Biology subjects

Groth, T.

Publications and source records attributed to Groth, T..

5 recordsLinked to original sources

bioRxiv2024

Three dimensionally printed microstructured alginate scaffolds for neural tissue engineering

The integration of scaffolds, signalling cues, and cellular components is essential in tissue engineering to create an in vivo equivalent environment that supports physiological function. Scaffolds provide mechanical reinforcement for cellular proliferation and differentiation while providing cues that instruct the development of cells during culture. Alginate (Alg) is a versatile biopolymer for scaffold engineering. However, due to a lack of intrinsic cell-binding sites, thus far, Alg must be functionalized for cellular adhesion. Here, we demonstrate proof-of-concept, bioactive additive-free, microstructured Alg (M-Alg) scaffolds for neuron culture. The M-Alg scaffold was formed by introducing tetrapod-shaped ZnO (t-ZnO) microparticles as structural templates in the Alg that were subsequently removed. These transparent, porous, additive-free Alg-based scaffolds with neuron affinity are promising for neuroregenerative and organoid- related research. HighlightsTetrapod-shaped ZnO (t-ZnO) microparticles are used as a template for the fabrication of open interconnected channels and textured surfaces in 3D printed microstructured alginate (M-Alg) scaffolds. Primary mouse cortical neurons seeded on the 3D printed M-Alg scaffolds show improved adhesion and maturation with extensive neural projections forming inside the scaffolds.

bioengineering↗

bioRxiv2022

Free-Standing Multilayer Films as Growth Factor Reservoirs for Future Wound Dressing Applications

Chronic skin wounds place a high burden on patients and health care systems. The use of angiogenic and mitogenic growth factors (GF) can facilitate the healing but GF are quickly inactivated by the wound environment if added exogenously. Here, free-standing multilayer films (FSF) are fabricated from chitosan (CHI) and alginate (ALG) as opposing polyelectrolytes in an alternating manner using layer-by-layer technique (LbL). One hundred bilayers form an about 450 {micro}m thick, detachable free-standing film (N-FSF) that is subsequently crosslinked by either ethyl (dimethylaminopropyl) carbodiimide (EDC) combined with N-hydroxysuccinimide (NHS) (E-FSF) or genipin (G-FSF). The characterization of swelling, oxygen permeability and crosslinking density shows reduced swelling and oxygen permeability for both crosslinked films compared to N-FSF. Loading of fibroblast growth factor 2 (FGF2) into the films results in a sustained release of GF from crosslinked in comparison to N-FSF. Biocompatibility studies in vitro with human dermal fibroblasts (HDF) cultured underneath the films demonstrate increased cell growth and cell migration for all films with and without FGF2. Especially G-FSF loaded with FGF2 greatly increases cell proliferation and migration. In vivo biocompatibility studies by subcutaneous implantation in mice show that E-FSF causes a strong inflammatory response while G-FSF is of high biocompatibility. N-FSF also represents a biocompatible film but shows early degradation. All FSF possess antibacterial properties against gram+ and gram-bacteria demonstrated by an agar diffusion disc assay. In summary, FSF made of ALG and CHI crosslinked with genipin can act as a reservoir for the sustained release of FGF2, possessing high biocompatibility in vitro and in vivo. Moreover, G-FSF promotes growth and migration of HDF and has antibacterial properties which makes it an interesting candidate for bioactive wound dressings.

bioengineering↗

bioRxiv2022

3D Printed Neural Tissues with in situ Optical Dopamine Sensors

Engineered neural tissues serve as models for studying neurological conditions and drug screening. Besides observing the cellular physiological properties, in situ monitoring of neurochemical concentrations with cellular spatial resolution in such neural tissues can provide additional valuable insights in models of disease and drug efficacy. In this work, we demonstrate the first three-dimensional (3D) tissue cultures with embedded optical dopamine (DA) sensors. We developed an alginate/Pluronic F127 based bio-ink for human dopaminergic brain tissue printing with tetrapodal-shaped-ZnO microparticles (t-ZnO) additive as the DA sensor. DA quenches the autofluorescence of t-ZnO in physiological environments, and the reduction of the fluorescence intensity serves as an indicator of the DA concentration. The neurons that were 3D printed with the t-ZnO showed good viability, and extensive 3D neural networks were formed within one week after printing. The t-ZnO can sense DA in the 3D printed neural network with a detection limit of 0.137 M. The results are a first step toward integrating tissue engineering with intensiometric biosensing for advanced artificial tissue/organ monitoring.

bioengineering↗

bioRxiv2022

GlycoEnzOnto: A GlycoEnzyme Pathway and Molecular Function Ontology

The glycoEnzymes include a set of proteins having related enzymatic, metabolic, transport, structural and cofactor functions. Current there is no established ontology to describe glycoEnzyme properties and to relate them to glycan biosynthesis pathways. We present GlycoEnzOnto, an ontology describing 386 human glycoEnzymes curated along 135 glycosylation pathways, 134 molecular functions and 22 cellular compartments. The pathways described regulate nucleotide-sugar metabolism, glycosyl-substrate/donor transport, glycan biosynthesis, and degradation. The role of each enzyme in the glycosylation initiation, elongation/branching, and capping/termination phases is described. IUPAC linear strings present systematic human/machine readable descriptions of individual reaction steps and enable automated knowledge-based curation of biochemical networks. All GlycoEnzOnto knowledge is integrated with the Gene Ontology (GO) biological processes. GlycoEnzOnto enables improved transcript overrepresentation analyses and glycosylation pathway identification compared to other available schema, e.g. KEGG and Reactome. Overall, GlycoEnzOnto represents a holistic glycoinformatics resource for systems-level analyses. Availabilityhttps://github.com/neel-lab/GlycoEnzOnto

bioinformatics↗

bioRxiv2020

A systems based framework to deduce transcription factors and signaling pathways regulating glycan biosynthesis

Glycosylation is a common post-translational modification, and glycan biosynthesis is regulated by a set of glycogenes. The role of transcription factors (TFs) in regulating the glycogenes and related glycosylation pathways is largely unknown. This manuscript presents a multi-omics data-mining framework to computationally predict putative, tissue-specific TF regulators of glycosylation. It combines existing ChIP-Seq (Chromatin Immunoprecipitation Sequencing) and RNA-Seq data to suggest 22,519 potentially significant TF-glycogene relationships. This includes interactions involving 524 unique TFs and 341 glycogenes that span 29 TCGA (The Cancer Genome Atlas) cancer types. Here, TF-glycogene interactions appeared in clusters or communities, suggesting that changes in single TF expression during both health and disease may affect multiple carbohydrate structures. Upon applying the Fishers exact test along with glycogene pathway classification, we identify TFs that may specifically regulate the biosynthesis of individual glycan types. Integration with knowledge from the Reactome database provided an avenue to relate cell-signaling pathways to TFs and cellular glycosylation state. Whereas analysis results are presented for all 29 cancer types, specific focus is placed on human luminal and basal breast cancer disease progression. Overall, the computational predictions in this manuscript present a starting point for systems-wide validation of TF-glycogene relationships.

systems biology↗