title: Thermally triggered release of a pro-osteogenic peptide from a functionalized collagen-based scaffold using thermosensitive liposomes.
abstract: Collagen is one of the most attractive materials for the development of matrices for tissue engineering, due to its excellent biocompatibility and non-toxic bioresorption. The present work describes a collagen-based externally controlled drug-eluting scaffold which consists of drug encapsulated thermoresponsive liposomes covalently attached to the surface of a functionalized collagen-based scaffold. The model drug used in this work was PTHrP 107-111, a pentapeptide with pro-osteogenic and antiosteoclastic activity. An osteoconductive collagen-hydroxyapatite scaffold, designed specifically for bone repair, was used as a model scaffold. The results demonstrate that it is possible to modify the kinetics of release of the drug from the scaffold with the application of an external thermal stimulus (42°C, 20min). In vitro studies carried out with pre-osteoblastic MC3T3-E1 cells demonstrated that neither the attachment of liposomes to the surface of the scaffolds nor the hyperthermic pulse negatively affected the ability of cells to attach and proliferate on the scaffolds. Importantly, the on-demand release of PTHrP 107-111 had a pro-osteogenic effect, as shown by the enhancement of alkaline phosphatase activity, an early osteogenic marker, which correlated with increased expression of the osteogenic genes osteopontin and osteocalcin. In conclusion, the scaffold-based release system developed in this study has immense potential for tuning the delivery of a diverse range of drugs which can be applied for the regeneration of a variety of tissue types.
authors.affiliation: School of Pharmacy, Royal College of Surgeons in Ireland, 121 St. Stephen's Green, Dublin 2, Ireland; Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; Trinity Centre for Bioengineering, Trinity College, Dublin 2, Ireland; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Ireland.
authors.forename: Adolfo
authors.initials: A
authors.lastname: López-Noriega
authors.affiliation: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; Trinity Centre for Bioengineering, Trinity College, Dublin 2, Ireland; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Ireland; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ruiz-Hernández
authors.affiliation: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; Trinity Centre for Bioengineering, Trinity College, Dublin 2, Ireland; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Ireland.
authors.forename: Elaine
authors.initials: E
authors.lastname: Quinlan
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands; Inst. Biomed. Technol. & Techn. Med. (MIRA), University of Twente, 7522 NB Enschede, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, 3584 CG Utrecht, The Netherlands.
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.affiliation: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland; Trinity Centre for Bioengineering, Trinity College, Dublin 2, Ireland; Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Ireland. Electronic address: fjobrien@rcsi.ie.
authors.forename: Fergal J
authors.initials: FJ
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D002460:Cell Line; D003094:Collagen / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry; D006358:Hot Temperature; D008081:Liposomes; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry*; D054457:Tissue Scaffolds
chemical_list: D008081:Liposomes; D010446:Peptide Fragments; D003094:Collagen; D017886:Durapatite
keywords: Collagen; Drug delivery; Scaffold; Thermally responsive material; Thermosensitive liposomes; Tissue engineering