title: Synergistic interaction of platelet derived growth factor (PDGF) with the surface of PLLA/Col/HA and PLLA/HA scaffolds produces rapid osteogenic differentiation.
abstract: Scaffolds with structural features similar to the extracellular matrix stimulate rapid osteogenic differentiation in favorable microenvironment and with growth factor supplementation. In this study, the osteogenic potential of electrospun poly-l-lactide/hydroxyapatite/collagen (PLLA/Col/HA, PLLA/HA and PLLA/Col) scaffolds were tested in vitro with the supplementation of platelet derived growth factor-BB (PDGF-BB). Cell attachment and topography, mineralization, extracellular matrix protein localization, and gene expression of the human mesenchymal stromal cells were compared between the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA. The levels of osteocalcin, calcium, and mineralization were significantly greater in the PLLA/Col/HA and PLLA/HA compared with PLLA/Col. High expression of fibronectin, intracellular adhesion molecule, cadherin, and collagen 1 (Col1) suggests that PLLA/Col/HA and PLLA/HA scaffolds had superior osteoinductivity than PLLA/Col. Additionally, osteopontin, osteocalcin, osterix, Runt-related transcription factor 2 (Runx2), and bone morphogenic protein (BMP2) expression were higher in PLLA/Col/HA and PLLA/HA compared with PLLA/Col. In comparison with PLLA/Col, the PLLA/Col/HA and PLLA/HA scaffolds presented a significant upregulation of the genes Runx2, Col 1, Integrin, osteonectin (ON), bone gamma-carboxyglutamic acid-containing protein (BGALP), osteopontin (OPN), and BMP2. The upregulation of these genes was further increased with PDGF-BB supplementation. These results show that PDGF-BB acts synergistically with PLLA/Col/HA and PLLA/HA to enhance the osteogenic differentiation potential. Therefore, this combination can be used for the rapid expansion of bone marrow stromal cells into bone-forming cells for tissue engineering.
authors.affiliation: Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: hbr_bala@yahoo.com.
authors.forename: Hanumantha Rao Balaji
authors.initials: HR
authors.lastname: Raghavendran
authors.affiliation: Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Saktiswaren
authors.initials: S
authors.lastname: Mohan
authors.affiliation: Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK.
authors.forename: Krishnamurithy
authors.initials: K
authors.lastname: Genasan
authors.affiliation: Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Malliga Raman
authors.initials: MR
authors.lastname: Murali
authors.affiliation: Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Sangeetha Vasudevaraj
authors.initials: SV
authors.lastname: Naveen
authors.affiliation: Department of Mechanical engineering, Engineering Faculty, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Sepehr
authors.initials: S
authors.lastname: Talebian
authors.affiliation: The Electrospinning Company Ltd., Rutherford Appleton Laboratory, Harwell Oxford Didcot, Oxfordshire OX11 0QX, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: McKean
authors.affiliation: Tissue Engineering Group (TEG), National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), Department of Orthopaedic Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Clinical Investigation Centre, Faculty of Medicine, University of Malaya Medical Center, Kuala Lumpur, Malaysia. Electronic address: tkzrea@um.edu.my.
authors.forename: Tunku
authors.initials: T
authors.lastname: Kamarul
mesh_terms: D000077214:Becaplermin; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D017886:Durapatite / Q000737:chemistry / Q000494:pharmacology*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry / Q000494:pharmacology*; D061251:Primary Cell Culture; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D000076182:Sp7 Transcription Factor; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C525718:BMP2 protein, human; D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D005353:Fibronectins; D011091:Polyesters; D020574:Proto-Oncogene Proteins c-sis; C493709:RUNX2 protein, human; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D015675:Osteocalcin; D053495:Osteopontin; D000077214:Becaplermin; C033616:poly(lactide); D017886:Durapatite
keywords: Bone marrow; Electrospinning; Osteoblast; Osteocalcin; Scaffold