Immunoengineering

The role of extracellular vesicles (EVs) in human health and disease has garnered considerable attention over the past two decades. However, while several types of EVs are known to interact dynamically with the extracellular matrix and there is great potential value in producing high-fidelity EV micropatterns, there are currently no label-free, high-resolution, and tunable platform technologies with this capability. We introduce Light-induced Extracellular Vesicle Adsorption (LEVA) as a powerful solution to rapidly advance the study of matrix- and surface-bound EVs and other particles...

Traumatic spinal cord injury (SCI), often resulting from external physical trauma, initiates a series of complex pathophysiological cascades, with severe cases leading to paralysis and presenting significant clinical challenges. Traditional diagnostic and therapeutic approaches, particularly X-ray imaging, are prevalent in clinical practice, yet the limited efficacy and notable side effects of pharmacological treatments at the injury site continue to pose substantial hurdles. Addressing these challenges, recent advancements have been made in the development of multifunctional nanotechnology and synergistic therapies, enhancing both the efficacy and safety of radiographic techniques...

Nutrients are essential for supporting tumor growth and immune cell function in the tumor microenvironment, but emerging evidence reveals a paradoxical competition and collaboration between the metabolic demands of proliferating cancer cells and immune cell activation. Dietary interventions and metabolic immunoengineering offer promise to selectively modulate cancer and immune cell metabolism by targeting metabolic sensing processes rather than pathways directly, moving beyond conventional ideas and heralding an exciting new era of immunometabolism discovery and translation...

Translational research in biomaterials and immunoengineering is leading to the development of novel advanced therapeutics to treat diseases such as cancer, autoimmunity, and viral infections. Dendritic cells (DCs) are at the center of these therapeutics given that they bridge innate and adaptive immunity. The biomaterial system developed herein uses a hydrogel carrier to deliver immunomodulatory DCs for amelioration of autoimmunity. This biomaterial vehicle is comprised of a poly (ethylene glycol)-4 arm maleimide (PEG-4MAL) hydrogels, conjugated with the immunosuppressive cytokine, interleukin-10, IL-10, and cross-linked with a collagenase-degradable peptide sequence for the injectable delivery of immunosuppressive DCs to an anatomical disease-relevant site of the cervical lymph nodes, for intended application to treat multiple sclerosis...

Advances in cell immunotherapy underscore the need for effective methods to produce large populations of effector T cells, driving growing interest in T-cell bioprocessing and immunoengineering. Research suggests that T cells demonstrate enhanced expansion and differentiation on soft matrices in contrast to rigid ones. Nevertheless, the influence of antibody conjugation chemistry on these processes remains largely unexplored. In this study, we examined the effect of antibody conjugation chemistry on T cell activation, expansion and differentiation using a soft and biocompatible polydimethylsiloxane (PDMS) platform...

Beyond SARS-CoV2 vaccines, mRNA drugs are being explored to overcome today's greatest healthcare burdens, including cancer and cardiovascular disease. Synthetic mRNA triggers immune responses in transfected cells, which can be reduced by chemically modified nucleotides. However, the side effects of mRNA-triggered immune activation on cell function and how different nucleotides, such as the N1-methylpseudouridine (m1Ψ) used in SARS-CoV2 vaccines, can modulate cellular responses is not fully understood...

Artificial protein hydrogels are an emerging class of biomaterials with numerous prospective applications in tissue engineering and regenerative medicine. These materials are likely to be immunogenic due to their frequent incorporation of novel amino acid sequence domains, which often serve a functional role within the material itself. We engineered injectable "self" and "nonself" artificial protein hydrogels, which were predicted to have divergent immune outcomes in vivo on the basis of their primary amino acid sequence...

Adoptive T cell immunotherapies, including engineered T cell receptor (eTCR) and chimeric antigen receptor (CAR) T cell immunotherapies, have shown efficacy in treating a subset of hematologic malignancies, exhibit promise in solid tumors, and have many other potential applications, such as in fibrosis, autoimmunity, and regenerative medicine. While immunoengineering has focused on designing biomaterials to present biochemical cues to manipulate T cells ex vivo and in vivo , mechanical cues that regulate their biology have been largely underappreciated...

Musculoskeletal diseases and injuries are among the leading causes of pain and morbidity worldwide. Broad efforts have focused on developing pro-regenerative biomaterials to treat musculoskeletal conditions; however, these approaches have yet to make a significant clinical impact. Recent studies have demonstrated that the immune system is central in orchestrating tissue repair and that targeting pro-regenerative immune responses can improve biomaterial therapeutic outcomes. However, aging is a critical factor negatively affecting musculoskeletal tissue repair and immune function...

A wide variety of cell surface receptors found on immune cells are essential to the body's immunological defense mechanisms. Cell surface receptors enable immune cells to sense extracellular stimuli and identify pathogens, transmitting activating or inhibitory signals that regulate the immune cell state and coordinate immunological responses. These receptors can dynamically aggregate or disperse due to the fluidity of the cell membrane, particularly during interactions between cells or between cells and pathogens...

Disease-modifying drugs have transformed the treatment options for many systemic autoimmune diseases. However, an evolving understanding of disease mechanisms, which might vary between individuals, is paving the way for the development of novel agents that operate in a patient-tailored manner through immunophenotypic regulation of disease-relevant cells and the microenvironment of affected tissue domains. Immunoengineering is a field that is focused on the application of engineering principles to the modulation of the immune system, and it could enable future personalized and immunoregulatory therapies for rheumatic diseases...

The durability of a protective immune response generated by a vaccine depends on its ability to induce long-term T cell immunity, which tends to decline in aging populations. The longest protection appears to arise from T memory stem cells (TMSCs) that confer high expandability and effector functions when challenged. Here we engineered artificial antigen presenting cells (aAPC) with optimized size, stiffness and activation signals to induce human and mouse CD8+ TMSCs in vitro . This platform was optimized as a vaccine booster of TMSCs (Vax-T) with prolonged release of small-molecule blockade of the glycogen synthase kinase-3β together with target antigens...

Cancer cell glycocalyx is a major line of defence against immune surveillance. However, how specific physical properties of the glycocalyx are regulated on a molecular level, contribute to immune evasion and may be overcome through immunoengineering must be resolved. Here we report how cancer-associated mucins and their glycosylation contribute to the nanoscale material thickness of the glycocalyx and consequently modulate the functional interactions with cytotoxic immune cells. Natural-killer-cell-mediated cytotoxicity is inversely correlated with the glycocalyx thickness of the target cells...

Injectable scaffold delivery is a strategy to enhance the efficacy of cancer vaccine immunotherapy. The choice of scaffold biomaterial is crucial, impacting both vaccine release kinetics and immune stimulation via the host response. Extracellular matrix (ECM) scaffolds prepared from decellularized tissues facilitate a pro-healing inflammatory response that promotes local cancer immune surveillance. Here, an ECM scaffold-assisted therapeutic cancer vaccine that maintains an immune microenvironment consistent with tissue reconstruction is engineered...

Disease progression is usually accompanied by changes in the biochemical composition of cells and tissues and their biophysical properties. For instance, hallmarks of cancer include the stiffening of tissues caused by extracellular matrix remodelling and the softening of individual cancer cells. In this context, accumulating evidence has shown that immune cells sense and respond to mechanical signals from the environment. However, the mechanisms regulating these mechanical aspects of immune surveillance remain partially understood...

Development of effective vaccines for infectious diseases has been one of the most successful global health interventions in history. Though, while ideal subunit vaccines strongly rely on antigen and adjuvant(s) selection, the mode and time scale of exposure to the immune system has often been overlooked. Unfortunately, poor control over the delivery of many adjuvants, which play a key role in enhancing the quality and potency of immune responses, can limit their efficacy and cause off-target toxicities. There is a critical need for improved adjuvant delivery technologies to enhance their efficacy and boost vaccine performance...

Immunoengineering is a rapidly evolving field that has been driving innovations in manipulating immune system for new treatment tools and methods. The need for materials for immunoengineering applications has gained significant attention in recent years due to the growing demand for effective therapies that can target and regulate the immune system. Biologics and biomaterials are emerging as promising tools for controlling immune responses, and a wide variety of materials, including proteins, polymers, nanoparticles, and hydrogels, are being developed for this purpose...

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Cancer immunotherapy is a groundbreaking strategy that has revolutionized the field of oncology compared to other therapeutic strategies, such as surgery, chemotherapy, or radiotherapy. However, cancer complexity, tumor heterogeneity, and immune escape have become the main hurdles to the clinical application of immunotherapy. Moreover, conventional immunotherapies cause many harmful side effects owing to hyperreactivity in patients, long treatment durations and expensive cost. Nanotechnology is considered a transformative approach that enhances the potency of immunotherapy by capitalizing on the superior physicochemical properties of nanocarriers, creating highly targeted tissue delivery systems...

New experimental approaches for tissue repair have recently been proposed and include the application of natural or synthetic biomaterials and immune cells. Herein, fully synthetic poly(glycidyl ether) (PGE) copolymer coatings are evaluated as bioinstructive materials for the in vitro culture and intrinsic activation of human immune cells. Immature monocyte-derived dendritic cells (moDCs) are exposed to PGE brush and gel coatings of varying copolymer composition, wettability, and deformability immobilized on polystyrene culture dishes...