Document Detail


Biodegradable gelatin microparticles as delivery systems for the controlled release of bone morphogenetic protein-2.
MedLine Citation:
PMID:  18474452     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This work evaluated gelatin microparticles and biodegradable composite scaffolds for the controlled release of bone morphogenetic protein-2 (BMP-2) in vitro and in vivo. Gelatin crosslinking (10 and 40mM glutaraldehyde), BMP-2 dose (6 and 60ng BMP-2 per mg dry microparticles), buffer type (phosphate buffered saline (PBS) and collagenase-containing PBS), and gelatin type (acidic and basic) were investigated for their effects on BMP-2 release. Release profiles were also observed using poly(lactic-co-glycolic acid) (PLGA) microparticles with varying molecular weights (8300 and 57,500). In vitro and in vivo studies were conducted using radiolabeled BMP-2; the chloramine-T method was preferred over Bolton-Hunter reagent for radioiodination with this system. BMP-2 release from PLGA microparticles resulted in a moderate burst release followed by minimal cumulative release, while BMP-2 release from gelatin microparticles exhibited minimal burst release followed by linear release kinetics in vitro. Growth factor dose had a small effect on its normalized release kinetics probably because of an equilibrium between gelatin-bound and unbound BMP-2. Differences in release from acidic and basic gelatin microparticles may result from the different pretreatment conditions used for gelatin synthesis. The in vitro release kinetics for both gelatin microparticles alone and within composite scaffolds were dependent largely on the extent of gelatin crosslinking; varying buffer type served to confirm that controlled release relies on enzymatic degradation of the gelatin for controlled release. Finally, in vivo studies with composite scaffolds exhibited minimal burst and linear release up to 28 days. In summary, dose effects on BMP-2 release were found to be minimal while varying gelatin type and release medium can alter release kinetics. These results demonstrate that a systematic control of BMP-2 delivery from gelatin microparticles can be achieved by altering the extent of basic gelatin crosslinking.
Authors:
Zarana S Patel; Masaya Yamamoto; Hiroki Ueda; Yasuhiko Tabata; Antonios G Mikos
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-04-22
Journal Detail:
Title:  Acta biomaterialia     Volume:  4     ISSN:  1742-7061     ISO Abbreviation:  Acta Biomater     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-11     Completed Date:  2008-11-18     Revised Date:  2011-07-20    
Medline Journal Info:
Nlm Unique ID:  101233144     Medline TA:  Acta Biomater     Country:  England    
Other Details:
Languages:  eng     Pagination:  1126-38     Citation Subset:  IM    
Affiliation:
Department of Bioengineering, Rice University, P.O. Box 1892, MS-142, Houston, TX 77251-1892, United States.
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MeSH Terms
Descriptor/Qualifier:
Absorbable Implants*
Animals
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins / administration & dosage*,  chemistry*
Delayed-Action Preparations / administration & dosage*,  chemistry*
Female
Gelatin / chemistry*
Materials Testing
Mice
Mice, Inbred Strains
Microspheres
Transforming Growth Factor beta / administration & dosage*,  chemistry*
Grant Support
ID/Acronym/Agency:
R01 DE015164-01A1/DE/NIDCR NIH HHS; R01-DE15164/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Bmp2 protein, mouse; 0/Bone Morphogenetic Protein 2; 0/Bone Morphogenetic Proteins; 0/Delayed-Action Preparations; 0/Transforming Growth Factor beta; 9000-70-8/Gelatin
Comments/Corrections

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