/PLGA microsphere matrix of rhBMP-2 on bone healing

et al. 2001

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The hypothesis of this research was that implants of poly(lactide-co-glycolide) (PLGA) microspheres loaded with bone morphogenetic protein-2 (rhBMP-2) and distributed in a freeze-dried carboxymethylcellulose (CMC) m atrix would produce more new bone than would matrix implants of non-protein-loaded microspheres or matrix implants of only CMC. To test this hypothesis it was necessary to fashion microsphereloaded CMC implants that were simple to insert, fit precisely into a defect, and would not elicit swelling. Microspheres were produced via a water-in-oil-in-water double-emulsion system and were loaded with rhBMP-2 by soaking them in a buffered solution of the protein at a concentration of 5.4 mg protein per gram of PLGA. Following recovery of the loaded microspheres by lyophilization, matrices for implantation were prepared by lyophilizing a suspension of the microspheres in 2% CMC in flat-bottom tissue culture plates. Similar matrices were made with 2% CMC and with 2% CMC containing blank microspheres. A full-thickness calvarial defect model in New Zealand white rabbits was used to assess bone growth. Implants fit the defect well, allowing for direct application. Six weeks postsurgery, defects were collected and processed for undecalcified histology. In vitro, 60% of the loaded rhBMP-2 released from devices or microspheres in 5 to 7 days, with the unembedded microspheres releasing faster than those embedded in CMC. In vivo, the rhBMP-2 microspheres greatly enhanced bone healing, whereas nonloaded PLGA microspheres in the CMC implants had little effect. The results showed that a lyophilized device of rhBMP-2/PLGA microspheres in CMC was an effective implantable protein-delivery system for use in bone repair.

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Section: In Vitrosupporting

confidence: 84%

“…The need to deliver rhBMP-2 to its target cells in optimal timing and dose has been stated repeatedly [28][29][30]. Not yet available is the knowledge of what is the optimal dose and timing.…”

Section: Discussionmentioning

confidence: 99%

Effect of a freeze-dried CMC/PLGA microsphere matrix of rhBMP-2 on bone healing

et al. 2001

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“…It has been reported previously that the polylactic acid/polyglycolic acid (PLGA) gelatin sponge (PGS) copolymer is an effective carrier for BMPs 28,29 . So PGS has been successfully used for bone repair with rhBMP-2 in bone defect models of periodontal tissues, mandible and ulna in experimental animals 30,31,32. .…”

Section: Discussionmentioning

confidence: 99%

Expression of bone morphogenetic protein 2 and fibroblast growth factor 2 during bone regeneration using different implant materials as an onlay bone graft in rabbit mandibles

Alam

Ueki

Marukawa

et al. 2007

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, an

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1 AbstractPurpose: The purpose of this study was to histologically and immunohistochemically evaluate bone regeneration using three different implant materials in rabbit mandibles and also to compare the bone regenerative capability of these materials in an animal model. Study design:Adult male Japanese white rabbits (n=48, 12-16 weeks, 2.5-3.0 kg) were divided into four groups, consisting of twelve animals each. The implant materials were β-tricalcium phosphate (β-TCP), autologous bone derived from the radius, and recombinant human bone morphogenetic protein-2 (rhBMP-2) with polylactic acid/polyglycolic acid copolymer and gelatin sponge (PGS) complex. After incising along the inferior border of mandible, the materials were implanted as onlay grafts and covered by titanium mesh with screws. No material was implanted into the control group.The rabbits were sacrificed at 2, 4, 8, 12 and 24 weeks postoperatively, and formalin-fixed specimens containing titanium mesh were embedded in acrylic resin. The specimens were stained with hematoxylin and eosin. For immunohistochemical analysis, the specimens were treated with BMP-2 (bone morphogenetic protein-2) and FGF-2 (fibroblast growth factor-2) antibodies. Finally, these were evaluated microscopically.2

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“…At the moment, two polymers are commercially available as a bone substitution material, first a PLA granulate (TruGraft™, Osteobiologics, San Antonio, U.S.A.) and second NovoSorb (PolyNovo Biomaterials, Port Melbourne, Australia). The poly(-hydroxy acid) polymers such as PLA, polygylcolide (PLG) and their copolymers PLGA are the most commonly used synthetic polymers to deliver BMPs (Isobe et al 1999). Additional polymers used as BMP delivery systems include polyanhydrides, polypropylene fumurate, polyethylene glycol-PLA as well as polyphosphate (Lucas et al 1990;Miyamoto et al 1992;Renier and Kohn 1997;Behravesh et al 1999).…”

Section: Polymersmentioning

confidence: 99%