Study on a 3D Hydrogel-Based Culture Model for Characterizing Growth of Fibroblasts under Viral Infection and Drug Treatment

Abstract

Three-dimensional (3D) in vitro tissue models provide an approach for the systematic, repetitive, and quantitative study of drugs. In this study, we constructed an in vitro 3D acrylated hyaluronic acid (AHA) hydrogel model encapsulating fibroblasts, performed long-period 3D culture, and tested cellular topological changes and proliferation variation in the presence of herpes simplex virus-1 (HSV-1) as an infecting virus and acyclovir (ACV) as the treatment drug. The AHA hydrogels were formed by using Michael addition chemistry of bis-cysteine containing MMP-degradable cross-linker onto AHA prefunctionalized with cell adhesion peptides (RGD). Cellular structures of 3T3 fibroblasts in hydrogel presented different morphological evolution processes and proliferation rates between different groups, including HSV-1 treated alone, ACV treated alone, HSV-1 and ACV cotreated, and control samples. In AHA hydrogel, ACV blocked HSV-1 infection/replication on fibroblasts. Yet, the proliferation of ACV-treated fibroblasts was slower than that of the control group. A significantly longer period was required for cells in 3D AHA gel to regain a healthy status when compared with cells in two-dimensional (2D) culture. This hydrogel-based 3D culture model potentially lays a foundation for analyzing the response of self-organized 3D tissues to viruses and drugs in a way that is closer to nature.

Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy

“…To document that these organoids are amenable to infectious disease modeling, we performed infection with HSV1 and HPV16. Previous studies have applied 3-D models of fibroblasts, vaginal epithelium, and melanoma cells to study the interaction of HSV1 with epithelial cells (65,66). Yet to our knowledge a 3-D model to study HSV1 infection in oral mucosa cells has not been reported.…”

Turing Instability-Driven Biofabrication of Branching Tissue Structures: A Dynamic Simulation and Analysis Based on the Reaction–Diffusion Mechanism †

“…After the tip splits completely, the inhibitor peak also divides into two peaks, and its distribution along the spatial axis k is almost the same as that of activator A ( Figure 4 c,f). Further research for the 4D biofabrication may rely on the 3D culture techniques [ 3 , 27 , 40 ] that are essentially constructing and regulating the dynamic structures composed of numerous cells.…”

4D Biofabrication of Branching Multicellular Structures: A Morphogenesis Simulation Based on Turing’s Reaction-Diffusion Dynamics

“…After the tip splits completely, the inhibitor peak also divides into two peaks, and its distribution along the spatial axis k is almost the same as that of activator A (steps 3600). Further research work for the 4D biofabrication may rely on the 3D culture techniques [3,24,25] that are essentially constructing and regulating the dynamic structures composed of numeral cells.…”