Figure - available from: Materials Advances
This content is subject to copyright. Terms and conditions apply.
Hypoxia is a hallmark of cancer. (A) Solid tumors account for approximately 90% of adult human cancers and can develop in many parts of the human body, including breast, lung, prostate, colon, rectum, and skin. (B) Illustration of a solid tumor harboring profound chronic hypoxia and necrosis in regions distant from the vasculature
Source publication
Recent advances in our understanding of hypoxia and hypoxia-mediated mechanisms shed light on the critical implications of the hypoxic stress on cellular behavior. However, tools emulating hypoxic conditions (i.e., low oxygen tensions) for research are limited and often suffer from major shortcomings, such as lack of reliability and off-target effe...
Citations
... For the past two decades, EPROI has been primarily used for cancer hypoxia research with few notable results, such as the demonstration of oxygen-guided radiation therapy in three different tumor models and rabbit VX-2 tumor pO 2 imaging using a human-sized EPROI instrument [38][39][40][41][42][43] . Recently, the applications of EPROI have been extended to the assessment of biomaterials, engineered grafts, and cell encapsulation devices 13,14,24,30,[44][45][46][47][48] . ...
The use of oxygen by cells is an essential aspect of cell metabolism and a reliable indicator of viable and functional cells. Here, we report partial pressure oxygen (pO 2 ) mapping of live cells as a reliable indicator of viable and metabolically active cells. For pO 2 imaging, we utilized trityl OX071-based pulse electron paramagnetic resonance oxygen imaging (EPROI), in combination with a 25 mT EPROI instrument, JIVA-25™, that provides 3D oxygen maps with high spatial, temporal, and pO 2 resolution. To perform oxygen imaging in an environment-controlled apparatus, we developed a novel multi-well-plate incubator-resonator (MWIR) system that could accommodate 3 strips from a 96-well strip-well plate and image the middle 12 wells noninvasively and simultaneously. The MWIR system was able to keep a controlled environment (temperature at 37 °C, relative humidity between 70%–100%, and a controlled gas flow) during oxygen imaging and could keep cells alive for up to 24 h of measurement, providing a rare previously unseen longitudinal perspective of 3D cell metabolic activities. The robustness of MWIR was tested using an adherent cell line (HEK-293 cells), a nonadherent cell line (Jurkat cells), a cell-biomaterial construct (Jurkat cells seeded in a hydrogel), and a negative control (dead HEK-293 cells). For the first time, we demonstrated that oxygen concentration in a multi-well plate seeded with live cells reduces exponentially with the increase in cell seeding density, even if the cells are exposed to incubator-like gas conditions. For the first time, we demonstrate that 3D, longitudinal oxygen imaging can be used to assess cells seeded in a hydrogel. These results demonstrate that MWIR-based EPROI is a versatile and robust method that can be utilized to observe the cell metabolic activity nondestructively, longitudinally, and in 3D. This approach may be useful for characterizing cell therapies, tissue-engineered medical products, and other advanced therapeutics.
... The versatility of carbon chemistry has facilitated the fabrication of a wide range of organic materials, encompassing small molecules to substantial macromolecular structures, including emerging synthetic polymers [3,4]. Over the past three decades, chemical and materials science advancements have transformed health science, leading to significant progress in using biomaterials for medical applications [5][6][7][8][9][10]. However, for in vivo applications, candidate materials must meet strict criteria concerning biocompatibility, biodegradation, and bioactivity. ...
The continuing wave of technological breakthroughs and advances is critical for engineering well-defined materials, particularly biomaterials, with tailored microstructure and properties. Over the last few decades, controlled radical polymerization (CRP) has become a very promising option for the synthesis of precise polymeric materials with an unprecedented degree of control over molecular architecture. Atom Transfer Radical Polymerization (ATRP), one of the most robust and efficient CRPs, has been at the forefront of the synthesis of well-defined polymers with controlled/predetermined molecular weights, polydispersity, topology, composition, and site-specific functionality. ATRP has been leveraged to prepare a wide range of polymers with properties tailored for a number of biomedical applications. Furthermore, ATRP can also be utilized to introduce stimuli-responsive properties into the chemical structure of polymers. Moreover, the degradation behavior of ATRP-derived polymers can be tailored by incorporating chemical bonds susceptible to hydrolysis or proteolysis. This strategy allows the design of degradable polymers for in vivo applications. This review summarizes the recent advances in ATRP for the design of functional materials and techniques implemented to advance the biomedical field, such as surface modification and functionalization. Additionally, the latest applications and progress of ATRP-derived materials in various biomedical arenas such as drug delivery, tissue engineering, bioimaging, and biosensing are reported. Lastly, the current limitations and future perspectives of ATRP-derived biomaterials are carefully discussed to support further improvement of their properties and performance for translatability into the clinic. Moving forward, there is a need for further development of ATRP to align with green chemistry principles. This entails exploring the use of renewable monomers, environmentally friendly and nontoxic solvents, as well as metal-free and biocompatible catalysts. Additionally, researchers should thoroughly investigate the bioactivity, biodegradation behavior, and in vivo fate of ATRP-derived polymers and polymer conjugates before considering their translation into clinical applications.
... Additionally, while standard hydrogels embedded with microcapsules containing oxygen-depleting enzymes have shown good spatiotemporal control of hypoxia [26], they tend to create a physical barrier due to their mesoporous structure. This restricts tumor cell organization, immune cell infiltration, as well as the diffusion of solutes such as biomolecules, drugs, nutrients, etc. [27] Therefore, designing scaffolds mimicking tumor ECM with a highly interconnected macroporous network is critical to facilitate the diffusion of solutes, allow immune cell infiltration, and promote cell-cell interactions and organization [28][29][30]. Our team has recently reported the development of innovative macroporous and injectable cryogels as promising biomaterial for tissue engineering, tumor modeling, and immunotherapies [31][32][33][34][35][36][37]. ...
Hypoxia is a major factor shaping the immune landscape, and several cancer models have been developed to emulate hypoxic tumors. However, to date, they still have several limitations, such as the lack of reproducibility, inadequate biophysical cues, limited immune cell infiltration, and poor oxygen (O2) control, leading to non-pathophysiological tumor responses. Therefore, it is essential to develop better cancer models that mimic key features of the tumor extracellular matrix and recreate tumor-associated hypoxia while allowing cell infiltration and cancer-immune cell interactions. Herein, hypoxia-inducing cryogels (HICs) have been engineered using hyaluronic acid (HA) to fabricate three-dimensional microtissues and model a hypoxic tumor microenvironment. Specifically, tumor cell-laden HICs have been designed to deplete O2 locally and induce long-standing hypoxia. HICs promoted changes in hypoxia-responsive gene expression and phenotype, a metabolic adaptation to anaerobic glycolysis, and chemotherapy resistance. Additionally, HIC-supported tumor models induced dendritic cell (DC) inhibition, revealing a phenotypic change in the plasmacytoid DC (pDC) subset and an impaired conventional DC (cDC) response in hypoxia. Lastly, our HIC-based melanoma model induced CD8+ T cell inhibition, a condition associated with the downregulation of pro-inflammatory cytokine secretion, increased expression of immunomodulatory factors, and decreased degranulation and cytotoxic capacity of T cells. Overall, these data suggest that HICs can be used as a tool to model solid-like tumor microenvironments and has great potential to deepen our understanding of cancer-immune cell relationship in low O2 conditions and may pave the way for developing more effective therapies.
