title: Surface modification of PdlLGA microspheres with gelatine methacrylate: Evaluation of adsorption, entrapment, and oxygen plasma treatment approaches.
abstract: Injectable poly (dl-lactic-co-glycolic acid) (PdlLGA) microspheres are promising candidates as biodegradable controlled release carriers for drug and cell delivery applications; however, they have limited functional groups on the surface to enable dense grafting of tissue specific biocompatible molecules. In this study we have evaluated surface adsorption, entrapment and oxygen plasma treatment as three approaches to modify the surfaces of PdlLGA microspheres with gelatine methacrylate (gel-MA) as a biocompatible and photo cross-linkable macromolecule. Time of flight secondary ion mass spectroscopy (TOF SIMS) and X-ray photoelectron spectroscopy (XPS) were used to detect and quantify gel-MA on the surfaces. Fluorescent and scanning electron microscopies (SEM) were used to image the topographical changes. Human mesenchymal stem cells (hMSCs) of immortalised cell line were cultured on the surface of gel-MA modified PdlLGA microspheres and Presto-Blue assay was used to study the effect of different surface modifications on cell proliferation. Data analysis showed that the oxygen plasma treatment approach resulted in the highest density of gel-MA deposition. This study supports oxygen plasma treatment as a facile approach to modify the surface of injectable PdlLGA microspheres with macromolecules such as gel-MA to enhance proliferation rate of injected cells and potentially enable further grafting of tissue specific molecules.
  
  
  
  Poly (dl lactic-co-glycolic) acid (PdlLGA) microspheres offer limited functional groups on their surface to enable proper grafting of tissue specific bioactive molecules. To overcome this limitation, previous approaches have suggested using alkaline solutions to introduce active groups to the surface; however, they may compromise surface topography and lose any potential surface patterns. Plasma polymerisation of bioactive monomers has been suggested to enhance surface biocompatibility; however, it is not applicable on low vapour pressure macromolecules such as most extracellular matrix (ECM) proteins and growth factors. This study aims to evaluate three different approaches to modify the surface of PdlLGA microspheres with gelatine-methacrylate (gel-MA) to enable further grafting of cross-linkable biomolecules without compromising the surface topography or the biocompatibility of the system.
authors.affiliation: Division of Drug Delivery and Tissue Engineering, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: Abdulrahman
authors.initials: A
authors.lastname: Baki
authors.affiliation: Division of Drug Delivery and Tissue Engineering, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: Cheryl V
authors.initials: CV
authors.lastname: Rahman
authors.affiliation: Division of Drug Delivery and Tissue Engineering, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: White
authors.affiliation: Laboratory of Biophysics and Surface Analysis, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Scurr
authors.affiliation: Division of Drug Delivery and Tissue Engineering, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: Omar
authors.initials: O
authors.lastname: Qutachi
authors.affiliation: Division of Drug Delivery and Tissue Engineering, School of Pharmacy, University of Nottingham, University Park, Nottingham NG7 2RD, UK. Electronic address: kevin.shakesheff@nottingham.ac.uk.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Shakesheff
mesh_terms: D000327:Adsorption; D002214:Capsules / Q000008:administration & dosage* / Q000138:chemical synthesis*; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004339:Drug Compounding / Q000379:methods; D005780:Gelatin / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D007267:Injections; D019344:Lactic Acid / Q000737:chemistry*; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008689:Methacrylates / Q000008:administration & dosage / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry*; D058626:Plasma Gases / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties
chemical_list: D002214:Capsules; D003692:Delayed-Action Preparations; D008689:Methacrylates; D058626:Plasma Gases; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005780:Gelatin; D010100:Oxygen
keywords: Drug delivery; Gelatine methacrylate; PdlLGA microspheres; Surface modification; Tissue engineering