PMID- 12925613
OWN - NLM
STAT- MEDLINE
DCOM- 20031006
LR  - 20220331
IS  - 0021-9355 (Print)
IS  - 0021-9355 (Linking)
VI  - 85-A Suppl 3
DP  - 2003
TI  - rhBMP-2 release from injectable poly(DL-lactic-co-glycolic 
      acid)/calcium-phosphate cement composites.
PG  - 75-81
AB  - BACKGROUND: In bone tissue engineering, poly(DL-lactic-co-glycolic acid) (PLGA) 
      microparticles are frequently used as a delivery vehicle for bioactive molecules. 
      Calcium phosphate cement is an injectable, osteoconductive, and degradable bone 
      cement that sets in situ. The objective of this study was to create an injectable 
      composite based on calcium phosphate cement embedded with PLGA microparticles for 
      sustained delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2). 
      METHODS: (125) I-labeled rhBMP-2 was incorporated in PLGA microparticles. PLGA 
      microparticle/calcium-phosphate cement composites were prepared in a ratio of 
      30:70 by weight. Material properties were evaluated by scanning electron 
      microscopy, microcomputed tomography, and mechanical testing. Release kinetics of 
      rhBMP-2 from PLGA/calcium-phosphate cement disks and PLGA microparticles alone 
      were determined in vitro in two buffer solutions (pH 7.4 and pH 4.0) for up to 
      twenty-eight days. RESULTS: The entrapment yield of rhBMP-2 in PLGA 
      microparticles was a mean (and standard deviation) of 79% +/- 8%. Analysis showed 
      spherical PLGA microparticles (average size, 17.2 +/-1.3 micro m) distributed 
      homogeneously throughout the nanoporous disks. The average compressive strength 
      was significantly lower (p < 0.001) for PLGA and calcium-phosphate cement 
      composite scaffolds than for calcium-phosphate cement scaffolds alone (6.4 +/- 
      0.6 MPa compared with 38.6 +/- 2.6 MPa, respectively). Average rhBMP-2 loading 
      was 5.0 +/- 0.4 micro g per 75-mm (3) disk. Release of rhBMP-2 was limited for 
      all formulations. At pH 7.4, 3.1% +/- 0.1% of the rhBMP-2 was released from the 
      PLGA/calcium-phosphate cement disks and 18.0% +/- 1.9% was released from the PLGA 
      microparticles alone after twenty-eight days. At pH 4.0, PLGA/calcium-phosphate 
      cement disks revealed more release of rhBMP-2 than did PLGA microparticles alone 
      (14.5% +/- 6.3% compared with 5.4% +/- 0.7%) by day 28. CONCLUSIONS: These 
      results indicate that preparation of a PLGA/calcium-phosphate cement composite 
      for the delivery of rhBMP-2 is feasible and that the release of rhBMP-2 is 
      dependent on the composite composition and nanostructure as well as the pH of the 
      release medium.
FAU - Ruhe, P Quinten
AU  - Ruhe PQ
FAU - Hedberg, Elizabeth L
AU  - Hedberg EL
FAU - Padron, Nestor Torio
AU  - Padron NT
FAU - Spauwen, Paul H M
AU  - Spauwen PH
FAU - Jansen, John A
AU  - Jansen JA
FAU - Mikos, Antonios G
AU  - Mikos AG
LA  - eng
GR  - R01-AR42639/AR/NIAMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Bone Joint Surg Am
JT  - The Journal of bone and joint surgery. American volume
JID - 0014030
RN  - 0 (BMP2 protein, human)
RN  - 0 (Bone Cements)
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Bone Morphogenetic Proteins)
RN  - 0 (Calcium Phosphates)
RN  - 0 (Drug Carriers)
RN  - 0 (Glycolates)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (recombinant human bone morphogenetic protein-2)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
SB  - IM
MH  - *Bone Cements
MH  - Bone Morphogenetic Protein 2
MH  - Bone Morphogenetic Proteins/administration & dosage/*pharmacokinetics
MH  - Calcium Phosphates/*administration & dosage
MH  - Drug Carriers
MH  - *Glycolates
MH  - Humans
MH  - Injections
MH  - Lactic Acid
MH  - Microscopy, Electron, Scanning
MH  - Particle Size
MH  - Polyglycolic Acid
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Recombinant Proteins/administration & dosage/*pharmacokinetics
MH  - *Transforming Growth Factor beta
OTO - NASA
OT  - Non-programmatic
EDAT- 2003/08/20 05:00
MHDA- 2003/10/08 05:00
CRDT- 2003/08/20 05:00
PHST- 2003/08/20 05:00 [pubmed]
PHST- 2003/10/08 05:00 [medline]
PHST- 2003/08/20 05:00 [entrez]
AID - 10.2106/00004623-200300003-00013 [doi]
PST - ppublish
SO  - J Bone Joint Surg Am. 2003;85-A Suppl 3:75-81. doi: 
      10.2106/00004623-200300003-00013.