Next generation bone tissue engineering: non-viral miR-133a inhibition using collagen-nanohydroxyapatite scaffolds rapidly enhances osteogenesis.
Bone grafts are the second most transplanted materials worldwide at a global cost to healthcare systems valued over $30 billion every year. The influence of microRNAs in the regenerative capacity of stem cells offers vast therapeutic potential towards bone grafting; however their efficient delivery to the target site remains a major challenge. This study describes how the functionalisation of porous collagen-nanohydroxyapatite (nHA) scaffolds with miR-133a inhibiting complexes, delivered using non-viral nHA particles, enhanced human mesenchymal stem cell-mediated osteogenesis through the novel focus on a key activator of osteogenesis, Runx2. This study showed enhanced Runx2 and osteocalcin expression, as well as increased alkaline phosphatase activity and calcium deposition, thus demonstrating a further enhanced therapeutic potential of a biomaterial previously optimised for bone repair applications. The promising features of this platform offer potential for a myriad of applications beyond bone repair and tissue engineering, thus presenting a new paradigm for microRNA-based therapeutics.
Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), 123 St. Stephens Green, Dublin 2, Ireland.|Trinity Centre for Bioengineering, Trinity College Dublin (TCD), College Green, Dublin 2, Ireland.|Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI &TCD, Dublin 2, Ireland.
Irene
I
Mencía Castaño
Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), 123 St. Stephens Green, Dublin 2, Ireland.|Trinity Centre for Bioengineering, Trinity College Dublin (TCD), College Green, Dublin 2, Ireland.|Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI &TCD, Dublin 2, Ireland.
Caroline M
CM
Curtin
Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), 123 St. Stephens Green, Dublin 2, Ireland.|Trinity Centre for Bioengineering, Trinity College Dublin (TCD), College Green, Dublin 2, Ireland.|Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI &TCD, Dublin 2, Ireland.
Garry P
GP
Duffy
Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland (RCSI), 123 St. Stephens Green, Dublin 2, Ireland.|Trinity Centre for Bioengineering, Trinity College Dublin (TCD), College Green, Dublin 2, Ireland.|Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI &TCD, Dublin 2, Ireland.
Fergal J
FJ
O'Brien
D000469:Alkaline Phosphatase / Q000378:metabolism; D001672:Biocompatible Materials / Q000378:metabolism; D001861:Bone Regeneration / Q000235:genetics / Q000502:physiology*; D016025:Bone Transplantation / Q000379:methods*; D001842:Bone and Bones / Q000166:cytology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D017886:Durapatite / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D015675:Osteocalcin / Q000096:biosynthesis; D010012:Osteogenesis / Q000502:physiology*; D034622:RNA Interference; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
D001672:Biocompatible Materials; D050659:Core Binding Factor Alpha 1 Subunit; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; C493709:RUNX2 protein, human; C509317:nano-hydroxyapatite-collagen; D015675:Osteocalcin; D003094:Collagen; D017886:Durapatite; D000469:Alkaline Phosphatase; D002118:Calcium