Christoph S Nabzdyk1, Maggie C Chun2, Hunter S Oliver-Allen2, Saif G Pathan3, Matthew D Phaneuf3, Jin-Oh You4, Leena K Pradhan-Nabzdyk5, Frank W LoGerfo6. 1. Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Surgery, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA. 2. Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 3. BioSurfaces, Inc., Ashland, MA, USA. 4. Harvard School of Engineering and Applied Sciences, Cambridge, MA, USA; Department of Engineering Chemistry, Chungbuk National University, Cheongju, Republic of Korea. 5. Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: lpradhan@bidmc.harvard.edu. 6. Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address: flogerfo@bidmc.harvard.edu.
Abstract
An excessive tissue response to prosthetic arterial graft material leads to intimal hyperplasia (IH), the leading cause of late graft failure. Seroma and abnormal capsule formation may also occur after prosthetic material implantation. The matricellular protein Thrombospondin-2 (TSP-2) has shown to be upregulated in response to biomaterial implantation. This study evaluates the uptake and release of small interfering RNA (siRNA) from unmodified and surface functionalized electrospun PET graft materials. ePET graft materials were synthesized using electrospinning technology. Subsets of the ePET materials were then chemically modified to create surface functional groups. Unmodified and surface-modified ePET grafts were dip-coated in siRNAs alone or siRNAs complexed with transfection reagents polyethyleneimine (PEI) or Lipofectamine RNAiMax. Further, control and TSP-2 siRNA-PEI complex treated ePET samples were placed onto a confluent layer of human aortic smooth muscle cells (AoSMCs). Complexation of all siRNAs with PEI led to a significant increase in adsorption to unmodified ePET. TSP-2 siRNA-PEI released from unmodified-ePET silenced TSP-2 in AoSMC. Regardless of the siRNA-PEI complex evaluated, AoSMC migrated into the ePET. siRNA-PEI complexes delivered to AoSMC from dip-coated ePET can result in gene knockdown. This methodology for siRNA delivery may improve the tissue response to vascular and other prosthetics.
An excessive tissue response to prosthetic arterial graft material leads to intimal hyperplasia (IH), the leading cause of pan> class="Disease">late graft failure. Seroma and abnormal capsule formation may also occur after prosthetic material implantation. The matricellular protein Thrombospondin-2 (TSP-2) has shown to be upregulated in response to biomaterial implantation. This study evaluates the uptake and release of small interfering RNA (siRNA) from unmodified and surface functionalized electrospun PET graft materials. ePET graft materials were synthesized using electrospinning technology. Subsets of the ePET materials were then chemically modified to create surface functional groups. Unmodified and surface-modified ePET grafts were dip-coated in siRNAs alone or siRNAs complexed with transfection reagents polyethyleneimine (PEI) or Lipofectamine RNAiMax. Further, control and TSP-2 siRNA-PEI complex treated ePET samples were placed onto a confluent layer of human aortic smooth muscle cells (AoSMCs). Complexation of all siRNAs with PEI led to a significant increase in adsorption to unmodified ePET. TSP-2 siRNA-PEI released from unmodified-ePET silenced TSP-2 in AoSMC. Regardless of the siRNA-PEI complex evaluated, AoSMC migrated into the ePET. siRNA-PEI complexes delivered to AoSMC from dip-coated ePET can result in gene knockdown. This methodology for siRNA delivery may improve the tissue response to vascular and other prosthetics.
Authors: Nurazhani A Raof; Deepa Rajamani; Hsun-Chieh Chu; Aniket Gurav; Joel M Johnson; Frank W LoGerfo; Leena Pradhan-Nabzdyk; Manoj Bhasin Journal: BMC Genomics Date: 2016-01-05 Impact factor: 3.969
Authors: Frank LoGerfo; Leena Pradhan-Nabzdyk; Cindy Huynh; Ting-Yu Shih; Alexander Mammoo; Amruta Samant; Saif Pathan; David W Nelson; Christiane Ferran; David Mooney Journal: PeerJ Date: 2019-08-20 Impact factor: 2.984