title: Sustained PDGF-BB release from PHBHHx loaded nanoparticles in 3D hydrogel/stem cell model.
abstract: This study aimed to design a growth factor loaded copolyester of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx) nanoparticles containing 3D collagen matrix to achieve growth factor sustained release for long-term stimulation of human mesenchymal stem cells (hMSCs) proliferation/differentiation for tissue engineer application. Platelet-derived growth factor-BB (PDGF-BB), which is known to enhance hMSCs proliferation in human serum, was selected as a model growth factor, and biodegradable copolyester of PHBHHx was chosen to be the sustained release vehicle. PDGF-BB phospholipid complex encapsulated PHBHHx nanoparticles were fabricated, and their effect on hMSCs proliferation was investigated via assays of CCK-8 and live-dead staining to cells inoculated in 2D tissue culture plates and 3D collagen gel scaffolds, respectively. The resulting spherical PHBHHx nanoparticles were stable in terms of their mean particle size, polydispersity index and zeta potential before and after lyophilization. In vitro study revealed a sustained release of PDGF-BB with a low burst release. Furthermore, sustained released PDGF-BB was revealed to significantly promote hMSCs proliferation in both cell monolayer and cell seeded 3D collagen scaffolds inoculated in serum-free media. Therefore, the 3D collagen matrices with locally sustained release growth factor nanoparticles hold promise to be used for stem cell tissue engineering.
authors.affiliation: Guy Hilton Research Centre, Institute of Science and Technology in Medicine, Keele University, Stoke-on-Trent, ST4 7QB, United Kingdom.
authors.forename: Cui-Ling
authors.initials: CL
authors.lastname: Dong
authors.forename: William R
authors.initials: WR
authors.lastname: Webb
authors.forename: Qiang
authors.initials: Q
authors.lastname: Peng
authors.forename: James Z
authors.initials: JZ
authors.lastname: Tang
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Forsyth
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Chen
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: El Haj
mesh_terms: D000077214:Becaplermin; D002478:Cells, Cultured; D005612:Freeze Drying; D006801:Humans; D020100:Hydrogels; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D053758:Nanoparticles; D000091402:Prohibitins; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism* / Q000493:pharmacokinetics
chemical_list: D020100:Hydrogels; C000717328:PHB protein, human; D000091402:Prohibitins; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin
keywords: PHB; mesenchymal stem cell; nanoparticles; platelet-derived growth factor; polyhydroxyalkanoates; tissue engineering