Biology subjects

Aili, D.

Publications and source records attributed to Aili, D..

4 recordsLinked to original sources

bioRxiv2026

An Innervated and Vascularized HNSCC-on-a-Chip Model Built on Defined and Tunable Engineered Extracellular Matrices

Understanding the tumor microenvironment (TME) requires experimental platforms that faithfully recapitulate its key components. Here, we present an innervated and vascularized head and neck squamous cell carcinoma (HNSCC)-on-a-chip platform built with fully defined and tunable engineered extracellular matrices (eECMs). In a stepwise increase of complexity, we first co-cultured patient-derived HNSCC cells, cancer-associated fibroblasts, and endothelial cells within tailored eECMs, revealing matrix-dependent differences in self-organization and chemotherapeutic sensitivity. We then integrated these 3D constructs into a cancer-vasculature-interface, which enabled analysis of eECM-dependent directional collective migration and metastatization. Finally, we incorporated HNSCC-specific innervation through injectable 3D human bioengineered trigeminal ganglia, establishing a chip-based innervation-tumor-vasculature tri-interface. Together, this all-human platform captures fundamental determinants of HNSCC progression, including a fully defined ECM, vasculature, and innervation, within a single modular system that is broadly adaptable for interrogating how the tumor microenvironment shapes solid tumor behavior and therapeutic responses. TeaserHNSCC-on-a-chip integrates defined ECM, vasculature, and innervation to investigate tumor behavior and therapeutic responses.

bioengineering↗

bioRxiv2023

Proteolytic Remodeling of 3D Bioprinted Tumor Microenvironments

In native tissue, remodeling of the pericellular space is essential for cellular activities and is mediated by tightly regulated proteases. Protease activity is dysregulated in many diseases, including many forms of cancer. Increased proteolytic activity is directly linked to tumor invasion into stroma, metastasis, and angiogenesis as well as all other hallmarks of cancer. Here we show how integrated 3D bioprinted structures with distinctly different responses to proteolytic activity can be utilized for systematic investigation of proteolytic remodeling of the extra cellular matrix and the impact of stromal cells on protease driven processes. Bioprinted structures combining non-degradable and degradable hydrogels were designed and demonstrated to be selectively degraded by proteases allowing for protease-mediated material reorganization with high spatial resolution. Bioprinting of tumor microenvironments combining bioinks with different susceptibilities to proteolytic degradation shows that breast cancer cell proliferation, migration into stromal compartments, and spheroid size are significantly increased in protease degradable hydrogels, but only in the presence of fibroblasts. Proteolytic remodeling of the tumor microenvironment has a significant effect on tumor progression and is drastically influenced by the intimate crosstalk between fibroblast and breast cancer cells.

bioengineering↗

bioRxiv2021

Bioorthogonally Cross-Linked Hyaluronan-Laminin Hydrogels for 3D Neuronal Cell Culture and Biofabrication

Laminins (LNs) are key components in the extracellular matrix of neuronal tissues in the developing brain and neural stem cell niches. LN-presenting hydrogels can provide a biologically relevant matrix for the 3D culture of neurons towards development of advanced tissue models and cell-based therapies for the treatment of neurological disorders. Biologically derived hydrogels are rich in fragmented LN and are poorly defined concerning composition, which hampers clinical translation. Engineered hydrogels require elaborate and often cytotoxic chemistries for cross-linking and LN conjugation and provide limited possibilities to tailor the properties of the materials. Here we show a modular hydrogel system for neural 3D cell culture, based on hyaluronan (HA) and poly(ethylene glycol) (PEG), that is cross-linked and functionalized with human recombinant LN 521 using bioorthogonal copper-free click chemistry. Encapsulated human neuroblastoma cells demonstrate high viability and grow into spheroids. Neuroepithelial stem cells (lt-NES) cultured in the hydrogels can undergo spontaneous differentiation to neural fate and demonstrate significantly higher viability than cells cultured without LN. The hydrogels further support the structural integrity of 3D bioprinted structures and maintain high viability of syringe extruded lt-NES, which can facilitate the development of advanced neuronal tissue and disease models and translation of stem cell-based therapies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/461549v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1ef2167org.highwire.dtl.DTLVardef@79f22eorg.highwire.dtl.DTLVardef@ae8d3org.highwire.dtl.DTLVardef@3ba3da_HPS_FORMAT_FIGEXP M_FIG The authors present an extracellular matrix mimicking hydrogel for 3D culture of neural cell models. Based on hyaluronic acid and poly(ethylene glycol), the hydrogel immobilizes recombinant laminin 521, associated with neuronal development. The study demonstrates support of neuroblastoma cell viability, spontaneous human neuroepithelial stem cell differentiation, and the protective effect of the hydrogels during bioprinting and syringe needle ejection. C_FIG

bioengineering↗

bioRxiv2021

Long-lasting humoral immunity in Covid-19 infected patients at a University Hospital Clinic in Ostergotland County Council during 2020-2021.

Longitudinal serum samples and nasopharyngeal/nasal swab samples were collected from forty-eight individuals (median age 66yrs) with Covid-19 PCR-positive test results at Linkoping University Hospital. Samples were collected from initial visit and for 6 months follow up. Presence of serum IgG and IgA against SARS-CoV-2 antigens (S1-spike, nucleocapsid and NSP3) were analyzed. Nasal swabs were tested for presence of IgA against the outer envelope S1 spike protein. Ninety-two percent of participants were seropositive against SARS-CoV-2 recombinant proteins at day 28 from study entry and all (100%) were seropositive from samples collected at 2 months or later. The most common antibody responses (both serum IgG, mainly IgG1 and IgA) were detected against the S1-spike protein and the nucleoprotein. In samples collected from nasal tissues considerably lower frequencies of IgA-positive reactivities were detected. Sixteen to 18 percent of study participants showed detectable IgA levels in nasal samples, except at day 60 when 36% of tested individuals showed presence of IgA against the S1-spike protein. The study suggests that the absolute majority of studied naturally infected Covid-19 patient in the Linkoping, Ostergotland health region develop over 6 months lasting detectable levels of serum IgG and IgA responses towards the SARS-CoV-2 S1-spike protein as well as against the nucleoprotein, but not against the non-structural protein 3.

immunology↗