Document Detail

Effect of triple growth factor controlled delivery by a brushite-PLGA system on a bone defect.
MedLine Citation:
PMID:  22035848     Owner:  NLM     Status:  Publisher    
Bone regeneration is a complex process that involves multiple cell types, growth factors (GFs) and cytokines. A synergistic contribution of various GFs and a crosstalk between their signalling pathways was suggested as determinative for the overall osteogenic outcome. The purpose of this work was to develop a brushite-PLGA system, which controls the release rate of the integrated growth factors (GFs) to enhance bone formation. The brushite cement implants were prepared by mixing a phosphate solid phase with an acid liquid phase. PDGF (250ng) and TGF-β1 (100ng) were incorporated into the liquid phase. PLGA microsphere-encapsulated VEGF (350ng) was pre-blended with the solid phase. VEGF, PDGF and TGF-β1 release kinetics and tissue distributions were determined using iodinated ((125)I) GFs. In vivo results showed that PDGF and TGF-β1 were delivered more rapidly from these systems implanted in an intramedullary defect in rabbit femurs than VEGF. The three GFs released from the brushite-PLGA system remained located around the implantation site (5cm) with negligible systemic exposure. Bone peak concentrations of approximately 4ng/g and 1.5ng/g of PDGF and TGF-β1, respectively were achieved on day 3. Thereafter, PDGF and TGF-β1 concentrations stayed above 1ng/g during the first week. The scaffolds also provided a VEGF peak concentration of nearly 6ng/g on day 7 and a local concentration of approximately 1.5ng/g during at least 4 weeks. Four weeks post implantation bone formation was considerably enhanced with the brushite-PLGA system loaded with each of the three GFs separately as well as with the combination of PDGF and VEGF. The addition of TGF-β1 did not further improve the outcome. In conclusion, the herein presented brushite-PLGA system effectively controlled the release kinetics and localisation of the three GFs within the defect site resulting in markedly enhanced bone regeneration.
Ricardo Reyes; Beatriz De la Riva; Araceli Delgado; Antonio Hernández; Esther Sánchez; Carmen Evora
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-28
Journal Detail:
Title:  Injury     Volume:  -     ISSN:  1879-0267     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0226040     Medline TA:  Injury     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Department of Chemical Engineering and Pharmaceutical Technology, University of La Laguna, 38200 La Laguna, Spain.
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