Commercial articulated collaborative in situ 3D bioprinter for skin wound healing

In situ bioprinting is one of the most clinically relevant techniques in the emerging bioprinting technology because it could be performed directly on the human body in the operating room and it does not require bioreactors for post-printing tissue maturation. However, commercial in situ bioprinters are still not available on the market. In this study, we demonstrated the benefit of the originally developed first commercial articulated collaborative in situ bioprinter for the treatment of full-thickness wounds in rat and porcine models. We used an articulated and collaborative robotic arm from company KUKA and developed original printhead and correspondence software enabling in situ bioprinting on curve and moving surfaces. The results of in vitro and in vivo experiments show that in situ bioprinting of bioink induces a strong hydrogel adhesion and enables printing on curved surfaces of wet tissues with a high level of fidelity. The in situ bioprinter was convenient to use in the operating room. Additional in vitro experiments (in vitro collagen contraction assay and in vitro 3D angiogenesis assay) and histological analyses demonstrated that in situ bioprinting improves the quality of wound healing in rat and porcine skin wounds. The absence of interference with the normal process of wound healing and even certain improvement in the dynamics of this process strongly suggests that in situ bioprinting could be used as a novel therapeutic modality in wound healing.publishersversionPeer reviewe

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Experimentally Created Magnetic Force in Microbiological Space and On-Earth Studies: Perspectives and Restrictions

Magnetic force and gravity are two fundamental forces affecting all living organisms, including bacteria. On Earth, experimentally created magnetic force can be used to counterbalance gravity and place living organisms in conditions of magnetic levitation. Under conditions of microgravity, magnetic force becomes the only force that moves bacteria, providing an acceleration towards areas of the lowest magnetic field and locking cells in this area. In this review, we consider basic principles and experimental systems used to create a magnetic force strong enough to balance gravity. Further, we describe how magnetic levitation is applied in on-Earth microbiological studies. Next, we consider bacterial behavior under combined conditions of microgravity and magnetic force onboard a spacecraft. At last, we discuss restrictions on applications of magnetic force in microbiological studies and the impact of these restrictions on biotechnological applications under space and on-Earth conditions

Scaffold-free and label-free biofabrication technology using levitational assembly in a high magnetic field

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Bioprinting of functional vascularized mouse thyroid gland construct.

Bioprinting can be defined as additive biofabrication of 3D tissues and organ constructs using tissue spheroids, capable of self-assembly, as building blocks. Thyroid gland, a relatively simple endocrine organ, is suitable for testing the proposed bioprinting technology. Here we report the bioprinting of functional vascularized mouse thyroid gland construct from embryonic tissue spheroids as a proof of concept. Based on the self-assembly principle, we generated thyroid tissue starting from thyroid spheroids (TS) and allantoic spheroids (AS), as a source of thyrocytes and endothelial cells (EC), respectively. Inspired by mathematical modelling of spheroid fusion, we used an original 3D bioprinter to print TS in close association with AS within collagen hydrogel. During the culture, closely placed embryonic tissue spheroids fused into a single integral construct, endothelial cells from AS invaded and vascularized TS, and epithelial cells from the TS progressively formed follicles. In this experimental setting, we observed formation of capillary network around follicular cells, as observed during in utero thyroid development when thyroid epithelium controls the recruitment, invasion and expansion of EC around follicles. To prove that EC from AS are responsible for vascularization of thyroid gland construct, we depleted endogenous EC from thyroid spheroids before bioprinting. EC from allantoic spheroids completely revascularized depleted thyroid tissue. Cultured bioprinted construct was functional as it could normalize blood thyroxin levels and body temperature after grafting under the kidney capsule of hypothyroid mice. Bioprinting of functional vascularized mouse thyroid gland construct represents further advance in bioprinting technology exploring self-assembling properties of tissue spheroids

Bioprinting of a functional vascularized mouse thyroid gland construct

Bioprinting can be defined as additive biofabrication of 3D tissues and organ constructs using tissue spheroids, capable of self-assembly, as building blocks. Thyroid gland, a relatively simple endocrine organ, is suitable for testing the proposed bioprinting technology. Here we report the bioprinting of functional vascularized mouse thyroid gland construct from embryonic tissue spheroids as a proof of concept. Based on the self-assembly principle, we generated thyroid tissue starting from thyroid spheroids (TS) and allantoic spheroids (AS), as a source of thyrocytes and endothelial cells (EC), respectively. Inspired by mathematical modelling of spheroid fusion, we used an original 3D bioprinter to print TS in close association with AS within collagen hydrogel. During the culture, closely placed embryonic tissue spheroids fused into a single integral construct, endothelial cells from AS invaded and vascularized TS, and epithelial cells from the TS progressively formed follicles. In this experimental setting, we observed formation of capillary network around follicular cells, as observed during in utero thyroid development when thyroid epithelium controls the recruitment, invasion and expansion of EC around follicles. To prove that EC from AS are responsible for vascularization of thyroid gland construct, we depleted endogenous EC from thyroid spheroids before bioprinting. EC from allantoic spheroids completely revascularized depleted thyroid tissue. Cultured bioprinted construct was functional as it could normalize blood thyroxin levels and body temperature after grafting under the kidney capsule of hypothyroid mice. Bioprinting of functional vascularized mouse thyroid gland construct represents further advance in bioprinting technology exploring self-assembling properties of tissue spheroids

Combined Impact of Magnetic Force and Spaceflight Conditions on Escherichia coli Physiology

Changes in bacterial physiology caused by the combined action of the magnetic force and microgravity were studied in Escherichia coli grown using a specially developed device aboard the International Space Station. The morphology and metabolism of E. coli grown under spaceflight (SF) or combined spaceflight and magnetic force (SF + MF) conditions were compared with ground cultivated bacteria grown under standard (control) or magnetic force (MF) conditions. SF, SF + MF, and MF conditions provided the up-regulation of Ag43 auto-transporter and cell auto-aggregation. The magnetic force caused visible clustering of non-sedimenting bacteria that formed matrix-containing aggregates under SF + MF and MF conditions. Cell auto-aggregation was accompanied by up-regulation of glyoxylate shunt enzymes and Vitamin B12 transporter BtuB. Under SF and SF + MF but not MF conditions nutrition and oxygen limitations were manifested by the down-regulation of glycolysis and TCA enzymes and the up-regulation of methylglyoxal bypass. Bacteria grown under combined SF + MF conditions demonstrated superior up-regulation of enzymes of the methylglyoxal bypass and down-regulation of glycolysis and TCA enzymes compared to SF conditions, suggesting that the magnetic force strengthened the effects of microgravity on the bacterial metabolism. This strengthening appeared to be due to magnetic force-dependent bacterial clustering within a small volume that reinforced the effects of the microgravity-driven absence of convectional flows

Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma

Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations. Within D3-UM, ElF1AX- and SRSF2/SF3B/-mutant tumors have distinct somatic copy number alterations and DNA methylation profiles, providing insight into the biology of these low- versus intermediate -risk clinical mutation subtypes