Xiaoyi Wu

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• Chen, H., Ma, Y., Wang, X., Wu, X., & Zha, Z. (2017). Facile synthesis of Prussian blue nanoparticles as pH-responsive drug carriers for combined photothermal-chemo treatment of cancer. RSC ADVANCES, 7(1), 248-255.
• Wang, X., Ma, Y., Chen, H., Wu, X., Qian, H., Yang, X., & Zha, Z. (2017). Novel doxorubicin loaded PEGylated cuprous telluride nanocrystals for combined photothermal-chemo cancer treatment. COLLOIDS AND SURFACES B-BIOINTERFACES, 152, 449-458.
• Cohn, C., Leung, S. L., Crosby, J., Lafuente, B., Zha, Z., Teng, W., Downs, R., & Wu, X. (2016). Lipid-mediated protein functionalization of electrospun polycaprolactone fibers. EXPRESS POLYMER LETTERS, 10(5), 430-437.
• Teng, W., Zhang, X., Merkle, V., & Wu, X. (2016). Deformation-induced mechanical anisotropy of gelatin films. Extreme Mechanics Letters, 7, 18-26. doi:10.1016/j.eml.2016.02.010
• Cohn, C., Leung, S. L., Zha, Z., Crosby, J., Teng, W., & Wu, X. (2015). Comparative study of antibody immobilization mediated by lipid and polymer fibers. COLLOIDS AND SURFACES B-BIOINTERFACES, 134, 1-7.
• Merkle, V. M., Martin, D., Hutchinson, M., Tran, P. L., Behrens, A., Hossainy, S., Sheriff, J., Bluestein, D., Wu, X., & Slepian, M. J. (2015). Hemocompatibility of Poly(vinyl alcohol)-Gelatin Core-Shell Electrospun Nanofibers: A Scaffold for Modulating Platelet Deposition and Activation. ACS APPLIED MATERIALS & INTERFACES, 7(15), 8302-8312.
• Merkle, V. M., Martin, D., Hutchinson, M., Tran, P. L., Behrens, A., Hossainy, S., Sheriff, J., Bluestein, D., Wu, X., & Slepian, M. J. (2015). Hemocompatibility of Poly(vinyl alcohol)-Gelatin Core-Shell Electrospun Nanofibers: A Scaffold for Modulating Platelet Deposition and Activation. ACS applied materials & interfaces, 7(15), 8302-12.
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  In this study, we evaluate coaxial electrospun nanofibers with gelatin in the shell and poly(vinyl alcohol) (PVA) in the core as a potential vascular material by determining fiber surface roughness, as well as human platelet deposition and activation under varying conditions. PVA scaffolds had the highest surface roughness (Ra=65.5±6.8 nm) but the lowest platelet deposition (34.2±5.8 platelets) in comparison to gelatin nanofibers (Ra=36.8±3.0 nm and 168.9±29.8 platelets) and coaxial nanofibers (1 Gel:1 PVA coaxial, Ra=24.0±1.5 nm and 150.2±17.4 platelets. 3 Gel:1 PVA coaxial, Ra=37.1±2.8 nm and 167.8±15.4 platelets). Therefore, the chemical structure of the gelatin nanofibers dominated surface roughness in platelet deposition. Due to their increased stiffness, the coaxial nanofibers had the highest platelet activation rate, rate of thrombin formation, in comparison to gelatin and PVA fibers. Our studies indicate that mechanical stiffness is a dominating factor for platelet deposition and activation, followed by biochemical signals, and lastly surface roughness. Overall, these coaxial nanofibers are an appealing material for vascular applications by supporting cellular growth while minimizing platelet deposition and activation.
• Merkle, V. M., Tran, P. L., Hutchinson, M., Ammann, K. R., DeCook, K., Wu, X., & Slepian, M. J. (2015). Core-shell PVA/gelatin electrospun nanofibers promote human umbilical vein endothelial cell and smooth muscle cell proliferation and migration. ACTA BIOMATERIALIA, 27, 77-87.
• Leung, S. L., Zha, Z., Cohn, C., Dai, Z., & Wu, X. (2014). Anti-EGFR Antibody Conjugated Organic-inorganic Hybrid Lipid Nanovesicles Selectively Target Tumor Cells. Colloids and Surfaces B: Biointerfaces, 121, 141-149.
• Merkle, V. M., Zeng, L., Slepian, M. J., & Wu, X. (2014). Core-shell Nanofibers: Integrating the Bioactivity of Gelatin and the Mechanical Property of Polyvinyl Alcohol. Biopolymers, 101(4), 336-346.
• Zeng, L., Jiang, L., Teng, W., Cappello, J., Zohar, Y., & Wu, X. (2014). Engineering Aqueous Fiber Assembly into Silk-elastin-like Protein Polymers. Macromolecular Rapid Communications, 35(14), 1273-1279.
• Zeng, L., Teng, W., Jiang, L., Cappello, J., & Wu, X. (2014). Ordering Recombinant Silk-elastic-like Nanofibers on the Mircoscale. Applied Physics Letters, 104(3), 033702.
• Merkle, V. M., Ammann, K. R., DeCook, K. J., Tran, P. L., Slepian, M. J., & Xiaoyi, W. u. (2013). In vitro biocompatibility of coaxial electrospun scaffolds for cardiovascular tissue engineering. ASME 2013 Summer Bioengineering Conference, SBC 2013, 1 A.
• Merkle, V. M., Hutchinson, M., Tran, P. L., Sheriff, J., Bluestein, D., Xiaoyi, W. u., & Slepian, M. J. (2013). Platelet activity of coaxial electrospun scaffolds for applications in cardiovascular tissue engineering. ASME 2013 Summer Bioengineering Conference, SBC 2013, 1 A.
• Merkle, V., Zeng, L., Teng, W., Slepian, M., & Wu, X. (2013). Gelatin shells strengthen polyvinyl alcohol core-shell nanofibers. POLYMER, 54(21), 6003-6007.
• Merkle, V., Zeng, L., Teng, W., Slepian, M., & Wu, X. (2013). Gelatin shells strengthen polyvinyl alcohol core-shell nanofibers. Polymer (United Kingdom), 54(21), 6003-6007.
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  Abstract: In this study, polyvinyl alcohol (PVA) and gelatin are coaxially electrospun into core-shell nanofibers to derive mechanical strength from PVA and bioactivity from gelatin. The core-shell nanofibers with PVA in the core and gelatin in the shell display an increased Young's modulus, improved tensile strength, and reduced plastic deformation than PVA nanofibers. When the order of gelatin and PVA is reversed in the core-shell nanofibers, however, the mechanical strengthening effects disappear. It thus suggests that the bioactive yet mechanically weak gelatin shell improves the molecular alignment of PVA in the core and transforms the weak, plastic PVA into a strong, elastic PVA. The use of a gelatin shell as a biological coating and a protecting barrier to strengthen the core in electrospinning presents a new strategy for fabricating advanced composite nanofibers. © 2013 Elsevier Ltd. All rights reserved.
• Cao, Z., Yue, X., Jin, Y., Wu, X., & Dai, Z. (2012). Modulation of release of paclitaxel from composite cerasomes. COLLOIDS AND SURFACES B-BIOINTERFACES, 98, 97-104.
• Cao, Z., Yue, X., Jin, Y., Xiaoyi, W. u., & Dai, Z. (2012). Modulation of release of paclitaxel from composite cerasomes. Colloids and Surfaces B: Biointerfaces, 98, 97-104.
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  PMID: 22659210;Abstract: Efforts to improve the stability of liposomes have recently led to the development of organic-inorganic liposomal cerasomes. In this study, we explore the potential to modulate the sustained release of paclitaxel from cerasomes by alteration in vesicle composition. Specifically, composite cerasomes have been prepared from mixtures of cerasome-forming lipid (lipid 1) and 1,2-distearoyl- sn-glycero-3-phosphocholine (lipid 2) via one-step construction. The influences of vesicle composition on the physical properties (e.g., particle diameter and surface charge density), physiochemical and long-term storage stability, drug-loading capacity, and release rates of paclitaxel have been investigated. Notably, a wide range of the release profiles of paclitaxel have been achieved by varying the contents of lipid 2, and the composite vesicles display excellent stability when the percentage content of lipid 2 is lower than 50%. Composite vesicles composed of lipids 1 and 2 at a 1:1 molar ratio also exhibited good cytocompatibility and the released paclitaxel effectively inhibit the proliferation of HeLa cancer cells. Together, the development of composite vesicles offers a promising strategy to obtain excellent stability, good drug-loading capacity and cytocompatibility, and enhanced paclitaxel release in single vesicles. © 2012 Elsevier B.V.
• Guo, C., Zeng, L., Liu, S., Chen, Q., Dai, Z., & Wu, X. (2012). In vitro evaluation and finite element simulation of drug release from polydiacetylene-polyethylene glycol stearate nanovesicles. Journal of Nanoscience and Nanotechnology, 12(1), 245-251.
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  PMID: 22523972;Abstract: Vesicles comprised of 10,12-pentacosadiynoic acid (PCDA) were modified, using polyethylene glycol 40 stearate (PEG40S), and crosslinked by ultraviolet (UV) irradiation to create polymerized nanovesicles for sustained drug release. Paclitaxel, a water-insoluble compound widely used in cancer chemotherapy, was used as a model drug to examine the physicochemical stability and release profiles of PCDA/PEG40S nanovesicles. TEM analysis revealed the formation of paclitaxelencapsulated PCDA/PEG40S nanovesicles of 40 to 200 nm in size. Upon the addition of ethanol, instantaneous releases of paclitaxel in the amount of 28 μg/mL from polymerized PCDA/PEG40S nanovesicles and 108 μg/ml from unpolymerized ones were observed. This suggested the noncomplete drug release from polymerized PCDA/PEG40S nanovesicles due to their enhanced physicochemical stability by ultraviolet irradiation-induced polymerization, if compared to unpolymerized ones. An in vitro study demonstrated that an accumulative release of 2401±3.1% and 8.1±1.7% of paclitaxel was obtained within 24 hrs from nanovesicles comprised of PCDA/PEG40S at a 9:1 and 7:3 molar ratio, respectively. A finite element model that considered the diffusion-driven releases and the reversible drug-vesicle interaction captured the sustained release of paclitaxel from polymerized PCDA/PEG40S nanovesicles. PCDA/PEG40S nanovesicles capable of sustained release and with enhanced physicochemical stability thus possess great potential for applications in drug release. Copyright © 2012 American Scientific Publishers All rights reserved.
• Jin, Y., Yue, X., Zhang, Q., Wu, X., Cao, Z., & Dai, Z. (2012). Cerasomal doxorubicin with long-term storage stability and controllable sustained release. ACTA BIOMATERIALIA, 8(9), 3372-3380.
• Jin, Y., Yue, X., Zhang, Q., Xiaoyi, W. u., Cao, Z., & Dai, Z. (2012). Cerasomal doxorubicin with long-term storage stability and controllable sustained release. Acta Biomaterialia, 8(9), 3372-3380.
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  PMID: 22659275;Abstract: Liposomal nanohybrid cerasomes display a remarkable ability to maintain their size and retain encapsulated doxorubicin (DOX) over a period of 90 days under storage conditions in solution compared with liposomes and liposils. Cerasomes retained 92.1 ± 2.9% of the drug payload after 90 days storage, much more than liposomes (35.2 ± 2.5%) and liposils (53.2 ± 5.5%). Under physiologically relevant conditions cerasomes exhibit a low initial burst in the first 5 h and subsequent sustained release of DOX over the next 150 h. Moreover, the magnitude of the initial burst and the rate of sustained release of DOX from cerasomes can be modulated by incorporating dipalmitoylphosphatidylglycerol (DPPG) in the cerasome structure and altering the ratios of the cerasome-forming lipid and phospholipids. Consequently, a wide range of release profiles can be achieved by altering the vesicle composition. Finally, human ovarian cancer cells are effectively killed by DOX released from cerasomes. Together these results suggest that cerasomes may be a promising drug delivery system for the long-term storage and controllable sustained release of the anticancer drug DOX. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
• Leung, S. L., Zha, Z., Teng, W., Cohn, C., Dai, Z., & Wu, X. (2012). Organic-inorganic nanovesicles for doxorubicin storage and release. Soft Matter, 8(21), 5756-5764.
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  Abstract: The potential of organic-inorganic liposomal cerasomes to store and release doxorubicin (DOX) is investigated. Specifically, cerasomes display sustained DOX release in serum-enriched cell culture medium but minimal drug leakage in deionized water. As revealed by a physics-based model, the medium-sensitive DOX release/leakage is attributed to serum-mediated dissociation of DOX molecules. DOX-loaded cerasomes effectively inhibit the proliferation of human prostate cancer DU145 cells. Furthermore, the kinetics of cerasome uptake/internalization and DOX release correlates well with the time scale for DOX-loaded cerasomes to inhibit the proliferation of the DU145 cells. © 2012 The Royal Society of Chemistry.
• Merkle, V., & Xiaoyi, W. u. (2012). Coaxial electrospinning of gelatin/polyvinyl alcohol composite nanofibers and evaluation of their material properties. 2012 38th Annual Northeast Bioengineering Conference, NEBEC 2012, 380-381.
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  Abstract: Electrospinning has been used to fabricate nanofibrous scaffolds from a variety of synthetic and natural materials, including polyvinyl alcohol (PVA) and gelatin. Although PVA possesses appealing mechanical properties for tissue engineering applications, it lacks adequate cellular recognition sites, which limits the material's bioactivity. In contrast, gelatin has desirable bioactivity but lacks adequate mechanical properties and can be difficult to handle. Therefore, coaxial electrospinning is employed to create nanofibers of these materials in a core/shell structure with gelatin forming the shell and PVA forming the core of the fibers. In this study, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), mechanical testing, and cellular studies were utilized to evaluate the morphology and material properties of coaxially electrospun PVA/gelatin nanocomposite scaffolds in comparison to scaffolds composed of solely PVA or gelatin. This study yields insight into the potential of combining synthetic and natural polymers together in the engineering of composite nanofibers for a variety of tissue engineering applications. © 2012 IEEE.
• Zha, Z., Jiang, L., Dai, Z., & Wu, X. -. (2012). A biomimetic mechanism for antibody immobilization on lipid nanofibers for cell capture. Applied physics letters, 101(19).
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  The immobilization of membrane-bound molecules on organic-inorganic cholesteryl-succinyl silane (CSS) nanofibers is investigated. Fluorescent microscopy and a cell capture assay confirm the stable and functional immobilization of membrane-bound antibodies and imaging agents on the electrospun CSS nanofibers. An insert-and-tighten mechanism is proposed for the observed hydration-induced reduction in lipid nanofiber diameter, the immobilization of membrane-bound molecules, and the improved efficiency of cell capture by the functionalized CSS nanofibers over their film counterparts. The ability to stably and functionally immobilize membrane-bound molecules on the CSS nanofibers presents a promising method to functionalize lipid-based nanomaterials.
• Zha, Z., Leung, S. L., Dai, Z., & Wu, X. (2012). Centering of organic-inorganic hybrid liposomal cerasomes in electrospun gelatin nanofibers. Applied Physics Letters, 100(3).
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  Abstract: A study investigating the embedding of stabilized organic-inorganic liposomal cerasomes in gelatin nanofibers through the electrospinning of cerasome-dispersed gelatin aqueous solution is presented. Fluorescent and transmission electron microscopy confirm the embedding and centering of cerasomes in the electrospun nanofibers. A simple mechanism is proposed for the centering of cerasomes in gelatin nanofibers. The ability to incorporate cerasomes capable of encapsulating a variety of bioactive molecules provides a promising method to functionalize polymer nanofibers. © 2012 American Institute of Physics.
• Zha, Z., Teng, W., Markle, V., Dai, Z., & Wu, X. (2012). Fabrication of gelatin nanofibrous scaffolds using ethanol/phosphate buffer saline as a benign solvent. BIOPOLYMERS, 97(12), 1026-1036.
• Zha, Z., Teng, W., Markle, V., Dai, Z., & Wu, X. -. (2012). Fabrication of gelatin nanofibrous scaffolds using ethanol/phosphate buffer saline as a benign solvent. Biopolymers, 97(12).
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  Electrospinning of natural polymer nanofibers useful for biomedical applications often requires the use of cytotoxic organic solvents. In this study, gelatin nanofibers are electrospun from phosphate buffer saline/ethanol binary mixtures as a benign solvent at ambient temperature. The influences of ionic strength, ethanol concentration, and gelatin concentration on the electrospinnability of gelatin solutions and the fiber microarchitectures are analyzed. The electrospun scaffolds retain their morphologies during vapor-phase crosslinking with glutaraldehyde in ethanol and the subsequent removal of salts contained in the nanofibers via water rinsing. When fully hydrated, the mechanically preconditioned scaffolds display a Young's modulus of 25.5 ± 5.3 kPa, tensile strength of 55.5 ± 13.9 kPa, deformability of 160 ± 15%, and resilience of 89.9 ± 1.8%. When cultured on the gelatin scaffolds, 3T3 fibroblasts displayed spindle-like morphology, similar to the cell's normal morphology in a 3D extracellular matrix.
• Qiu, W., Cappello, J., & Wu, X. (2011). Autoclaving as a chemical-free process to stabilize recombinant silk-elastinlike protein polymer nanofibers. Applied Physics Letters, 98(26).
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  Abstract: We report here that autoclaving is a chemical-free, physical crosslinking strategy capable of stabilizing electrospun recombinant silk-elastinlike protein (SELP) polymer nanofibers. Fourier transform infrared spectroscopy showed that the autoclaving of SELP nanofibers induced a conformational conversion of -turns and unordered structures to ordered -sheets. Tensile stress-strain analysis of the autoclaved SELP nanofibrous scaffolds in phosphate buffered saline at 37 °C revealed a Young's modulus of 1.02 ±0.28 MPa, an ultimate tensile strength of 0.34 ±0.04 MPa, and a strain at failure of 29% ±3%. © 2011 American Institute of Physics.
• Teng, W., Cappello, J., & Wu, X. (2011). Physical crosslinking modulates sustained drug release from recombinant silk-elastinlike protein polymer for ophthalmic applications. JOURNAL OF CONTROLLED RELEASE, 156(2), 186-194.
• Teng, W., Cappello, J., & Wu, X. -. (2011). Physical crosslinking modulates sustained drug release from recombinant silk-elastinlike protein polymer for ophthalmic applications. Journal of controlled release : official journal of the Controlled Release Society, 156(2).
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  We evaluated the drug release capability of optically transparent recombinant silk-elastinlike protein polymer, SELP-47K, films to sustainably deliver the common ocular antibiotic, ciprofloxacin. The ciprofloxacin release kinetics from drug-loaded SELP-47K films treated with ethanol or methanol vapor to induce different densities of physical crosslinking was investigated. Additionally, the drug-loaded protein films were embedded in a protein polymer coating to further prolong the release of the drug. Drug-loaded SELP-47K films released ciprofloxacin for up to 132 h with near first-order release kinetics. Polymer coating of drug-loaded films prolonged drug release for up to 220 h. The antimicrobial activity of ciprofloxacin released from the drug delivery matrices was not impaired by the film casting process or the ethanol or methanol treatments. The mechanism of drug release was elucidated by analyzing the physical properties of the film specimens, including equilibrium swelling, soluble fraction, surface roughness and hydrophobicity. Additionally, the conformation of the SELP-47K and its physical crosslinks in the films was analyzed by FTIR and Raman spectroscopy. A three-parameter physics based model accurately described the release rates observed for the various film and coating treatments and attributed the effects to the degree of physical crosslinking of the films and to an increasing affinity of the drug with the polymer network. Together, these results indicate that optically transparent silk-elastinlike protein films may be attractive material candidates for novel ophthalmic drug delivery devices.
• Teng, W., Huang, Y., Cappello, J., & Wu, X. (2011). Optically Transparent Recombinant Silk-Elastinlike Protein Polymer Films. JOURNAL OF PHYSICAL CHEMISTRY B, 115(7), 1608-1615.
• Teng, W., Huang, Y., Cappello, J., & Wu, X. -. (2011). Optically transparent recombinant silk-elastinlike protein polymer films. The journal of physical chemistry. B, 115(7).
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  Recombinant protein polymers, evaluated extensively as biomaterials for applications in drug delivery and tissue engineering, are rarely reported as being optically transparent. Here we report the notable optical transparency of films composed of a genetically engineered silk-elastinlike protein polymer SELP-47K. SELP-47K films of 100 μm in thickness display a transmittance of 93% in the wavelength range of 350-800 nm. While covalent cross-linking of SELP-47K via glutaraldehyde decreases its transmittance to 77% at the wavelength of 800 nm, noncovalent cross-linking using methanol slightly increases it to 95%. Non- and covalent cross-linking of SELP-47K films also influences their secondary structures and water contents. Cell viability and proliferation analyses further reveal the excellent cytocompatibility of both non- and covalently cross-linked SELP-47K films. The combination of high optical transparency and cytocompatibility of SELP-47K films, together with their previously reported outstanding mechanical properties, suggests that this protein polymer may be useful in unique, new biomedical applications.
• Zeng, L., An, L., & Wu, X. -. (2011). Modeling drug-carrier interaction in the drug release from nanocarriers. Journal of drug delivery, 2011.
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  Numerous nanocarriers of various compositions and geometries have been developed for the delivery and release of therapeutic and imaging agents. Due to the high specific surface areas of nanocarriers, different mechanisms such as ion pairing and hydrophobic interaction need to be explored for achieving sustained release. Recently, we developed a three-parameter model that considers reversible drug-carrier interaction and first-order drug release from liposomes. A closed-form analytical solution was obtained. Here, we further explore the ability of the model to capture the release of bioactive molecules such as drugs and growth factors from various nanocarriers. A parameter study demonstrates that the model is capable of resembling major categories of drug release kinetics. We further fit the model to 60 sets of experimental data from various drug release systems, including nanoparticles, hollow particles, fibers, and hollow fibers. Additionally, bootstrapping is used to evaluate the accuracy of parameter determination and validate the model in selected cases. The simplicity and universality of the model and the clear physical meanings of each model parameter render the model useful for the design and development of new drug delivery systems.
• Zha, Z., Cohn, C., Dai, Z., Qiu, W., Zhang, J., & Wu, X. -. (2011). Nanofibrous lipid membranes capable of functionally immobilizing antibodies and capturing specific cells. Advanced materials (Deerfield Beach, Fla.), 23(30).
• Qiu, W., Huang, Y., Cappello, J., & Xiaoyi, W. u. (2010). Electrospun recombinant protein polymer nanofibers as a biomaterial. Proceedings of the ASME 1st Global Congress on NanoEngineering for Medicine and Biology 2010, NEMB2010, 207-208.
• Qiu, W., Huang, Y., Teng, W., Cohn, C. M., Cappello, J., & Wu, X. (2010). Complete Recombinant Silk-Elastinlike Protein-Based Tissue Scaffold. BIOMACROMOLECULES, 11(12), 3219-3227.
• Qiu, W., Huang, Y., Teng, W., Cohn, C. M., Cappello, J., & Wu, X. -. (2010). Complete recombinant silk-elastinlike protein-based tissue scaffold. Biomacromolecules, 11(12).
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  Due to their improved biocompatibility and specificity over synthetic materials, protein-based biomaterials, either derived from natural sources or genetically engineered, have been widely fabricated into nanofibrous scaffolds for tissue engineering applications. However, their inferior mechanical properties often require the reinforcement of protein-based tissue scaffolds using synthetic polymers. In this study, we report the electrospinning of a completely recombinant silk-elastinlike protein-based tissue scaffold with excellent mechanical properties and biocompatibility. In particular, SELP-47K containing tandemly repeated polypeptide sequences derived from native silk and elastin was electrospun into nanofibrous scaffolds, and stabilized via chemical vapor treatment and mechanical preconditioning. When fully hydrated in 1× PBS at 37 °C, mechanically preconditioned SELP-47K scaffolds displayed elastic moduli of 3.4-13.2 MPa, ultimate tensile strengths of 5.7-13.5 MPa, deformabilities of 100-130% strain, and resilience of 80.6-86.9%, closely matching or exceeding those of protein-synthetic blend polymeric scaffolds. Additionally, SELP-47K nanofibrous scaffolds promoted cell attachment and growth, demonstrating their in vitro biocompatibility.
• Teng, W., Huang, Y., Cappello, J., & Xiaoyi, W. u. (2010). Mechanical and in-vitro cell compatibility properties of silk-elastinlike protein-based biomaterial. Proceedings of the ASME 1st Global Congress on NanoEngineering for Medicine and Biology 2010, NEMB2010, 209-210.
• Zeng, L., & Wu, X. (2010). Modeling the sustained release of lipophilic drugs from liposomes. Applied Physics Letters, 97(7).
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  Abstract: The bilayered structure of liposomes enables the encapsulation of lipophilic drugs in their lipid bilayers and water-soluble molecules in the interior aqueous compartments. We develop a convection-driven drug release model that considers the structural characteristics of liposomes and reversible drug-lipid interaction. An analytical solution to the model is obtained. The solution agrees well with experimental data on the sustained release of lipophilic anticancer drugs from liposomes. The model provides a useful tool for the rational design of liposomal drug delivery systems. © 2010 American Institute of Physics.
• Guo, C., Liu, S., Jiang, C., Li, W., Dai, Z., Fritz, H., & Wu, X. (2009). A Promising Drug Controlled-Release System Based on Diacetylene/Phospholipid Polymerized Vesicles. LANGMUIR, 25(22), 13114-13119.
• Guo, C., Liu, S., Jiang, C., Li, W., Dai, Z., Fritz, H., & Wu, X. (2009). A promising drug controlled-release system based on diacetylene/ phospholipid polymerized vesicles. Langmuir, 25(22), 13114-13119.
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  PMID: 19852472;Abstract: A novel polymerized vesicular carrier loaded with paclitaxel was developed by introducing the ultraviolet (UV) crosslinkable 10,12-pentacosadiynoic acid (PCDA) into bilayered phospholipid vesicles with the purpose of improving the physicochemical stability as well as the controlled-release property of liposomes. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results revealed the enhanced stability of PCDA-polymerized vesicles against Triton X-100. In particular, alteration in PCDA/phospholipids ratios and UV-irradiation time can modulate the cumulative paclitaxel released. For instance, vesicles composed of phospholipids only released 98.0 ± 2.1 % of paclitaxel within 24 h. Over the same time period, 72.0 ± 5.8%, 43.9 ± 6.5%, and 20.1 ± 5.4% of paclitaxel was released from polymerized PCDA/phospholipid vesicles at molar ratios of 1:3,1:1, and 3:1, respectively. Likewise, by increasing the UV-irradiation time from 20 to 40 min, the cumulative release of paclitaxel from polymerized PCDA/phospholipid vesicles at molar ratio of 1:1 decreased from 90.5 ± 3.7% to 37.6 ± 2.3% over a time period of experimental observation of 24 h. The influences of vesicle composition (i.e., PCDA/phospholipids ratio) and UV-irradiation time on the release rates of paclitaxel were further examined by finite element (FE) analyzed using Abaqus. Our results demonstrate that novel polymerized vesicles capable of regulating the release of anticancer drugs such as paclitaxel have been developed. © 2009 American Chemical Society.
• Qiu, W., Cappello, J., & Xiaoyi, W. u. (2009). Fabrication of genetically engineered silk-elastin-like protein polymer fibers. Proceedings of the ASME Summer Bioengineering Conference, SBC2008, 179-180.
• Qiu, W., Stokes, A., Cappello, J., & Xiaoyi, W. u. (2009). Electrospinning of recombinant protein polymer nanofibers. Proceedings of the ASME Summer Bioengineering Conference 2009, SBC2009, 1183-1184.
• Qiu, W., Teng, W., Cappello, J., & Wu, X. (2009). Wet-Spinning of Recombinant Silk-Elastin-Like Protein Polymer Fibers with High Tensile Strength and High Deformability. BIOMACROMOLECULES, 10(3), 602-608.
• Qiu, W., Teng, W., Cappello, J., & Wu, X. -. (2009). Wet-spinning of recombinant silk-elastin-like protein polymer fibers with high tensile strength and high deformability. Biomacromolecules, 10(3).
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  A recombinant silk-elastin-like protein copolymer SELP-47K containing tandemly repeated amino acid sequence blocks from silk, GAGAGS, and elastin, GVGVP, was fabricated into microdiameter fibers using a wet-spinning technique. Raman spectral analysis revealed the formation of antiparallel beta-sheet crystals of the silk-like blocks. Dry SELP-47K fibers display the dependence of mechanical properties such as Young's modulus on fiber diameter, suggesting more oriented and crystallized molecular chains in small-diameter fibers. Additionally, a brittle fracture mode was identified for dry fibers by SEM analysis of fracture surfaces. Hydration dramatically influenced the mechanical behavior of SELP-47K fibers. In contrast to the high tensile strength and limited strains to failure of dry fibers, fully hydrated SELP-47K fibers possessed strains to failure as high as 700%. Furthermore, upon chemical cross-linking, a tensile mechanical strength up to 20 MPa was achieved in hydrated fibers without compromising their high deformability. By combing the silk- and elastin-derived sequences into a single SELP-47K protein polymer, we demonstrated that protein fibers with high tensile strength and high deformability can be fabricated.
• Teng, W., Cappello, J., & Wu, X. (2009). Recombinant Silk-Elastinlike Protein Polymer Displays Elasticity Comparable to Elastin. BIOMACROMOLECULES, 10(11), 3028-3036.
• Teng, W., Cappello, J., & Wu, X. -. (2009). Recombinant silk-elastinlike protein polymer displays elasticity comparable to elastin. Biomacromolecules, 10(11).
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  We evaluated the mechanical properties of the genetically engineered, recombinant silk-elastinlike protein copolymer, SELP-47K. In tensile stress-strain analysis, methanol-treated non-cross-linked SELP-47K films exceeded the properties of native aortic elastin, attaining an ultimate tensile strength of 2.5 +/- 0.4 MPa, an elastic modulus of 1.7 +/- 0.4 MPa, an extensibility of 190 +/- 60%, and a resilience of 86 +/- 4% after 10 cycles of mechanical preconditioning. Stress-relaxation and creep analysis showed that films substantially maintained their elastic properties under sustained deformation. Chemical cross-linking of SELP-47K films doubled the elastic modulus and ultimate tensile strength and enhanced the extensibility and resilience. The underlying conformational and microstructural features of the films were examined. Raman spectroscopy revealed that the silklike blocks of SELP-47K existed in antiparallel beta-sheet crystals in the films, likely responsible for the robust physical cross-links. Scanning electron microscopy (SEM) revealed that the various processing treatments and the mechanical deformation of the films induced changes in their surface microstructure consistent with the coagulation and alignment of polymer chains. These results demonstrate that films with excellent elasticity, comparable to native aortic elastin, are obtainable from SELP-47K, a protein copolymer combining both silk- and elastin-derived sequences in a single polymer chain.
• Teng, W., Cappello, J., & Xiaoyi, W. u. (2009). Secondary structures and mechanical properties of biomimetic protein polymers. Proceedings of the ASME Summer Bioengineering Conference 2009, SBC2009, 797-798.
• Teng, W., Cappello, J., & Xiaoyi, W. u. (2009). Viscoelastic properties of genetically engineered silk-elastin-like protein polymers. Proceedings of the ASME Summer Bioengineering Conference, SBC2008, 231-232.
• Keyes, J., Junkin, M., Cappello, J., Xiaoyi, W. u., & Wong, P. K. (2008). Evaporation-induced assembly of biomimetic polypeptides. Applied Physics Letters, 93(2).
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  Abstract: We report an evaporation assisted plasma lithography (EAPL) process for guided self-assembly of a biomimetic silk-elastinlike protein (SELP). We demonstrate the formation of SELP structures from millimeter to submicrometer range on plasma-treatment surface templates during an evaporation-induced self-assembly process. The self-assembly processes at different humidities and droplet volumes were investigated. The process occurs efficiently in a window of optimized operating conditions found to be at 70% relative humidity and 8 μl volume of SELP solution. The EAPL approach provides a useful technique for the realization of functional devices and systems using these biomimetic materials. © 2008 American Institute of Physics.
• Wu, X., Sallach, R. E., Caves, J. M., Conticello, V. P., & Chaikof, E. L. (2008). Deformation responses of a physically cross-linked high molecular weight elastin-like protein polymer. BIOMACROMOLECULES, 9(7), 1787-1794.
• Wu, X., Sallach, R. E., Caves, J. M., Conticello, V. P., & Chaikof, E. L. (2008). Deformation responses of a physically cross-linked high molecular weight elastin-like protein polymer. Biomacromolecules, 9(7), 1787-1794.
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  PMID: 18558738;PMCID: PMC2702094;Abstract: Recombinant protein polymers were synthesized and examined under various loading conditions to assess the mechanical stability and deformation responses of physically cross-linked, hydrated, protein polymer networks designed as triblock copolymers with central elastomeric and flanking plastic-like blocks. Uniaxial stress-strain properties, creep and stress relaxation behavior, as well as the effect of various mechanical preconditioning protocols on these responses were characterized. Significantly, we demonstrate for the first time that ABA triblock protein copolymers when redesigned with substantially larger endblock segments can withstand significantly greater loads. Furthermore, the presence of three distinct phases of deformation behavior was revealed upon subjecting physically cross-linked protein networks to step and cyclic loading protocols in which the magnitude of the imposed stress was incrementally increased over time. We speculate that these phases correspond to the stretch of polypeptide bonds, the conformational changes of polypeptide chains, and the disruption of physical cross-links. The capacity to select a genetically engineered protein polymer that is suitable for its intended application requires an appreciation of its viscoelastic characteristics and the capacity of both molecular structure and conditioning protocols to influence these properties. © 2008 American Chemical Society.
• Wu, X., Levenston, M. E., & Chaikof, E. L. (2006). A constitutive model for protein-based materials. BIOMATERIALS, 27(30), 5315-5325.
• Wu, X., Levenston, M. E., & Chaikof, E. L. (2006). A constitutive model for protein-based materials. Biomaterials, 27(30), 5315-5325.
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  PMID: 16815545;Abstract: Protein-based materials are critical to the construction of tissue substitutes that exhibit precisely defined mechanical properties. Under physiologically relevant conditions, materials derived from natural or synthetic structural proteins are characterized by nonlinear elastic responses at medium and large deformations, time-dependent or viscoelastic behavior, and display the effects of strain-induced structural changes. Although a constitutive model that accurately describes mechanical behavior is essential for the rational design of tissue constructs, few models account for all of these characteristics. In this report, we present a new constitutive model for protein based materials, in which nonlinear elasticity is captured by the Arruda-Boyce eight-chain model, time dependant viscoelasticity is described by a generalized Maxwell model, and the effect of strain-induced structural change is incorporated using a network alteration theory originally proposed by Tobolsky. The model was applied to a number of protein-based materials and cell containing constructs, including recombinant elastin-mimetic protein polymers and fibroblast populated collagen gel matrices. Significantly, numerical implementation of this model is straightforward and mechanical behavior accurately described under a variety of loading conditions. Moreover, when calibrated using stress relaxation data alone, the model accurately predicted cyclic loading responses. Although limitations exist, this model provides a convenient tool to correlate viscoelastic data obtained by different testing modes and may assist in reducing the number of experimental tests required to fully capture the range of viscoelastic responses of protein-based materials. © 2006 Elsevier Ltd. All rights reserved.
• Dong, C., Xiaoyi, W. u., Caves, J., Rele, S. S., Thomas, B. S., & Chaikof, E. L. (2005). Photomediated crosslinking of C6-cinnamate derivatized type I collagen. Biomaterials, 26(18), 4041-4049.
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  PMID: 15626450;Abstract: Synthesis and characterization of cinnamated Type I collagen and its related mechanical properties after photomediated crosslinking were investigated in detail. Using an EDC/NHS conjugation method, collagen was chemically modified to incorporate a photosensitive cinnamate moiety. The cinnamated collagen was fully characterized by 1H NMR, UV-vis, and circular dichroism (CD) spectroscopy, as well as by rheological and mechanical analyses. Cinnamated collagens with varying degrees of derivatization retained collagen triple helical structure. The rheological spectra of collagen solutions demonstrate that the storage modulus decreases with increasing cinnamate content, owing to a decrease in physical crosslinking. The kinetics of the crosslinking process in both hydrated gels and dry films were monitored by UV-vis spectroscopy and confirmed that crosslinking was complete within 60 min of irradiation. The uniaxial stress-strain behavior of crosslinked collagen films, including Young's modulus and ultimate tensile strength, was comparable to values reported for glutaraldehyde-crosslinked monomeric collagen films. These data demonstrate that derivatization of collagen with photosensitive cinnamate moieties provides a facile route for solid-state crosslinking, thereby improving the mechanical properties of collagen and enhancing the potential applicability of collagen-based materials in tissue engineering and drug delivery. © 2004 Elsevier Ltd. All rights reserved.
• Nagapudi, K., Brinkman, W. T., Leisen, J., Thomas, B. S., Wright, E. R., Haller, C., Xiaoyi, W. u., Apkarian, R. P., Conticello, V. P., & Chaikof, E. L. (2005). Protein-based thermoplastic elastomers. Macromolecules, 38(2), 345-354.
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  Abstract: Investigations of high molecular weight recombinant protein triblock copolymers demonstrate unique opportunities to systematically modify material microstructure on both nano- and meso-length scales in a manner not been previously demonstrated for protein polymer systems. Significantly, through the biosynthesis of BAB-type copolymers containing flanking, plastic-like end blocks and an elastomeric midblock, virtually cross-linked protein-based materials were generated that exhibit tunable properties in a manner completely analogous to synthetic thermoplastic elastomers. Through the rational choice of processing conditions that control meso- and nanoscale structure, changes of greater than 3 orders of magnitude in Young's modulus (0.03-35 MPa) and 5-fold in elongation to break (250-1300%) were observed. Extensibility of this range or magnitude has not been previously reported for virtually cross-linked copolymers that have been produced by either chemical or biosynthetic approaches. We anticipate that these versatile protein-based thermoplastic elastomers will find applications as novel scaffolds for tissue engineering and as new biomaterials for controlled drug release and cell encapsulation.
• Sun, X., Haller, C. A., XiaoYi, W. u., Conticello, V. P., & Chaikof, E. L. (2005). One-pot glyco-affinity precipitation purification for enhanced proteomics: The flexible alignment of solution-phase capture/release and solid-phase separation. Journal of Proteome Research, 4(6), 2355-2359.
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  PMID: 16335985;Abstract: A one-pot affinity precipitation purification of carbohydrate-binding protein was demonstrated by designing thermally responsive glyco-polypeptide polymers, which were synthesized by selective coupling of pendant carbohydrate groups to a recombinant elastin-like triblock protein copolymer (ELP). The thermally driven inverse transition temperature of the ELP-based triblock polymer is maintained upon incorporation of carbohydrate ligands, which was confirmed by differential scanning calorimetry and 1H NMR spectroscopy experiments. As a test system, lactose derivatized ELP was used to selectively purify a galactose-specific binding lectin through simple temperature-triggered precipitation in a high level of efficiency. Potential opportunities might be provided for enhanced proteomic, cell isolation as well as pathogen detection applications. © 2005 American Chemical Society.
• Wu, X., Sallach, R., Haller, C. A., Caves, J. A., Nagapudi, K., Conticello, V. P., Levenston, M. E., & Chaikof, E. L. (2005). Alterations in physical cross-linking modulate mechanical properties of two-phase protein polymer networks. Biomacromolecules, 6(6), 3037-3044.
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  PMID: 16283724;Abstract: Physically cross-linked protein-based materials possess a number of advantages over their chemically cross-linked counterparts, including ease of processing and the ability to avoid the addition or removal of chemical reagents or unreacted intermediates. The investigations reported herein sought to examine the nature of physical cross-links within two-phase elastin-mimetic protein triblock copolymer networks through an analysis of macroscopic viscoelastic properties. Given the capacity of solution processing conditions, including solvent type and temperature to modulate the microstructure of two-phase protein polymer networks, viscoelastic properties were examined under conditions in which interphase block mixing had been either accentuated or diminished during network formation. Protein networks exhibited strikingly different properties in terms of elastic modulus, hysteresis, residual deformability, and viscosity in response to interdomain mixing. Thus, two-phase protein polymer networks exhibit tunable responses that extend the range of application of these materials to a variety of tissue engineering applications. © 2005 American Chemical Society.
• Wu, X., Ramesh, K. T., & Wright, T. W. (2003). The coupled effects of plastic strain gradient and thermal softening on the dynamic growth of voids. International Journal of Solids and Structures, 40(24), 6633-6651.
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  Abstract: This paper examines the combined effects of temperature, strain gradient and inertia on the growth of voids in ductile fracture. A dislocation-based gradient plasticity theory [J. Mech. Phys. Solids 47 (1999) 1239, J. Mech. Phys. Solids 48 (2000) 99] is applied, and temperature effects are incorporated. Since a strong size-dependence is introduced into the dynamic growth of voids through gradient plasticity, a cut-off size is then set by the stress level of the applied loading. Only those voids that are initially larger than the cut-off size can grow rapidly. At the early stages of void growth, the effects of strain gradients greatly increase the stress level. Therefore, thermal softening has a strong effect in lowering the threshold stress for the unstable growth of voids. Once the voids start rapid growth, however, the influence of strain gradients will decrease, and the rate of dynamic void growth predicted by strain gradient plasticity approaches that predicted by classical plasticity theories. © 2003 Elsevier Ltd. All rights reserved.
• Wu, X., Ramesh, K. T., & Wright, T. W. (2003). The dynamic growth of a single void in a viscoplastic material under transient hydrostatic loading. Journal of the Mechanics and Physics of Solids, 51(1), 1-26.
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  Abstract: We have examined the problem of the dynamic growth of a single spherical void in an elastic-viscoplastic medium, with a view towards addressing a number of problems that arise during the dynamic failure of metals. Particular attention is paid to inertial, thermal and rate-dependent effects, which have not previously been thoroughly studied in a combined setting. It is shown that the critical stress for unstable growth of the void in the quasistatic case is strongly affected by the thermal softening of the material (in adiabatic calculations). Thermal softening has the effect of lowering the critical stress, and has a stronger influence at high strain hardening exponents. It is shown that the thermally diffusive case for quasistatic void growth in rate-dependent materials is strongly affected by the initial void size, because of the length scale introduced by the thermal diffusion. The effects of inertia are quantified, and it is demonstrated that inertial effects are small in the early stages of void growth and are strongly dependent on the initial size of the void and the rate of loading. Under supercritical loading for the inertial problem, voids of all sizes achieve a constant absolute void growth rate in the long term. Inertia first impedes, but finally promotes dynamic void growth under a subcritical loading. For dynamic void growth, the effect of rate-hardening is to reduce the rate of void growth in comparison to the rate-independent case, and to reduce the final relative void growth achieved. © 2002 Elsevier Science Ltd. All rights reserved.
• Wu, X., Ramesh, K. T., & Wright, T. W. (2003). The effects of thermal softening and heat conduction on the dynamic growth of voids. International Journal of Solids and Structures, 40(17), 4461-4478.
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  Abstract: This paper seeks to examine the dynamic growth of a single void in an elastic-plastic medium through analytical and numerical approaches. Particular attention is paid to the instability of void growth, and to the effects of inertia, thermal softening and heat conduction. A critical stress is known to exist for the unstable growth of voids. The dependence of this critical stress on material properties is examined, and this critical stress is demonstrated to correspond to the lower limit for the ductile spall strength in many materials. The effects of heat conduction on the dynamic growth of voids strongly depend on the time and length scales in the early stages of the dynamic void growth. © 2003 Elsevier Ltd. All rights reserved.

Proceedings Publications

• Nicolini, A. M., Cohn, C. M., Gamboa, J. R., Slepian, M. J., Wu, X., & Yoon, J. (2014, Apr). Fabrication of a pro-adhesive surface using electrospun PCL nanofibers interspersed with peptide conjugated polystyrene particles. In IEEE-NEMS 2014.

Presentations

• Cohn, C., Frazer, L., Pearse, M., Leung, S., & Wu, X. (2014, February 28). Engineering Cholesterol-based Nanostructures as Diagnostic Platforms. BME Founder's Day. University of Arizona, Tucson, AZ.
• Cohn, C., Frazer, L., Pearse, M., Leung, S., & Wu, X. (2014, October 22-25). Engineering Minimally Invasive Diagnostic Platforms with Cholesterol-based Nanostructures. Biomedical Engineering Society Annual Meeting. San Antonio, TX.
• Nicolini, A. M., Cohn, C. M., Slepian, M. J., Wu, X., & Yoon, J. (2014, Mar). Fabrication of a pro-adhesive surface using electrospun PCL nanofibers interspersed with peptide conjugated polystyrene particles. Annual Meeting of IBE. Lexington, KY: IBE.

Others

• Wu, X. (2016, May). Bioinspired Materials for Applications in Regenerative Medicine.
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  An invited seminar was given in College of Preventive Medicine, Third Military Medical University, Chongqing, China