Unlocking Novel Anticancer Strategies: Bioactive Hydrogels for Local Delivery of Plasma-Derived Oxidants in an In Ovo Cancer Model.

Cold atmospheric plasma (CAP) is a tool with the ability to generate reactive oxygen and nitrogen species (RONS), which can induce therapeutic effects like disinfection, wound healing, and cancer treatment. In the plasma oncology field, CAP-treated hydrogels (PTHs) are being explored for the local administration of CAP-derived RONS as a novel anticancer approach. PTHs have shown anticancer effects in vitro, however, they have not yet been studied in more relevant cancer models.

Engineering alginate-based injectable hydrogels combined with bioactive polymers for targeted plasma-derived oxidative stress delivery in osteosarcoma therapy.

Reactive Oxygen and Nitrogen Species (RONS) in biological systems display hormetic effects, capable of either promoting cell regenerative effects or inducing cell death. Recently, hydrogels have emerged as a promising delivery platform for RONS generated from Cold Atmospheric Plasmas (CAP), known as Plasma-Treated Hydrogels (PTH). PTH have been proposed as an alternative therapy to conventional cancer treatments, offering reduced side effects through the controlled and localized delivery of plasma-derived RONS.

Does non-thermal plasma modify biopolymers in solution? A chemical and mechanistic study for alginate.

In the last decades, non-thermal plasma has been extensively investigated as a relevant tool for various biomedical applications, ranging from tissue decontamination to regeneration and from skin treatment to tumor therapies. This high versatility is due to the different kinds and amount of reactive oxygen and nitrogen species that can be generated during a plasma treatment and put in contact with the biological target. Some recent studies report that solutions of biopolymers with the ability to generate hydrogels, when treated with plasma, can enhance the generation of reactive species and influence their stability, resulting thus in the ideal media for indirect treatments of biological targets.

Current State of Cold Atmospheric Plasma and Cancer-Immunity Cycle: Therapeutic Relevance and Overcoming Clinical Limitations Using Hydrogels.

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.

Collagen-Sealed Polyester Vascular Prostheses Functionalized by Polycatecholamine Coatings.

Collagen-sealed polyester (PET) prostheses are commonly used in reconstructive vascular surgery due to their self-sealing properties. To prevent post-surgical infection, different modification methods have been tested but so far none have showed long-term satisfactory efficiency. For this reason, in the present study, a commercial collagen-sealed PET prosthesis was coated by a highly adhesive poly (L-DOPA) layer maintaining the sealing protein without losing the original properties and functionality.

Polycatecholamine and gentamicin as modifiers for antibacterial and blood-biocompatible polyester vascular prostheses.

Polyester (PET) prostheses are commonly used in reconstructive vascular surgery. The most serious complication after implantation is early or late infection of the graft. Therefore, there is high demand to protect prosthesis against bacterial adhesion and biofilm development.

Intrapericardial Delivery of APA-Microcapsules as Promising Stem Cell Therapy Carriers in an Experimental Acute Myocardial Infarction Model.

The administration of cardiosphere-derived cells (CDCs) after acute myocardial infarction (AMI) is very promising. CDC encapsulation in alginate-poly-l-lysine-alginate (APA) could increase cell survival and adherence. The intrapericardial (IP) approach potentially achieves high concentrations of the therapeutic agent in the infarcted area.

Development, characterization and sterilisation of Nanocellulose-alginate-(hyaluronic acid)- bioinks and 3D bioprinted scaffolds for tissue engineering.

3D-bioprinting is an emerging technology of high potential in tissue engineering (TE), since it shows effective control over scaffold fabrication and cell distribution. Biopolymers such as alginate (Alg), nanofibrillated cellulose (NC) and hyaluronic acid (HA) offer excellent characteristics for use as bioinks due to their excellent biocompatibility and rheological properties. Cell incorporation into the bioink requires sterilisation assurance, and autoclave, β-radiation and γ-radiation are widely used sterilisation techniques in biomedicine; however, their use in 3D-bioprinting for bioinks sterilisation is still in their early stages.

Characterization of encapsulated porcine cardiosphere-derived cells embedded in 3D alginate matrices.

Myocardial infarction is caused by an interruption of coronary blood flow, leading to one of the main death causes worldwide. Current therapeutic approaches are palliative and not able to solve the loss of cardiac tissue. Cardiosphere derived cells (CDCs) reduce scarring, and increase viable myocardium, with safety and adequate biodistribution, but show a low rate engraftment and survival after implantation.

Plasma-Conditioned Liquids as Anticancer Therapies In Vivo: Current State and Future Directions.

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.

Force Spectroscopy Imaging and Constriction Assays Reveal the Effects of Graphene Oxide on the Mechanical Properties of Alginate Microcapsules.

Microencapsulation of cells in hydrogel-based porous matrices is an approach that has demonstrated great success in regenerative cell therapy. These microcapsules work by concealing the exogenous cells and materials in a robust biomaterial that prevents their recognition by the immune system. A vast number of formulations and additives are continuously being tested to optimize cell viability and mechanical properties of the hydrogel.

BSA- and Elastin-Coated GO, but Not Collagen-Coated GO, Enhance the Biological Performance of Alginate Hydrogels.

The use of embedded cells within alginate matrices is a developing technique with great clinical applications in cell-based therapies. However, one feature that needs additional investigation is the improvement of alginate-cells viability, which could be achieved by integrating other materials with alginate to improve its surface properties. In recent years, the field of nanotechnology has shown the many properties of a huge number of materials.

Immobilization of INS1E Insulin-Producing Cells Within Injectable Alginate Hydrogels.

Alginate has demonstrated high applicability as a matrix-forming biomaterial for cell immobilization due to its ability to make hydrogels combined with cells in a rapid and non-toxic manner in physiological conditions, while showing excellent biocompatibility, preserving immobilized cell viability and function. Moreover, depending on its application, alginate hydrogel physicochemical properties such as porosity, stiffness, gelation time, and injectability can be tuned. This technology has been applied to several cell types that are able to produce therapeutic factors.

Review of Advanced Hydrogel-Based Cell Encapsulation Systems for Insulin Delivery in Type 1 Diabetes Mellitus.

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.

3D printed polyamide macroencapsulation devices combined with alginate hydrogels for insulin-producing cell-based therapies.

Cell macroencapsulation has shown a great potential overcoming the low survival of the transplanted pancreatic islets in the Type 1 Diabetes Mellitus (T1DM) treatment, as it avoids the need for lifelong immunosuppression. It is still not completely known how these devices interact with the host immune system when implanted. However, their surface properties seem to be crucial factors for a successful implant.

Type 1 Diabetes Mellitus reversal via implantation of magnetically purified microencapsulated pseudoislets.

Microencapsulation of pancreatic islets for the treatment of Type I Diabetes Mellitus (T1DM) generates a high quantity of empty microcapsules, resulting in high therapeutic graft volumes that can enhance the host's immune response. We report a 3D printed microfluidic magnetic sorting device for microcapsules purification with the objective to reduce the number of empty microcapsules prior transplantation. In this study, INS1E pseudoislets were microencapsulated within alginate (A) and alginate-poly-L-lysine-alginate (APA) microcapsules and purified through the microfluidic device.

Hyaluronic Acid Promotes Differentiation of Mesenchymal Stem Cells from Different Sources toward Pancreatic Progenitors within Three-Dimensional Alginate Matrixes.

Islet transplantation has shown to be a successful alternative in type 1 diabetes treatment, but donor scarcity precludes its worldwide clinical translation. Stem cells are an unlimited source that could circumvent the lack of donors if complete differentiation into insulin-producing cells (IPCs) could be accomplished. We have performed the differentiation of mesenchymal stem cells (MSCs) from different sources into IPCs within three-dimensional (3D) alginate matrixes.

Hyaluronic acid enhances cell survival of encapsulated insulin-producing cells in alginate-based microcapsules.

Pancreatic islet transplantation has proved to be a promising therapy for T1DM, in spite of the chronic immunosuppression required. Although cell microencapsulation technology represents an alternative to circumvent the immune system rejection of transplanted pancreatic islets, the environment provided by classical alginate microcapsules does not mimic the natural ECM, affecting the islet survival. Since hyaluronic acid, one of the major components of pancreatic ECM, is involved in cell adhesion and viability, we assessed the beneficial outcomes on encapsulated insulin-producing cells by the HA inclusion in alginate matrices.

3D Printed porous polyamide macrocapsule combined with alginate microcapsules for safer cell-based therapies.

Cell microencapsulation is an attractive strategy for cell-based therapies that allows the implantation of genetically engineered cells and the continuous delivery of de novo produced therapeutic products. However, the establishment of a way to retrieve the implanted encapsulated cells in case the treatment needs to be halted or when cells need to be renewed is still a big challenge. The combination of micro and macroencapsulation approaches could provide the requirements to achieve a proper immunoisolation, while maintaining the cells localized into the body.

Current advanced therapy cell-based medicinal products for type-1-diabetes treatment.

In the XXI century diabetes mellitus has become one of the main threats to human health with higher incidence in regions such as Europe and North America. Type 1 diabetes mellitus (T1DM) occurs as a consequence of the immune-mediated destruction of insulin producing β-cells located in the endocrine part of the pancreas, the islets of Langerhans. The administration of exogenous insulin through daily injections is the most prominent treatment for T1DM but its administration is frequently associated to failure in glucose metabolism control, finally leading to hyperglycemia episodes.

Tunable injectable alginate-based hydrogel for cell therapy in Type 1 Diabetes Mellitus.

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 Microcapsules Incorporating Hyaluronic Acid Recreate Closer in Vivo Environment for Mesenchymal Stem Cells.

The potential clinical application of alginate cell microencapsulation has advanced enormously during the past decade. However, the 3D environment created by alginate beads does not mimic the natural extracellular matrix surrounding cells in vivo, responsible of cell survival and functionality. As one of the most frequent macromolecules present in the extracellular matrix is hyaluronic acid, we have formed hybrid beads with alginate and hyaluronic acid recreating a closer in vivo cell environment.