Biomimetic Vasculatures by 3D-Printed Porous Molds

Anatomically and biologically relevant vascular models are critical to progress our understanding of cardiovascular diseases (CVDs) that can lead to effective therapies. Despite advances in 3D bioprinting, recapitulating complex architectures (i.e., freestanding, branching, multilayered, perfusable) of a cell-laden vascular construct remains technically challenging, and the development of new techniques that can recapitulate both anatomical and biological features of blood vessels is of paramount importance. In this work, we introduce a unique, microfluidics-enabled molding technique that allows us to fabricate anatomically-relevant, cell-laden hydrogel vascular models. Our approach employed 3D-printed porous molds of poly(ethylene glycol) diacrylate (PEGDA) as templates to cast alginate-containing bioinks. Due to the porous and aqueous nature of the PEGDA mold, the calcium ion (Ca2+) was diffusively released to crosslink the bioinks to create hollow structures. Applying this technique, multiscale, multilayered vascular constructs that were freestanding and perfusable were readily fabricated using cell-compatible bioinks (i.e., alginate and gelatin methacryloyl (GelMA)). The bioinks were also readily customizable to either improve the compatibility with specific vascular cells or tune the mechanical modulus to mimic native blood vessels. Importantly, we successfully integrated smooth muscle cells and endothelial cells in a biomimetic organization within our vessel constructs and demonstrated a significant increase in monocyte adhesion upon stimulation with an inflammatory cytokine, tumor necrosis factor-alpha (TNF-α). We also demonstrated that the fabricated vessels were amenable for testing percutaneous coronary interventions (i.e., drug-eluting balloons and stents) under physiologically-relevant mechanical states, such as vessel stretching and bending. Overall, we introduce a versatile fabrication technique with multi-faceted possibilities of generating biomimetic vascular models that can benefit future research in mechanistic understanding of CVD progression and the development of therapeutic interventions.

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Modeling the effects of hyaluronic acid degradation on the regulation of human astrocyte phenotype using multicomponent interpenetrating polymer networks (mIPNs)

Scientific Reports ◽

10.1038/s41598-020-77655-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Andrea C. Jimenez-Vergara ◽

Rachel Van Drunen ◽

Tyler Cagle ◽

Dany J. Munoz-Pinto

Keyword(s):

Hyaluronic Acid ◽

Calcium Binding ◽

Inflammatory Markers ◽

Polymer Networks ◽

Interpenetrating Polymer Networks ◽

Necrosis Factor Alpha ◽

Glycol Diacrylate ◽

Human Astrocyte ◽

Poly Ethylene ◽

Tissue Trauma

AbstractHyaluronic acid (HA) is a highly abundant component in the extracellular matrix (ECM) and a fundamental element to the architecture and the physiology of the central nervous system (CNS). Often, HA degradation occurs when an overreactive inflammatory response, derived from tissue trauma or neurodegenerative diseases such as Alzheimer’s, causes the ECM in the CNS to be remodeled. Herein, we studied the effects of HA content as a key regulator of human astrocyte (HAf) reactivity using multicomponent interpenetrating polymer networks (mIPNs) comprised of Collagen I, HA and poly(ethylene glycol) diacrylate. The selected platform facilities the modulation of HA levels independently of matrix rigidity. Total astrocytic processes length, number of endpoints, the expression of the quiescent markers: Aldehyde Dehydrogenase 1 Family Member L1 (ALDH1L1) and Glutamate Aspartate Transporter (GLAST); the reactive markers: Glial Fibrillary Acidic Protein (GFAP) and S100 Calcium-Binding Protein β (S100β); and the inflammatory markers: Inducible Nitric Oxide Synthase (iNOS), Interleukin 1β (IL-1β) and Tumor Necrosis Factor Alpha (TNFα), were assessed. Cumulatively, our results demonstrated that the decrease in HA concentration elicited a reduction in the total length of astrocytic processes and an increase in the expression of HAf reactive and inflammatory markers.

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A Non-Cytotoxic Resin for Micro-Stereolithography for Cell Cultures of HUVECs

Micromachines ◽

10.3390/mi11030246 ◽

2020 ◽

Vol 11 (3) ◽

pp. 246 ◽

Cited By ~ 5

Author(s):

Max Männel ◽

Carolin Fischer ◽

Julian Thiele

Keyword(s):

Cell Culture ◽

Ethylene Glycol ◽

Umbilical Vein ◽

Polymer Materials ◽

Poly Ethylene Glycol ◽

Glycol Diacrylate ◽

3D Printed ◽

Poly Ethylene ◽

The Impact

Three-dimensional (3D) printing of microfluidic devices continuously replaces conventional fabrication methods. A versatile tool for achieving microscopic feature sizes and short process times is micro-stereolithography (µSL). However, common resins for µSL lack biocompatibility and are cytotoxic. This work focuses on developing new photo-curable resins as a basis for µSL fabrication of polymer materials and surfaces for cell culture. Different acrylate- and methacrylate-based compositions are screened for material characteristics including wettability, surface roughness, and swelling behavior. For further understanding, the impact of photo-absorber and photo-initiator on the cytotoxicity of 3D-printed substrates is studied. Cell culture experiments with human umbilical vein endothelial cells (HUVECs) in standard polystyrene vessels are compared to 3D-printed parts made from our library of homemade resins. Among these, after optimizing material composition and post-processing, we identify selected mixtures of poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) methyl ethyl methacrylate (PEGMEMA) as most suitable to allow for fabricating cell culture platforms that retain both the viability and proliferation of HUVECs. Next, our PEGDA/PEGMEMA resins will be further optimized regarding minimal feature size and cell adhesion to fabricate microscopic (microfluidic) cell culture platforms, e.g., for studying vascularization of HUVECs in vitro.

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Impact of intermediate UV curing and yield stress of 3D printed poly(ethylene glycol) diacrylate hydrogels on interlayer connectivity and maximum build height

Additive Manufacturing ◽

10.1016/j.addma.2017.10.008 ◽

2017 ◽

Vol 18 ◽

pp. 136-144 ◽

Cited By ~ 9

Author(s):

Adrian Hiller ◽

Kirsten Borchers ◽

Günter E.M. Tovar ◽

Alexander Southan

Keyword(s):

Ethylene Glycol ◽

Yield Stress ◽

Uv Curing ◽

Poly Ethylene Glycol ◽

Glycol Diacrylate ◽

3D Printed ◽

Poly Ethylene

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Three-Dimensional Scaffold Fabrication with Inverse Photolithography

MRS Advances ◽

10.1557/adv.2016.620 ◽

2016 ◽

Vol 2 (19-20) ◽

pp. 1071-1075 ◽

Cited By ~ 1

Author(s):

Ramesh Prashad ◽

Ozlem Yasar

Keyword(s):

Interior Design ◽

Uv Light ◽

Three Dimensional ◽

Poly Ethylene Glycol ◽

Scaffold Fabrication ◽

Glycol Diacrylate ◽

Alternative Approach ◽

Cell Sources ◽

3D Printed ◽

Poly Ethylene

ABSTRACTIn recent years, tissue engineering has been utilized as an alternative approach to organ transplantation. Success rate of tissue regeneration influenced by the biomaterials, cell sources, growth factors and scaffold fabrication. Design and precise fabrication of scaffolds are required to support cells to expand and migrate to 3D environment. Common scaffold fabrication techniques use heat, adhesives, molds or light. In this research, “inverse-photolithography” which is a light based fabrication technique was used to generate the scaffolds. In order to control the interior architecture of the scaffold “a single vertical strut” and “a y-shape” were fabricated with the 3D printer by using the dissolvable filament. Then, the strut and the y-shape were immersed into the photo-curable solution which is poly(ethylene glycol) diacrylate (PEGDA) and photo-initiator mixture. UV light with the 365nm wavelength was placed up-side down under the solution. Photo-curable mixture was exposed to the UV light for 3 minutes to cure the entire scaffold. Solidified scaffold with the strut and y-shape inside was kept in the limonene solution. Limonene penetrated through the open ended strut and y-shape and it dissolved the 3D printed strut and y-shape away leaving the fabricated PEGDA based scaffolds. This preliminary research showcases, the 3D scaffolds with the controlled interior design, can be fabricated with the “inverse-photolithography” technique.

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On-demand modulation of 3D-printed elastomers using programmable droplet inclusions

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1917289117 ◽

2020 ◽

Vol 117 (26) ◽

pp. 14790-14797 ◽

Cited By ~ 3

Author(s):

Hing Jii Mea ◽

Luis Delgadillo ◽

Jiandi Wan

Keyword(s):

Three Dimensional ◽

Continuous Phase ◽

Direct Writing ◽

Poly Ethylene Glycol ◽

Glass Capillary ◽

Glycol Diacrylate ◽

Dynamic Tuning ◽

3D Printed ◽

Poly Ethylene

One of the key thrusts in three-dimensional (3D) printing and direct writing is to seamlessly vary composition and functional properties in printed constructs. Most inks used for extrusion-based printing, however, are compositionally static and available approaches for dynamic tuning of ink composition remain few. Here, we present an approach to modulate extruded inks at the point of print, using droplet inclusions. Using a glass capillary microfluidic device as the printhead, we dispersed droplets in a polydimethylsiloxane (PDMS) continuous phase and subsequently 3D printed the resulting emulsion into a variety of structures. The mechanical characteristics of the 3D-printed constructs can be tuned in situ by varying the spatial distribution of droplets, including aqueous and liquid metal droplets. In particular, we report the use of poly(ethylene glycol) diacrylate (PEGDA) aqueous droplets for local PDMS chemistry alteration resulting in significant softening (85% reduced elastic modulus) of the 3D-printed constructs. Furthermore, we imparted magnetic functionality in PDMS by dispersing ferrofluid droplets and rationally designed and printed a rudimentary magnetically responsive soft robotic actuator as a functional demonstration of our droplet-based strategy. Our approach represents a continuing trend of adapting microfluidic technology and principles for developing the next generation of additive manufacturing technology.

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A GelMA-PEGDA-nHA Composite Hydrogel for Bone Tissue Engineering

Materials ◽

10.3390/ma13173735 ◽

2020 ◽

Vol 13 (17) ◽

pp. 3735

Author(s):

Yihu Wang ◽

Xiaofeng Cao ◽

Ming Ma ◽

Weipeng Lu ◽

Bing Zhang ◽

...

Keyword(s):

Bone Repair ◽

Composite Hydrogel ◽

Hydroxyl Group ◽

Poly Ethylene Glycol ◽

Hydrogel Scaffold ◽

Glycol Diacrylate ◽

3D Printed ◽

Poly Ethylene ◽

The Stability

A new gelatin methacrylamine (GelMA)-poly (ethylene glycol) diacrylate (PEGDA)-nano hydroxyapatite (nHA) composite hydrogel scaffold was developed using UV photo-crosslinking technology. The Ca2+ from nHA can form a [HO]Ca2+ [OH] bridging structure with the hydroxyl group in GelMA, thereby enhancing the stability. Compared with GelMA-PEGDA hydrogel, the addition of nHA can control the mechanical properties of the composite hydrogel and reduce the degradation rate. In vitro cell culture showed that osteoblast can adhere and proliferate on the surface of the hydrogel, indicating that the GelMA-PEGDA-nHA hydrogel had good cell viability and biocompatibility. Furthermore, GelMA-PEGDA-nHA has excellent injectability and rapid prototyping properties and is a promising 3D printed bone repair scaffold material.

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Effect of Volatile Organic Compounds Adsorption on 3D-Printed PEGDA:PEDOT for Long-Term Monitoring Devices

Nanomaterials ◽

10.3390/nano11010094 ◽

2021 ◽

Vol 11 (1) ◽

pp. 94

Author(s):

Giorgio Scordo ◽

Valentina Bertana ◽

Alberto Ballesio ◽

Rocco Carcione ◽

Simone Luigi Marasso ◽

...

Keyword(s):

Volatile Organic Compounds ◽

Organic Compounds ◽

Host Matrix ◽

Glycol Diacrylate ◽

3D Objects ◽

Volatile Organic ◽

3D Printed ◽

Poly Ethylene ◽

Monitoring Devices

We report on the preparation and stereolithographic 3D printing of a resin based on the composite between a poly(ethylene glycol) diacrylate (PEGDA) host matrix and a poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) filler, and the related cumulative volatile organic compounds’ (VOCs) adsorbent properties. The control of all the steps for resin preparation and printing through morphological (SEM), structural (Raman spectroscopy) and functional (I/V measurements) characterizations allowed us to obtain conductive 3D objects of complex and reproducible geometry. These systems can interact with chemical vapors in the long term by providing a consistent and detectable variation of their structural and conductive characteristics. The materials and the manufacture protocol here reported thus propose an innovative and versatile technology for VOCs monitoring systems based on cumulative adsorption effects.

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The Role of Resilience in Sexual and Gender Minority Mental Health

The Oxford Handbook of Sexual and Gender Minority Mental Health ◽

10.1093/oxfordhb/9780190067991.013.38 ◽

2020 ◽

pp. 428-442

Author(s):

Dawn M. Szymanski ◽

Kirsten A. Gonzalez

Keyword(s):

Mental Health ◽

Minority Stress ◽

Quantitative Research ◽

Social Stigma ◽

Therapeutic Interventions ◽

Future Research ◽

Minority Mental Health ◽

And Gender ◽

Structural Levels

Many lesbian, gay, bisexual, transgender, and queer (LGBTQ) persons are able to persevere and flourish despite pervasive social stigma and minority stress based on their sexual orientation and gender identity. This chapter reviews the research on LGBTQ resilience that can occur at individual, interpersonal/family, community, and contextual/structural levels. The authors describe qualitative research that has examined pathways to resilience and positive LGBTQ identity. The authors also review quantitative research on LGBTQ resilience via mediator, moderator, and moderated mediation models. Variables are described that have been found to explain or buffer the links between external and internalized minority stressors and mental health outcomes. The authors review the small but growing body of research that has begun to examine the efficacy of therapeutic interventions aimed at promoting LGBTQ resilience. Limitations are discussed and directions for future research are suggested.

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1-Methylnicotinamide is an immune regulatory metabolite in human ovarian cancer

Science Advances ◽

10.1126/sciadv.abe1174 ◽

2021 ◽

Vol 7 (4) ◽

pp. eabe1174

Author(s):

Marisa K. Kilgour ◽

Sarah MacPherson ◽

Lauren G. Zacharias ◽

Abigail E. Ellis ◽

Ryan D. Sheldon ◽

...

Keyword(s):

T Cells ◽

Immune Modulation ◽

Human Cancer ◽

Serous Carcinoma ◽

Necrosis Factor Alpha ◽

Methyl Group ◽

Cytokine Tumor Necrosis Factor ◽

Factor Alpha ◽

Immunotherapy Target ◽

Necrosis Factor

Immune regulatory metabolites are key features of the tumor microenvironment (TME), yet with a few exceptions, their identities remain largely unknown. Here, we profiled tumor and T cells from tumor and ascites of patients with high-grade serous carcinoma (HGSC) to uncover the metabolomes of these distinct TME compartments. Cells within the ascites and tumor had pervasive metabolite differences, with a notable enrichment in 1-methylnicotinamide (MNA) in T cells infiltrating the tumor compared with ascites. Despite the elevated levels of MNA in T cells, the expression of nicotinamide N-methyltransferase, the enzyme that catalyzes the transfer of a methyl group from S-adenosylmethionine to nicotinamide, was restricted to fibroblasts and tumor cells. Functionally, MNA induces T cells to secrete the tumor-promoting cytokine tumor necrosis factor alpha. Thus, TME-derived MNA contributes to the immune modulation of T cells and represents a potential immunotherapy target to treat human cancer.

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