3D Hydrogel

3D Hydrogel

3D Hydrogel, as a biochemically defined hydrogel platform, does not contain any products from the animal-origin that could interfere with or contaminate your experiments. This hydrogel preserve viability of the cells and replicate native cellular environments similar to those of tissues. This technology provides mechanical and biochemical cues to investigate both morphological and physiological properties of cells in the 3D environment.

Hribar et al., presented a novel three-dimensional (3D) ECM hydrogel system, VersaGel, for assaying ex vivo growth and therapeutic response with standard image microscopy. Specifically, multicellular spheroids deriving from either 5 patients with glioblastoma (GBM) or a renal cell carcinoma (RCC) PDX model were incorporated into VersaGel and treated with temozolomideand several other therapies, guided by the most recent advances in GBM treatment. RCC ex vivo tissue displayed invasive phenotypes in conditioned media. For the GBM patient tumor testing, all five clinical responses were predicted by the results of our 3D-temozolomide assay. In contrast, the MTT assay found no response to temozolomide regardless of the clinical outcome, and moreover, basement membrane extract failed to predict the 2 patient responders. Finally, 1 patient was tested with repurposed drugs currently being administered in GBM clinical trials. Interestingly, IC50s were lower than C max for crizotinib and chloroquine, but higher for sorafenib. In conclusion, a novel hydrogel platform, VersaGel, enables ex vivo tumor growth of patient and PDX tissue and offers insight into patient response to clinically relevant therapies. They proposed a novel 3D hydrogel platform, VersaGel, to grow ex vivo tissue (patient and PDX) and assay therapeutic response using time-course image analysis 1).

Wang et al., reported the development of poly(ethylene-glycol)-based hydrogels as 3D niche that supported GBM proliferation and invasion. To further mimic the microanatomical architecture of tumor-endothelial interactions in vivo, here they developed a hydrogel-based co-culture model that mimics the spatial organization of tumor and endothelial cells. To increase the physiological relevance, patient-derived GBM cells and mouse brain endothelial cells were used as model cell types. Using hydrolytically-degradable alginate fibers as porogens, endothelial cells were deployed and patterned into vessel-like structures in 3D hydrogels with high cell viability and retention of endothelial phenotype. Co-culture led to a significant increase in GBM cell proliferation and decrease in endothelial cell expression of cell adhesion proteins. In summary, they developed a novel 3D co-culture model that mimics the in vivo spatial organization of brain tumor and endothelial cells. Such model may provide a valuable tool for future mechanistic studies to elucidate the effects of tumor-endothelial interactions on tumor progression in a more physiologically-relevant manner 2).

In 2018 Wang et al., used extrusion-based three-dimensional (3D) bioprinting technology to fabricate GSCs tumor model. In this study, the viability of cells after bioprinting was 86.27 ± 2.41%. Furthermore, compared with traditional suspension culture, the proliferation of 3D printed GSCs was more stable. Through the transmission electron microscopy (TEM), numerous long microvilli of cells cultured in 3D bioprinted scaffolds were observed. 3D bioprinted GSCs also have more abundant mitochondria and rough endoplasmic reticulum. Additionally, the stemness properties, the expression of tumor angiogenesis-related genes and vascularization potential of 3D bioprinted GSCs in vitro were higher than that of suspension cultured cells. In summary, 3D bioprinted cell-laden hydrogel scaffolds provide a proper model for investigating the biological characteristics of GSCs and tumor angiogenesis 3).

Li et al., aimed at building in vitro Schwann cell 3D microenvironment with customized shapes through 3D bioprinting technology. Rat Schwann cell RSC96s encapsulated in composite alginate-gelatin hydrogel were printed with an extrusion-based bioprinter. Cells maintained high viability of 85.35 ± 6.19% immediately after printing and the printed hydrogel supported long-term Schwann cell proliferation for 2 weeks. Furthermore, after 14 days of culturing, Schwann cells cultured in printed structures maintained viability of 92.34 ± 2.19% and showed enhanced capability of nerve growth factor (NGF) release (142.41 ± 8.99 pg/ml) compared with cells from two-dimensional culture (92.27 ± 9.30 pg/ml). Specific Schwann cell marker S100β was also expressed by cells in printed structures. These printed structures may have the potential to be used as in vitro neurotrophic factor carriers and could be integrated into complex biomimetic artificial structures with the assistance of 3D bioprinting technology 4).

A study of Huang et al., applied a three‑dimensional (3D) hydrogel model to rebuild the tumor architecture in vitro. Treatment with NSC23766, a specific inhibitor of Ras‑related C3 botulinum toxin substrate 1 (Rac1), inhibited the mesenchymal invasiveness however triggered the amoeboid motility called mesenchymal‑amoeboid transition (MAT). Notably, NSC23766 stimulated U87 GBM cell migration in the 3D hydrogel. However, this compound inhibited cell motility in 2D monolayer culture without tumor architecture for MAT, suggesting the advantage of 3D hydrogel to investigate tumor cell invasion. Due to the inverse interaction of Rac1 and Ras homolog family member A (RhoA) signaling in the transition between mesenchymal and amoeboid morphology, simultaneous treatment of NSC23766 and Y27632 (selective Rho associated coiled‑coil containing protein kinase 1 inhibitor), abolished U87 GBM cell migration through inhibiting MAT and amoeboid‑mesenchymal transition. In addition, Y27632 induced integrin expression which gave rise to the focal adhesion to facilitate the mesenchymal invasion. The results of the present study demonstrated that the 3D hydrogel was a preferable model in vitro to study tumor cell invasion and migration. The combined inhibition of Rac1 and RhoA signaling would be a promising strategy to suppress GBM invasion 5).



Hribar KC, Wheeler CJ, Bazarov A, Varshneya K, Yamada R, Buckley P, Patil CG. A Simple Three-dimensional Hydrogel Platform Enables Ex Vivo Cell Culture of Patient and PDX Tumors for Assaying Their Response to Clinically Relevant Therapies. Mol Cancer Ther. 2019 Mar;18(3):718-725. doi: 10.1158/1535-7163.MCT-18-0359. Epub 2019 Feb 12. PubMed PMID: 30755456.

Wang C, Li J, Sinha S, Peterson A, Grant GA, Yang F. Mimicking brain tumor-vasculature microanatomical architecture via co-culture of brain tumor and endothelial cells in 3D hydrogels. Biomaterials. 2019 Feb 27;202:35-44. doi: 10.1016/j.biomaterials.2019.02.024. [Epub ahead of print] PubMed PMID: 30836243.

Wang X, Li X, Dai X, Zhang X, Zhang J, Xu T, Lan Q. Bioprinting of glioma stem cells improves their endotheliogenic potential. Colloids Surf B Biointerfaces. 2018 Nov 1;171:629-637. doi: 10.1016/j.colsurfb.2018.08.006. Epub 2018 Aug 7. PubMed PMID: 30107336.

Li X, Wang X, Wang X, Chen H, Zhang X, Zhou L, Xu T. 3D bioprinted rat Schwann cell-laden structures with shape flexibility and enhanced nerve growth factor expression. 3 Biotech. 2018 Aug;8(8):342. doi: 10.1007/s13205-018-1341-9. Epub 2018 Jul 27. PubMed PMID: 30073127; PubMed Central PMCID: PMC6063810.

Huang Y, Tong L, Yi L, Zhang C, Hai L, Li T, Yu S, Wang W, Tao Z, Ma H, Liu P, Xie Y, Yang X. Three-dimensional hydrogel is suitable for targeted investigation of amoeboid migration of glioma cells. Mol Med Rep. 2018 Jan;17(1):250-256. doi: 10.3892/mmr.2017.7888. Epub 2017 Oct 26. PubMed PMID: 29115617; PubMed Central PMCID: PMC5780134.

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