Cold atmospheric plasma (CAP) is a partially ionized gas that gains attention as a well‐tolerated cancer treatment that can enhance anti‐tumor immune responses, which are important for durable therapeutic effects. This review offers a comprehensive and critical summary on the current understanding of mechanisms in which CAP can assist anti‐tumor immunity: induction of immunogenic cell death, oxidative post‐translational modifications of the tumor and its microenvironment, epigenetic regulation of aberrant gene expression, and enhancement of immune cell functions. This should provide a rationale for the effective and meaningful clinical implementation of CAP. As discussed here, despite its potential, CAP faces different clinical limitations associated with the current CAP treatment modalities: direct exposure of cancerous cells to plasma, and indirect treatment through injection of plasma‐treated liquids in the tumor. To this end, a novel modality is proposed: plasma‐treated hydrogels (PTHs) that can not only help overcome some of the clinical limitations but also offer a convenient platform for combining CAP with existing drugs to improve therapeutic responses and contribute to the clinical translation of CAP. Finally, by integrating expertise in biomaterials and plasma medicine, practical considerations and prospective for the development of PTHs are offered.

Islet transplantation has the potential of reestablishing naturally-regulated insulin production in Type 1 diabetic patients. Nevertheless, this procedure is limited due to the low islet survival after transplantation and the lifelong immunosuppression to avoid rejection. Islet embedding within a biocompatible matrix provides mechanical protection and a physical barrier against the immune system thus, increasing islet survival. Alginate is the preferred biomaterial used for embedding insulin-producing cells because of its biocompatibility, low toxicity and ease of gelation. However, alginate gelation is poorly controlled, affecting its physicochemical properties as an injectable biomaterial. Including different concentrations of the phosphate salt Na2HPO4 in alginate hydrogels, we can modulate their gelation time, tuning their physicochemical properties like stiffness and porosity while maintaining an appropriate injectability. Moreover, these hydrogels showed good biocompatibility when embedding a rat insulinoma cell line, especially at low Na2HPO4 concentrations, indicating that these hydrogels have potential as injectable biomaterials for Type 1 Diabetes Mellitus treatment.

: Type 1 Diabetes Mellitus (T1DM) is characterized by the autoimmune destruction of β-cells in the pancreatic islets. In this regard, islet transplantation aims for the replacement of the damaged β-cells through minimally invasive surgical procedures, thereby being the most suitable strategy to cure T1DM. Unfortunately, this procedure still has limitations for its widespread clinical application, including the need for long-term immunosuppression, the lack of pancreas donors and the loss of a large percentage of islets after transplantation. To overcome the aforementioned issues, islets can be encapsulated within hydrogel-like biomaterials to diminish the loss of islets, to protect the islets resulting in a reduction or elimination of immunosuppression and to enable the use of other insulin-producing cell sources. This review aims to provide an update on the different hydrogel-based encapsulation strategies of insulin-producing cells, highlighting the advantages and drawbacks for a successful clinical application.

Plasma-conditioned liquids (PCL) are gaining increasing attention in the medical field, especially in oncology, and translation to the clinics is advancing on a good path. This emerging technology involving cold plasmas has great potential as a therapeutic approach in cancer diseases, as PCL have been shown to selectively kill cancer cells by triggering apoptotic mechanisms without damaging healthy cells. In this context, PCL can be injected near the tumor or intratumorally, thereby allowing the treatment of malignant tumors located in internal organs that are not accessible for direct cold atmospheric plasma (CAP) treatment. Therefore, PCL constitutes a very interesting and minimally invasive alternative to direct CAP treatment in cancer therapy, avoiding surgeries and allowing multiple local administrations. As the field advances, it is progressively moving to the evaluation of the therapeutic effects of PCL in in vivo scenarios. Exciting developments are pushing forward the clinical translation of this novel therapy. However, there is still room for research, as the quantification and identification of reactive oxygen and nitrogen species (RONS) in in vivo conditions is not yet clarified, dosage regimens are highly variable among studies, and other more relevant in vivo models could be used. In this context, this work aims to present a critical review of the state of the field of PCL as anticancer agents applied in in vivo studies.