Ganjun Feng1, Zhanpeng Zhang1, Ming Dang2, Kunal J Rambhia3, Peter X Ma4. 1. Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA. 2. Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109, USA. 3. Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA. 4. Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48109, USA; Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address: mapx@umich.edu.
Abstract
Lower back pain is mainly caused by intervertebral disc degeneration, in which calcification is frequently involved. Here novel nanofibrous spongy microspheres (NF-SMS) are used to carry rabbit bone marrow mesenchymal stromal cells (MSCs) to regenerate nucleus pulposus tissues. NF-SMS are shown to significantly enhance the MSC seeding, proliferation and differentiation over control microcarriers. Furthermore, a hyperbranched polymer (HP) with negligible cytotoxicity and high microRNA (miRNAs) binding affinity is synthesized. The HP can complex with anti-miR-199a and self-assemble into "double shell" polyplexes which are able to achieve high transfection efficiency into MSCs. A double-emulsion technique is used to encapsulate these polyplexes in biodegradable nanospheres (NS) to enable sustained anti-miR-199 delivery. Our results demonstrate that MSC/HP-anti-miR-199a/NS/NF-SMS constructs can promote the nucleus pulposus (NP) phenotype and resist calcification in vitro and in a subcutaneous environment. Furthermore, injection of MSC/HP-anti-miR-199a/NS/NF-SMS can stay in place, produce functional extracellular matrix, maintain disc height and prevent intervertebral disc (IVD) calcification in a rabbit lumbar degeneration model.
Lower back pain is mainly caused by intervertebral n>an class="Disease">disc degeneration, in which calcification is frequently involved. Here novel nanofibrous spongy microspheres (NF-SMS) are used to carry rabbit bone marrow mesenchymal stromal cells (MSCs) to regenerate nucleus pulposus tissues. NF-SMS are shown to significantly enhance theMSC seeding, proliferation and differentiation over control microcarriers. Furthermore, a hyperbranched polymer (HP) with negligible cytotoxicity and high microRNA (miRNAs) binding affinity is synthesized. The HP can complex with anti-miR-199a and self-assemble into "double shell" polyplexes which are able to achieve high transfection efficiency into MSCs. A double-emulsion technique is used to encapsulate these polyplexes in biodegradable nanospheres (NS) to enable sustained anti-miR-199 delivery. Our results demonstrate that MSC/HP-anti-miR-199a/NS/NF-SMS constructs can promote the nucleus pulposus (NP) phenotype and resist calcification in vitro and in a subcutaneous environment. Furthermore, injection of MSC/HP-anti-miR-199a/NS/NF-SMS can stay in place, produce functional extracellular matrix, maintain disc height and prevent intervertebral disc (IVD) calcification in a rabbit lumbar degeneration model.
Authors: Ganjun Feng; Zhanpeng Zhang; Ming Dang; Xiaojin Zhang; Yasmine Doleyres; Yueming Song; Di Chen; Peter X Ma Journal: Biomaterials Date: 2017-03-24 Impact factor: 12.479
Authors: Jessica E Frith; Donna J Menzies; Andrew R Cameron; P Ghosh; Darryl L Whitehead; S Gronthos; Andrew C W Zannettino; Justin J Cooper-White Journal: Biomaterials Date: 2013-11-08 Impact factor: 12.479