title: Nanofibrous scaffolds incorporating PDGF-BB microspheres induce chemokine expression and tissue neogenesis in vivo.
abstract: 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.
authors.affiliation: Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Jin
authors.forename: Guobao
authors.initials: G
authors.lastname: Wei
authors.forename: Zhao
authors.initials: Z
authors.lastname: Lin
authors.forename: James V
authors.initials: JV
authors.lastname: Sugai
authors.forename: Samuel E
authors.initials: SE
authors.lastname: Lynch
authors.forename: Peter X
authors.initials: PX
authors.lastname: Ma
authors.forename: William V
authors.initials: WV
authors.lastname: Giannobile
mesh_terms: D000818:Animals; D000077214:Becaplermin; D001808:Blood Vessels / Q000502:physiology*; D002465:Cell Movement; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism*; D054426:Chemokine CXCL2 / Q000235:genetics / Q000378:metabolism*; D054365:Chemokine CXCL5 / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D020007:Implants, Experimental; D019344:Lactic Acid / Q000737:chemistry; D008863:Microspheres; D049329:Nanostructures; D018919:Neovascularization, Physiologic; D020411:Oligonucleotide Array Sequence Analysis; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage* / Q000494:pharmacology; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D023822:Tissue Engineering; D014945:Wound Healing
chemical_list: D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D054365:Chemokine CXCL5; C513297:Cxcl1 protein, rat; C513296:Cxcl2 protein, rat; D010982:Platelet-Derived Growth Factor; D011091:Polyesters; D011108:Polymers; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)