For decades, bioadhesive materials have garnered great attention due to their potential to replace sutures and staples for sealing tissues during minimally invasive surgical procedures. However, the ...complexities of delivering bioadhesives through narrow spaces and achieving strong adhesion in fluid‐rich physiological environments continue to present substantial limitations to the surgical translation of existing sealants. In this work, a new strategy for minimally invasive tissue sealing based on a multilayer bioadhesive patch, which is designed to repel body fluids, to form fast, pressure‐triggered adhesion with wet tissues, and to resist biofouling and inflammation is introduced. The multifunctional patch is realized by a synergistic combination of three distinct functional layers: i) a microtextured bioadhesive layer, ii) a dynamic, blood‐repellent hydrophobic fluid layer, and iii) an antifouling zwitterionic nonadhesive layer. The patch is capable of forming robust adhesion to tissue surfaces in the presence of blood, and exhibits superior resistance to bacterial adhesion, fibrinogen adsorption, and in vivo fibrous capsule formation. By adopting origami‐based fabrication strategies, it is demonstrated that the patch can be readily integrated with a variety of minimally invasive end effectors to provide facile tissue sealing in ex vivo porcine models, offering new opportunities for minimally invasive tissue sealing in diverse clinical scenarios.
A multifunctional patch presents new opportunities for sealing tissues in minimally invasive surgeries. Integration of a dynamic hydrophobic fluid layer, a microtextured bioadhesive layer, and a zwitterionic‐interpenetrated elastomer layer enables the patch to withstand fluid‐rich environments, maintain a robust seal, and minimize biofouling and inflammation. By employing various origami‐based designs, the patch can be adapted for different clinical applications.
Bioadhesive Technology Platforms Wu, Sarah J.; Zhao, Xuanhe
Chemical reviews,
12/2023, Letnik:
123, Številka:
24
Journal Article
Recenzirano
Bioadhesives have emerged as transformative and versatile tools in healthcare, offering the ability to attach tissues with ease and minimal damage. These materials present numerous opportunities for ...tissue repair and biomedical device integration, creating a broad landscape of applications that have captivated clinical and scientific interest alike. However, fully unlocking their potential requires multifaceted design strategies involving optimal adhesion, suitable biological interactions, and efficient signal communication. In this Review, we delve into these pivotal aspects of bioadhesive design, highlight the latest advances in their biomedical applications, and identify potential opportunities that lie ahead for bioadhesives as multifunctional technology platforms.
Tissue adhesive semiconductors Wu, Sarah J; Zhao, Xuanhe
Science (American Association for the Advancement of Science),
2023-Aug-11, 2023-08-11, 20230811, Letnik:
381, Številka:
6658
Journal Article
Recenzirano
Bioelectronic implants could use semiconductors that adhere to wet, dynamic tissues.
Large-scale single-cell analyses have become increasingly important given the role of cellular heterogeneity in complex biological systems. However, no current techniques enable optical imaging of ...uniquely-tagged individual cells. Fluorescence-based approaches can only distinguish a small number of distinct cells or cell groups at a time because of spectral crosstalk between conventional fluorophores. Here we investigate large-scale cell tracking using intracellular laser particles as imaging probes that emit coherent laser light with a characteristic wavelength. Made of silica-coated semiconductor microcavities, these laser particles have single-mode emission over a broad range from 1170 to 1580 nm with sub-nm linewidths, enabling massive spectral multiplexing. We explore the stability and biocompatibility of these probes in vitro and their utility for wavelength-multiplexed cell tagging and imaging. We demonstrate real-time tracking of thousands of individual cells in a 3D tumour model over several days showing different behavioural phenotypes.
When CdTe solar cells are doped with Cl, the grain boundaries no longer act as recombination centers but actively contribute to carrier collection efficiency. The physical origin of this remarkable ...effect has been determined through a combination of aberration-corrected scanning transmission electron microscopy, electron energy loss spectroscopy, and first-principles theory. Cl substitutes for a large proportion of the Te atoms within a few unit cells of the grain boundaries. Density functional calculations reveal the mechanism, and further indicate the grain boundaries are inverted to n type, establishing local p-n junctions which assist electron-hole pair separation. The mechanism is electrostatic, and hence independent of the geometry of the boundary, thereby explaining the universally high collection efficiency of Cl-doped CdTe solar cells.
Female eutherian mammals use X chromosome inactivation (XCI) to epigenetically regulate gene expression from ∼4% of the genome. To quantitatively map the topography of XCI for defined cell types at ...single cell resolution, we have generated female mice that carry X-linked, Cre-activated, and nuclear-localized fluorescent reporters--GFP on one X chromosome and tdTomato on the other. Using these reporters in combination with different Cre drivers, we have defined the topographies of XCI mosaicism for multiple CNS cell types and of retinal vascular dysfunction in a model of Norrie disease. Depending on cell type, fluctuations in the XCI mosaic are observed over a wide range of spatial scales, from neighboring cells to left versus right sides of the body. These data imply a major role for XCI in generating female-specific, genetically directed, stochastic diversity in eutherian mammals on spatial scales that would be predicted to affect CNS function within and between individuals.
Directed energy deposition (DED) additive manufacturing (AM) is receiving growing attention in many applications, such as repair, remanufacturing, and fabrication of functionally graded structures. ...However, the laser-matter interactions and melt pool dynamics in laser DED with powder flow are still unclear, particularly in how pores form and flow inside the melt pool during the process. Understanding the porosity formation mechanisms is critical in the qualification, certification, and overall properties of a DED AM part. Porosity is a common phenomenon and can significantly hinder the quality of DED fabricated parts, as the pores can act as sites of crack nucleation and propagation. Here, we reveal four types of pore formation mechanisms through in-situ and operando high-speed high-resolution X-ray imaging in the DED AM process. Our results confirm that porosity within the feedstock powder induces pores in the process. We also observed pore formation mechanisms unique to the laser-based, powder-blown DED process as a result of powder delivery, keyhole dynamics, melt pool dynamics, and shield gas. High-speed X-ray images provide direct evidence for pore formation mechanisms and show that the pores related to the interaction between the delivered powder and melt pool are the largest in size in laser-based powder-blown DED AM. These results will guide porosity mitigation, elimination, and control in DED AM.
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•Pore formation dynamics in the directed energy deposition (DED) process were directly observed.•Pore formation mechanisms unique to the laser-based DED process were revealed.•Four types of pore formation mechanisms were reported.•The mitigation strategies for each type of pore were provided based on the pore formation analysis.•Comparisons were made with pore formation mechanisms in LPBF.
Growth differentiation factor 15 (GDF15; also known as MIC-1) is a divergent member of the TGF-β superfamily and is associated with body-weight regulation in humans and rodents. However, the cognate ...receptor of GDF15 is unknown. Here we show that GDF15 binds specifically to GDNF family receptor α-like (GFRAL) with high affinity, and that GFRAL requires association with the coreceptor RET to elicit intracellular signaling in response to GDF15 stimulation. We also found that GDF15-mediated reductions in food intake and body weight of mice with obesity were abolished in GFRAL-knockout mice. We further found that GFRAL expression was limited to hindbrain neurons and not present in peripheral tissues, which suggests that GDF15-GFRAL-mediated regulation of food intake is by a central mechanism. Lastly, given that GDF15 did not increase energy expenditure in treated mice with obesity, the anti-obesity actions of the cytokine are likely driven primarily by a reduction in food intake.
A 3D printable tissue adhesive Wu, Sarah J; Wu, Jingjing; Kaser, Samuel J ...
Nature communications,
02/2024, Letnik:
15, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Tissue adhesives are promising alternatives to sutures and staples for joining tissues, sealing defects, and immobilizing devices. However, existing adhesives mostly take the forms of glues or ...hydrogels, which offer limited versatility. We report a direct-ink-write 3D printable tissue adhesive which can be used to fabricate bioadhesive patches and devices with programmable architectures, unlocking new potential for application-specific designs. The adhesive is conformable and stretchable, achieves robust adhesion with wet tissues within seconds, and exhibits favorable biocompatibility. In vivo rat trachea and colon defect models demonstrate the fluid-tight tissue sealing capability of the printed patches, which maintained adhesion over 4 weeks. Moreover, incorporation of a blood-repelling hydrophobic matrix enables the printed patches to seal actively bleeding tissues. Beyond wound closure, the 3D printable adhesive has broad applicability across various tissue-interfacing devices, highlighted through representative proof-of-concept designs. Together, this platform offers a promising strategy toward developing advanced tissue adhesive technologies.
Super-enhancers are large clusters of enhancers that activate gene expression. Broad trimethyl histone H3 lysine 4 (H3K4me3) often defines active tumor suppressor genes. However, how these epigenomic ...signatures are regulated for tumor suppression is little understood. Here we show that brain-specific knockout of the H3K4 methyltransferase MLL4 (a COMPASS-like enzyme, also known as KMT2D) in mice spontaneously induces medulloblastoma. Mll4 loss upregulates oncogenic Ras and Notch pathways while downregulating neuronal gene expression programs. MLL4 enhances DNMT3A-catalyzed DNA methylation and SIRT1/BCL6-mediated H4K16 deacetylation, which antagonize expression of Ras activators and Notch pathway components, respectively. Notably, Mll4 loss downregulates tumor suppressor genes (e.g., Dnmt3a and Bcl6) by diminishing broad H3K4me3 and super-enhancers and also causes widespread impairment of these epigenomic signatures during medulloblastoma genesis. These findings suggest an anti-tumor role for super-enhancers and provide a unique tumor-suppressive mechanism in which MLL4 is necessary to maintain broad H3K4me3 and super-enhancers at tumor suppressor genes.
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•Brain-specific Mll4 loss in mice results in spontaneous medulloblastoma•MLL4 upregulates DNMT3A-catalyzed DNA methylation to repress Ras activators•MLL4 enhances SIRT1/BCL6-mediated H4K16 deacetylation to downregulate Notch pathways•MLL4 establishes broad H3K4me3 and super-enhancers to activate tumor suppressor genes
Dhar et al. show that MLL4 suppresses medulloblastoma by establishing super-enhancers and broad H3K4me3 to activate multiple mechanisms that lead to activation of tumor suppressor genes and repression of oncogenes.
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