PMID- 18320048
OWN - NLM
STAT- MEDLINE
DCOM- 20080626
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 3
IP  - 3
DP  - 2008 Mar 5
TI  - Nanofibrous scaffolds incorporating PDGF-BB microspheres induce chemokine 
      expression and tissue neogenesis in vivo.
PG  - e1729
LID - 10.1371/journal.pone.0001729 [doi]
LID - e1729
AB  - Platelet-derived growth factor (PDGF) exerts multiple cellular effects that 
      stimulate wound repair in multiple tissues. However, a major obstacle for its 
      successful clinical application is the delivery system, which ultimately controls 
      the in vivo release rate of PDGF. Polylactic-co-glycolic acid (PLGA) microspheres 
      (MS) in nanofibrous scaffolds (NFS) have been shown to control the release of 
      rhPDGF-BB in vitro. In order to investigate the effects of rhPDGF-BB release from 
      MS in NFS on gene expression and enhancement of soft tissue engineering, 
      rhPDGF-BB was incorporated into differing molecular weight (MW) polymeric MS. By 
      controlling the MW of the MS over a range of 6.5 KDa-64 KDa, release rates of 
      PDGF can be regulated over periods of weeks to months in vitro. The NFS-MS 
      scaffolds were divided into multiple groups based on MS release characteristics 
      and PDGF concentration ranging from 2.5-25.0 microg and evaluated in vivo in a 
      soft tissue wound repair model in the dorsa of rats. At 3, 7, 14 and 21 days 
      post-implantation, the scaffold implants were harvested followed by assessments 
      of cell penetration, vasculogenesis and tissue neogenesis. Gene expression 
      profiles using cDNA microarrays were performed on the PDGF-releasing NFS. The 
      percentage of tissue invasion into MS-containing NFS at 7 days was higher in the 
      PDGF groups when compared to controls. Blood vessel number in the HMW groups 
      containing either 2.5 or 25 microg PDGF was increased above those of other groups 
      at 7d (p<0.01). Results from cDNA array showed that PDGF strongly enhanced in 
      vivo gene expression of the CXC chemokine family members such as CXCL1, CXCL2 and 
      CXCL5. Thus, sustained release of rhPDGF-BB, controlled by slow-releasing MS 
      associated with the NFS delivery system, enhanced cell migration and angiogenesis 
      in vivo, and may be related to an induced expression of chemokine-related genes. 
      This approach offers a technology to accurately control growth factor release to 
      promote soft tissue engineering in vivo.
FAU - Jin, Qiming
AU  - Jin Q
AD  - Department of Periodontics and Oral Medicine, School of Dentistry, University of 
      Michigan, Ann Arbor, Michigan, USA.
FAU - Wei, Guobao
AU  - Wei G
FAU - Lin, Zhao
AU  - Lin Z
FAU - Sugai, James V
AU  - Sugai JV
FAU - Lynch, Samuel E
AU  - Lynch SE
FAU - Ma, Peter X
AU  - Ma PX
FAU - Giannobile, William V
AU  - Giannobile WV
LA  - eng
GR  - DE13397/DE/NIDCR NIH HHS/United States
GR  - R01 DE013397/DE/NIDCR NIH HHS/United States
GR  - DE15384/DE/NIDCR NIH HHS/United States
GR  - R01 DE015384/DE/NIDCR NIH HHS/United States
GR  - DE14755/DE/NIDCR NIH HHS/United States
GR  - R21 DE014755/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080305
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Chemokine CXCL1)
RN  - 0 (Chemokine CXCL2)
RN  - 0 (Chemokine CXCL5)
RN  - 0 (Cxcl1 protein, rat)
RN  - 0 (Cxcl2 protein, rat)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Polyesters)
RN  - 0 (Polymers)
RN  - 0 (Proto-Oncogene Proteins c-sis)
RN  - 0 (Recombinant Proteins)
RN  - 1B56C968OA (Becaplermin)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 459TN2L5F5 (poly(lactide))
SB  - IM
MH  - Animals
MH  - Becaplermin
MH  - Blood Vessels/*physiology
MH  - Cell Movement
MH  - Chemokine CXCL1/genetics/*metabolism
MH  - Chemokine CXCL2/genetics/*metabolism
MH  - Chemokine CXCL5/genetics/*metabolism
MH  - Gene Expression Profiling
MH  - Implants, Experimental
MH  - Lactic Acid/chemistry
MH  - Microspheres
MH  - *Nanostructures
MH  - Neovascularization, Physiologic
MH  - Oligonucleotide Array Sequence Analysis
MH  - Platelet-Derived Growth Factor/*administration & dosage/pharmacology
MH  - Polyesters
MH  - Polyglycolic Acid/chemistry
MH  - Polymers/chemistry
MH  - Proto-Oncogene Proteins c-sis
MH  - Rats
MH  - Recombinant Proteins/administration & dosage/pharmacology
MH  - Tissue Engineering
MH  - Wound Healing
PMC - PMC2248711
COIS- Competing Interests: WVG is a member of the Scientific Advisory Board of 
      BioMimetic Therapeutics, Inc. SEL is President and CEO of BioMimetic Therapeutics 
      and has significant financial interest.
EDAT- 2008/03/06 09:00
MHDA- 2008/06/27 09:00
PMCR- 2008/03/05
CRDT- 2008/03/06 09:00
PHST- 2007/12/04 00:00 [received]
PHST- 2008/01/24 00:00 [accepted]
PHST- 2008/03/06 09:00 [pubmed]
PHST- 2008/06/27 09:00 [medline]
PHST- 2008/03/06 09:00 [entrez]
PHST- 2008/03/05 00:00 [pmc-release]
AID - 07-PONE-RA-02930R1 [pii]
AID - 10.1371/journal.pone.0001729 [doi]
PST - epublish
SO  - PLoS One. 2008 Mar 5;3(3):e1729. doi: 10.1371/journal.pone.0001729.