Cellular models are needed to study human development and disease in vitro, and to screen drugs for toxicity and efficacy. Current approaches are limited in the engineering of functional tissue ...models with requisite cell densities and heterogeneity to appropriately model cell and tissue behaviors. Here, we develop a bioprinting approach to transfer spheroids into self-healing support hydrogels at high resolution, which enables their patterning and fusion into high-cell density microtissues of prescribed spatial organization. As an example application, we bioprint induced pluripotent stem cell-derived cardiac microtissue models with spatially controlled cardiomyocyte and fibroblast cell ratios to replicate the structural and functional features of scarred cardiac tissue that arise following myocardial infarction, including reduced contractility and irregular electrical activity. The bioprinted in vitro model is combined with functional readouts to probe how various pro-regenerative microRNA treatment regimes influence tissue regeneration and recovery of function as a result of cardiomyocyte proliferation. This method is useful for a range of biomedical applications, including the development of precision models to mimic diseases and the screening of drugs, particularly where high cell densities and heterogeneity are important.
Bone tissue engineering strategies that recapitulate the developmental process of endochondral ossification offer a promising route to bone repair. Clinical translation of such endochondral tissue ...engineering strategies will require overcoming a number of challenges, including the engineering of large and often anatomically complex cartilage grafts, as well as the persistence of core regions of avascular cartilage following their implantation into large bone defects. Here 3D printing technology is utilized to develop a versatile and scalable approach to guide vascularisation during endochondral bone repair. First, a sacrificial pluronic ink was used to 3D print interconnected microchannel networks in a mesenchymal stem cell (MSC) laden gelatin-methacryloyl (GelMA) hydrogel. These constructs (with and without microchannels) were next chondrogenically primed in vitro and then implanted into critically sized femoral bone defects in rats. The solid and microchanneled cartilage templates enhanced bone repair compared to untreated controls, with the solid cartilage templates (without microchannels) supporting the highest levels of total bone formation. However, the inclusion of 3D printed microchannels was found to promote osteoclast/immune cell invasion, hydrogel degradation, and vascularisation following implantation. In addition, the endochondral bone tissue engineering strategy was found to support comparable levels of bone healing to BMP-2 delivery, whilst promoting lower levels of heterotopic bone formation, with the microchanneled templates supporting the lowest levels of heterotopic bone formation. Taken together, these results demonstrate that 3D printed hypertrophic cartilage grafts represent a promising approach for the repair of complex bone fractures, particularly for larger defects where vascularisation will be a key challenge.
We introduce a model of monetary policy with downward nominal wage rigidities and show that both the slope and curvature of the Phillips curve depend on the level of inflation and the extent of ...downward nominal wage rigidities. This is true for the both the long-run and the short-run Phillips curve. Comparing simulation results from the model with data on U.S. wage patterns, we show that downward nominal wage rigidities likely have played a role in shaping the dynamics of unemployment and wage growth during the last three recessions and subsequent recoveries.
The leaves of angiosperms contain highly complex venation networks consisting of recursively nested, hierarchically organized loops. We describe a new phenotypic trait of reticulate vascular networks ...based on the topology of the nested loops. This phenotypic trait encodes information orthogonal to widely used geometric phenotypic traits, and thus constitutes a new dimension in the leaf venation phenotypic space. We apply our metric to a database of 186 leaves and leaflets representing 137 species, predominantly from the Burseraceae family, revealing diverse topological network traits even within this single family. We show that topological information significantly improves identification of leaves from fragments by calculating a "leaf venation fingerprint" from topology and geometry. Further, we present a phenomenological model suggesting that the topological traits can be explained by noise effects unique to specimen during development of each leaf which leave their imprint on the final network. This work opens the path to new quantitative identification techniques for leaves which go beyond simple geometric traits such as vein density and is directly applicable to other planar or sub-planar networks such as blood vessels in the brain.
Cartilage is a dense connective tissue with limited self-repair capabilities. Mesenchymal stem cell (MSC) laden hydrogels are commonly used for fibrocartilage and articular cartilage tissue ...engineering, however they typically lack the mechanical integrity for implantation into high load bearing environments. This has led to increased interested in 3D bioprinting of cell laden hydrogel bioinks reinforced with stiffer polymer fibres. The objective of this study was to compare a range of commonly used hydrogel bioinks (agarose, alginate, GelMA and BioINK™) for their printing properties and capacity to support the development of either hyaline cartilage or fibrocartilage in vitro. Each hydrogel was seeded with MSCs, cultured for 28 days in the presence of TGF-β3 and then analysed for markers indicative of differentiation towards either a fibrocartilaginous or hyaline cartilage-like phenotype. Alginate and agarose hydrogels best supported the development of hyaline-like cartilage, as evident by the development of a tissue staining predominantly for type II collagen. In contrast, GelMA and BioINK
(a PEGMA based hydrogel) supported the development of a more fibrocartilage-like tissue, as evident by the development of a tissue containing both type I and type II collagen. GelMA demonstrated superior printability, generating structures with greater fidelity, followed by the alginate and agarose bioinks. High levels of MSC viability were observed in all bioinks post-printing (∼80%). Finally we demonstrate that it is possible to engineer mechanically reinforced hydrogels with high cell viability by co-depositing a hydrogel bioink with polycaprolactone filaments, generating composites with bulk compressive moduli comparable to articular cartilage. This study demonstrates the importance of the choice of bioink when bioprinting different cartilaginous tissues for musculoskeletal applications.
3D printing involves the development of inks that exhibit the requisite properties for both printing and the intended application. In bioprinting, these inks are often hydrogels with controlled ...rheological properties that can be stabilized after deposition. Here, an alternate approach is developed where the ink is composed exclusively of jammed microgels, which are designed to incorporate a range of properties through microgel design (e.g., composition, size) and through the mixing of microgels. The jammed microgel inks are shear‐thinning to permit flow and rapidly recover upon deposition, including on surfaces or when deposited in 3D within hydrogel supports, and can be further stabilized with secondary cross‐linking. This platform allows the use of microgels engineered from various materials (e.g., thiol‐ene cross‐linked hyaluronic acid (HA), photo‐cross‐linked poly(ethylene glycol), thermo‐sensitive agarose) and that incorporate cells, where the jamming process and printing do not decrease cell viability. The versatility of this particle‐based approach opens up numerous potential biomedical applications through the printing of a more diverse set of inks.
Microgels are jammed to formulate inks useful for 3D printing. Microgels are fabricated on microfluidic devices and jammed to form shear‐thinning solids where individual microgels can be designed with various chemical compositions or to contain cells. The microgel inks can be printed onto surfaces or into 3D hydrogels to produce diverse structures.
The Central African Plateau (CAP) covers a million square kilometers of African lithosphere absent of recent volcanism and intense seismicity. Treating the CAP erosion surface as a reference frame ...for measuring continental deformation reveals an active landscape of normal fault systems and crustal flexures. Free‐air gravity anomalies over the CAP reveal both a short‐wavelength (100–200 km) flexural and a longer‐wavelength (>500 km) mantle convective signature. Apatite fission track thermochronometry records the onset of regional cooling of the erosion surface below 60 °C between 38 and 22 Ma. The erosion surface was formed by the Latest Miocene and elevated to its present altitude (1,200 ± 50 m) in the Latest Miocene/Pliocene. High‐resolution Shuttle Radar Topography Mission‐ and LIDAR‐based digital elevation models of the erosion surface show active fault terraces and alluvial fan deformation associated with pre‐existing rift border faults. Flexural modeling of the footwall uplift of the Luangwa Rift border fault yields an effective elastic thickness of the CAP lithosphere of ~35 km. The rifting initiated in the Pliocene with, or soon after, elevation of the CAP. Subsequent Plio‐Pleistocene deformation of the CAP surface controls the Congo and Zambezi drainage systems and wetland locations. The CAP rifts link southwestward through the Zambezi, Kafue and Muchili Rifts to the Pleistocene aged Okavango and Eiseb Rifts of Botswana and Namibia, defining a propagating Southwestern Rift cutting the Nubian Plate. This active rift system developed along relatively thin (~150 km) lithosphere between the Congo and Kalahari cratons within crust inherited from Neoproterozoic collisional tectonics.
Key Points
The Late Cenozoic erosion surface of the Central African Plateau can be used as a datum to analyze the neotectonics of central Africa
Pliocene uplift and later rifting has resulted in flexure of the central African lithosphere that controls river basin and wetland location
The Plio‐Quaternary rifts of central Africa can be traced SW across Africa as a continuous Southwestern Rift and embryonic plate boundary
The bioprinting roadmap Sun, Wei; Starly, Binil; Daly, Andrew C ...
Biofabrication,
04/2020, Letnik:
12, Številka:
2
Journal Article
Recenzirano
Odprti dostop
This bioprinting roadmap features salient advances in selected applications of the technique and highlights the status of current developments and challenges, as well as envisioned advances in ...science and technology, to address the challenges to the young and evolving technique. The topics covered in this roadmap encompass the broad spectrum of bioprinting; from cell expansion and novel bioink development to cell/stem cell printing, from organoid-based tissue organization to bioprinting of human-scale tissue structures, and from building cell/tissue/organ-on-a-chip to biomanufacturing of multicellular engineered living systems. The emerging application of printing-in-space and an overview of bioprinting technologies are also included in this roadmap. Due to the rapid pace of methodological advancements in bioprinting techniques and wide-ranging applications, the direction in which the field should advance is not immediately clear. This bioprinting roadmap addresses this unmet need by providing a comprehensive summary and recommendations useful to experienced researchers and newcomers to the field.
The angiopoietin-Tie signaling system is a vascular-specific receptor tyrosine kinase pathway that is essential for normal vascular development. Although the basic functioning of the pathway is ...understood, many uncertainties remain about the role of certain members of the pathway, particularly angiopoietin-2 (Ang2), in pathological vascular remodeling and angiogenesis. We summarize the components of the angiopoietin-Tie pathway and then focus on studies that highlight the role of Ang2 in disease settings, including cancer and inflammation. The expression of Ang2 is elevated in many cancers and types of inflammation, which prompted the development of specific reagents to block its interaction with the Tie2 receptor. The application of these reagents in preclinical models of inflammation and cancer has begun to elucidate the role of Ang2 in vascular remodeling and disease pathogenesis and has led to emerging clinical tests of Ang2 inhibitors.
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