title: Dual growth factor releasing multi-functional nanofibers for wound healing.
abstract: The objective of this research is to develop a dual growth factor-releasing nanoparticle-in-nanofiber system for wound healing applications. In order to mimic and promote the natural healing procedure, chitosan and poly(ethylene oxide) were electrospun into nanofibrous meshes as mimics of extracellular matrix. Vascular endothelial growth factor (VEGF) was loaded within nanofibers to promote angiogenesis in the short term. In addition, platelet-derived growth factor-BB (PDGF-BB) encapsulated poly(lactic-co-glycolic acid) nanoparticles were embedded inside nanofibers to generate a sustained release of PDGF-BB for accelerated tissue regeneration and remodeling. In vitro studies revealed that our nanofibrous composites delivered VEGF quickly and PDGF-BB in a relayed manner, supported fibroblast growth and exhibited anti-bacterial activities. A preliminary in vivo study performed on normal full thickness rat skin wound models demonstrated that nanofiber/nanoparticle scaffolds significantly accelerated the wound healing process by promoting angiogenesis, increasing re-epithelialization and controlling granulation tissue formation. For later stages of healing, evidence also showed quicker collagen deposition and earlier remodeling of the injured site to achieve a faster full regeneration of skin compared to the commercial Hydrofera Blue® wound dressing. These results suggest that our nanoparticle-in-nanofiber system could provide a promising treatment for normal and chronic wound healing.
authors.affiliation: Department of Bioengineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA; Department of Bioengineering, The University of Texas at Arlington, Arlington, TX 76019, USA.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Xie
authors.forename: Christian B
authors.initials: CB
authors.lastname: Paras
authors.forename: Hong
authors.initials: H
authors.lastname: Weng
authors.forename: Primana
authors.initials: P
authors.lastname: Punnakitikashem
authors.forename: Lee-Chun
authors.initials: LC
authors.lastname: Su
authors.forename: Khanh
authors.initials: K
authors.lastname: Vu
authors.forename: Liping
authors.initials: L
authors.lastname: Tang
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Kytai T
authors.initials: KT
authors.lastname: Nguyen
mesh_terms: D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D003094:Collagen / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013211:Staphylococcus aureus / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; D000077214:Becaplermin; D011092:Polyethylene Glycols; D003094:Collagen; D048271:Chitosan
keywords: Dual-release; Growth factors; Nanofibers; Nanoparticles; Wound healing
references.citation: Burns. 2009 Mar;35(2):171-80
references.pmid: 18603379
references.citation: ACS Nano. 2009 Nov 24;3(11):3719-29
references.pmid: 19824655
references.citation: Biomaterials. 2012 Oct;33(28):6783-92
references.pmid: 22784602
references.citation: J Pharm Sci. 2010 Dec;99(12):4805-11
references.pmid: 20821381
references.citation: J Pharm Sci. 2008 Aug;97(8):2892-923
references.pmid: 17963217
references.citation: J Biomed Mater Res A. 2012 Aug;100(8):1998-2005
references.pmid: 22566409
references.citation: J Pathol. 2011 Apr;223(5):659-71
references.pmid: 21341267
references.citation: Biomacromolecules. 2003 Nov-Dec;4(6):1457-65
references.pmid: 14606868
references.citation: Acta Biomater. 2009 Oct;5(8):2872-83
references.pmid: 19416766
references.citation: Lancet. 1992 Jan 4;339(8784):23-5
references.pmid: 1345953
references.citation: Biomacromolecules. 2012 Apr 9;13(4):952-62
references.pmid: 22401557
references.citation: Biomaterials. 2008 Feb;29(5):587-96
references.pmid: 17997153
references.citation: Int J Pharm. 2012 Dec 15;439(1-2):296-306
references.pmid: 22989981
references.citation: Wound Repair Regen. 2003 Mar;11 Suppl 1:S1-28
references.pmid: 12654015
references.citation: N Engl J Med. 1999 Sep 2;341(10):738-46
references.pmid: 10471461
references.citation: Adv Mater. 2009 Sep 4;21(32-33):3307-29
references.pmid: 20882499
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10207-10212
references.pmid: 16801543
references.citation: J Biol Chem. 1995 May 26;270(21):12607-13
references.pmid: 7759509
references.citation: Am J Pathol. 2010 Jan;176(1):122-33
references.pmid: 19959815
references.citation: Biomaterials. 2011 Jun;32(18):4243-54
references.pmid: 21402405
references.citation: Eur Surg Res. 2011;47(2):81-9
references.pmid: 21720165
references.citation: Lab Invest. 2008 Jun;88(6):579-90
references.pmid: 18427552
references.citation: J Surg Res. 1994 Jun;56(6):562-70
references.pmid: 8015312
references.citation: Int J Mol Med. 2011 May;27(5):647-53
references.pmid: 21373751
references.citation: Biomaterials. 2003 Sep;24(20):3437-44
references.pmid: 12809772
references.citation: Int J Pharm. 2010 Jun 15;392(1-2):232-40
references.pmid: 20230884
references.citation: Wound Repair Regen. 2008 Sep-Oct;16(5):585-601
references.pmid: 19128254
references.citation: Biomaterials. 2012 Oct;33(28):6709-20
references.pmid: 22770570
references.citation: Angew Chem Int Ed Engl. 2007;46(30):5670-703
references.pmid: 17585397
references.citation: J Biomed Mater Res A. 2010 Aug;94(2):499-508
references.pmid: 20186775
references.citation: J Biomed Mater Res B Appl Biomater. 2004 Aug 15;70(2):286-96
references.pmid: 15264311
references.citation: Biomed Mater. 2011 Feb;6(1):015001
references.pmid: 21205999
references.citation: Microsc Res Tech. 2003 Jan 1;60(1):107-14
references.pmid: 12500267
references.citation: Am J Pathol. 1992 Jun;140(6):1375-88
references.pmid: 1376557
references.citation: Science. 1997 Apr 4;276(5309):75-81
references.pmid: 9082989
references.citation: Trends Biotechnol. 2012 Dec;30(12):638-48
references.pmid: 22981509
references.citation: Chem Rev. 2001 Jul;101(7):1869-79
references.pmid: 11710233
references.citation: Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010 Sep-Oct;2(5):510-25
references.pmid: 20607703
references.citation: Mol Pharm. 2012 Jan 1;9(1):48-58
references.pmid: 22091745
references.citation: Biomaterials. 2013 Jan;34(2):340-52
references.pmid: 23088838
references.citation: Biomaterials. 2006 Mar;27(8):1452-61
references.pmid: 16143390
references.citation: J Biomed Mater Res A. 2010 Jun 15;93(4):1539-50
references.pmid: 20014288
references.citation: Annu Rev Med. 1995;46:467-81
references.pmid: 7598479
references.citation: Am J Pathol. 1990 Jun;136(6):1235-46
references.pmid: 2356856