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Polymer-loaded hydrogels serve as depots for lactate and mimic "cold" tumor microenvironments.

ABSTRACT: The burgeoning field of biomaterials for immunotherapy has aided in the understanding of foundational mechanisms of cancer immunology. In particular, implantable biomaterials can be engineered to investigate specific aspects of the tumor microenvironment either singularly or in combination. Of note, the metabolite - lactate, a byproduct of anaerobic glycolysis, is known to reprogram immune cells, resulting in increased tumor survival. An adequate model that can recapitulate intratumoral lactate concentrations does not exist. In this study, we demonstrate that a simple biomaterial platform could be developed as an instructive tool to decipher the effects of lactate in vivo. Briefly, we demonstrate that a peptide hydrogel loaded with granulocyte-macrophage colony stimulating factor and poly-(lactic-co-glycolic acid)/(lactic acid) microparticles can generate the localized lactate concentrations (∼2-22 mM) and cellular makeup of the tumor microenvironment, following subcutaneous implantation in mice. Furthermore, infiltrating immune cells adopt phenotypes similar to those seen in other in vitro and in vivo cancer models, including immunosupressive dendritic cells. This hydrogel system is a framework to interrogate immune cell modulation in cancer-like environments using safe and degradable biomaterials. Moreover, this system can be multifaceted, as incorporation of other cancer tumor environmental factors or chemotherapeutic drugs is facile and could be insightful in developing or improving immunotherapies.

SUBMITTER: Allen R

PROVIDER: S-EPMC7606634 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Foams made with polymer hydrogels can be used in a variety of applications, such as scaffolds for biomedical applications or decontamination processes. However, from a practical point of view, it is difficult to introduce bubbles into viscous or viscoelastic fluids and to produce large volumes of hydrogel foams. In the present article, we investigate the foaming process of poly(vinyl alcohol) (PVA)/borax transient hydrogels, where PVA chains reversibly bind to borax molecules. In a previous article, we showed that foams obtained with PVA/borax mixtures are highly stable because of both high interfacial and bulk viscosities and can be used to quickly absorb liquids, which make them suitable for detergency or decontamination processes. To produce these foams, we use a two-step foaming process which consists in first shearing a PVA solution to obtain a PVA foam and second adding borax to the PVA foam under continuous shearing. The obtained PVA/borax foams are stable for weeks. In this study, we observe a shear-induced collapse of the foams for formulations containing a low borax/PVA ratio, whereas they remain stable under shear for high PVA/borax ratios. Using scaling arguments, we find that the shear-induced collapse of the foams and bubbles is obtained below a critical ratio, N E/N B = 15, of the number of entanglements per chain, N E, and the number of borax per chain, N B. Rheology measurements show that the samples present a shear-thickening behavior that increases with the borax concentration. We suggest that during the foaming process when the shearing rate is of the order of 100 s-1, the viscosity of these samples diverges, leading to a viscous to fragile transition. To mimic the fast stretching of the PVA/borax thin films during the foaming process, we study the stretching of individual PVA/borax catenoid-shaped thin films at high stretching rates. We observe that the films containing low PVA/borax ratios do not minimize their surface area unlike what is theoretically expected for standard surfactant films. Moreover, the films tend to be unstable and fracture because the PVA/borax network does not have time to rearrange and relax stresses for high stretching rates.

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Polymer-loaded hydrogels serve as depots for lactate and mimic "cold" tumor microenvironments.

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