title: Chemical group-dependent plasma polymerisation preferentially directs adipose stem cell differentiation towards osteogenic or chondrogenic lineages.
abstract: Human adipose derived stem cells (ADSCs) are being explored for the repair of craniofacial defects due to their multi-differentiation potential and ease of isolation and expansion. Crucial to using ADSCs for craniofacial repair is the availability of materials with appropriate biomechanical properties that can support their differentiation into bone and cartilage. We tested the hypothesis that different modifications of chemical groups on the surface of a nanocomposite polymer could increase human ADSC adhesion and selectively enhance their osteogenic and chondrogenic differentiation. We show that the COOH modification significantly promoted initial cell adhesion and proliferation over 14days compared to NH2surfaces. Expression of focal adhesion kinase and vinculin was enhanced after plasma surface polymerisation at 24h. The COOH modification significantly enhanced chondrogenic differentiation as indicated by up-regulation of aggrecan and collagen II transcripts. In contrast, NH2group functionalised scaffolds promoted osteogenic differentiation with significantly enhanced expression of collagen I, alkaline phosphatase and osteocalcin both at the gene and protein level. Finally, chorioallantoic membrane grafting demonstrated that both NH2and COOH functionalised scaffolds seeded with ADSCs were biocompatible and supported vessel ingrowth apparently to a greater degree than unmodified scaffolds. In summary, our study shows the ability to direct ADSC chondrogenic and osteogenic differentiation by deposition of different chemical groups through plasma surface polymerisation. Hence this approach could be used to selectively enhance bone or cartilage formation before implantation in vivo to repair skeletal defects.
  
  
  
  Human adipose derived stem cells (hADSCs) are an exciting stem cell source for regenerative medicine due to their plentiful supply and ease of isolation. However, the optimal environmental cues to direct stem cells towards certain lineages change have to has not been identified. We have shown that by modifying the surface of the scaffold with specific chemical groups using plasma surface polymerisation techniques we can control ADSCs differentiation. This study shows that ADSCs can be differentiated towards osteogenic and chondrogenic lineages on amine (NH2) and carboxyl (COOH) modified scaffolds respectively. Plasma polymerisation can be easily applied to other biomaterial surfaces to direct stem cell differentiation for the regeneration of bone and cartilage.
authors.affiliation: UCL Centre for Nanotechnology and Regenerative Medicine, Division of Surgery & Interventional Science, University College London, London, United Kingdom; Royal Free London NHS Foundation Trust Hospital, London, United Kingdom; Stem Cells and Regenerative Medicine Section, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, United Kingdom. Electronic address: 12michellegriffin@gmail.com.
authors.forename: M F
authors.initials: MF
authors.lastname: Griffin
authors.affiliation: Stem Cells and Regenerative Medicine Section, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Ibrahim
authors.affiliation: UCL Centre for Nanotechnology and Regenerative Medicine, Division of Surgery & Interventional Science, University College London, London, United Kingdom.
authors.forename: A M
authors.initials: AM
authors.lastname: Seifalian
authors.affiliation: UCL Centre for Nanotechnology and Regenerative Medicine, Division of Surgery & Interventional Science, University College London, London, United Kingdom; Royal Free London NHS Foundation Trust Hospital, London, United Kingdom.
authors.forename: P E M
authors.initials: PEM
authors.lastname: Butler
authors.affiliation: UCL Centre for Nanotechnology and Regenerative Medicine, Division of Surgery & Interventional Science, University College London, London, United Kingdom; Royal Free London NHS Foundation Trust Hospital, London, United Kingdom. Electronic address: d.kalaskar@ucl.ac.uk.
authors.forename: D M
authors.initials: DM
authors.lastname: Kalaskar
authors.affiliation: Stem Cells and Regenerative Medicine Section, UCL Great Ormond Street Institute of Child Health, University College London, London WC1N 1EH, United Kingdom. Electronic address: p.ferretti@ucl.ac.uk.
authors.forename: P
authors.initials: P
authors.lastname: Ferretti
mesh_terms: D000199:Actins / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects; D000327:Adsorption; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D019070:Cell Lineage / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D020219:Chondrogenesis / Q000187:drug effects*; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects; D017646:Organosilicon Compounds; D010012:Osteogenesis / Q000187:drug effects*; D058626:Plasma Gases / Q000494:pharmacology*; D011076:Polycarboxylate Cement / Q000737:chemistry; D058105:Polymerization; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D000199:Actins; D015415:Biomarkers; D017646:Organosilicon Compounds; D058626:Plasma Gases; D011076:Polycarboxylate Cement; C521417:polyhedraloligosilsesquioxane; C005506:polycarbonate
keywords: Adipose stem cell; Amine; Carboxyl; Chondrogenesis; Osteogenesis; Plasma polymerisation; Surface chemistry