Two Lyophilized Polymer Matrix Recombinant Human Bone Morphogenetic Protein-2 Carriers in Rabbit Calvarial Defects

Rodgers, Janet B.; Vásconez, Henry C.; Wells, Mark D.; DeLuca, Patrick P.; Faugere, Marie-claude; Fink, Betsy F.; Hamilton, David A.

doi:10.1097/00001665-199803000-00012

Cited by 27 publications

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“…The new materials emerged in dental research; Bone Morphogenetic Proteins, Growth factors etc. [22][23][24][25] Maybe the promising drugs will be possible to raise the success rate of endodontic treatment, so we should to concentrate our efforts in developing new intracanal medications.…”

Section: )mentioning

confidence: 99%

Tissue reactions to implanted intracanal medicaments in rats

Kim

2004

J Korean Acad Conserv Dent

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Section: )mentioning

confidence: 99%

Tissue reactions to implanted intracanal medicaments in rats

Kim

2004

J Korean Acad Conserv Dent

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“…The left defect was an untreated control, whereas the right defect had 1 of 3 types of implants: (1) CMC, (2) CMC with PLGA microspheres, or (3) CMC with rhBMP-2 loaded microspheres (90 µg rhBMP-2). Previous work [ 26] had shown that a subjective evaluation (with n = 4 evaluations) performed in a larger diameter defect model at 2, 4, and 8 weeks postoperatively could be effectively used for trend analysis and that peak bone healing may occur between 4 and 8 weeks. A 6 -week healing period was thus selected and the number of subjects in each group increased (to n = 10) to increase the probability of seeing significant differences in a subjective evaluation.…”

Section: In Vivo Evaluationmentioning

confidence: 99%

“…PLGA microsphere delivery systems for rhBMP-2 have been previously reported [16,[24][25][26]. In a study of various carriers for rhBMP-2 microspheres, Rodgers et al [26] found that methylcellulose elicited more fibrosis than did carboxymethylcellulose (CMC) and that CMC alone (ie, with no added rhBMP-2 microspheres) showed a mild promotion of bone growth.…”

Section: Introductionmentioning

confidence: 99%

“…In a study of various carriers for rhBMP-2 microspheres, Rodgers et al [26] found that methylcellulose elicited more fibrosis than did carboxymethylcellulose (CMC) and that CMC alone (ie, with no added rhBMP-2 microspheres) showed a mild promotion of bone growth. However, distinct swelling around implant sites was observed during the first few days of treatment.…”

Section: Introductionmentioning

confidence: 99%

“…The process included loading PLGA microspheres with rhBMP-2 and suspending the loaded microspheres in a solution of CMC for subsequent lyophilization and cutting the dry wafers to fit the defect. A target dose of 90 µg was chosen because it had been tested previously in a rabbit calvarial model [26]. A bilateral 7.9 mm defect size was used because preliminary work had indicated no apparent effect of protein from the treated defect to the untreated defect.…”

Section: Introductionmentioning

confidence: 99%

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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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Controlled release of transforming growth factor ?1 from biodegradable polymer microparticles

Stamatas

Mikos

2000

J. Biomed. Mater. Res.

159

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Recombinant human transforming growth factor beta1 (TGF-beta1) was incorporated into biodegradable microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) at 6 ng/1 mg microparticles. Fluorescein isothiocynate labeled bovine serum albumin (FITC-BSA) was coencapsulated as a porogen at 4 microg/1 mg of microparticles. The effects of PEG content (0, 1, or 5 wt %) and buffer pH (3, 5, or 7.4) on the protein release kinetics and the degradation of PLGA were determined in vitro for up to 28 days. The entrapment yield of TGF-beta1 was 83.4 +/- 13.1 and 54.2 +/- 12.1% for PEG contents of 0 and 5%, respectively. The FITC-BSA and TGF-beta1 were both released in a multiphasic fashion including an initial burst effect. Increasing the PEG content resulted in the decreased cumulative mass of released proteins. By day 28, 3.8 +/- 0. 1 and 2.8 +/- 0.3 microg (based on 1 mg microparticles) of loaded FITC-BSA and 3.4 +/- 0.2 and 2.2 +/- 0.3 ng of loaded TGF-beta1 were released into pH 7.4 phosphate buffered saline (PBS) from microparticles with 0 and 5% PEG, respectively. Aggregation of FITC-BSA occurred at lower buffer pH, which led to decreased release rates of both proteins. For microparticles with 5% PEG, 2.3 +/- 0.1 microg of FITC-BSA and 2.0 +/- 0.2 ng of TGF-beta1 were released in pH 7.4 buffer after 28 days, while only 1.7 +/- 0.3 microg and 1.3 +/- 0.4 ng of the corresponding proteins were released in pH 3 buffer. The degradation of PLGA was also enhanced at 5% PEG content, which was significantly accelerated at acidic pH conditions. The calculated half-lives of PLGA were 20.3 +/- 0.9 and 15.9 +/- 1.2 days for PEG contents of 0 and 5%, respectively, in pH 7.4 PBS and 14.8 +/- 0.4 and 5.5 +/- 0.1 days for 5% PEG in pH 7.4 and 3 buffers, respectively. These results suggest that PLGA/PEG blend microparticles are useful as delivery vehicles for controlled release of growth factors.

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Two Lyophilized Polymer Matrix Recombinant Human Bone Morphogenetic Protein-2 Carriers in Rabbit Calvarial Defects

Cited by 27 publications

References 0 publications

Tissue reactions to implanted intracanal medicaments in rats

Tissue reactions to implanted intracanal medicaments in rats

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

Controlled release of transforming growth factor ?1 from biodegradable polymer microparticles

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