Biology subjects

Yang, Y. P.

Publications and source records attributed to Yang, Y. P..

4 recordsLinked to original sources

bioRxiv2025

3D Hybrid Bioprinting for Complex Multi-Tissue Engineering

3D bioprinting has revolutionized tissue engineering, enabling intricate, physiologically relevant constructs unattainable with conventional techniques, yet it remains limited in integrating soft and rigid multifunctional components for complex multi-tissue applications. In this study, we introduce a 3D hybrid bioprinting approach implementing the Hybprinter platform, which integrates multiple 3D printing modules under optimized conditions for a continuous bioprinting process with multiple soft and hard biomaterials. This approach demonstrates robust biocompatibility and broad tissue engineering potential for modeling and therapeutic applications. The capacity to fabricate multi-hydrogel hybrid constructs is illustrated by representative examples highlighting vascularization, multifunctionality, mechanical robustness, and implant suturability. Notably, compared with commonly fabricated hydrogel-only constructs, the resulting hybrid constructs achieve over a 1000-fold increase in mechanical strength, and demonstrated enhanced osteogenic differentiation, underscoring their suitability for load-bearing musculoskeletal and orthopedic tissue engineering. Additionally, cell-laden hydrogel constructs demonstrated robust chondrogenic differentiation, highlighting the capacity for lineage-specific tissue development in vitro. Beyond these outcomes, the presented hybrid bioprinting approach integrates essential tissue engineering attributes that unites mechanical robustness and suturable capacity with multi-material integration, gradient property design, incorporation of bioactive agents, and support for multi-cell loading. This versatile platform advances complex tissue engineering and holds promise for patient specific, organ-on-demand applications.

bioengineering↗

bioRxiv2025

A Lung Tumor-on-a-Chip Model Recapitulates the Effect of Hypoxia on Radiotherapy Response and FDG-PET Imaging

Most solid tumors contain regions of hypoxia that pose a significant challenge to the efficacy of radiation therapy. This study introduces a novel 3D lung tumor-on-a-chip (ToC) model designed to replicate the hypoxic tumor microenvironment in vitro while also providing a platform for clinically relevant interventions such as radiotherapy and positron emission tomography (PET) imaging. To simulate the heterogeneous oxygen distribution found in tumors, the ToC model incorporates an oxygen gradient achieved through a straightforward chemical oxygen scavenging system. A unique innovation of this device is the integration of a thin scintillator plate, which enables high-resolution radioluminescence microscopy imaging of tumor metabolism under hypoxia and normoxia conditions using clinically approved PET tracers such as fluorodeoxyglucose (FDG). The response of this hypoxic model to radiation therapy (10 Gy X-ray) demonstrated [~]4-fold higher radioresistance compared to the normoxic ToC model, as assessed by colony formation potential. Additionally, DNA damage observed in the normoxic ToC model was [~]5-fold higher than that in the hypoxic model. Furthermore, the metabolic consumption of glucose was found to mirror the localization of hypoxia, validating the use of this biomarker for planning radiation therapy. The integration of high-resolution radionuclide imaging within ToC models enables on-chip PET imaging and facilitates oncology research and discovery, offering innovative capabilities for the preclinical testing of novel cancer therapies in a clinically relevant environment.

bioengineering↗

bioRxiv2024

Development of a Novel Hybprinter-SAM for Functionally Graded Tissue Engineering Constructs with Patterned and Localized Biochemical Signals

Engineering native-mimetic tissue constructs is challenging due to their intricate biological and structural gradients. To address this, Hybprinter-SAM was developed by integrating three bioprinting technologies: syringe extrusion (SE), acoustic droplet ejection (ADE) and molten material extrusion (MME). This system enables not only the creation of mechanical gradients by combining soft and rigid materials but also precise patterning and controlled localization of biochemical signals within printed scaffolds. This capability is beneficial in replicating the complexity of native tissues to enhance functionality. Both the printing process and biomaterials were optimized to balance printability, mechanical integrity, and biocompatibility. As a proof of concept, Hybprinter-SAM was used in a bone-tendon regeneration study to engineer a multi-material construct with patterned fibroblast growth factor 2 (FGF-2), resulting in markers indicative of fibrocartilage development. These findings highlight the potential of Hybprinter-SAM as a versatile platform for diverse tissue engineering applications that require complex, functionally graded tissue constructs.

bioengineering↗

bioRxiv2020

High-resolution radioluminescence microscopy of FDG uptake in an engineered 3D tumor-stoma model

PURPOSEThe increased glucose metabolism of cancer cells is the basis for 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). However, due to its coarse image resolution, PET is unable to resolve the metabolic role of cancer-associated stroma, which often influences the metabolic reprogramming of a tumor. This study investigates the feasibility of imaging engineered 3D tumor models with high resolution using FDG. METHODMulticellular tumor spheroids (A549 lung adenocarcinoma) were co-cultured with GFP-expressing human umbilical vein endothelial cells (HUVECs) within an artificial extracellular matrix to mimic a tumor and its surrounding stroma. The tumor model was constructed as a thin 3D layer over a transparent CdWO4 scintillator plate to allow high-resolution imaging of the cultured cells. The radioluminescence signal was collected by a highly sensitive microscope and camera. Fluorescence microscopy was performed in the same instrument to localize endothelial and tumor cells. RESULTSSimultaneous brightfield and fluorescence imaging, co-localized with radioluminescence signal, provided high-resolution information on FDG accumulation in the engineered tissue. The microvascular stromal compartment took up a large fraction of FDG, comparable to the tumor spheroids. In vitro gamma counting also revealed that both A549 and HUVEC cells were highly glycolytic and characterized by rapid FDG-uptake kinetics. CONCLUSIONOur study demonstrates the feasibility of imaging FDG distribution in tumor and stromal components separately with high spatial resolution in engineered in vitro tumor models. Our imaging method is safe, simple, rapid, and can be easily used for other in vitro cancer models, surgical tissue slices, and tumor biopsies to interrogate PET radiotracer uptake at high resolution.

bioengineering↗