Journal Article


Daniel J Kelly
Eben Alsberg
Oju Jeon
Binulal N Sathy
Andrew Daly
Tomas Gonzalez-Fernandez
Gráinne M Cunniffe



mesenchymal stem cells genes reporter bone marrow cells bone growth mechanical properties three dimensional cell free bone tissue engineering

Three-Dimensional Bioprinting of Polycaprolactone Reinforced Gene Activated Bioinks for Bone Tissue Engineering. (2017)

Abstract Regeneration of complex bone defects remains a significant clinical challenge. Multi-tool biofabrication has permitted the combination of various biomaterials to create multifaceted composites with tailorable mechanical properties and spatially controlled biological function. In this study we sought to use bioprinting to engineer nonviral gene activated constructs reinforced by polymeric micro-filaments. A gene activated bioink was developed using RGD-γ-irradiated alginate and nano-hydroxyapatite (nHA) complexed to plasmid DNA (pDNA). This ink was combined with bone marrow-derived mesenchymal stem cells (MSCs) and then co-printed with a polycaprolactone supporting mesh to provide mechanical stability to the construct. Reporter genes were first used to demonstrate successful cell transfection using this system, with sustained expression of the transgene detected over 14 days postbioprinting. Delivery of a combination of therapeutic genes encoding for bone morphogenic protein and transforming growth factor promoted robust osteogenesis of encapsulated MSCs in vitro, with enhanced levels of matrix deposition and mineralization observed following the incorporation of therapeutic pDNA. Gene activated MSC-laden constructs were then implanted subcutaneously, directly postfabrication, and were found to support superior levels of vascularization and mineralization compared to cell-free controls. These results validate the use of a gene activated bioink to impart biological functionality to three-dimensional bioprinted constructs.
Collections Ireland -> Trinity College Dublin -> PubMed

Full list of authors on original publication

Daniel J Kelly, Eben Alsberg, Oju Jeon, Binulal N Sathy, Andrew Daly, Tomas Gonzalez-Fernandez, Gráinne M Cunniffe

Experts in our system

Daniel Kelly
Trinity College Dublin
Total Publications: 190
Eben Alsberg
Trinity College Dublin
Total Publications: 3
Binulal N Sathy
Trinity College Dublin
Total Publications: 8
Andrew C Daly
Trinity College Dublin
Total Publications: 9
Tomas Gonzalez-Fernandez
Trinity College Dublin
Total Publications: 5
Grainne M Cunniffe
Royal College of Surgeons in Ireland
Total Publications: 16