title: Delivering Nucleic-Acid Based Nanomedicines on Biomaterial Scaffolds for Orthopedic Tissue Repair: Challenges, Progress and Future Perspectives.
abstract: As well as acting to fill defects and allow for cell infiltration and proliferation in regenerative medicine, biomaterial scaffolds can also act as carriers for therapeutics, further enhancing their efficacy. Drug and protein delivery on scaffolds have shown potential, however, supraphysiological quantities of therapeutic are often released at the defect site, causing off-target side effects and cytotoxicity. Gene therapy involves the introduction of foreign genes into a cell in order to exert an effect; either replacing a missing gene or modulating expression of a protein. State of the art gene therapy also encompasses manipulation of the transcriptome by harnessing RNA interference (RNAi) therapy. The delivery of nucleic acid nanomedicines on biomaterial scaffolds - gene-activated scaffolds -has shown potential for use in a variety of tissue engineering applications, but as of yet, have not reached clinical use. The current state of the art in terms of biomaterial scaffolds and delivery vector materials for gene therapy is reviewed, and the limitations of current procedures discussed. Future directions in the clinical translation of gene-activated scaffolds are also considered, with a particular focus on bone and cartilage tissue regeneration.
authors: Tissue Engineering Research Group (TERG), Dept. of Anatomy, Royal College of Surgeons in Ireland (RCSI), 123, St. Stephens Green, Dublin 2, Dublin, Ireland.|Trinity Centre for Bioengineering (TCBE), Trinity College Dublin, Dublin 2, Dublin, Ireland.|Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, Ireland.|Drug Delivery and Advanced Materials Research Team, School of Pharmacy, Royal College of Surgeons in Ireland, 123, St. Stephens Green, Dublin 2, Dublin, Ireland.|Centre for Research in Medical Devices (CÚRAM), National University of Ireland Galway, Galway, Ireland.
authors: Rosanne M
authors: RM
authors: Raftery
authors: Tissue Engineering Research Group (TERG), Dept. of Anatomy, Royal College of Surgeons in Ireland (RCSI), 123, St. Stephens Green, Dublin 2, Dublin, Ireland.|Trinity Centre for Bioengineering (TCBE), Trinity College Dublin, Dublin 2, Dublin, Ireland.|Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, Ireland.|Drug Delivery and Advanced Materials Research Team, School of Pharmacy, Royal College of Surgeons in Ireland, 123, St. Stephens Green, Dublin 2, Dublin, Ireland.|Centre for Research in Medical Devices (CÚRAM), National University of Ireland Galway, Galway, Ireland.
authors: David P
authors: DP
authors: Walsh
authors: Tissue Engineering Research Group (TERG), Dept. of Anatomy, Royal College of Surgeons in Ireland (RCSI), 123, St. Stephens Green, Dublin 2, Dublin, Ireland.|Trinity Centre for Bioengineering (TCBE), Trinity College Dublin, Dublin 2, Dublin, Ireland.|Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, Ireland.
authors: Irene Mencía
authors: IM
authors: Castaño
authors: Tissue Engineering Research Group (TERG), Dept. of Anatomy, Royal College of Surgeons in Ireland (RCSI), 123, St. Stephens Green, Dublin 2, Dublin, Ireland.
authors: Andreas
authors: A
authors: Heise
authors: Tissue Engineering Research Group (TERG), Dept. of Anatomy, Royal College of Surgeons in Ireland (RCSI), 123, St. Stephens Green, Dublin 2, Dublin, Ireland.|Trinity Centre for Bioengineering (TCBE), Trinity College Dublin, Dublin 2, Dublin, Ireland.|Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, Ireland.
authors: Garry P
authors: GP
authors: Duffy
authors: Tissue Engineering Research Group (TERG), Dept. of Anatomy, Royal College of Surgeons in Ireland (RCSI), 123, St. Stephens Green, Dublin 2, Dublin, Ireland.|Trinity Centre for Bioengineering (TCBE), Trinity College Dublin, Dublin 2, Dublin, Ireland.|Drug Delivery and Advanced Materials Research Team, School of Pharmacy, Royal College of Surgeons in Ireland, 123, St. Stephens Green, Dublin 2, Dublin, Ireland.|Centre for Research in Medical Devices (CÚRAM), National University of Ireland Galway, Galway, Ireland.
authors: Sally-Ann
authors: SA
authors: Cryan
authors: Tissue Engineering Research Group (TERG), Dept. of Anatomy, Royal College of Surgeons in Ireland (RCSI), 123, St. Stephens Green, Dublin 2, Dublin, Ireland.|Trinity Centre for Bioengineering (TCBE), Trinity College Dublin, Dublin 2, Dublin, Ireland.|Advanced Materials and Bioengineering Research Centre (AMBER), RCSI and TCD, Dublin, Ireland.
authors: Fergal J
authors: FJ
authors: O'Brien
mesh_terms: D001672:Biocompatible Materials; D050997:Nanomedicine; D044968:Regenerative Medicine; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials
keywords: RNAi; gene-activated scaffolds; non-viral gene therapy; orthopedic tissue engineering