Biology subjects

Zauchner, D.

Publications and source records attributed to Zauchner, D..

3 recordsLinked to original sources

bioRxiv2026

A Modular Synthetic Hydrogel with Cell-scale Micropores Modulates Osteocyte-like Morphogenesis and Osteogenic Differentiation In Vitro

One crucial step during early osteogenesis is the embedding of osteoblasts within a collagen-rich extracellular matrix (osteoid), where they subsequently differentiate into a functional network of osteocytes. However, reconstructing 3D osteocyte networks in vitro remains a major challenge. We recently developed a synthetic microporous hydrogel to support the in vitro culture of 3D bone cell networks. Although matrix biodegradability facilitates cell-material interactions, the influence of micropores on bone tissue morphogenesis and differentiation remains poorly understood. Here, we investigate the effect of cell-scale micropores on bone cell morphogenesis and osteogenic differentiation in vitro. By exploiting polymerization-induced phase separation (PIPS) between 4-arm polyethylene glycol vinyl sulfones and dextran in the presence of hyaluronan, we generated matrix metalloproteinase-sensitive hydrogels with cell-scale micropores. Increasing the dextran concentration enlarged the average pore size from 4 m to 8 m, accompanied by a slight decrease in mechanical stiffness. Following encapsulation within these hydrogels, primary human osteoblasts remained highly viable. Hydrogels with larger pores supported extensive 3D cell network formation, whereas hydrogels with smaller pores exhibited enhanced osteogenic differentiation following 21 days of osteogenic culture. Together, these findings highlight that bone cells are sensitive to microporous physical cues and even minor changes over pore sizes can make an impact on osteocyte-like morphogenesis and differentiation in vitro.

bioengineering↗

bioRxiv2025

Volumetric Bioprinting of Bone-like Mineralizing Hydrogel Constructs in the Presence of High Cell Densities and Mineral Precursors

A major challenge in bone tissue engineering is the embedding of osteocyte-like cells at high density within a mineralized matrix at the micro-scale and a trabecular-like architecture at the macro-scale. Volumetric bioprinting (VBP) enables rapid creation of complex cell-laden constructs through tomographic light projections. However, integrating both high cell densities and inorganic mineral precursors into VBP processes poses challenges due to light scattering, which can compromise print fidelity. In this study, we aim to combine bioinspired polymer-induced liquid-phase precursor (PILP) mineralization with VBP to fabricate cell-laden gelatin methacryloyl hydrogel constructs with amorphous mineral precursors. By stabilizing amorphous mineral precursors with poly-aspartic acid, light scattering is sufficiently reduced to enable printing. Tuning the refractive index of this mineralizing bioresin allows fast VBP of mineralized bone-like constructs with cell densities of up to 3 million cells ml-1. The constructs display high cell viability (>90%) and enhanced mineralization when cultured in osteogenic conditions with {beta}-glycerophosphate. Encapsulated human mesenchymal stromal cells exhibit an early osteocytic phenotype after 28 days of differentiation. Collectively, this PILP-assisted VBP platform holds promise for the development of advanced in vitro bone models with more physiologically relevant architecture and cellular composition.

bioengineering↗

bioRxiv2023

Synthetic Biodegradable Void-forming Hydrogels for In Vitro 3D Culture of Functional Human Bone Cell Networks

Generating 3D bone cell networks in vitro that accurately mimic the dynamic process of osteoblast embedding during early bone formation poses a significant challenge. Herein, we report a synthetic biodegradable macroporous hydrogel for efficient formation of 3D networks from human primary cells, analysis of cell-secreted extracellular matrix (ECM) and microfluidic integration. Using polymerization-induced phase separation, matrix metalloproteinase-sensitive polyethylene glycol hydrogels are formed with interconnected porosity in the presence of living cells. The pore size (5-20 m) and permeability can be fine-tuned by adjusting the concentration and molecular weight of dextran. After encapsulation in these hydrogels, human mesenchymal stem cells and osteoblasts form a 3D cell network within 24 hours. The synthetic nature of this hydrogel enables histological analysis of cell-secreted collagen, a task previously challenging using collagen-derived hydrogels. Moreover, this hydrogel is integrated with a commercial chip, showcasing the potential for microfluidic perfusion cultures. Time-lapsed imaging of fluid flow and fast formation of 3D cell networks is demonstrated on chip. Altogether, this work introduces a versatile synthetic macroporous hydrogel, which can be integrated with microfluidic chip to enable 3D culture of human bone cell networks and analysis of cell-secreted ECM. This hydrogel may facilitate future mechanistic studies on bone development.

bioengineering↗