Immunoengineering Frontiers – Transforming Healthcare Through Advanced Materials
Authors: Ankur Singh
Journal: Advanced Healthcare Materials (2025)

The field of immunoengineering, an interdisciplinary domain combining immunology with bioengineering, is rapidly advancing, driven by the imperative to harness and modulate immune responses for therapeutic benefits. Immunoengineering leverages insights into the immune system's complexity to design innovative biomaterials, therapeutic delivery systems, and immunomodulatory strategies. Its applications include tissue regeneration, cancer immunotherapy, infectious disease treatment, inflammation and autoimmune disorder management. The field's primary challenges are achieving precise control over immune responses, developing potent immune cell therapies, addressing systemic toxicities, and improving clinical translation of experimental therapies. This issue of Advanced Healthcare Materials brings together key contributions that illustrate the state-of-the-art in immunoengineering, highlights its transformative potential, and identifies future challenges in the field. The featured research articles collectively illuminate the transformative potential of immunoengineering in addressing diverse biomedical challenges, such as innovative biomaterial designs, immune system modeling, and advanced therapeutic platforms, emphasizing their role in enhancing immune modulation and clinical outcomes. First of all, a series of Reviews explore the design and application of biomaterials, ranging from nanoparticles and hydrogels to biofabrication technologies and immunomodulatory peptides, to modulate immune responses for therapeutic benefits. Park et al. (2304496) provide an overview of advanced immunomodulatory biomaterials, exploring how the physicochemical properties of nanoparticles, hydrogels, and graphene-based materials influence innate and adaptive immune responses. Their work underscores the importance of tailoring biomaterial designs to modulate mechanobiological cues and immune cell behavior, advancing tissue engineering and cancer therapy. The review by Dravid et al. (2400586) focuses on biomaterial-based delivery systems for immune cell therapies, addressing the limitations of adoptively transferred immune cells such as toxicity and poor tissue penetration. They discuss how biomaterials improve localization, reduce adverse effects, and preserve immune cell phenotypes, paving the way for enhanced clinical outcomes. Pham et al. (2400965) provide an in-depth review of biomaterials in transplant immunology, emphasizing their role in inducing tolerance and reducing chronic immunosuppression reliance. They explore diverse strategies, from graft coatings to in situ immune cell reprogramming, highlighting the potential for precision-engineered biomaterials to achieve operational tolerance. Janssen et al. (2304569) examine biofabrication technologies in immune system-on-a-chip platforms, which aim to replicate immune system functions within microfluidic environments. They discuss breakthroughs in immune cell behavior modeling and the challenges of achieving physiologically relevant biomimicry, with implications for studying immune disorders and therapeutic development. Song et al. (2400512) review immunomodulatory peptides for tumor immunotherapy, categorizing peptides based on their effects on innate and adaptive immune cells. They also explore innovative delivery strategies, such as peptide-functionalized nanocarriers, to enhance antitumor immune responses and overcome biological barriers. Several original studies in this issue focus on immune modulation through novel biomaterials and therapeutic platforms: Steele et al. (2303044) investigate the effects of bioengineered allogeneic cellularized constructs on macrophage phenotypes. Their study reveals that these constructs promote a reparative macrophage phenotype, enhancing fibroblast and endothelial cell activities critical for wound healing. This work emphasizes the importance of macrophage modulation in regenerative medicine. Thumsi et al. (2303995) investigate inverse vaccines for rheumatoid arthritis, demonstrating their ability to restore immunological and metabolic homeostasis in joint tissues. Their work reveals critical pathways and metabolites affected by disease progression, providing new targets for therapeutic intervention. Palmer et al. (2303815) advance Ribonucleic acid (RNA) therapeutics with covalent polymer-RNA conjugates designed for RIG-I pathway activation. Their innovative nanoparticle platform improves RNA stability, cellular uptake, and immunostimulatory activity, highlighting a novel approach to antiviral and cancer therapies. Sobral et al. (2304574) explore how tuning the release kinetics of Toll-like receptor 9 agonists in scaffold vaccines impacts adaptive immune responses. Their findings suggest that rapid adjuvant release paired with sustained antigen delivery enhances T helper (Th)1-skewed immune responses, providing insights for more effective vaccine design. Kapate et al. (2304144) present a strategy leveraging polymer backpacks on tissue-infiltrating monocytes to treat solid tumors. This approach reprograms monocyte differentiation within the tumor microenvironment, reducing tumor burden and reshaping the immunosuppressive landscape. Ferro et al. (2401523) demonstrate that selenium nanoparticles combined with a Kirsten rat sarcoma virus nano vaccine significantly reduce tumor growth in a breast cancer model. This synergistic approach highlights the potential of integrating nanotechnology with immunotherapy. Ex vivo models explored in the research articles of this issue underscore the transformative potential of biomimetic platforms in the immunoengineering space: By recreating physiologically relevant microenvironments, these models provide critical insights into immune interactions and therapeutic responses, bridging the gap between in vitro studies and in vivo applications. Britto et al. (2401192) use synthetic hydrogel-based lymphoma organoids to study how T cells and their synpase influence histone modifications in B-cell lymphomas. Their work identifies pathways that could be targeted to overcome therapeutic resistance, offering hope for better treatment outcomes in high-risk lymphoma patients. Gupta et al. (2304299) present a 3D hydrogel culture system that mimics the lung microenvironment for tuberculosis studies. This biomimetic model reproduces key in vivo phenotypes and demonstrates the efficacy of anti-TB drug pyrazinamide under clinically relevant conditions, offering a powerful tool for drug screening and disease modeling. Other works delve into leveraging immunoengineering for tissue regeneration and disease treatment: Jeong et al. (2400232) design multifunctional nanoparticles that simultaneously modulate immune, angiogenic, and osteogenic responses. Their approach achieves 80% regeneration of critical-sized bone defects with mature lamellar structures, demonstrating the power of coordinated immune and tissue engineering. Wiesli et al. (2400077) demonstrate that functionalizing scaffolds with Bone morphogenetic protein 7 and Interleukin 10 enhances bone regeneration in a fracture hematoma-like environment. Their approach addresses inflammation-driven limitations in biomaterial efficacy. Saunders et al. (2400237) show that allergen-encapsulating nanoparticles reprogram Th2 cells to suppress food allergy symptoms in a mouse model. Their findings offer a promising avenue for rapid and sustained allergy treatments. Couto et al. (2400496) developed a 4D-bioprinted cartilage microtissue loaded with ibuprofen nanoparticles to mitigate inflammation in osteoarthritis. Their work demonstrates the potential of combining bioprinting with nanotechnology for targeted tissue repair. Furthermore, Brannon et al. (2400443) develop salicylic acid-based polymer particles to inhibit Neutrophil extracellular traps (NET), a contributor to inflammatory disease. Their high-throughput platform enables the optimization of particle-based therapies, paving the way for innovative treatments for NET-mediated conditions. Lokwani et al. (2400134) examine the role of eosinophils in muscle regeneration following extracelullar matrix (ECM) treatment. Their findings suggest that while eosinophils are responsive to ECM-treated injuries, they are not required for macrophage polarization, providing insights into the systemic effects of biomaterials. Macias et al. (2400602) investigate immunometabolic strategies to mitigate the foreign body response. Their work identifies key pathways and gene targets associated with foreign body response modulation, providing a foundation for designing better implantable materials, while Capuani et al. (2304003) develop a computational model to predict the performance of cell encapsulation platforms for Type 1 diabetes. Their work highlights the importance of vascularization and localized immunosuppression in optimizing cell therapy outcomes. Lastly, He et al. (2400150) developed an inflammation-responsive hydrogel loaded with Prussian blue nanoparticles and Vascular endothelial growth factor. The hydrogel alleviates oxidative stress and enhances angiogenesis, leading to accelerated wound healing in diabetic models. This strategy highlights the potential of integrating immune modulation with advanced materials. The articles in this issue collectively showcase the versatility and promise of immunoengineering. However, significant challenges remain, including the need for a deeper mechanistic understanding of biomaterial-immune system interactions, scalable manufacturing processes, and rigorous clinical validation. Future research must bridge these gaps to unlock the full potential of immunoengineering in transforming healthcare. We hope this collection inspires further innovation and collaboration within the scientific community to address these pressing challenges and translate immunoengineering breakthroughs into life-changing therapies. The authors declare no conflict of interest. Ankur Singh is the Carl Ring Family Professor in Mechanical Engineering at Georgia Institute of Technology, with a joint appointment in Biomedical Engineering at Georgia Tech and Emory University. He directs the Center for Immunoengineering, focusing on developing immune organoids and technologies to study immune cells in health and disease and advance therapeutics. A Fellow of AIMBE, he actively contributes to immunoengineering through leadership, editorial roles, and innovation in biomaterials and immune cell modulation.