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The survival of vertebrate organisms depends on highly regulated delivery of oxygen and nutrients through vascular networks that pervade nearly all tissues in the body. Dysregulation of these vascular networks is implicated in many common human diseases such as hypertension, coronary artery disease, diabetes and cancer. Therefore, engineers have sought to create vascular networks within engineered tissues for applications such as regenerative therapies, human disease modelling and pharmacological testing. Yet engineering vascular networks has historically remained difficult, owing to both incomplete understanding of vascular structure and technical limitations for vascular fabrication. This Review highlights the materials advances that have enabled transformative progress in vascular engineering by ushering in new tools for both visualizing and building vasculature. New methods such as bioprinting, organoids and microfluidic systems are discussed, which have enabled the fabrication of 3D vascular topologies at a cellular scale with lumen perfusion. These approaches to vascular engineering are categorized into technology-driven and nature-driven approaches. Finally, the remaining knowledge gaps, emerging frontiers and opportunities for this field are highlighted, including the steps required to replicate the multiscale complexity of vascular networks found in nature. Engineers have long sought to fabricate vascular networks to deliver oxygen and nutrients within engineered human tissues for regenerative medicine applications. This Review highlights how materials advances have enabled the development of vascular engineering approaches driven by both technology and nature.

Hydrogel biomaterials derived from natural biopolymers (e.g., fibrin, collagen, decellularized extracellular matrix) are regularly utilized in three-dimensional (3D) cell culture and tissue engineering. In contrast to those based on synthetic polymers, natural materials permit enhanced cytocompatibility, matrix remodeling, and biological integration. Despite these advantages, natural protein-based gels have lagged behind synthetic alternatives in their tunability; methods to selectively modulate the biochemical properties of these networks in a user-defined and heterogeneous fashion that can drive encapsulated cell function have not yet been established. Here, we report a generalizable strategy utilizing a photomediated oxime ligation to covalently decorate naturally derived hydrogels with bioactive proteins including growth factors. This bioorthogonal photofunctionalization is readily amenable to mask-based and laser-scanning lithographic patterning, enabling full four-dimensional (4D) control over protein immobilization within virtually any natural protein-based biomaterial. Such versatility affords exciting opportunities to probe and direct advanced cell fates inaccessible using purely synthetic approaches in response to anisotropic environmental signaling.

Solid organs transport fluids through distinct vascular networks that are biophysically and biochemically entangled, creating complex three-dimensional (3D) transport regimes that have remained difficult to produce and study. We establish intravascular and multivascular design freedoms with photopolymerizable hydrogels by using food dye additives as biocompatible yet potent photoabsorbers for projection stereolithography. We demonstrate monolithic transparent hydrogels, produced in minutes, comprising efficient intravascular 3D fluid mixers and functional bicuspid valves. We further elaborate entangled vascular networks from space-filling mathematical topologies and explore the oxygenation and flow of human red blood cells during tidal ventilation and distension of a proximate airway. In addition, we deploy structured biodegradable hydrogel carriers in a rodent model of chronic liver injury to highlight the potential translational utility of this materials innovation.

Tissues with perfusable vascular networks can be fabricated through layer-by-layer assembly, bioprinting or sacrificial moulding, but current approaches are slow, have limited resolution, or place significant constraints on the materials or the processing conditions. A rapid and general vascular casting approach using carbohydrate glass as a sacrificial template to generate tissues containing cylindrical networks that can be lined with endothelial cells and perfused with blood under high-pressure pulsatile flow is now reported. In the absence of perfusable vascular networks, three-dimensional (3D) engineered tissues densely populated with cells quickly develop a necrotic core 1 . Yet the lack of a general approach to rapidly construct such networks remains a major challenge for 3D tissue culture 2 , 3 , 4 . Here, we printed rigid 3D filament networks of carbohydrate glass, and used them as a cytocompatible sacrificial template in engineered tissues containing living cells to generate cylindrical networks that could be lined with endothelial cells and perfused with blood under high-pressure pulsatile flow. Because this simple vascular casting approach allows independent control of network geometry, endothelialization and extravascular tissue, it is compatible with a wide variety of cell types, synthetic and natural extracellular matrices, and crosslinking strategies. We also demonstrated that the perfused vascular channels sustained the metabolic function of primary rat hepatocytes in engineered tissue constructs that otherwise exhibited suppressed function in their core.

People continue to use technology in new ways, and how governments harness digital information should consider privacy and security concerns. During COVID19, numerous countries deployed digital contact tracing that collect location data from user’s smartphones. However, these apps had low adoption rates and faced opposition. We launched an interdisciplinary study to evaluate smartphone location data concerns among college students in the US. Using interviews and a large survey, we find that college students have higher concerns regarding privacy, and place greater trust in local government with their location data. We discuss policy recommendations for implementing improved contact tracing efforts.

This study evaluates the impact of a U.S. government-sponsored research program on advanced natural gas combined cycle (NGCC) innovations in the 1990s. From 1992–2000, the U.S. Department of Energy (U.S. DOE) partnered with turbine manufacturers General Electric (GE) and Siemens Westinghouse Power Corporation (SWPC) in a cost-sharing partnership called the Advanced Turbine System program to promote efficiency innovations for NGCC technology. Using data from the European Patent Office’s worldwide patent database (PATSTAT), this study evaluates advanced turbine technology innovations by the program participants and their competitors. Using a negative binomial model, this approach shows GE increased the relative quantity of their patents towards the end of the program and afterwards, indicating the program led to more advanced NGCC innovations for GE. SWPC, on the other hand, had higher patent citations for patents filed during the DOE program relative to competitors, indicating SWPC had higher-quality advanced NGCC innovations due to new partnerships from the U.S. DOE program. However, this analysis reveals there was not a lack of this activity taking place before the program started, and that the overall impact of the program appears small based on the patent analysis.

Tissue vascularization and integration with host circulation remains a key barrier to the translation of engineered tissues into clinically relevant therapies. Here, we used a microtissue molding approach to demonstrate that constructs containing highly aligned \"cords\" of endothelial cells triggered the formation of new capillaries along the length of the patterned cords. These vessels became perfused with host blood as early as 3 d post implantation and became progressively more mature through 28 d. Immunohistochemical analysis showed that the neovessels were composed of human and mouse endothelial cells and exhibited a mature phenotype, as indicated by the presence of alpha-smooth muscle actin-positive pericytes. Implantation of cords with a prescribed geometry demonstrated that they provided a template that defined the neovascular architecture in vivo. To explore the utility of this geometric control, we implanted primary rat and human hepatocyte constructs containing randomly organized endothelial networks vs. ordered cords. We found substantially enhanced hepatic survival and function in the constructs containing ordered cords following transplantation in mice. These findings demonstrate the importance of multicellular architecture in tissue integration and function, and our approach provides a unique strategy to engineer vascular architecture.

There are calls for researchers to study existing community assets and activities that appear to improve health and have achieved longevity. The TR14ers Community Dance Charity Limited is a community youth dance group that has been running since 2005 providing free weekly sessions for children and adolescents in an economically disadvantaged town in the UK. An in-depth case study employing qualitative, quantitative and participatory methods was undertaken with the TR14ers (current participants and those who have left, co-ordinators and families) over 6 months with the aim of understanding the sustainable processes and impact of the Group. The 12 complex systems’ leverage points described by Meadows and the five domains of adolescent wellbeing developed by the United Nations H6+ Technical Working Group on Adolescent Health and Well-Being were used as frameworks to recognise the complexity of community assets like the TR14ers. The quantitative and qualitative data indicated that being part of the TR14ers contributed to multiple health and wellbeing outcomes. The positive experiences of being a TR14er led members to actively recruit others through word of mouth and public performances. Central to the TR14ers is a commitment to children’s rights, which is communicated formally and informally throughout the membership informing how and what the Group does, leading to the structure and delivery of the Group evolving over time. Members sought to ensure the sustainability of the Group after they had left and were keen to mentor younger members to develop and become the leaders. Based on the insights from this case study we suggest that efforts to develop cultures of health, like the TR14ers, should focus on the core values of the activity or intervention that underpin what it does and how within the local context.

Low-cost air quality sensor networks have gained tremendous popularity in the past decade, and they are increasingly being used for air quality related research and public outreach. They are also being used by different levels of governments as a governance tool to handle the ‘wicked’ problem of ambient air pollution. The smart and trustworthy air quality network is a multi-disciplinary, large-scale, low-cost sensor network designed for air quality, cybersecurity, and public administration research purposes for the Orlando, FL area. The custom designed monitors measure fine and coarse particulate matter at 2 min intervals across an approximately 30 km by 60 km area. In this article, we describe the establishment of two interlinked networks: one technological and one human-focused following a community-engaged research approach. In this paper, we explain design elements of both sides of the network and reflect on how well the outcomes achieved the principles of our design. Information presented in this article will inform other researchers who wish to operate their own low-cost sensor networks utilizing community-centered science and collaborative design for research purposes.

Developing vascular networks that integrate with the host circulation and support cells engrafted within engineered tissues remains a key challenge in tissue engineering. Most previous work in this field has focused on developing new methods to build human vascular networks within engineered tissues prior to their implant in vivo, with substantively less attention paid to the role of the host in tissue vascularization and engraftment. Here, we assessed the role that different host animal models and anatomic implant locations play in vascularization and cardiomyocyte survival within engineered tissues. We found major differences in the formation of graft-derived blood vessels and survival of cardiomyocytes after implantation of identical tissues in immunodeficient athymic nude mice versus rats. Athymic mice supported robust guided vascularization of human microvessels carrying host blood but relatively sparse cardiac grafts within engineered tissues, regardless of implant site. Conversely, athymic rats produced substantive inflammatory changes that degraded grafts (abdomen) or disrupted vascular patterning (heart). Despite disrupted vascular patterning, athymic rats supported > 3-fold larger human cardiomyocyte grafts compared to athymic mice. This work demonstrates the critical importance of the host for vascularization and engraftment of engineered tissues, which has broad translational implications across regenerative medicine.