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Elastic 3d-printed Conduit with Mesoporous Silica/graphene Oxide Nanoparticles for Sciatic Nerve Regeneration of Sd Rats
Presentation Number:0011 Time:13:32 - 13:44
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Jen-Hung Fang, Peng Chih-Kang, Hsu Hao-Hsiang, Lu Yu-Jen and Hu Shang-Hsiu
Peripheral nerve injuries (PNI) is a common clinical challenge and issue to human health that arise from industrial injuries, natural disasters, war wounds, motor vehicle accidents, tumor damage and even some systemic diseases result in complete loss of motor functionality and paralysis. Approximately 2–5% of trauma patients experience a PNI and about 500,000 surgical procedures are carried out each year in the America. In the Europe alone, more than 300,000 PNI cases per year and esti-mated that more than 5 million cases of PNI occur annually worldwide due to traumatic events.
Here, we developed an elastic 3D printed conduit fabricated by digital light processing (DLP)-type additive manufacturing for nerve regeneration. In 3D printing technologies, we can fabricate various scaffold in any length as well as diameter and overcome the geometries from individual differences according to individual patients. Especially, unique pattern inside the conduit could also be easily designed. Besides, mesoporous silica/graphene oxide nanoparticles (PSGO NPs) provide the large cargo to deliver growth factor and some specific protein for nerve regeneration. By means of 3D-printing process, we could prepare gradient concentration of PSGO NPs inside for guiding nerve growth. PSGO NPs also generated microcurrent to aid sciatica regeneration under high frequency magnetic field (MFMF). Nerve would grow along the micro-groove and gradient concentration of PSGO NPs in the lumen of the guide we designed in vitro and in vivo test. Over 1 month, Sprague-Dawley (SD) rats successfully regenerated across a 5 mm nerve gap and resulted in functional return.
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Endogenous Stimuli-responsive Amino Acid-based Nanoparticles with Tailor-designed Release of Therapeutic Agents for Resistant Cancer
Presentation Number:0146 Time:14:10 - 14:22
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Pei Hsuan Hsieh and Tzu-Wei Wang
Stimuli-responsive polymeric nanoparticles have been utilized as effective vehicles for escorting chemotherapeutic agents with optimal therapeutic effect. However, solid tumor microenvironment restrains deep drugs transportation due to its dense extracellular matrix, irregular vascular network and high interstitial fluid pressure. Therefore, the objective of this study is to develop reductive and enzyme sensitive polypeptide-based nanoparticles with programmable degradation manner for solid tumor treatment. The backbone of copolymers is composed of polyCys, polyHis and polyLeu blocks which exhibited a reversible disulfide bond protective layer, proton sponge effect and hydrophilic domain, respectively. Vismodegib, a hedgehog signal pathway inhibitor, was complexed in the core of the nanoparticles to show synergistic effect with anti-cancer drug, doxorubicin. From NMR and FTIR spectra, the mPEG and doxorubicin were successfully conjugated onto the polypeptide sequence through chemical reactions, respectively. The nanoparticles self-assembled into spherical shape through sonication with a size around 220 nm. Also, the programmable dissociation process could be clearly seen from the TEM images. In in vitro cell culture model, the nanoparticle decorated with active targeting ligand, tLyP-1, performed high selectivity toward the expression of neuropilin-1 (NRP-1) receptor on breast cancer cells. Moreover, in tumor spheroid 3D model, the nanoparticles exerted desirable therapeutics on collapsing ECM matrix and anticancer effect. These nanocarriers are expected to process through adverse ECM barrier with multiple endogenous stimuli-responsive properties and exert a safe and precise delivery. This tailored-designed vehicle has potential in treating NRP-1 over-expressed solid tumor and diseases with intense fibrosis problem.
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