The encapsulation of cells within gel‐phase materials to form bioinks offers distinct advantages for next‐generation 3D bioprinting. 3D bioprinting has emerged as a promising tool for patterning ...cells, but the technology remains limited in its ability to produce biofunctional, tissue‐like constructs due to a dearth of materials suitable for bioinks. While early demonstrations commonly used viscous polymers optimized for printability, these materials often lacked cell compatibility and biological functionality. In response, advanced materials that exist in the gel phase during the entire printing process are being developed, since hydrogels are uniquely positioned to both protect cells during extrusion and provide biological signals to embedded cells as the construct matures during culture. Here, an overview of the design considerations for gel‐phase materials as bioinks is presented, with a focus on their mechanical, biochemical, and dynamic gel properties. Current challenges and opportunities that arise due to the fact that bioprinted constructs are active, living hydrogels composed of both acellular and cellular components are also evaluated. Engineering hydrogels with consideration of cells as an intrinsic component of the printed bioink will enable control over the evolution of the living construct after printing to achieve greater biofunctionality.
This review describes recent progress and future opportunities to design dual‐stage crosslinked bioinks, which are gels both prior to and after printing. These active, living materials are composed of both acellular and cellular components. Engineering hydrogels with consideration of cells as an intrinsic component of the printed bioink will enable greater biofunctionality.
The COVID-19 pandemic and its sequelae have created scenarios of scarce medical resources, leading to the prospect that health care systems have faced or will face difficult decisions about triage, ...allocation, and reallocation. These decisions should be guided by ethical principles and values, should not be made before crisis standards have been declared by authorities, and, in most cases, will not be made by bedside clinicians. Do not attempt resuscitation and withholding and withdrawing decisions should be made according to standard determination of medical appropriateness and futility, but there are unique considerations during a pandemic. Transparent and clear communication is crucial, coupled with dedication to provide the best possible care to patients, including palliative care. As medical knowledge about COVID-19 grows, more will be known about prognostic factors that can guide these difficult decisions.
Three-dimensional (3D) bioprinting is a promising technique for spatially patterning cells and materials into constructs that mimic native tissues and organs. However, a trade-off exists between ...printability and biological function, where weak materials are typically more suited for 3D cell culture but exhibit poor shape fidelity when printed in air. Recently, a new class of assistive materials has emerged to overcome this limitation and enable fabrication of more complex, biologically relevant geometries, even when using soft materials as bioinks. These materials include support baths, which bioinks are printed into, and sacrificial inks, which are printed themselves and then later removed. Support baths are commonly yield-stress materials that provide physical confinement during the printing process to improve resolution and shape fidelity. Sacrificial inks have primarily been used to create void spaces and pattern perfusable networks, but they can also be combined directly with the bioink to change its mechanical properties for improved printability or increased porosity. Here, we outline the advantages of using such assistive materials in 3D bioprinting, define their material property requirements, and offer case study examples of how these materials are used in practice. Finally, we discuss the remaining challenges and future opportunities in the development of assistive materials that will propel the bioprinting field forward toward creating full-scale, biomimetic tissues and organs.
Shortages of life-saving medical resources caused by COVID-19 have prompted hospitals, healthcare systems, and governmentsto develop crisis standards of care, including 'triage protocols' to ...potentially ration medical supplies during the public health emergency. At the same time, the pandemic has highlighted and exacerbated racial, ethnic, and socioeconomic health disparities that together constitute a form of structural racism. These disparities pose a critical ethical challenge in developing fair triage systems that will maximize lives saved without perpetuating systemic inequities. Here we review alternatives to 'utilitarian' triage, including first-come first-served, egalitarian, and prioritarian systems of allocating scarce medical resources. We assess the comparative advantages and disadvantages of these allocation schemes. Ultimately, we argue that while triage protocols should not exacerbate disparities, they are not an adequate mechanism for redressing systemic health inequities. Entrenched health disparities must be addressed through broader social change.
The typical Western diet, high in processed and animal-based foods, is nutritionally and ethically problematic. Beyond the well-documented cruelty to animals that characterizes the practices of the ...factory-farming industry, current patterns of meat consumption contribute to medical and moral harm in humans on both an individual level and a public health scale. We aim to deconstruct, by highlighting their fallacies, the common positive and normative arguments that are used to defend current nutritional patterns. Animal-based foods promote the mechanisms that underlie chronic cardiometabolic disease, whereas whole-food plant-based nutrition can reverse them. Factory farming of animals also contributes to climate change, antibiotic resistance, and the spread of infectious diseases. Finally, the current allocation of nutritional resources in the United States is unjust. A societal shift toward more whole-food plant-based patterns of eating stands to provide significant health benefits and ethical advantages, and the medical profession has a duty to advocate accordingly. Although it remains important for individuals to make better food choices to promote their own health, personal responsibility is predicated on sound advice and on resource equity, including the availability of healthy options. Nutrition equity is a moral imperative and should be a top priority in the promotion of public health.
Three‐dimensional (3D) bioprinting is a promising technology to produce tissue‐like structures, but a lack of diversity in bioinks is a major limitation. Ideally each cell type would be printed in ...its own customizable bioink. To fulfill this need for a universally applicable bioink strategy, a versatile bioorthogonal bioink crosslinking mechanism that is cell compatible and works with a range of polymers is developed. This family of materials is termed UNIversal, Orthogonal Network (UNION) bioinks. As demonstration of UNION bioink versatility, gelatin, hyaluronic acid (HA), recombinant elastin‐like protein (ELP), and polyethylene glycol (PEG) are each used as backbone polymers to create inks with storage moduli spanning from 200 to 10 000 Pa. Because UNION bioinks are crosslinked by a common chemistry, multiple materials can be printed together to form a unified, cohesive structure. This approach is compatible with any support bath that enables diffusion of UNION crosslinkers. Both matrix‐adherent human corneal mesenchymal stromal cells and non‐matrix‐adherent human induced pluripotent stem cell‐derived neural progenitor spheroids are printed with UNION bioinks. The cells retained high viability and expressed characteristic phenotypic markers after printing. Thus, UNION bioinks are a versatile strategy to expand the toolkit of customizable materials available for 3D bioprinting.
A family of materials, termed UNIversal, Orthogonal Network (UNION) bioinks, is developed for 3D bioprinting of multi‐material structures using a cell‐compatible, bioorthogonal crosslinking mechanism. UNION bioinks can be created from a wide range of polymers, work with a variety of cell types, and offer biochemical and mechanical tunability, thus expanding the toolkit of customizable materials available for 3D bioprinting.
Leber congenital amaurosis (LCA) is an inherited retinal dystrophy that causes childhood blindness. Photoreceptors are especially sensitive to an intronic mutation in the cilia-related gene CEP290, ...which causes missplicing and premature termination, but the basis of this sensitivity is unclear. Here, we generated differentiated photoreceptors in three-dimensional optic cups and retinal pigment epithelium (RPE) from iPSCs with this common CEP290 mutation to investigate disease mechanisms and evaluate candidate therapies. iPSCs differentiated normally into RPE and optic cups, despite abnormal CEP290 splicing and cilia defects. The highest levels of aberrant splicing and cilia defects were observed in optic cups, explaining the retinal-specific manifestation of this CEP290 mutation. Treating optic cups with an antisense morpholino effectively blocked aberrant splicing and restored expression of full-length CEP290, restoring normal cilia-based protein trafficking. These results provide a mechanistic understanding of the retina-specific phenotypes in CEP290 LCA patients and potential strategies for therapeutic intervention.
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•Generation of 3D optic cups with opsin-expressing photoreceptors and outer segments•A CEP290-LCA intronic mutation creates a cryptic exon that impairs ciliogenesis•Aberrant splicing is increased in photoreceptors compared to other cell types•Antisense oligonucleotide can block the cryptic exon and restore CEP290 function
Parfitt et al. derived human 3D optic cup organoids to model LCA, a retinal dystrophy associated with aberrant CEP290 splicing leading to cilia defects. Retinal-specific defects result from higher aberrant CEP290 splicing in photoreceptors versus other cells, and treating cups with an antisense oligonucleotide restored CEP290 protein, function, and ciliation.
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