New Hydrogel Lab Technique Allows for Creating Precise Environments for 3D Tumor Growth

Glioma (brain cancer) cells growing in a 3-D hydrogel. The green fluorescent dye reflects the cytoskeletons of the cells. Scale bar is 50 mm. | Photo courtesy Brendan Harley

Tumor growth is very much affected by its biochemical environment, but studying how all that happens requires creating special biomaterials that can sustain the growth of the tumor in three dimensions and allow for experiments to be conducted.

Hydrogels have been used to grow volumes of glioma tumors in the lab, but now researchers at University of Illinois, Urbana-Champaign are reporting the development of a new technique that allows them to grow tumors while changing some characteristics of the environment, like the stiffness of the hydrogel and the amount of signaling molecules that it releases. The technique allows researchers to create reproducible dynamic environments that should help uncover the mechanisms of cancer growth.

Study abstract in journal Biomaterials:

The design of biomaterials for regenerative medicine can require biomolecular cues such as growth factors to induce a desired cell activity. Signal molecules are often incorporated into the biomaterial in either freely-diffusible or covalently-bound forms. However, biomolecular environments in vivo are often complex and dynamic. Notably, glycosaminoglycans (GAGs), linear polysaccharides found in the extracellular matrix, are involved in transient sequestration of growth factors via charge interactions. Biomaterials mimicking this phenomenon may offer the potential to amplify local biomolecular signals, both endogenously produced and exogenously added. GAGs of increasing sulfation (hyaluronic acid, chondroitin sulfate, heparin) were incorporated into a collagen–GAG (CG) scaffold under development for tendon tissue engineering. Manipulating the degree of GAG sulfation significantly impacts sequestration of growth factors from the media. Increasing GAG sulfation improved equine tenocyte metabolic activity in normal serum (10% FBS), low serum (1% FBS), and IGF-1 supplemented media conditions. Notably, previously reported dose-dependent changes in tenocyte bioactivity to soluble IGF-1 within the CG scaffold were replicated by using a single dose of soluble IGF-1 in scaffolds containing increasingly sulfated GAGs. Collectively, these results suggest that CG scaffold GAG content can be systematically manipulated to regulate the sequestration and resultant enhanced bioactivity of growth factor signals on cell behavior within the matrix.

Study in Biomaterials: The use of bioinspired alterations in the glycosaminoglycan content of collagen–GAG scaffolds to regulate cell activity

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