Shang Song

Interests

Research

Using engineered biomaterials and cell therapy to develop organ-on-chip systems and artificial implantable organs/devices for diagnostics and therapeutics.

Teaching

I focus on student-centered teaching with hands-on learning experience. I'm a strong advocate for women, URM, first-gen, and non-traditional students (veterans) in STEM education.

Courses

Scholarly Contributions

Journals/Publications

• Reynolds, M., Stoy, L. M., Sun, J., Opoku Amponsah, P. E., Li, L., Soto, M., & Song, S. (2024). Fabrication of Sodium Trimetaphosphate-Based PEDOT:PSS Conductive Hydrogels. Gels (Basel, Switzerland), 10(2).
• Song, S., McConnell, K. W., Shan, D., Chen, C., Oh, B., Sun, J., Poon, A. S., & George, P. M. (2024). Conductive gradient hydrogels allow spatial control of adult stem cell fate. Journal of materials chemistry. B, 12(7), 1854-1863.
• Sun, J., & Song, S. (2024). Advances in modeling permeability and selectivity of the blood-brain barrier using microfluidics. Microfluidics and Nanofluidics, 28(7), 44.
• Omer, S. A., McKnight, K. H., Young, L. I., & Song, S. (2023). Stimulation strategies for electrical and magnetic modulation of cells and tissues. Cell regeneration (London, England), 12(1), 21.
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  Electrical phenomena play an important role in numerous biological processes including cellular signaling, early embryogenesis, tissue repair and remodeling, and growth of organisms. Electrical and magnetic effects have been studied on a variety of stimulation strategies and cell types regarding cellular functions and disease treatments. In this review, we discuss recent advances in using three different stimulation strategies, namely electrical stimulation via conductive and piezoelectric materials as well as magnetic stimulation via magnetic materials, to modulate cell and tissue properties. These three strategies offer distinct stimulation routes given specific material characteristics. This review will evaluate material properties and biological response for these stimulation strategies with respect to their potential applications in neural and musculoskeletal research.
• Santhanam, S., Feig, V. R., McConnell, K. W., Song, S., Gardner, E. E., Patel, J. J., Shan, D., Bao, Z., & George, P. M. (2023). Controlling the Stem Cell Environment Via Conducting Polymer Hydrogels to Enhance Therapeutic Potential. Advanced Materials Technologies, 8(10), 2201724.
• Oh, B., Santhanam, S., Azadian, M., Swaminathan, V., Lee, A. G., McConnell, K. W., Levinson, A., Song, S., Patel, J. J., Gardner, E. E., & George, P. M. (2022). Electrical modulation of transplanted stem cells improves functional recovery in a rodent model of stroke. Nature communications, 13(1), 1366.
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  Stroke is a leading cause of long-term disability worldwide, intensifying the need for effective recovery therapies. Stem cells are a promising stroke therapeutic, but creating ideal conditions for treatment is essential. Here we developed a conductive polymer system for stem cell delivery and electrical modulation in animals. Using this system, electrical modulation of human stem cell transplants improve functional stroke recovery in rodents. Increased endogenous stem cell production corresponds with improved function. Transcriptome analysis identified stanniocalcin 2 (STC2) as one of the genes most significantly upregulated by electrical stimulation. Lentiviral upregulation and downregulation of STC2 in the transplanted stem cells demonstrate that this glycoprotein is an essential mediator in the functional improvements seen with electrical modulation. Moreover, intraventricular administration of recombinant STC2 post-stroke confers functional benefits. In summation, our conductive polymer system enables electrical modulation of stem cells as a potential method to improve recovery and identify important therapeutic targets.
• Song, S., McConnell, K. W., Amores, D., Levinson, A., Vogel, H., Quarta, M., Rando, T. A., & George, P. M. (2021). Electrical stimulation of human neural stem cells via conductive polymer nerve guides enhances peripheral nerve recovery. Biomaterials, 275, 120982.
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  Severe peripheral nerve injuries often result in permanent loss of function of the affected limb. Current treatments are limited by their efficacy in supporting nerve regeneration and behavioral recovery. Here we demonstrate that electrical stimulation through conductive nerve guides (CNGs) enhances the efficacy of human neural progenitor cells (hNPCs) in treating a sciatic nerve transection in rats. Electrical stimulation strengthened the therapeutic potential of NPCs by upregulating gene expression of neurotrophic factors which are critical in augmenting synaptic remodeling, nerve regeneration, and myelination. Electrically-stimulated hNPC-containing CNGs are significantly more effective in improving sensory and motor functions starting at 1-2 weeks after treatment than either treatment alone. Electrophysiology and muscle assessment demonstrated successful re-innervation of the affected target muscles in this group. Furthermore, histological analysis highlighted an increased number of regenerated nerve fibers with thicker myelination in electrically-stimulated hNPC-containing CNGs. The elevated expression of tyrosine kinase receptors (Trk) receptors, known to bind to neurotrophic factors, indicated the long-lasting effect from electrical stimulation on nerve regeneration and distal nerve re-innervation. These data suggest that electrically-enhanced stem cell-based therapy provides a regenerative rehabilitative approach to promote peripheral nerve regeneration and functional recovery.
• Suhar, R., Marquardt, L., Song, S., Buabbas, H., Doulames, V., Johansson, P., Klett, K., Dewi, R., Enejder, A., Plant, G., George, P., & Heilshorn, S. (2021). Elastin-like Proteins to Support Peripheral Nerve Regeneration in Guidance Conduits. ACS Biomaterials Science and Engineering, 7(9). doi:10.1021/acsbiomaterials.0c01053
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  Synthetic nerve guidance conduits (NGCs) offer an alternative to harvested nerve grafts for treating peripheral nerve injury (PNI). NGCs have been made from both naturally derived and synthesized materials. While naturally derived materials typically have an increased capacity for bioactivity, synthesized materials have better material control, including tunability and reproducibility. Protein engineering is an alternative strategy that can bridge the benefits of these two classes of materials by designing cell-responsive materials that are also systematically tunable and consistent. Here, we tested a recombinantly derived elastin-like protein (ELP) hydrogel as an intraluminal filler in a rat sciatic nerve injury model. We demonstrated that ELPs enhance the probability of forming a tissue bridge between the proximal and distal nerve stumps compared to an empty silicone conduit across the length of a 10 mm nerve gap. These tissue bridges have evidence of myelinated axons, and electrophysiology demonstrated that regenerated axons innervated distal muscle groups. Animals implanted with an ELP-filled conduit had statistically higher functional control at 6 weeks than those that had received an empty silicone conduit, as evaluated by the sciatic functional index. Taken together, our data support the conclusion that ELPs support peripheral nerve regeneration in acute complete transection injuries when used as an intraluminal filler. These results support the further study of protein engineered recombinant ELP hydrogels as a reproducible, off-the-shelf alternative for regeneration of peripheral nerves.
• Liu, Y., Li, J., Song, S., Kang, J., Tsao, Y., Chen, S., Mottini, V., McConnell, K., Xu, W., Zheng, Y. Q., Tok, J. B., George, P. M., & Bao, Z. (2020). Morphing electronics enable neuromodulation in growing tissue. Nature biotechnology, 38(9), 1031-1036.
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  Bioelectronics for modulating the nervous system have shown promise in treating neurological diseases. However, their fixed dimensions cannot accommodate rapid tissue growth and may impair development. For infants, children and adolescents, once implanted devices are outgrown, additional surgeries are often needed for device replacement, leading to repeated interventions and complications. Here, we address this limitation with morphing electronics, which adapt to in vivo nerve tissue growth with minimal mechanical constraint. We design and fabricate multilayered morphing electronics, consisting of viscoplastic electrodes and a strain sensor that eliminate the stress at the interface between the electronics and growing tissue. The ability of morphing electronics to self-heal during implantation surgery allows a reconfigurable and seamless neural interface. During the fastest growth period in rats, morphing electronics caused minimal damage to the rat nerve, which grows 2.4-fold in diameter, and allowed chronic electrical stimulation and monitoring for 2 months without disruption of functional behavior. Morphing electronics offers a path toward growth-adaptive pediatric electronic medicine.
• Liu, Y., Li, J., Song, S., Kang, J., Tsao, Y., Chen, S., Mottini, V., McConnell, K., Xu, W., Zheng, Y., Tok, J., George, P., & Bao, Z. (2020). Author Correction: Morphing electronics enable neuromodulation in growing tissue (Nature Biotechnology, (2020), 38, 9, (1031-1036), 10.1038/s41587-020-0495-2). Nature Biotechnology, 38(9). doi:10.1038/s41587-020-0533-0
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  An amendment to this paper has been published and can be accessed via a link at the top of the paper.
• Suhar, R. A., Marquardt, L. M., Song, S., Buabbas, H., Doulames, V. M., Johansson, P. K., Klett, K. C., Dewi, R. E., Enejder, A. M., Plant, G. W., George, P. M., & Heilshorn, S. C. (2020). Elastin-like Proteins to Support Peripheral Nerve Regeneration in Guidance Conduits. ACS biomaterials science & engineering, 7(9), 4209-4220.
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  Synthetic nerve guidance conduits (NGCs) offer an alternative to harvested nerve grafts for treating peripheral nerve injury (PNI). NGCs have been made from both naturally derived and synthesized materials. While naturally derived materials typically have an increased capacity for bioactivity, synthesized materials have better material control, including tunability and reproducibility. Protein engineering is an alternative strategy that can bridge the benefits of these two classes of materials by designing cell-responsive materials that are also systematically tunable and consistent. Here, we tested a recombinantly derived elastin-like protein (ELP) hydrogel as an intraluminal filler in a rat sciatic nerve injury model. We demonstrated that ELPs enhance the probability of forming a tissue bridge between the proximal and distal nerve stumps compared to an empty silicone conduit across the length of a 10 mm nerve gap. These tissue bridges have evidence of myelinated axons, and electrophysiology demonstrated that regenerated axons innervated distal muscle groups. Animals implanted with an ELP-filled conduit had statistically higher functional control at 6 weeks than those that had received an empty silicone conduit, as evaluated by the sciatic functional index. Taken together, our data support the conclusion that ELPs support peripheral nerve regeneration in acute complete transection injuries when used as an intraluminal filler. These results support the further study of protein engineered recombinant ELP hydrogels as a reproducible, off-the-shelf alternative for regeneration of peripheral nerves.
• Song, S., Amores, D., Chen, C., McConnell, K., Oh, B., Poon, A., & George, P. M. (2019). Controlling properties of human neural progenitor cells using 2D and 3D conductive polymer scaffolds. Scientific reports, 9(1), 19565.
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  Human induced pluripotent stem cell-derived neural progenitor cells (hNPCs) are a promising cell source for stem cell transplantation to treat neurological diseases such as stroke and peripheral nerve injuries. However, there have been limited studies investigating how the dimensionality of the physical and electrical microenvironment affects hNPC function. In this study, we report the fabrication of two- and three-dimensional (2D and 3D respectively) constructs composed of a conductive polymer to compare the effect of electrical stimulation of hydrogel-immobilized hNPCs. The physical dimension (2D vs 3D) of stimulating platforms alone changed the hNPCs gene expression related to cell proliferation and metabolic pathways. The addition of electrical stimulation was critical in upregulating gene expression of neurotrophic factors that are important in regulating cell survival, synaptic remodeling, and nerve regeneration. This study demonstrates that the applied electrical field controls hNPC properties depending on the physical nature of stimulating platforms and cellular metabolic states. The ability to control hNPC functions can be beneficial in understanding mechanistic changes related to electrical modulation and devising novel treatment methods for neurological diseases.
• Oh, B., Levinson, A., Lam, V., Song, S., & George, P. (2018). Electrically Conductive Scaffold to Modulate and Deliver Stem Cells. Journal of visualized experiments : JoVE.
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  Stem cell therapy has emerged as an exciting stroke therapeutic, but the optimal delivery method remains unclear. While the technique of microinjection has been used for decades to deliver stem cells in stroke models, this technique is limited by the lack of ability to manipulate the stem cells prior to injection. This paper details a method of using an electrically conductive polymer scaffold for stem cell delivery. Electrical stimulation of stem cells using a conductive polymer scaffold alters the stem cell's genes involved in cell survival, inflammatory response, and synaptic remodeling. After electrical preconditioning, the stem cells on the scaffold are transplanted intracranially in a distal middle cerebral artery occlusion rat model. This protocol describes a powerful technique to manipulate stem cells via a conductive polymer scaffold and creates a new tool to further develop stem cell-based therapy.
• Oh, B., Song, S., Lam, V., Levinson, A., & George, P. (2018). In vivo Electrical Stimulation of Neural Stem Cells via Conductive Polymer Scaffold Improves Endogenous Repair Mechanisms of Stroke Recovery (P4.028). Neurology. doi:10.1212/wnl.90.15_supplement.p4.028
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  April 25, 2018April 10, 2018Free AccessIn vivo Electrical Stimulation of Neural Stem Cells via Conductive Polymer Scaffold Improves Endogenous Repair Mechanisms of Stroke Recovery (P4.028)Byeongtaek Oh, Shang Song, Vivek Lam, Alexa Levinson, and Paul GeorgeAuthors Info & AffiliationsApril 10, 2018 issue90 (15_supplement) Letters to the Editor
• Oh, B., Song, S., Levinson, A., Lam, V., & George, P. (2018). Abstract 59: Combining Electrical Stimulation With Stem Cell Therapy Improves Endogenous Mechanisms of Stroke Recovery. Stroke. doi:10.1161/str.49.suppl_1.59
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  Introduction: Brain stimulation techniques to enhance stroke recovery are a promising area of research; however, in vivo electrical stimulation combined with neural progenitor cell (NPC) transplantation has not been fully investigated. We propose the use of a conductive polymer scaffold to optimize stem cell therapy and determine mechanisms driving stroke recovery. Methods: The conductive polymer system consisting of a polypyrrole scaffold was seeded with NPCs (Aruna Biomedical) and implanted along with a reference electrode ( Fig. 1a ). Immunocompromised rats underwent a distal middle cerebral artery occlusion stroke. After 1 week post-stroke, implantation surgeries were performed. Electrical stimulation (AC: ±400 mV/100Hz for 1 hr, starting 1 day after implantation, n=10) was applied daily for 3 consecutive days. Blinded, behavior testing was performed for 6 weeks. Immunostaining was performed to determine endogenous NPC population (anti-BrdU, Abcam). Results: We designed a cannula system to deliver NPCs with in vivo electrical stimulation ( Fig. 1a ). Electrically stimulated NPCs (NPC+ES) had an earlier recovery than the other groups ( Fig. 1b ). The unstimulated NPCs (NPC) also outperformed the cannula with the electrical stimulation alone (Polymer+ES), the cannula alone (Polymer), and the sham (Sham) groups. Combined NPC+ES increased post-stroke endogenous stem cells production in the subventricular zones (SVZ) ( Fig. 1b,c ). Conclusion: In conclusion, electrical stimulation of NPCs via a conductive polymer implant enhances stroke recovery and increases endogenous stem cell production. Our platform enables the manipulation of NPCs in vivo to optimize recovery and evaluate the important mechanisms for functional improvement.
• Song, S., & George, P. M. (2017). Conductive polymer scaffolds to improve neural recovery. Neural regeneration research, 12(12), 1976-1978.
• Song, S., Blaha, C., Moses, W., Park, J., Wright, N., Groszek, J., Fissell, W., Vartanian, S., Posselt, A. M., & Roy, S. (2017). An intravascular bioartificial pancreas device (iBAP) with silicon nanopore membranes (SNM) for islet encapsulation under convective mass transport. Lab on a chip, 17(10), 1778-1792.
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  Diffusion-based bioartificial pancreas (BAP) devices are limited by poor islet viability and functionality due to inadequate mass transfer resulting in islet hypoxia and delayed glucose-insulin kinetics. While intravascular ultrafiltration-based BAP devices possess enhanced glucose-insulin kinetics, the polymer membranes used in these devices provide inadequate ultrafiltrate flow rates and result in excessive thrombosis. Here, we report the silicon nanopore membrane (SNM), which exhibits a greater hydraulic permeability and a superior pore size selectivity compared to polymer membranes for use in BAP applications. Specifically, we demonstrate that the SNM-based intravascular BAP with ∼10 and ∼40 nm pore sized membranes support high islet viability (>60%) and functionality (85%) at clinically relevant islet density (5700 IE per cm), c-peptide concentration of 144 pM in the outflow ultrafiltrate, and hemocompatibility under convection. These promising findings offer insights on the development of next generation of full-scale intravascular devices to treat T1D patients in the future.
• Song, S., Yeung, R., Park, J., Posselt, A. M., Desai, T. A., Tang, Q., & Roy, S. (2017). Glucose-Stimulated Insulin Response of Silicon Nanopore-Immunoprotected Islets under Convective Transport. ACS biomaterials science & engineering, 3(6), 1051-1061.
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  Major clinical challenges associated with islet transplantation for type 1 diabetes include shortage of donor organs, poor engraftment due to ischemia, and need for immunosuppressive medications. Semipermeable membrane capsules can immunoprotect transplanted islets by blocking passage of the host's immune components while providing exchange of glucose, insulin, and other small molecules. However, capsules-based diffusive transport often exacerbates ischemic injury to islets by reducing the rate of oxygen and nutrient transport. We previously reported the efficacy of a newly developed semipermeable ultrafiltration membrane, the silicon nanopore membrane (SNM) under convective-driven transport, in limiting the passage of pro-inflammatory cytokines while overcoming the mass transfer limitations associated with diffusion through nanometer-scale pores. In this study, we report that SNM-encapsulated mouse islets perfused in culture solution under convection outperformed those under diffusive conditions in terms of magnitude (1.49-fold increase in stimulation index and 3.86-fold decrease in shutdown index) and rate of insulin secretion (1.19-fold increase and 6.45-fold decrease during high and low glucose challenges), respectively. Moreover, SNM-encapsulated mouse islets under convection demonstrated rapid glucose-insulin sensing within a physiologically relevant time-scale while retaining healthy islet viability even under cytokine exposure. We conclude that encapsulation of islets with SNM under convection improves islet in vitro functionality. This approach may provide a novel strategy for islet transplantation in the clinical setting.
• Song, S., & Roy, S. (2016). Progress and challenges in macroencapsulation approaches for type 1 diabetes (T1D) treatment: Cells, biomaterials, and devices. Biotechnology and bioengineering, 113(7), 1381-402.
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  Macroencapsulation technology has been an attractive topic in the field of treatment for Type 1 diabetes due to mechanical stability, versatility, and retrievability of the macro-capsule design. Macro-capsules can be categorized into extravascular and intravascular devices, in which solute transport relies either on diffusion or convection, respectively. Failure of macroencapsulation strategies can be due to limited regenerative capacity of the encased insulin-producing cells, sub-optimal performance of encapsulation biomaterials, insufficient immunoisolation, excessive blood thrombosis for vascular perfusion devices, and inadequate modes of mass transfer to support cell viability and function. However, significant technical advancements have been achieved in macroencapsulation technology, namely reducing diffusion distance for oxygen and nutrients, using pro-angiogenic factors to increase vascularization for islet engraftment, and optimizing membrane permeability and selectivity to prevent immune attacks from host's body. This review presents an overview of existing macroencapsulation devices and discusses the advances based on tissue-engineering approaches that will stimulate future research and development of macroencapsulation technology. Biotechnol. Bioeng. 2016;113: 1381-1402. © 2015 Wiley Periodicals, Inc.
• Song, S., Faleo, G., Yeung, R., Kant, R., Posselt, A. M., Desai, T. A., Tang, Q., & Roy, S. (2016). Silicon nanopore membrane (SNM) for islet encapsulation and immunoisolation under convective transport. Scientific reports, 6, 23679.
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  Problems associated with islet transplantation for Type 1 Diabetes (T1D) such as shortage of donor cells, use of immunosuppressive drugs remain as major challenges. Immune isolation using encapsulation may circumvent the use of immunosuppressants and prolong the longevity of transplanted islets. The encapsulating membrane must block the passage of host's immune components while providing sufficient exchange of glucose, insulin and other small molecules. We report the development and characterization of a new generation of semipermeable ultrafiltration membrane, the silicon nanopore membrane (SNM), designed with approximately 7 nm-wide slit-pores to provide middle molecule selectivity by limiting passage of pro-inflammatory cytokines. Moreover, the use of convective transport with a pressure differential across the SNM overcomes the mass transfer limitations associated with diffusion through nanometer-scale pores. The SNM exhibited a hydraulic permeability of 130 ml/hr/m(2)/mmHg, which is more than 3 fold greater than existing polymer membranes. Analysis of sieving coefficients revealed 80% reduction in cytokines passage through SNM under convective transport. SNM protected encapsulated islets from infiltrating cytokines and retained islet viability over 6 hours and remained responsive to changes in glucose levels unlike non-encapsulated controls. Together, these data demonstrate the novel membrane exhibiting unprecedented hydraulic permeability and immune-protection for islet transplantation therapy.
• Song, S., Kim, E. J., Bahney, C. S., Miclau, T., Marcucio, R., & Roy, S. (2015). The synergistic effect of micro-topography and biochemical culture environment to promote angiogenesis and osteogenic differentiation of human mesenchymal stem cells. Acta biomaterialia, 18, 100-11.
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  Critical failures associated with current engineered bone grafts involve insufficient induction of osteogenesis of the implanted cells and lack of vascular integration between graft scaffold and host tissue. This study investigated the combined effects of surface microtextures and biochemical supplements to achieve osteogenic differentiation of human mesenchymal stem cells (hMSCs) and revascularization of the implants in vivo. Cells were cultured on 10μm micropost-textured polydimethylsiloxane (PDMS) substrates in either proliferative basal medium (BM) or osteogenic medium (OM). In vitro data revealed that cells on microtextured substrates in OM had dense coverage of extracellular matrix, whereas cells in BM displayed more cell spreading and branching. Cells on microtextured substrates in OM demonstrated a higher gene expression of osteoblast-specific markers, namely collagen I, alkaline phosphatase, bone sialoprotein, and osteocalcin, accompanied by substantial amount of bone matrix formation and mineralization. To further investigate the osteogenic capacity, hMSCs on microtextured substrates under different biochemical stimuli were implanted into subcutaneous pockets on the dorsal aspect of immunocompromised mice to study capacity for ectopic bone formation. In vivo data revealed greater expression of osteoblast-specific markers coupled with increased vascular invasion on microtextured substrates with hMSCs cultured in OM. Together, these data represent a novel regenerative strategy that incorporates defined surface microtextures and biochemical stimuli to direct combined osteogenesis and re-vascularization of engineered bone scaffolds for musculoskeletal repair and relevant bone tissue engineering applications.
• Chen, Y., Song, S., Yan, Z., Fenniri, H., & Webster, T. J. (2011). Self-assembled rosette nanotubes encapsulate and slowly release dexamethasone. International journal of nanomedicine, 6, 1035-44.
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  Rosette nanotubes (RNTs) are novel, self-assembled, biomimetic, synthetic drug delivery materials suitable for numerous medical applications. Because of their amphiphilic character and hollow architecture, RNTs can be used to encapsulate and deliver hydrophobic drugs otherwise difficult to deliver in biological systems. Another advantage of using RNTs for drug delivery is their biocompatibility, low cytotoxicity, and their ability to engender a favorable, biologically-inspired environment for cell adhesion and growth. In this study, a method to incorporate dexamethasone (DEX, an inflammatory and a bone growth promoting steroid) into RNTs was developed. The drug-loaded RNTs were characterized using diffusion ordered nuclear magnetic resonance spectroscopy (DOSY NMR) and UV-Vis spectroscopy. Results showed for the first time that DEX can be easily and quickly encapsulated into RNTs and released to promote osteoblast (bone-forming cell) functions over long periods of time. As a result, RNTs are presented as a novel material for the targeted delivery of hydrophobic drugs otherwise difficult to deliver.
• Song, S., Chen, Y., Yan, Z., Fenniri, H., & Webster, T. J. (2011). Self-assembled rosette nanotubes for incorporating hydrophobic drugs in physiological environments. International journal of nanomedicine, 6, 101-7.
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  Rosette nanotubes (RNTs) are novel, biomimetic, injectable, self-assembled nanomaterials. In previous studies, materials coated with RNTs have significantly increased cell growth (eg, osteoblasts, chondrocytes, and endothelial cells) due to the favorable cellular environment created by RNTs. It has also been suggested that the tubular RNT structures formed by base stacking and hydrophobic interactions can be used for drug delivery, and this possibility has not been studied to date. Here we investigated methods to load and deliver tamoxifen (TAM, a hydrophobic anticancer drug) using two different types of RNTs: single- base RNTs and twin-base RNTs. Drug-loaded RNTs were characterized by nuclear magnetic resonance spectroscopy, diffusion-ordered nuclear magnetic resonance spectroscopy (DOSY NMR), and ultraviolet-visible (UV-Vis) spectroscopy at different ratios of twin-base RNTs to TAM. The results demonstrated successful incorporation of hydrophobic TAM into RNTs. Importantly, because of the hydrophilicity of the outer surface of the RNTs, TAM-loaded RNTs were dissolved in water, and thus have great potential to deliver hydrophobic drugs in various physiological environments. The results also showed that twin-base RNTs further improved TAM loading. Therefore, this study demonstrated that hydrophobic pharmaceutical agents (such as TAM), once considered hard to deliver, can be easily incorporated into RNTs for anticancer treatment purposes.
• Song, S., Yupeng, C., Fenniri, H., & Webster, T. J. (2010). A novel drug delivery device for orthopedic applications. IEEE. doi:10.1109/nebc.2010.5458247
• Ward, C. J., Song, S., & Davis, E. W. (2010). Controlled release of tetracycline-HCl from halloysite-polymer composite films. Journal of nanoscience and nanotechnology, 10(10), 6641-9.
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  The first direct comparison between two common methods for loading halloysite with a small molecule for controlled release is presented. While the methods differ in the degree of simplicity, they provide essentially the same level of loading and release kinetics. A tentative explanation of the "burst" effect often seen in the release of low molecular weight molecules from halloysite is provided. The ability of halloysite to mediate the release rate of a water soluble drug, tetracycline, from solution cast polyvinyl alcohol and polymethyl methacrylate films was evaluated. In some films, montmorillonite was also incorporated. The addition of montmorillonite to solutions used to cast tetracycline containing films significantly reduced the release rate from the dried films. The same overall effect was seen when the drug was loaded into halloysite prior to preparation of the films. In both cases, the release was best fit with the simple Higuchi model. However, when montmorillonite was added to solutions of polyvinyl alcohol and drug loaded halloysite the release profiles were better fit by the Ritgar-Peppas model for anomalous transport. Release from polymethyl methacrylate was reduced by a factor of three by incorporating the drug in halloysite prior to producing the films.
• Chen, Y., Song, S., Fenniri, H., & Webster, T. J. (2009). Drug Deliverable, Self-assembled Rosette Nanotubes (RNTs) for Orthopedic Applications. MRS Proceedings. doi:10.1557/proc-1209-yy07-17
• Song, S., Chen, Y., & Webster, T. J. (2009). Studies of controlled release of drug from Helical Rosette Nanotubes (HRN). IEEE. doi:10.1109/nebc.2009.4967646
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  Helical Rosette Nanotubes (HRN) are novel biomimetic self-asssembled supramolecular, whose DNA base-pairs (G & C) can solidify in water under physiological conditions. Due to electrostatic force and interactions effects, a stable stack with an inner channel 11a in diameter is formed. Because of their hollow structure and amino side chains (lysine), they can either trap or be functionalized with high-density of peptides and drugs. Research has shown that current bone implants (Ti) coated with simple HRN enhance the proliferation of osteoblasts [1]. Thus, using drug-loaded HRN with better efficacy and release rate is crucial to drug delivery, especially when they can be directly injected in damaged cartilage areas along with other tissue healing growth factors and stem cells for anti-inflammatory effects, promoting healthy tissue growth to its maximum capacity. Our experiments study the controlled release of HRN incorporated with dexamethosone and their encapsulation in alginate polymer. Results suggest that HRN increase surface wettability and enhance drug absorption onto glass slide surface. Furthermore, the drug-loaded HRN exhibits a sustainable and prolongs releasing time in the experiments. The polymer incorporated drug-loaded HRN also confirms this trend. Unlike the traditional drug delivery system, properties such as injectability, self-assembly, functional groups of HRN strengthen the binding association between the drug and the delivery agents.

Proceedings Publications

• Oh, B., Song, S., Lam, V., Levinson, A., & George, P. (2018). In vivo Electrical Stimulation of Neural Stem Cells via Conductive Polymer Scaffold Improves Endogenous Repair Mechanisms of Stroke Recovery (P4.028). In Neurology.
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  Objective: The electrically conductive scaffold for human neural progenitor cell (NPC) implantation provides a novel tool to analyze mechanisms of stroke recovery and optimize stem cells for stroke therapy. Proposed research will help further dissect how NPCs enhance stroke recovery. Background: Brain stimulation to enhance post-stroke recovery are a promising area of research; however, in vivo electrical stimulation combined with NPCs transplantation has not been fully understood. Our proposal offers a novel platform to electrically interact with NPCs in vivo to elucidate recovery mechanisms and optimize therapeutic efficiency. Design/Methods: The conductive polymer scaffold consisting of a polypyrrole polymer was seeded with NPCs (Aruna Biomedical) and implanted along with a reference electrode. Immunocompromised rats underwent a distal middle cerebral artery occlusion stroke. After 1 week post-stroke, implantation surgeries were performed. Electrical stimulation (ES) (AC: ±400 mV/100Hz for 1 hr, starting 1 day after implantation, n=10) was applied daily for 3 consecutive days. Blinded, behavior testing was performed for 6 weeks. Immunostaining was performed to determine endogenous NPC population (anti-BrdU, Abcam). Results: A cannula system has been designed to locally deliver NPCs with in vivo ES. NPCs with in vivo ES had an earlier recovery than the other groups. The NPC without in vivo ES also outperformed the cannula with the ES alone, the cannula alone, and the sham groups. Combination therapy of NPCs with in vivo ES enhanced post-stroke endogenous stem cells population in the subventricular zones. Conclusions: In conclusion, the electrically conductive scaffold for NPC implantation with in vivo ES provides a novel tool to analyze mechanisms of stroke recovery and optimize stem cells for stroke therapy. The results dissected how NPCs with in vivo ES enhance stroke recovery and increase endogenous stem cell population. Our platform enables the manipulation of NPCs in vivo to optimize recovery and evaluate the important mechanisms for functional improvement. Disclosure: Dr. Oh has nothing to disclose. Dr. Song has nothing to disclose. Dr. Lam has nothing to disclose. Dr. Levinson has nothing to disclose. Dr. George has nothing to disclose.
• Song, S., Chen, Y., Fenniri, H., & Webster, T. (2010). A novel drug delivery device for orthopedic applications. In IEEE.
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  Rosette nanotubes (RNTs) are novel, biomimetic, synthetic, self-assembled drug delivery agents. Because of base stacking and hydrophobic interactions, the RNT hollow-tube structure can be used for incorporating drugs. Another advantage of using RNTs is their ability to be injected and become solid at body temperatures for orthopedic applications without the use of any external stimuli (such as UV light or crosslinking agents). The nano-features of RNTs create a favorable, biologically-inspired, cellular environment. In this study, methods to incorporate DEX (DEX, a bone growth promoting drug) into RNTs were investigated. The drug-loaded RNTs were characterized using Nuclear Magnetic Resonance (NMR), Diffusion Ordered Spectroscopy (DOSY) and Ultraviolet-visible Spectroscopy (UV-vis). Results showed that small molecular drugs with hydrophobic aromatic rings were incorporated into RNTs. Subsequent drug release experiments demonstrated that DEX was released from the RNTs and had a positive impact on osteoblast functions. Importantly, compared to other drug carriers, RNTs increased the total drug loading and was the highest when DEX was incorporated during the RNT self-assembly process. Thus, this study offered a novel drug delivery device that itself is bioactive and can be used to deliver a variety of drugs for various orthopedic applications. ©2010 IEEE.
• Song, S., Chen, Y., & Webster, T. (2009). Studies of controlled release of drug from Helical Rosette Nanotubes (HRN). In IEEE.
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  Helical Rosette Nanotubes (HRN) are novel biomimetic self-asssembled supramolecular, whose DNA base-pairs (G & C) can solidify in water under physiological conditions. Due to electrostatic force and interactions effects, a stable stack with an inner channel 11Å in diameter is formed. Because of their hollow structure and amino side chains (lysine), they can either trap or be functionalized with high-density of peptides and drugs. Research has shown that current bone implants (Ti) coated with simple HRN enhance the proliferation of osteoblasts [I]. Thus, using drugloaded HRN with better efficacy and release rate is crucial to drug delivery, especially when they can be directly injected in damaged cartilage areas along with other tissue healing growth factors aud stem cells for anti-inflammatory effects, promoting healthy tissue growth to its maximum capacity. Our experiments study the controlled release of HRN incorporated with dexamethosone and their encapsulation in alginate polymer. Results suggest that HRN increase surface wettability and enhance drug absorption onto glass slide surface. Furthermore, the drug-loaded HRN exhibits a sustainable and prolongs releasing time in the experiments. The polymer incorporated drug-loaded HRN also confirms this trend. Unlike the traditional drug delivery system, properties such as injectability, self-assembly, functional groups of HRN strengthen the binding association between the drug aud the delivery agents.