@article{nguyen_nelson_skoog_jaipan_petrochenko_kaiser_lo_moreno_narayan_goering_et al._2022, title={Effect of simulated body fluid formulation on orthopedic device apatite-forming ability assessment}, ISSN={["1552-4981"]}, DOI={10.1002/jbm.b.35207}, abstractNote={AbstractIntegration of native bone into orthopedic devices is a key factor in long‐term implant success. The material‐tissue interface is generally accepted to consist of a hydroxyapatite layer so bioactive materials that can spontaneously generate this hydroxyapatite layer after implantation may improve patient outcomes. Per the ISO 22317:2014 standard, “Implants for surgery – In vitro evaluation for apatite‐forming ability of implant materials,” bioactivity performance statements can be assessed by soaking the material in simulated body fluid (SBF) and evaluating the surface for the formation of a hydroxyapatite layer; however, variations in test methods may alter hydroxyapatite formation and result in false‐positive assessments. The goal of this study was to identify the effect of SBF formulation on bioactivity assessment. Bioglass® (45S5 and S53P4) and non‐bioactive Ti‐6Al‐4V were exposed to SBF formulations varying in calcium ion and phosphate concentrations as well as supporting ion concentrations. Scanning electron microscopy and X‐ray powder diffraction evaluation of the resulting hydroxyapatite layers revealed that SBF enriched with double or quadruple the calcium and phosphate ion concentrations increased hydroxyapatite crystal size and quantity compared to the standard formulation and can induce hydroxyapatite crystallization on surfaces traditionally considered non‐bioactive. Altering concentrations of other ions, for example, bicarbonate, changed hydroxyapatite induction time, quantity, and morphology. For studies evaluating the apatite‐forming ability of a material to support bioactivity performance statements, test method parameters must be adequately described and controlled. It is unclear if apatite formation after exposure to any of the SBF formulations is representative of an in vivo biological response. The ISO 23317 standard test method should be further developed to provide additional guidance on apatite characterization and interpretation of the results.}, journal={JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS}, author={Nguyen, Alexander K. K. and Nelson, Sarah B. B. and Skoog, Shelby A. A. and Jaipan, Panupong and Petrochenko, Peter E. E. and Kaiser, Aric and Lo, Linh and Moreno, Jose and Narayan, Roger J. J. and Goering, Peter L. L. and et al.}, year={2022}, month={Nov} } @article{azizi machekposhti_nguyen_vanderwal_stafslien_narayan_2022, title={Micromolding of Amphotericin-B-Loaded Methoxyethylene-Maleic Anhydride Copolymer Microneedles}, volume={14}, ISSN={["1999-4923"]}, DOI={10.3390/pharmaceutics14081551}, abstractNote={Biocompatible and biodegradable materials have been used for fabricating polymeric microneedles to deliver therapeutic drug molecules through the skin. Microneedles have advantages over other drug delivery methods, such as low manufacturing cost, controlled drug release, and the reduction or absence of pain. The study examined the delivery of amphotericin B, an antifungal agent, using microneedles that were fabricated using a micromolding technique. The microneedle matrix was made from GantrezTM AN-119 BF, a benzene-free methyl vinyl ether/maleic anhydride copolymer. The GantrezTM AN-119 BF was mixed with water; after water evaporation, the polymer exhibited sufficient strength for microneedle fabrication. Molds cured at room temperature remained sharp and straight. SEM images showed straight and sharp needle tips; a confocal microscope was used to determine the height and tip diameter for the microneedles. Nanoindentation was used to obtain the hardness and Young’s modulus values of the polymer. Load–displacement testing was used to assess the failure force of the needles under compressive loading. These two mechanical tests confirmed the mechanical properties of the needles. In vitro studies validated the presence of amphotericin B in the needles and the antifungal properties of the needles. Amphotericin B GantrezTM microneedles fabricated in this study showed appropriate characteristics for clinical translation in terms of mechanical properties, sharpness, and antifungal properties.}, number={8}, journal={PHARMACEUTICS}, author={Azizi Machekposhti, Sina and Nguyen, Alexander K. and Vanderwal, Lyndsi and Stafslien, Shane and Narayan, Roger J.}, year={2022}, month={Aug} } @misc{lindberg_lim_soliman_nguyen_hooper_narayan_woodfield_2021, title={Biological function following radical photo-polymerization of biomedical polymers and surrounding tissues: Design considerations and cellular risk factors}, volume={8}, ISSN={["1931-9401"]}, DOI={10.1063/5.0015093}, abstractNote={Radical photo-cross-linking of polymers has been at the forefront in the development of biomedical applications to meet many of the biomaterial design criteria needed to address clinical and healthcare challenges, particularly in relation to regenerative and restorative medicine strategies, to treat damaged or diseased tissues and organs. Exciting new hybrid designs, elegantly expanding the range of properties and applications available to individual polymeric materials, are starting to offer detailed customization with complex and dynamic interactions similar to the events occurring within native tissue microenvironments in vivo. Yet the variety in success reported in the literature highlights the many unknown design criteria and parameters affecting functional restoration of damaged tissues and organs. The applied light curing units and radical initiating system, as well as underlying chemical reactions and resultant network structures, all require detailed consideration as means to modulate biological function while further being assessed as sources of toxicity. This is especially important when cells embedded in the polymeric material (or in surrounding tissues) are directly exposed to photo-irradiation. Ultimately, achieving successful clinical translation necessitates the chemical photo-polymerization platforms to be efficacious, safe, and customizable but also convenient for clinical use and cost-effective production. This review thus aims to summarize current and emerging toolkits to photo-polymerize biomedical polymers requiring the direct irradiation of cells and/or mammalian tissues and its associated impact on biological functionality. This specifically includes (1) in vitro photo-polymerization of cell-laden 3D-hydrogels for tissue engineering and regeneration medicine applications, (2) in vivo transdermal photo-polymerization of injectable hydrogels for cell/drug delivery, and (3) in vivo photo-polymerization of cell-free, injectable resin-based composites for load-bearing restorative surgery, all fast-growing and highly competitive fields of modern medicine. We herein summarize both design considerations and biological risk factors associated with selecting suitable light sources, photo-initiators, functional groups, chemical propagation, as well as how subsequent network properties can modulate biological function and ultimately clinical applicability. As more knowledge is continuously accumulated through materials science, matrix biology, and technology, this review provides recommendations for researchers to extend their chemical, biological, and structural characterizations to systematically enrich the paradigm of photo-polymerizable materials for biomedical applications to help ensure efficient and safe radical photo-processing.}, number={1}, journal={APPLIED PHYSICS REVIEWS}, author={Lindberg, Gabriella C. J. and Lim, Khoon S. and Soliman, Bram G. and Nguyen, Alexander and Hooper, Gary J. and Narayan, Roger J. and Woodfield, Tim B. F.}, year={2021}, month={Mar} } @article{sachan_nguyen_lu_erdmann_zhang_narayan_2021, title={Digital light processing-based 3D printing of polytetrafluoroethylene solid microneedle arrays}, ISSN={["2159-6867"]}, DOI={10.1557/s43579-021-00121-0}, abstractNote={This study evaluated the structural and skin penetration properties of solid microneedle arrays made by digital light processing-based 3D printing of polytetrafluoroethylene. Confocal laser scanning microscopy and scanning electron microscopy revealed that the microneedles exhibited uniform heights. Raman spectroscopy, X-ray photoelectron spectroscopy, nanoindentation, and contact angle results indicated that the composition, carbon–fluorine bonding, reduced elastic modulus, and contact angle values of the 3D-printed polytetrafluoroethylene corresponded with those of bulk polytetrafluoroethylene, respectively. Methyl blue was used to evaluate the human skin penetration functionality of the microneedle array. Our results indicate that digital light processing is appropriate for manufacturing polytetrafluoroethylene medical devices.}, journal={MRS COMMUNICATIONS}, author={Sachan, Roger and Nguyen, Alexander K. and Lu, Junqi and Erdmann, Detlev and Zhang, Jennifer Y. and Narayan, Roger J.}, year={2021}, month={Nov} } @article{zhang_nguyen_narayan_huang_2021, title={Direct ink writing of vancomycin-loaded polycaprolactone/ polyethylene oxide/ hydroxyapatite 3D scaffolds}, ISSN={["1551-2916"]}, DOI={10.1111/jace.18048}, abstractNote={AbstractNovel inks were formulated by dissolving polycaprolactone (PCL), a hydrophobic polymer, in organic solvent systems; polyethylene oxide (PEO) was incorporated to extend the range of hydrophilicity of the system. Hydroxyapatite (HAp) with a weight ratio of 55–85% was added to the polymer‐based solution to mimic the material composition of natural bone tissue. The direct ink writing (DIW) technique was applied to extrude the formulated inks to fabricate the predesigned tissue scaffold structures; the influence of HAp concentration was investigated. The results indicate that in comparison to other inks containing HAp (55%, 75%, and 85%w/w), the ink containing 65% w/w HAp had faster ink recovery behavior; the fabricated scaffold had a rougher surface as well as better mechanical properties and wettability. It is noted that the 65% w/w HAp concentration is similar to the inorganic composition of natural bone tissue. The elastic modulus values of PCL/PEO/HAp scaffolds were in the range of 4–12 MPa; the values were dependent on the HAp concentration. Furthermore, vancomycin as a model drug was successfully encapsulated in the PCL/PEO/HAp composite scaffold for drug release applications. This paper presents novel drug‐loaded PCL/PEO/HAp inks for 3D scaffold fabrication using the DIW printing technique for potential bone scaffold applications.}, journal={JOURNAL OF THE AMERICAN CERAMIC SOCIETY}, author={Zhang, Bin and Nguyen, Alexander K. and Narayan, Roger J. and Huang, Jie}, year={2021}, month={Jul} } @article{movahed_nguyen_goering_skoog_narayan_2020, title={Argon and oxygen plasma treatment increases hydrophilicity and reduces adhesion of silicon-incorporated diamond-like coatings}, volume={15}, ISSN={["1559-4106"]}, DOI={10.1116/6.0000356}, abstractNote={In this study, the structure, adhesion, and cell viability characteristics of silicon-incorporated diamond-like carbon (Si-DLC) coatings on fused silica substrates were investigated. The effects of argon and oxygen postprocessing plasma treatments on the Si-DLC coatings were also studied. The contact angle results showed that the Si-DLC coatings were more hydrophilic than the uncoated surfaces, and postprocessing plasma treatment increased the hydrophilicity of the Si-DLC coatings. Atomic force microscopy and profilometry confirmed that postprocessing plasma treatment increased the thickness and roughness of the Si-DLC coatings. The results of microscratch testing indicated that the plasma treatments reduced the adhesion of the coatings. The x-ray photoelectron spectroscopy (XPS) showed the presence of carbon, oxygen, and silicon in the Si-DLC coatings before and after the plasma treatments. These results show that the postprocessing plasma treatment significantly reduced the atomic percentage of the carbon in the Si-DLC coatings. XPS also confirmed the presence of carbon in the form of sp3(C—C), sp2(C=C), C—O, and C=O bonds in the Si-DLC coatings; it showed that postprocessing treatments significantly increased the percentage of oxygen in the Si-DLC coatings. Fourier transform infrared spectroscopy (FTIR) analysis showed features associated with C—OH stretching, C—H bending, as well as Si—CH2 and C—H bending in the Si-DLC coating. The XPS and FTIR results confirmed that the plasma treatment caused dissociation of the sp2 and sp3 bonds and formation of C—OH bonds. The contact angle data indicated that postprocessing treatment increased the hydrophilicity of the Si-DLC coating. Similar to the uncoated substrates, L929 cells showed no change in cell viability when cultured on Si-DLC coatings. These results of the study indicate the suitability of Si-DLC coatings as inert coatings for medical and biotechnology applications.}, number={4}, journal={BIOINTERPHASES}, author={Movahed, Saeid and Nguyen, Alexander K. and Goering, Peter L. and Skoog, Shelby A. and Narayan, Roger J.}, year={2020}, month={Jul} } @article{cristescu_negut_visan_nguyen_sachan_goering_chrisey_narayan_2020, title={Matrix-Assisted Pulsed laser Evaporation-deposited Rapamycin Thin Films Maintain Antiproliferative Activity}, volume={6}, ISSN={["2424-8002"]}, DOI={10.18063/ijb.v6i1.188}, abstractNote={Matrix-assisted pulsed laser evaporation (MAPLE) has many benefits over conventional methods (e.g., dip-coating, spin coating, and Langmuir–Blodgett dip-coating) for manufacturing coatings containing pharmacologic agents on medical devices. In particular, the thickness of the coating that is applied to the surface of the medical device can be tightly controlled. In this study, MAPLE was used to deposit rapamycin-polyvinylpyrrolidone (rapamycin-PVP) thin films onto silicon and borosilicate optical glass substrates. Alamar Blue and PicoGreen studies were used to measure the metabolic health and DNA content of L929 mouse fibroblasts as measures of viability and proliferation, respectively. The cells on the MAPLE-deposited rapamycin-PVP surfaces exhibited 70.6% viability and 53.7% proliferation compared to a borosilicate glass control. These data indicate that the antiproliferative properties of rapamycin were maintained after MAPLE deposition.}, number={1}, journal={INTERNATIONAL JOURNAL OF BIOPRINTING}, author={Cristescu, Rodica and Negut, Irina and Visan, Anita Ioana and Nguyen, Alexander K. and Sachan, Andrew and Goering, Peter L. and Chrisey, Douglas B. and Narayan, Roger J.}, year={2020}, pages={105–111} } @article{nguyen_goering_skoog_narayan_2020, title={Physical characterization and in vitro evaluation of 3D printed hydroxyapatite, tricalcium phosphate, zirconia, alumina, and SiAlON structures made by lithographic ceramic manufacturing}, volume={5}, ISSN={["2059-8521"]}, DOI={10.1557/adv.2020.229}, abstractNote={In this study, lithographic ceramic manufacturing was used to create solid chips out of hydroxyapatite, tricalcium phosphate, zirconia, alumina, and SiAlON ceramic. X-ray powder diffraction of each material confirmed that the chips were crystalline, with little amorphous character that could result from remaining polymeric binder, and were composed entirely out of the ceramic feedstock. Surface morphologies and roughnesses were characterized using atomic force microscopy. Human bone marrow stem cells cultured with osteogenic supplements on each material type expressed alkaline phosphatase levels, an early marker of osteogenic differentiation, on par with cells cultured on a glass control. However, cells cultured on the tricalcium phosphate-containing material expressed lower levels of ALP suggesting that osteoinduction was impaired on this material. Further analyses should be conducted with these materials to identify underlying issues of the combination of material and analysis method.}, number={46-47}, journal={MRS ADVANCES}, author={Nguyen, Alexander K. and Goering, Peter L. and Skoog, Shelby A. and Narayan, Roger J.}, year={2020}, pages={2419–2428} } @article{nguyen_goering_elespuru_das_narayan_2020, title={The Photoinitiator Lithium Phenyl (2,4,6-Trimethylbenzoyl) Phosphinate with Exposure to 405 nm Light Is Cytotoxic to Mammalian Cells but Not Mutagenic in Bacterial Reverse Mutation Assays}, volume={12}, ISSN={["2073-4360"]}, DOI={10.3390/polym12071489}, abstractNote={Lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate (LAP) is a free radical photo-initiator used to initiate free radical chain polymerization upon light exposure, and is combined with gelatin methacryloyl (GelMA) to produce a photopolymer used in bioprinting. The free radicals produced under bioprinting conditions are potentially cytotoxic and mutagenic. Since these photo-generated free radicals are highly-reactive but short-lived, toxicity assessments should be conducted with light exposure. In this study, photorheology determined that 10 min exposure to 9.6 mW/cm2 405 nm light from an LED light source fully crosslinked 10 wt % GelMA with >3.4 mmol/L LAP, conditions that were used for subsequent cytotoxicity and mutagenicity assessments. These conditions were cytotoxic to M-1 mouse kidney collecting duct cells, a cell type susceptible to lithium toxicity. Exposure to ≤17 mmol/L (0.5 wt %) LAP without light was not cytotoxic; however, concurrent exposure to ≥3.4 mmol/L LAP and light was cytotoxic. No condition of LAP and/or light exposure evaluated was mutagenic in bacterial reverse mutation assays using S. typhimurium strains TA98, TA100 and E. coli WP2 uvrA. These data indicate that the combination of LAP and free radicals generated from photo-excited LAP is cytotoxic, but mutagenicity was not observed in bacteria under typical bioprinting conditions.}, number={7}, journal={POLYMERS}, author={Nguyen, Alexander K. and Goering, Peter L. and Elespuru, Rosalie K. and Das, Srilekha Sarkar and Narayan, Roger J.}, year={2020}, month={Jul} } @article{huckaby_parker_jacobs_schaefer_wadsworth_nguyen_wang_newby_lai_2019, title={Engineering Polymer-Binding Bispecific Antibodies for Enhanced Pretargeted Delivery of Nanoparticles to Mucus-Covered Epithelium}, volume={58}, ISSN={["1521-3773"]}, DOI={10.1002/anie.201814665}, abstractNote={AbstractMucus represents a major barrier to sustained and targeted drug delivery to mucosal epithelium. Ideal drug carriers should not only rapidly diffuse across mucus, but also bind the epithelium. Unfortunately, ligand‐conjugated particles often exhibit poor penetration across mucus. In this work, we explored a two‐step “pretargeting” approach through engineering a bispecific antibody that binds both cell‐surface ICAM‐1 and polyethylene glycol (PEG) on the surface of nanoparticles, thereby effectively decoupling cell targeting from particle design and formulation. When tested in a mucus‐coated Caco‐2 culture model that mimics the physiological process of mucus clearance, pretargeting increased the amount of PEGylated particles binding to cells by around 2‐fold or more compared to either non‐targeted or actively targeted PEGylated particles. Pretargeting also markedly enhanced particle retention in mouse intestinal tissues. Our work underscores pretargeting as a promising strategy to improve the delivery of therapeutics to mucosal surfaces.}, number={17}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, author={Huckaby, Justin T. and Parker, Christina L. and Jacobs, Tim M. and Schaefer, Alison and Wadsworth, Daniel and Nguyen, Alexander and Wang, Anting and Newby, Jay and Lai, Samuel K.}, year={2019}, month={Apr}, pages={5604–5608} } @article{nguyen_yang_bryant_li_joice_werbovetz_narayan_2019, title={Microneedle-Based Delivery of Amphotericin B for Treatment of Cutaneous Leishmaniasis}, volume={21}, ISSN={["1572-8781"]}, DOI={10.1007/s10544-018-0355-8}, abstractNote={Current therapeutic options against cutaneous leishmaniasis are plagued by several weaknesses. The effective topical delivery of an antileishmanial drug would be useful in treating some forms of cutaneous leishmaniasis. Toward this end, a microneedle based delivery approach for the antileishmanial drug amphotericin B was investigated in murine models of both New World (Leishmania mexicana) and Old World (Leishmania major) infection. In the L. mexicana model, ten days of treatment began on day 35 post infection, when the area of nodules averaged 9–15 mm2. By the end of the experiment, a significant difference in nodule area was observed for all groups receiving topical amphotericin B at 25 mg/kg/day after application of microneedle arrays of 500, 750, and 1000 μM in nominal length compared to the group that received this dose of topical amphotericin B alone. In the L. major model, ten days of treatment began on day 21 post infection when nodule area averaged 51–65 mm2 in the groups. By the end of the experiment, there was no difference in nodule area between the group receiving 25 mg/kg of topical amphotericin B after microneedle application and any of the non-AmBisome groups. These results show the promise of topical delivery of amphotericin B via microneedles in treating relatively small nodules caused by L. mexicana. These data also show the limitations of the approach against a disseminated L. major infection. Further optimization of microneedle delivery is needed to fully exploit this strategy for cutaneous leishmaniasis treatment.}, number={1}, journal={BIOMEDICAL MICRODEVICES}, author={Nguyen, Alexander K. and Yang, Kai-Hung and Bryant, Kelsey and Li, Junan and Joice, April C. and Werbovetz, Karl A. and Narayan, Roger J.}, year={2019}, month={Mar} } @article{nguyen_goering_olenick_olenick_narayan_2019, title={Sintered Tape-cast 3YSZ Supports Human Bone Marrow Derived Stem Cell Osteogenic Differentiation}, volume={4}, ISSN={["2059-8521"]}, DOI={10.1557/adv.2019.335}, abstractNote={Sintered tape-cast yttria-stabilized zirconia (YSZ) was evaluated for its elemental composition, crystal structure, and imaged with atomic force microscopy (AFM) and scanning electron microscopy (SEM). Human bone marrow stem cells (hBMSC) were cultured on the ceramic and differentiated into the osteoblast lineage; alkaline phosphatase (ALP) activity was tracked as a differentiation marker. The YSZ was composed of purely tetragonal grains with a median equivalent circular diameter of 283 nm. Zirconium, yttrium, oxygen, and adventitious carbon was detected on the substrate with no other elements in significant quantities detected. YSZ samples had an RMS roughness value of 27 nm, elastic modulus of 206 ± 14 GPa, and hardness of 14 ± 2 GPa. hBMSC were observed to attach and proliferate on the YSZ surfaces and had significantly increased ALP versus the undifferentiated control cultured on glass. This method for producing a YSZ ceramic yields a typical material of this type and supports attachment and differentiation of hBMSC; thus, making it useful as a bone implant material.}, number={46-47}, journal={MRS ADVANCES}, author={Nguyen, Alexander K. and Goering, Peter L. and Olenick, John A. and Olenick, Kathy and Narayan, Roger J.}, year={2019}, pages={2541–2549} } @article{nguyen_goering_reipa_narayan_2019, title={Toxicity and photosensitizing assessment of gelatin methacryloyl-based hydrogels photoinitiated with lithium phenyl-2,4,6-trimethylbenzoylphosphinate in human primary renal proximal tubule epithelial cells}, volume={14}, ISSN={["1559-4106"]}, DOI={10.1116/1.5095886}, abstractNote={Gelatin methacryloyl (GelMA) and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) photoinitiator are commonly used in combination to produce a photosensitive polymer but there are concerns that must be addressed: the presence of unreacted monomer is well known to be cytotoxic, and lithium salts are known to cause acute kidney injury. In this study, acellular 10% GelMA hydrogels cross-linked with different LAP concentrations and cross-linking illumination times were evaluated for their cytotoxicity, photosensitizing potential, and elastic moduli. Alamar Blue and CyQuant Direct Cell viability assays were performed on human primary renal proximal tubule epithelial cells (hRPTECs) exposed to extracts of each formulation. UV exposure during cross-linking was not found to affect extract cytotoxicity in either assay. LAP concentration did not affect extract cytotoxicity as determined by the Alamar Blue assay but reduced hRPTEC viability in the CyQuant Direct cell assay. Photocatalytic activity of formulation extracts toward NADH oxidation was used as a screening method for photosensitizing potential; longer UV exposure durations yielded extracts with less photocatalytic activity. Finally, elastic moduli determined using nanoindentation was found to plateau to approximately 20–25 kPa after exposure to 342 mJ/cm2 at 2.87 mW of UV-A exposure regardless of LAP concentration. LAP at concentrations commonly used in bioprinting (<0.5% w/w) was not found to be cytotoxic although the differences in cytotoxicity evaluation determined from the two viability assays imply cell membrane damage and should be investigated further. Complete cross-linking of all formulations decreased photocatalytic activity while maintaining predictable final elastic moduli.}, number={2}, journal={BIOINTERPHASES}, author={Nguyen, Alexander K. and Goering, Peter L. and Reipa, Vytas and Narayan, Roger J.}, year={2019} } @article{nguyen_narayan_shafiee_2019, title={3D Printing in the Biomedical Field}, DOI={10.1016/B978-0-12-801238-3.99875-1}, abstractNote={Recent advances in materials and computing technologies have resulted in a large progress in the use of 3D printing for biomedical applications. 3D printing encompasses multiple fabrication technologies and materials ranging from extrusion to laser processing. Additionally, materials such as live cells or metal powders can be processed for applications ranging from soft tissue to rigid prosthetics. Printers are being employed different aspects of medical field such as tissue engineering, surgical planning model fabrication, medical training, and education. Herein, we overview the applications of printers for biomedical purposes.}, journal={ENCYCLOPEDIA OF BIOMEDICAL ENGINEERING, VOL 2}, author={Nguyen, Alexander K. and Narayan, Roger J. and Shafiee, Ashkan}, year={2019}, pages={275–280} } @article{nguyen_narayan_2017, title={Two-photon polymerization for biological applications}, volume={20}, ISSN={["1873-4103"]}, DOI={10.1016/j.mattod.2017.06.004}, abstractNote={Two-photon polymerization (2PP) leverages the two-photon absorption (TPA) of near-infrared (NIR) radiation for additive manufacturing with sub-diffraction limit resolution within the bulk of a photosensitive material. This technology draws heavily on photosensitive polymers from the microelectronics industry, which were not optimized for TPA or for biocompatibility. 2PP with sub 100 nm resolution has been repeatedly demonstrated; however, this level of fabrication resolution comes at the expense of long fabrication times. Manufacturing of medical devices beyond surface texturing would be prohibitively slow using the current state of the art 2PP technology. Current research into TPA-sensitive photopolymers with good biocompatibility and holographic projections using spatial light modulators address current technological limitations by providing materials specifically formulated for biological applications and by making better use of available laser power for applications in which nanoscale resolution is not required.}, number={6}, journal={MATERIALS TODAY}, author={Nguyen, Alexander K. and Narayan, Roger J.}, year={2017}, pages={314–322} } @article{koroleva_deiwick_nguyen_schlie-wolter_narayan_timashev_popov_bagratashvili_chichkov_2015, title={Osteogenic Differentiation of Human Mesenchymal Stem Cells in 3-D Zr-Si Organic-Inorganic Scaffolds Produced by Two-Photon Polymerization Technique}, volume={10}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0118164}, abstractNote={Two-photon polymerization (2PP) is applied for the fabrication of 3-D Zr-Si scaffolds for bone tissue engineering. Zr-Si scaffolds with 150, 200, and 250 μm pore sizes are seeded with human bone marrow stem cells (hBMSCs) and human adipose tissue derived stem cells (hASCs) and cultured in osteoinductive and control media for three weeks. Osteogenic differentiation of hASCs and hBMSCs and formation of bone matrix is comparatively analyzed via alkaline phosphatase activity (ALP), calcium quantification, osteocalcin staining and scanning electron microscopy (SEM). It is observed that the 150 μm pore size Zr-Si scaffolds support the strongest matrix mineralization, as confirmed by calcium deposition. Analysis of ALP activity, osteocalcin staining and SEM observations of matrix mineralization reveal that mesenchymal stem cells cultured on 3-D scaffolds without osteogenic stimulation spontaneously differentiate towards osteogenic lineage. Nanoindentation measurements show that aging of the 2PP-produced Zr-Si scaffolds in aqueous or alcohol media results in an increase in the scaffold Young’s modulus and hardness. Moreover, accelerated formation of bone matrix by hASCs is noted, when cultured on the scaffolds with lower Young’s moduli and hardness values (non aged scaffolds) compared to the cells cultured on scaffolds with higher Young’s modulus and hardness values (aged scaffolds). Presented results support the potential application of Zr-Si scaffolds for autologous bone tissue engineering.}, number={2}, journal={PLOS ONE}, author={Koroleva, Anastasia and Deiwick, Andrea and Nguyen, Alexander and Schlie-Wolter, Sabrina and Narayan, Roger and Timashev, Peter and Popov, Vladimir and Bagratashvili, Viktor and Chichkov, Boris}, year={2015}, month={Feb} } @article{skoog_nguyen_kumar_zheng_goering_koroleva_chichkov_narayan_2014, title={Two-photon polymerization of 3-D zirconium oxide hybrid scaffolds for long-term stem cell growth}, volume={9}, ISSN={["1559-4106"]}, DOI={10.1116/1.4873688}, abstractNote={Two-photon polymerization is a technique that involves simultaneous absorption of two photons from a femtosecond laser for selective polymerization of a photosensitive material. In this study, two-photon polymerization was used for layer-by-layer fabrication of 3-D scaffolds composed of an inorganic–organic zirconium oxide hybrid material. Four types of scaffold microarchitectures were created, which exhibit layers of parallel line features at various orientations as well as pores between the line features. Long-term cell culture studies involving human bone marrow stromal cells were conducted using these 3-D scaffolds. Cellular adhesion and proliferation were demonstrated on all of the scaffold types; tissuelike structure was shown to span the pores. This study indicates that two-photon polymerization may be used to create microstructured scaffolds out of an inorganic–organic zirconium oxide hybrid material for use in 3-D tissue culture systems.}, number={2}, journal={BIOINTERPHASES}, author={Skoog, Shelby A. and Nguyen, Alexander K. and Kumar, Girish and Zheng, Jiwen and Goering, Peter L. and Koroleva, Anastasia and Chichkov, Boris N. and Narayan, Roger J.}, year={2014}, month={Jun} }