Publications by authors named "Jennifer A Lewis"

125 Publications

Association of Rurality With Annual Repeat Lung Cancer Screening in the Veterans Health Administration.

J Am Coll Radiol 2022 Jan;19(1 Pt B):131-138

Veterans Health Administration - Tennessee Valley Health Care System Geriatric Research, Education and Clinical Center, Nashville, Tennessee; Division of General Internal Medicine and Public Health, Vanderbilt University Medical Center, Nashville, Tennessee; Deputy Director, Quality Scholars Program, VA Tennessee Valley Healthcare System; and Director, Vanderbilt University School of Medicine Mater of Public Health Program.

Purpose: Lung cancer causes the largest number of cancer-related deaths in the United States. Lung cancer incidence rates, mortality rates, and rates of advanced stage disease are higher among those who live in rural areas. Known disparities in lung cancer outcomes between rural and nonrural populations may be in part because of barriers faced by rural populations. The authors tested the hypothesis that among Veterans who receive initial lung cancer screening, rural Veterans would be less likely to complete annual repeat screening than nonrural Veterans.

Methods: A retrospective cohort study was conducted of 10 Veterans Affairs medical centers from 2015 to 2019. Rural and nonrural Veterans undergoing lung cancer screening were identified. Rural status was defined using the rural-urban commuting area codes. The primary outcome was annual repeat lung cancer screening in the 9- to 15-month window (primary analysis) and 31-day to 18-month window (sensitivity analysis) after the first documented lung cancer screening. To examine rurality as a predictor of annual repeat lung cancer screening, multivariable logistic regression models were used.

Results: In the final analytic sample of 11,402 Veterans, annual repeat lung cancer screening occurred in 27.7% of rural Veterans (641 of 2,316) and 31.8% of nonrural Veterans (2,891 of 9,086) (adjusted odds ratio: 0.86; 95% confidence interval: 0.73-1.03). Similar results were seen in the sensitivity analysis, with 41.6% of rural Veterans (963 of 2,316) versus 45.2% of nonrural Veterans (4,110 of 9,086) (adjusted odds ratio: 0.88; 95% confidence interval: 0.73-1.04) having annual repeat screening in the expanded 31-day to 18-month window.

Conclusions: Among a national cohort of Veterans, rural residence was associated with numerically lower odds of annual repeat lung cancer screening than nonrural residence. Continued, intentional outreach efforts to increase annual repeat lung cancer screening among rural Veterans may offer an opportunity to decrease deaths from lung cancer.
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http://dx.doi.org/10.1016/j.jacr.2021.08.027DOI Listing
January 2022

Photoswitchable Covalent Adaptive Networks Based on Thiol-Ene Elastomers.

ACS Appl Mater Interfaces 2022 Jan 10. Epub 2022 Jan 10.

School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, United States.

Covalent adaptive networks combine the advantages of cross-linked elastomers and dynamic bonding in a single system. In this work, we demonstrate a simple one-pot method to prepare thiol-ene elastomers that exhibit reversible photoinduced switching from an elastomeric gel to fluid state. This behavior can be generalized to thiol-ene cross-linked elastomers composed of different backbone chemistries (e.g., polydimethylsiloxane, polyethylene glycol, and polyurethane) and vinyl groups (e.g., allyl, vinyl ether, and acrylate). Photoswitching from the gel to fluid state occurs in seconds upon exposure to UV light and can be repeated over at least 180 cycles. These thiol-ene elastomers also exhibit the ability to heal, remold, and serve as reversible adhesives.
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http://dx.doi.org/10.1021/acsami.1c22287DOI Listing
January 2022

Innervated, Self-Sensing Liquid Crystal Elastomer Actuators with Closed Loop Control.

Adv Mater 2021 Jul 31;33(27):e2101814. Epub 2021 May 31.

John A. Paulson School of Engineering and Applied Sciences and Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, 02138, USA.

The programmable assembly of innervated LCE actuators (iLCEs) with prescribed contractile actuation, self-sensing, and closed loop control via core-shell 3D printing is reported. This extrusion-based direct ink writing method enables coaxial filamentary features composed of pure LM core surrounded by an LCE shell, whose director is aligned along the print path. Specifically, the thermal response of the iLCE fiber-type actuators is programmed, measured, and modeled during Joule heating, including quantifying the concomitant changes in fiber length and resistance that arise during simultaneous heating and self-sensing. Due to their reversible, high-energy actuation and their resistive feedback, it is also demonstrated that iLCEs can be regulated with closed loop control even when perturbed with large bias loads. Finally, iLCE architectures capable of programmed, self-sensing 3D shape change with closed loop control are fabricated.
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http://dx.doi.org/10.1002/adma.202101814DOI Listing
July 2021

The NIH Somatic Cell Genome Editing program.

Nature 2021 04 7;592(7853):195-204. Epub 2021 Apr 7.

McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.

The move from reading to writing the human genome offers new opportunities to improve human health. The United States National Institutes of Health (NIH) Somatic Cell Genome Editing (SCGE) Consortium aims to accelerate the development of safer and more-effective methods to edit the genomes of disease-relevant somatic cells in patients, even in tissues that are difficult to reach. Here we discuss the consortium's plans to develop and benchmark approaches to induce and measure genome modifications, and to define downstream functional consequences of genome editing within human cells. Central to this effort is a rigorous and innovative approach that requires validation of the technology through third-party testing in small and large animals. New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled-along with validated datasets-into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit-and the knowledge generated by its applications-as a means to accelerate the clinical development of new therapies for a wide range of conditions.
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http://dx.doi.org/10.1038/s41586-021-03191-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026397PMC
April 2021

Hierarchically Porous Ceramics via Direct Writing of Binary Colloidal Gel Foams.

ACS Appl Mater Interfaces 2021 Feb 12;13(7):8976-8984. Epub 2021 Feb 12.

School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, United States.

Hierarchically porous ceramics with a high specific surface area and interconnected porosity may find potential application as particulate filters, catalyst supports, and battery electrodes. We report the design and programmable assembly of cellular ceramic architectures with controlled pore size, volume, and interconnectivity across multiple length scales via direct foam writing. Specifically, binary colloidal gel foams are created that contain entrained bubbles stabilized by the irreversible adsorption of attractive alumina and carbon (porogen) particles at their air-water interfaces. Composition effects on foam ink rheology and printing behavior are investigated. Sintered ceramic foams exhibited specific permeabilities that increased from 2 × 10 to 1 × 10 m and compressive strengths that decreased from 40 to 1 MPa, respectively, with increasing specific interfacial area. Using direct foam writing, 3D ceramic lattices composed of open-cell foam struts were fabricated with tailored mechanical properties and interconnected porosity across multiple length scales.
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http://dx.doi.org/10.1021/acsami.0c22292DOI Listing
February 2021

National Lung Cancer Screening Utilization Trends in the Veterans Health Administration.

JNCI Cancer Spectr 2020 Oct 13;4(5):pkaa053. Epub 2020 Jun 13.

Veterans Affairs Tennessee Valley Healthcare System, Geriatric Research, Education and Clinical Center (GRECC), Nashville, TN, USA.

Background: Many Veterans are high risk for lung cancer. Low-dose computed tomography (LDCT) is an effective strategy for lung cancer early detection in a high-risk population. Our objective was to describe and compare annual and geographic utilization trends for LDCT screening in the Veteran's Health Administration (VHA).

Methods: A national retrospective cohort of screened Veterans from January 1, 2011 to May 31, 2018 was used to calculate annual and regional rates of initial LDCT utilization per 1000 eligible Veterans. We identified Veterans with a first LDCT exam using common procedure terminology codes G0297 or 71250 and described as "lung cancer screening," "screening," or "LCS." The number of screen-eligible Veterans per year was calculated as unique Veterans aged 55 to 80 years seen at a Veterans Affairs medical center (VAMC) in that year, multiplied by 32% (estimated proportion with eligible smoking history). We present 95% confidence intervals (CI) for rates.

Results: Screened Veterans had a mean age of 66.1 years (standard deviation [SD] = 5.6); 95.5% male; 77.4% Caucasian. There were 119 300 LDCT exams, of which 80 819 (67.7%) were initial. Nationally, initial screens increased from 0 (95% CI = 0.00 to 0.00) in 2011 to 29.6 (95% CI = 29.26 to 29.88) scans per 1000 eligible Veterans in 2018 ( < .001). Initial screens increased over time within all geographic regions, most prominently in northeastern and Florida VAMCs.

Conclusion: VHA LDCT utilization increased from 2011 to 2018. However, overall utilization remained low. Future interventions are needed to increase lung cancer screening utilization among eligible Veterans.
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http://dx.doi.org/10.1093/jncics/pkaa053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7583162PMC
October 2020

Protocol to evaluate an enterprise-wide initiative to increase access to lung cancer screening in the Veterans Health Administration.

Clin Imaging 2021 May 26;73:151-161. Epub 2020 Dec 26.

VA Tennessee Valley Healthcare System, Geriatric Research, Education and Clinical Center (GRECC), Nashville, TN, United States of America; Division of General Internal Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN, United States of America.

Introduction: The Veterans Affairs Partnership to increase Access to Lung Screening (VA-PALS) is an enterprise-wide initiative to implement lung cancer screening programs at VA medical centers (VAMCs). VA-PALS will be using implementation strategies that include program navigators to coordinate screening activities, trainings for navigators and radiologists, an open-source software management system, tools to standardize low-dose computed tomography image quality, and access to a support network. VAMCs can utilize strategies according to their local needs. In this protocol, we describe the planned program evaluation for the initial 10 VAMCs participating in VA-PALS.

Materials And Methods: The implementation of programs will be evaluated using the Consolidated Framework for Implementation Research to ensure broad contextual guidance. Program evaluation measures have been developed using the Reach, Effectiveness, Adoption, Implementation and Maintenance framework. Adaptations of screening processes will be assessed using the Framework for Reporting Adaptations and Modifications to Evidence Based Interventions. Measures collected will reflect the inner settings, estimate and describe the population reached, adoption by providers, implementation of the programs, report clinical outcomes and maintenance of programs. Analyses will include descriptive statistics and regression to evaluate predictors and assess implementation over time.

Discussion: This theory-based protocol will evaluate the implementation of lung cancer screening programs across the Veterans Health Administration using scientific frameworks. The findings will inform plans to expand the VA-PALS initiative beyond the original sites and can guide implementation of lung cancer screening programs more broadly.
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http://dx.doi.org/10.1016/j.clinimag.2020.11.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479827PMC
May 2021

Organizational Readiness for Lung Cancer Screening: A Cross-Sectional Evaluation at a Veterans Affairs Medical Center.

J Am Coll Radiol 2021 Jun 7;18(6):809-819. Epub 2021 Jan 7.

Deputy Director, VA Tennessee Valley Healthcare System VA Quality Scholars Program, Veterans Health Administration-Tennessee Valley Health Care System Geriatric Research, Education and Clinical Center (GRECC), Nashville, Tennessee; Director, Vanderbilt Master of Public Health Program, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Objectives: Lung cancer has the highest cancer-related mortality in the United States and among Veterans. Screening of high-risk individuals with low-dose CT (LDCT) can improve survival through detection of early-stage lung cancer. Organizational factors that aid or impede implementation of this evidence-based practice in diverse populations are not well described. We evaluated organizational readiness for change and change valence (belief that change is beneficial and valuable) for implementation of LDCT screening.

Methods: We performed a cross-sectional survey of providers, staff, and administrators in radiology and primary care at a single Veterans Affairs Medical Center. Survey measures included Shea's validated Organizational Readiness for Implementing Change (ORIC) scale and Shea's 10 items to assess change valence. ORIC and change valence were scored on a scale from 1 to 7 (higher scores representing higher readiness for change or valence). Multivariable linear regressions were conducted to determine predictors of ORIC and change valence.

Results: Of 523 employees contacted, 282 completed survey items (53.9% overall response rate). Higher ORIC scores were associated with radiology versus primary care (mean 5.48, SD 1.42 versus 5.07, SD 1.22, β = 0.37, P = .039). Self-identified leaders in lung cancer screening had both higher ORIC (5.56, SD 1.39 versus 5.11, SD 1.26, β = 0.43, P = .050) and change valence scores (5.89, SD 1.21 versus 5.36, SD 1.19, β = 0.51, P = .012).

Discussion: Radiology health professionals have higher levels of readiness for change for implementation of LDCT screening than those in primary care. Understanding health professionals' behavioral determinants for change can inform future lung cancer screening implementation strategies.
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http://dx.doi.org/10.1016/j.jacr.2020.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180484PMC
June 2021

Evidence-based smoking cessation treatment: a comparison by healthcare system.

BMC Health Serv Res 2021 Jan 7;21(1):33. Epub 2021 Jan 7.

Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research, Education and Clinical Center (GRECC), Nashville, TN, USA.

Background: A systems-level approach to smoking cessation treatment may optimize healthcare provider adherence to guidelines. Institutions such as the Veterans Health Administration (VHA) are unique in their systematic approach, but comparisons of provider behavior in different healthcare systems are limited.

Methods: We surveyed general medicine providers and specialists in a large academic health center (AHC) and its affiliated VHA in the Mid-South in 2017 to determine the cross-sectional association of healthcare system in which the provider practiced (exposure: AHC versus VHA) with self-reported provision of evidence-based smoking cessation treatment (delivery of counseling plus smoking cessation medication or referral) at least once in the past 12 months (composite outcome). Multivariable logistic regression with adjustment for specialty was performed in 2017-2019.

Results: Of 625 healthcare providers surveyed, 407 (65%) responded, and 366 (59%) were analyzed. Most respondents practiced at the AHC (273[75%] vs VHA 93[25%]) and were general internists (215[59%]); pulmonologists (39[11%]); hematologists/oncologists (69[19%]); and gynecologists (43[12%]). Most respondents (328[90%]) reported the primary outcome. The adjusted odds of evidence-based smoking cessation treatment were higher among VHA vs. AHC healthcare providers (aOR = 4.3; 95% CI 1.3-14.4; p = .02). Health systems differed by provision of individual treatment components, including smoking cessation medication use (98% VHA vs. 90% AHC, p = 0.02) and referral to smoking cessation services (91% VHA vs. 65% AHC p = 0.001).

Conclusions: VHA healthcare providers were significantly more likely to provide evidence-based smoking cessation treatment compared to AHC healthcare providers. Healthcare systems' prioritization of and investment in smoking cessation treatment is critical to improving providers' adherence to guidelines.
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http://dx.doi.org/10.1186/s12913-020-06016-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792006PMC
January 2021

Effect of luminal flow on doming of mpkCCD cells in a 3D perfusable kidney cortical collecting duct model.

Am J Physiol Cell Physiol 2020 07 13;319(1):C136-C147. Epub 2020 May 13.

Division of Pediatric Nephrology and Hypertension, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York.

The cortical collecting duct (CCD) of the mammalian kidney plays a major role in the maintenance of total body electrolyte, acid/base, and fluid homeostasis by tubular reabsorption and excretion. The mammalian CCD is heterogeneous, composed of Na-absorbing principal cells (PCs) and acid-base-transporting intercalated cells (ICs). Perturbations in luminal flow rate alter hydrodynamic forces to which these cells in the cylindrical tubules are exposed. However, most studies of tubular ion transport have been performed in cell monolayers grown on or epithelial sheets affixed to a flat support, since analysis of transepithelial transport in native tubules by in vitro microperfusion requires considerable expertise. Here, we report on the generation and characterization of an in vitro, perfusable three-dimensional kidney CCD model (3D CCD), in which immortalized mouse PC-like mpkCCD cells are seeded within a cylindrical channel embedded within an engineered extracellular matrix and subjected to luminal fluid flow. We find that a tight epithelial barrier composed of differentiated and polarized PCs forms within 1 wk. Immunofluorescence microscopy reveals the apical epithelial Na channel ENaC and basolateral Na/K-ATPase. On cessation of luminal flow, benzamil-inhibitable cell doming is observed within these 3D CCDs consistent with the presence of ENaC-mediated Na absorption. Our 3D CCD provides a geometrically and microphysiologically relevant platform for studying the development and physiology of renal tubule segments.
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http://dx.doi.org/10.1152/ajpcell.00405.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468887PMC
July 2020

Voxelated soft matter via multimaterial multinozzle 3D printing.

Nature 2019 11 13;575(7782):330-335. Epub 2019 Nov 13.

Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.

There is growing interest in voxelated matter that is designed and fabricated voxel by voxel. Currently, inkjet-based three-dimensional (3D) printing is the only widely adopted method that is capable of creating 3D voxelated materials with high precision, but the physics of droplet formation requires the use of low-viscosity inks to ensure successful printing. By contrast, direct ink writing, an extrusion-based 3D printing method, is capable of patterning a much broader range of materials. However, it is difficult to generate multimaterial voxelated matter by extruding monolithic cylindrical filaments in a layer-by-layer manner. Here we report the design and fabrication of voxelated soft matter using multimaterial multinozzle 3D (MM3D) printing, in which the composition, function and structure of the materials are programmed at the voxel scale. Our MM3D printheads exploit the diode-like behaviour that arises when multiple viscoelastic materials converge at a junction to enable seamless, high-frequency switching between up to eight different materials to create voxels with a volume approaching that of the nozzle diameter cubed. As exemplars, we fabricate a Miura origami pattern and a millipede-like soft robot that locomotes by co-printing multiple epoxy and silicone elastomer inks of stiffness varying by several orders of magnitude. Our method substantially broadens the palette of voxelated materials that can be designed and manufactured in complex motifs.
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http://dx.doi.org/10.1038/s41586-019-1736-8DOI Listing
November 2019

3D Printable and Reconfigurable Liquid Crystal Elastomers with Light-Induced Shape Memory via Dynamic Bond Exchange.

Adv Mater 2020 Jan 30;32(1):e1905682. Epub 2019 Oct 30.

John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.

3D printable and reconfigurable liquid crystal elastomers (LCEs) that reversibly shape-morph when cycled above and below their nematic-to-isotropic transition temperature (T ) are created, whose actuated shape can be locked-in via high-temperature UV exposure. By synthesizing LCE-based inks with light-triggerable dynamic bonds, printing can be harnessed to locally program their director alignment and UV light can be used to enable controlled network reconfiguration without requiring an imposed mechanical field. Using this integrated approach, 3D LCEs are constructed in both monolithic and heterogenous layouts that exhibit complex shape changes, and whose transformed shapes could be locked-in on demand.
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http://dx.doi.org/10.1002/adma.201905682DOI Listing
January 2020

Shape-shifting structured lattices via multimaterial 4D printing.

Proc Natl Acad Sci U S A 2019 10 2;116(42):20856-20862. Epub 2019 Oct 2.

Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138;

Shape-morphing structured materials have the ability to transform a range of applications. However, their design and fabrication remain challenging due to the difficulty of controlling the underlying metric tensor in space and time. Here, we exploit a combination of multiple materials, geometry, and 4-dimensional (4D) printing to create structured heterogeneous lattices that overcome this problem. Our printable inks are composed of elastomeric matrices with tunable cross-link density and anisotropic filler that enable precise control of their elastic modulus () and coefficient of thermal expansion [Formula: see text] The inks are printed in the form of lattices with curved bilayer ribs whose geometry is individually programmed to achieve local control over the metric tensor. For independent control of extrinsic curvature, we created multiplexed bilayer ribs composed of 4 materials, which enables us to encode a wide range of 3-dimensional (3D) shape changes in response to temperature. As exemplars, we designed and printed planar lattices that morph into frequency-shifting antennae and a human face, demonstrating functionality and geometric complexity, respectively. Our inverse geometric design and multimaterial 4D printing method can be readily extended to other stimuli-responsive materials and different 2-dimensional (2D) and 3D cell designs to create scalable, reversible, shape-shifting structures with unprecedented complexity.
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http://dx.doi.org/10.1073/pnas.1908806116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800333PMC
October 2019

Architected Polymer Foams via Direct Bubble Writing.

Adv Mater 2019 Nov 19;31(46):e1904668. Epub 2019 Sep 19.

Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.

Polymer foams are cellular solids composed of solid and gas phases, whose mechanical, thermal, and acoustic properties are determined by the composition, volume fraction, and connectivity of both phases. A new high-throughput additive manufacturing method, referred to as direct bubble writing, for creating polymer foams with locally programmed bubble size, volume fraction, and connectivity is reported. Direct bubble writing relies on rapid generation and patterning of liquid shell-gas core droplets produced using a core-shell nozzle. The printed polymer foams are able to retain their overall shape, since the outer shell of these bubble droplets consist of a low-viscosity monomer that is rapidly polymerized during the printing process. The transition between open- and closed-cell foams is independently controlled by the gas used, while the foam can be tailored on-the-fly by adjusting the gas pressure used to produce the bubble droplets. As exemplars, homogeneous and graded polymer foams in several motifs, including 3D lattices, shells, and out-of-plane pillars are fabricated. Conductive composite foams with controlled stiffness for use as soft pressure sensors are also produced.
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http://dx.doi.org/10.1002/adma.201904668DOI Listing
November 2019

Biomanufacturing of organ-specific tissues with high cellular density and embedded vascular channels.

Sci Adv 2019 09 6;5(9):eaaw2459. Epub 2019 Sep 6.

Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, USA.

Engineering organ-specific tissues for therapeutic applications is a grand challenge, requiring the fabrication and maintenance of densely cellular constructs composed of ~10 cells/ml. Organ building blocks (OBBs) composed of patient-specific-induced pluripotent stem cell-derived organoids offer a pathway to achieving tissues with the requisite cellular density, microarchitecture, and function. However, to date, scant attention has been devoted to their assembly into 3D tissue constructs. Here, we report a biomanufacturing method for assembling hundreds of thousands of these OBBs into living matrices with high cellular density into which perfusable vascular channels are introduced via embedded three-dimensional bioprinting. The OBB matrices exhibit the desired self-healing, viscoplastic behavior required for sacrificial writing into functional tissue (SWIFT). As an exemplar, we created a perfusable cardiac tissue that fuses and beats synchronously over a 7-day period. Our SWIFT biomanufacturing method enables the rapid assembly of perfusable patient- and organ-specific tissues at therapeutic scales.
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http://dx.doi.org/10.1126/sciadv.aaw2459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731072PMC
September 2019

Association of a Lung Screening Program Coordinator With Adherence to Annual CT Lung Screening at a Large Academic Institution.

J Am Coll Radiol 2020 Feb 6;17(2):208-215. Epub 2019 Sep 6.

Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research, Education and Clinical Center (GRECC), Nashville, Tennessee; Department of Internal Medicine/Division of General Internal Medicine and Public Health, Vanderbilt University Medical Center, Nashville, Tennessee.

Background: Detection of early-stage lung cancer improves during subsequent rounds of screening with low-dose CT and potentially leads to saving lives with curative treatment. Therefore, adherence to annual lung screening is important. We hypothesized that adherence to annual screening would increase after hiring of a dedicated program coordinator.

Methods: We performed a mixed-methods study in a retrospective cohort of patients who underwent lung screening at our academic institution between January 1, 2014, and March 31, 2018. Patients with baseline lung screening examinations performed between January 1, 2014, and September 30, 2016, with Lung CT Screening Reporting & Data System 1 or 2 scores and a 12-month follow-up recommendation were included. We tracked patient adherence to annual follow-up lung screening over time (before and after hiring of a program coordinator) and conducted a cross-sectional survey of patients nonadherent to annual follow-up to elicit quantitative and qualitative feedback.

Results: Of the 319 patients who completed baseline lung screening with normal results, 189 (59%) were adherent to annual follow-up recommendations and 130 (41%) were nonadherent. Patient adherence varied over time: 21.7% adherence (10 of 46) before hiring a program coordinator and 65.6% adherence (179 of 273) after the program coordinator's hire date. Patients reported the following reasons for nonadherence to annual lung screening: lack of transportation, financial cost, lack of communication by physicians, and lack of current symptoms.

Conclusions: Adherence to annual lung screening after normal baseline studies increased significantly over time. Hiring a full-time program coordinator was likely associated with this increased in adherence.
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http://dx.doi.org/10.1016/j.jacr.2019.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767624PMC
February 2020

Untethered soft robotic matter with passive control of shape morphing and propulsion.

Sci Robot 2019 Aug;4(33)

John A. Paulson School of Engineering and Applied Sciences, Wyss Institute of Biologically Inspired Engineering, Cambridge, MA 02138, USA.

There is growing interest in creating untethered soft robotic matter that can repeatedly shape-morph and self-propel in response to external stimuli. Toward this goal, we printed soft robotic matter composed of liquid crystal elastomer (LCE) bilayers with orthogonal director alignment and different nematic-to-isotropic transition temperatures ( ) to form active hinges that interconnect polymeric tiles. When heated above their respective actuation temperatures, the printed LCE hinges exhibit a large, reversible bending response. Their actuation response is programmed by varying their chemistry and printed architecture. Through an integrated design and additive manufacturing approach, we created passively controlled, untethered soft robotic matter that adopts task-specific configurations on demand, including a self-twisting origami polyhedron that exhibits three stable configurations and a "rollbot" that assembles into a pentagonal prism and self-rolls in programmed responses to thermal stimuli.
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http://dx.doi.org/10.1126/scirobotics.aax7044DOI Listing
August 2019

Perovskite nanowire-block copolymer composites with digitally programmable polarization anisotropy.

Sci Adv 2019 May 31;5(5):eaav8141. Epub 2019 May 31.

School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.

One-dimensional (1D) nanomaterials with highly anisotropic optoelectronic properties are key components in energy harvesting, flexible electronics, and biomedical imaging devices. 3D patterning methods that precisely assemble nanowires with locally controlled composition and orientation would enable new optoelectronic device designs. As an exemplar, we have created and 3D-printed nanocomposite inks composed of brightly emitting colloidal cesium lead halide perovskite (CsPbX, X = Cl, Br, and I) nanowires suspended in a polystyrene-polyisoprene-polystyrene block copolymer matrix. The nanowire alignment is defined by the programmed print path, resulting in optical nanocomposites that exhibit highly polarized absorption and emission properties. Several devices have been produced to highlight the versatility of this method, including optical storage, encryption, sensing, and full-color displays.
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http://dx.doi.org/10.1126/sciadv.aav8141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544451PMC
May 2019

Low Provider Knowledge Is Associated With Less Evidence-Based Lung Cancer Screening.

J Natl Compr Canc Netw 2019 04;17(4):339-346

aGeriatric Research, Education and Clinical Center, Veterans Health Administration - Tennessee Valley Healthcare System, Nashville, Tennessee.

Background: Despite widespread recommendation and supportive policies, screening with low-dose CT (LDCT) is incompletely implemented in the US healthcare system. Low provider knowledge of the lung cancer screening (LCS) guidelines represents a potential barrier to implementation. Therefore, we tested the hypothesis that low provider knowledge of guidelines is associated with less provider-reported screening with LDCT.

Patients And Methods: A cross-sectional survey was performed in a large academic medical center and affiliated Veterans Health Administration in the Mid-South United States that comprises hospital and community-based practices. Participants included general medicine providers and specialists who treat patients aged >50 years. The primary exposure was LCS guideline knowledge (US Preventive Services Task Force/Centers for Medicare & Medicaid Services). High knowledge was defined as identifying 3 major screening eligibility criteria (55 years as initial age of screening eligibility, smoking status as current or former smoker, and smoking history of ≥30 pack-years), and low knowledge was defined as not identifying these 3 criteria. The primary outcome was self-reported LDCT order/referral within the past year, and the secondary outcome was screening chest radiograph. Multivariable logistic regression evaluated the adjusted odds ratio (aOR) of screening by knowledge.

Results: Of 625 providers recruited, 407 (65%) responded, and 378 (60.5%) were analyzed. Overall, 233 providers (62%) demonstrated low LCS knowledge, and 224 (59%) reported ordering/referring for LDCT. The aOR of ordering/referring LDCT was less among providers with low knowledge (0.41; 95% CI, 0.24-0.71) than among those with high knowledge. More providers with low knowledge reported ordering screening chest radiographs (aOR, 2.7; 95% CI, 1.4-5.0) within the past year.

Conclusions: Referring provider knowledge of LCS guidelines is low and directly proportional to the ordering rate for LDCT in an at-risk US population. Strategies to advance evidence-based LCS should incorporate provider education and system-level interventions to address gaps in provider knowledge.
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http://dx.doi.org/10.6004/jnccn.2018.7101DOI Listing
April 2019

Renal reabsorption in 3D vascularized proximal tubule models.

Proc Natl Acad Sci U S A 2019 03 4;116(12):5399-5404. Epub 2019 Mar 4.

Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115;

Three-dimensional renal tissues that emulate the cellular composition, geometry, and function of native kidney tissue would enable fundamental studies of filtration and reabsorption. Here, we have created 3D vascularized proximal tubule models composed of adjacent conduits that are lined with confluent epithelium and endothelium, embedded in a permeable ECM, and independently addressed using a closed-loop perfusion system to investigate renal reabsorption. Our 3D kidney tissue allows for coculture of proximal tubule epithelium and vascular endothelium that exhibits active reabsorption via tubular-vascular exchange of solutes akin to native kidney tissue. Using this model, both albumin uptake and glucose reabsorption are quantified as a function of time. Epithelium-endothelium cross-talk is further studied by exposing proximal tubule cells to hyperglycemic conditions and monitoring endothelial cell dysfunction. This diseased state can be rescued by administering a glucose transport inhibitor. Our 3D kidney tissue provides a platform for in vitro studies of kidney function, disease modeling, and pharmacology.
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http://dx.doi.org/10.1073/pnas.1815208116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431199PMC
March 2019

Flow-enhanced vascularization and maturation of kidney organoids in vitro.

Nat Methods 2019 03 11;16(3):255-262. Epub 2019 Feb 11.

Renal Division, Brigham and Women's Hospital, Boston, MA, USA.

Kidney organoids derived from human pluripotent stem cells have glomerular- and tubular-like compartments that are largely avascular and immature in static culture. Here we report an in vitro method for culturing kidney organoids under flow on millifluidic chips, which expands their endogenous pool of endothelial progenitor cells and generates vascular networks with perfusable lumens surrounded by mural cells. We found that vascularized kidney organoids cultured under flow had more mature podocyte and tubular compartments with enhanced cellular polarity and adult gene expression compared with that in static controls. Glomerular vascular development progressed through intermediate stages akin to those involved in the embryonic mammalian kidney's formation of capillary loops abutting foot processes. The association of vessels with these compartments was reduced after disruption of the endogenous VEGF gradient. The ability to induce substantial vascularization and morphological maturation of kidney organoids in vitro under flow opens new avenues for studies of kidney development, disease, and regeneration.
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http://dx.doi.org/10.1038/s41592-019-0325-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488032PMC
March 2019

Cure of Oligometastatic Classic Biphasic Pulmonary Blastoma Using Aggressive Tri-modality Treatment: Case Series and Review of the Literature.

Cureus 2018 Nov 13;10(11):e3586. Epub 2018 Nov 13.

Internal Medicine, Wake Forest School of Medicine, Winston-Salem, USA.

Pulmonary blastoma is a rare lung cancer classified into three subtypes: classic biphasic pulmonary blastoma (CBPB), well-differentiated fetal adenocarcinoma (WDFA), and pleuropulmonary blastoma (PPB) of childhood. Compared to the other subtypes, CPPB is an aggressive tumor with an overall five-year survival of 16% across all stages. We present two cases of biopsy-proven metastatic CBPB, who have been disease-free for over 10 years since treatment completion. Both patients were treated with surgery to the primary tumor followed by an adjuvant cisplatin-based chemotherapy for four cycles and thoracic radiation. One patient relapsed shortly after the completion of thoracic radiation with brain metastases and underwent craniotomy, gamma knife radiosurgery (GKRS), and whole brain radiation therapy. The other patient presented with synchronous pelvic metastases and underwent metastasectomy after the completion of chemotherapy but before the initiation of thoracic radiation. We review the literature regarding surgical, chemotherapeutic, and radiation treatment for patients with metastatic pulmonary blastoma. Based on our experience and review of the existing case reports, aggressive tri-modality treatment including surgery, chemotherapy with a cisplatin backbone, and a definitive treatment of oligometastatic lesions amenable to local therapy including resection or radiosurgery is reasonable to consider for medically fit patients with CBPB.
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http://dx.doi.org/10.7759/cureus.3586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333266PMC
November 2018

High-Power Aqueous Zinc-Ion Batteries for Customized Electronic Devices.

ACS Nano 2018 Dec 8;12(12):11838-11846. Epub 2018 Nov 8.

Wyss Institute for Biologically Inspired Engineering , Harvard University , 3 Blackfan Circle , Boston , Massachusetts 02115 , United States.

Wireless electronic devices require small, rechargeable batteries that can be rapidly designed and fabricated in customized form factors for shape conformable integration. Here, we demonstrate an integrated design and manufacturing method for aqueous zinc-ion batteries composed of polyaniline (PANI)-coated carbon fiber (PANI/CF) cathodes, laser micromachined zinc (Zn) anodes, and porous separators that are packaged within three-dimensional printed geometries, including rectangular, cylindrical, H-, and ring-shapes. The PANI/CF cathode possesses high surface area and conductivity giving rise to high rate (∼600 C) performance. Due to outstanding stability of Zn-PANI batteries against oxygen and moisture, they exhibit long cycling stability in an aqueous electrolyte solution. As exemplar, we demonstrated rechargeable battery packs with tunable voltage and capacity using stacked electrodes that are integrated with electronic components in customized wearable devices.
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http://dx.doi.org/10.1021/acsnano.8b02744DOI Listing
December 2018

In vitro human tissues via multi-material 3-D bioprinting.

Altern Lab Anim 2018 Sep;46(4):209-215

Wyss Institute for Biologically Inspired Engineering and Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA.

This paper highlights the foundational research on multi-material 3-D bioprinting of human tissues, for which the Lewis Bioprinting team at Harvard University was awarded the 2017 Lush Science Prize. The team's bioprinting platform enables the rapid fabrication of 3-D human tissues that contain all of the essential components found in their in vivo counterparts: cells, vasculature (or other tubular features) and extracellular matrix. The printed 3-D tissues are housed within a customised perfusion system and are subjected to controlled microphysiological environments over long durations (days to months). As exemplars, the team created a thick, stem cell-laden vascularised tissue that was controllably differentiated toward an osteogenic lineage in situ, and a 3-D kidney tissue that recapitulated the proximal tubule, a subunit of the nephron responsible for solute reabsorption. This highly versatile platform for manufacturing 3-D human tissue in vitro opens new avenues for replacing animal models used to develop next-generation therapies, test toxicity and study disease pathology.
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http://dx.doi.org/10.1177/026119291804600404DOI Listing
September 2018

Mechanics of biomimetic 4D printed structures.

Soft Matter 2018 Nov;14(43):8771-8779

John A. Paulson School of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, Cambridge, Massachusetts 02138, USA.

Recent progress in additive manufacturing and materials engineering has led to a surge of interest in shape-changing plate and shell-like structures. Such structures are typically printed in a planar configuration and, when exposed to an ambient stimulus such as heat or humidity, swell into a desired three-dimensional geometry. Viewed through the lens of differential geometry and elasticity, the application of the physical stimulus can be understood as a local change in the metric of a two dimensional surface embedded in three dimensions. To relieve the resulting elastic frustration, the structure will generally bend and buckle out-of-plane. Here, we propose a numerical approach to convert the discrete geometry of filament bilayers, associated with print paths of inks with given material properties, into continuous plates with inhomogeneous growth patterns and thicknesses. When subject to prescribed growth anisotropies, we can then follow the evolution of the shapes into their final form. We show that our results provide a good correspondence between experiments and simulations, and lead to a framework for the prediction and design of shape-changing structures.
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http://dx.doi.org/10.1039/c8sm00990bDOI Listing
November 2018

Acoustophoretic printing.

Sci Adv 2018 08 31;4(8):eaat1659. Epub 2018 Aug 31.

John A. Paulson School of Engineering and Applied Sciences, Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, USA.

Droplet-based printing methods are widely used in applications ranging from biological microarrays to additive manufacturing. However, common approaches, such as inkjet or electrohydrodynamic printing, are well suited only for materials with low viscosity or specific electromagnetic properties, respectively. While in-air acoustophoretic forces are material-independent, they are typically weak and have yet to be harnessed for printing materials. We introduce an acoustophoretic printing method that enables drop-on-demand patterning of a broad range of soft materials, including Newtonian fluids, whose viscosities span more than four orders of magnitude (0.5 to 25,000 mPa·s) and yield stress fluids (τ > 50 Pa). By exploiting the acoustic properties of a subwavelength Fabry-Perot resonator, we have generated an accurate, highly localized acoustophoretic force that can exceed the gravitational force by two orders of magnitude to eject microliter-to-nanoliter volume droplets. The versatility of acoustophoretic printing is demonstrated by patterning food, optical resins, liquid metals, and cell-laden biological matrices in desired motifs.
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http://dx.doi.org/10.1126/sciadv.aat1659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118516PMC
August 2018

Stretchable Optomechanical Fiber Sensors for Pressure Determination in Compressive Medical Textiles.

Adv Healthc Mater 2018 08 29;7(15):e1800293. Epub 2018 May 29.

Mechanical Engineering Department, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Medical textiles are widely used to exert pressure on human tissues during treatment of post-surgical hematoma, burn-related wounds, chronic venous ulceration, and other maladies. However, the inability to dynamically sense and adjust the applied pressure often leads to suboptimal pressure application, prolonging treatment or resulting in poor patient outcomes. Here, a simple strategy for measuring sub-bandage pressure by integrating stretchable optomechanical fibers into elastic bandages is demonstrated. Specifically, these fibers possess an elastomeric photonic multilayer cladding that surrounds an extruded stretchable core filament. They can sustain repetitive strains of over 100%, and respond to deformation with a predictable and reversible color variation. Integrated into elastic textiles, which apply pressure as a function of their strain, these fibers can provide instantaneous and localized pressure feedback. These colorimetric fiber sensors are well suited for medical textiles, athletic apparel, and other smart wearable technologies, especially when repetitive, large deformations are required.
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http://dx.doi.org/10.1002/adhm.201800293DOI Listing
August 2018

All-Printed, Self-Aligned Carbon Nanotube Thin-Film Transistors on Imprinted Plastic Substrates.

ACS Appl Mater Interfaces 2018 May 30;10(18):15926-15932. Epub 2018 Apr 30.

Department of Chemical Engineering and Materials Science , University of Minnesota , Minneapolis , Minnesota 55455 , United States.

We present a self-aligned process for printing thin-film transistors (TFTs) on plastic with single-walled carbon nanotube (SWCNT) networks as the channel material. The SCALE (self-aligned capillarity-assisted lithography for electronics) process combines imprint lithography with inkjet printing. Specifically, inks are jetted into imprinted reservoirs, where they then flow into narrow device cavities due to capillarity. Here, we incorporate a composite high- k gate dielectric and an aligned conducting polymer gate electrode in the SCALE process to enable a smaller areal footprint than prior designs that yields low-voltage SWCNT TFTs with average p-type carrier mobilities of 4 cm/V·s and ON/OFF current ratios of 10. Our work demonstrates the promising potential of the SCALE process to fabricate SWCNT-based TFTs with favorable I- V characteristics on plastic substrates.
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http://dx.doi.org/10.1021/acsami.8b01581DOI Listing
May 2018

3D Printing of Customized Li-Ion Batteries with Thick Electrodes.

Adv Mater 2018 Apr 15;30(16):e1703027. Epub 2018 Mar 15.

John A. Paulson School of Engineering and Applied Sciences, Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, 02138, USA.

The growing demand for rechargeable lithium-ion batteries (LIBs) with higher capacity in customized geometries underscores the need for new battery materials, architectures, and assembly strategies. Here, the design, fabrication, and electrochemical performance of fully 3D printed LIBs composed of thick semisolid electrodes that exhibit high areal capacity are reported. Specifically, semisolid cathode and anode inks, as well as UV curable packaging and separator inks for direct writing of LIBs in arbitrary geometries are created. These fully 3D printed and packaged LIBs, which are encased between two glassy carbon current collectors, deliver an areal capacity of 4.45 mAh cm at a current density of 0.14 mA cm , which is equivalent to 17.3 Ah L . The ability to produce high-performance LIBs in customized form factors opens new avenues for integrating batteries directly within 3D printed objects.
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http://dx.doi.org/10.1002/adma.201703027DOI Listing
April 2018

Viscoplastic Matrix Materials for Embedded 3D Printing.

ACS Appl Mater Interfaces 2018 Jul 16;10(27):23353-23361. Epub 2018 Mar 16.

Department of Mechanical and Aerospace Engineering , Princeton University , Princeton , New Jersey 08544 , United States.

Embedded three-dimensional (EMB3D) printing is an emerging technique that enables free-form fabrication of complex architectures. In this approach, a nozzle is translated omnidirectionally within a soft matrix that surrounds and supports the patterned material. To optimize print fidelity, we have investigated the effects of matrix viscoplasticity on the EMB3D printing process. Specifically, we determine how matrix composition, print path and speed, and nozzle diameter affect the yielded region within the matrix. By characterizing the velocity and strain fields and analyzing the dimensions of the yielded regions, we determine that scaling relationships based on the Oldroyd number, Od, exist between these dimensions and the rheological properties of the matrix materials and printing parameters. Finally, we use EMB3D printing to create complex architectures within an elastomeric silicone matrix. Our methods and findings will both facilitate future characterization of viscoplastic matrices and motivate the development of new materials for EMB3D printing.
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http://dx.doi.org/10.1021/acsami.7b19818DOI Listing
July 2018
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