Danial Khorsandi

Carbon‐based nanomaterials (CBNs), including graphene oxide (GO), carbon nanospheres (CNSs), carbon nitrides (CNs), carbon nanotubes (CNTs), carbon dots (CDs), nanoporous carbon, and nanocomposites, possess exceptional thermal, mechanical, electrical, and optical properties with highly versatile surface chemistries. Their tunable size, shape, and surface functionalities facilitate strong π–π interactions and semiconductor‐like behavior, enabling efficient light absorption and intimate biomolecular interfacing. These attributes have positioned CBNs as leading candidates in biomedical engineering, inspiring biomimetic designs that integrate organic and inorganic functions within unified architectures. This review highlights recent advances in the use of CBNs for next‐generation biosensing and theranostics. Approaches such as physicochemical engineering, deoxyribonucleic acid (DNA) origami templating, peptide‐ or enzyme‐assisted assembly, polysaccharide anchoring, and lipid modification have enhanced their biocompatibility, selectivity, and catalytic activity. Innovations in fluorescence switching, aptamer–CNT photophysics, and spacer‐controlled energy transfer enable ultra‐sensitive detection of metal ions, metabolites, neurotransmitters, pathogens, drugs, and cancer biomarkers. Furthermore, integrated CBN‐based platforms, including field‐effect transistors and laser‐scribed graphene electrodes, demonstrate capabilities for single‐virus or single‐cell diagnostics and responsive therapeutic intervention. Finally, translational challenges related to scalable synthesis, biosafety, regulatory harmonization, and public acceptance are discussed, and interdisciplinary strategies combining flexible electronics, organ‐on‐chip models, and AI‐guided design to advance clinical translation of CBN‐enabled precision diagnostics and personalized theranostics are proposed.

Blood vessel embolization is a well-established treatment modality for liver cancer. Novel shear-thinning hydrogels (STH) have been developed to address the need for safer and more effective local delivery of embolic agents and therapeutics. However, embolization therapies are currently optimized in animal models, which often differ from humans at the cellular, tissue, and organ levels. We aim to evaluate the efficacy of novel embolic agents such as STH using a human-relevant in vitro model that recapitulates human hepatocellular carcinoma capillary networks. A vascularized human liver-tumor-on-a-chip model was developed to assess embolic agent performance. The effects of drug-eluting STH (DESTH) on tumor cell viability, surface marker expression, vasculature morphology, and cytokine responses were evaluated. To study the effects of embolization on microvasculature morphology independent of the chemotherapy compound, we evaluated the effect of different drug-free embolic agents on the vascular tumor microenvironment under flow conditions. DESTH treatment induced tumor cell death, downregulated the expression of epithelial cell adhesion molecules in HepG2, increased levels of cytokines such as interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor, and vascular endothelial growth factor, and decreased albumin secretion. Furthermore, different embolic agents exert distinct effects on microvascular morphology, with STH causing complete regression of the microvascular networks. This vascularized liver tumor-on-a-chip model enables human-relevant, real-time assessment of embolic agent efficacy and vascular response and can be applied for the development of innovative and effective embolization therapies for liver cancer.

Immunosenescence dramatically reduces cancer vaccine efficacy in elderly patients, who represent the majority of cancer cases. Despite this clinical reality, age-related immune decline is rarely considered in preclinical testing. Therefore, novel in vitro models to test cancer vaccine efficacy, considering immunosenescence, are needed. Our novel lymph node paracortex on-a-chip (LNPoC) platform addresses this gap by recapitulating age-dependent immune responses against cancer vaccines, specifically antigen presentation, antigen-specific T cell activation, and antitumoral responses. Using this platform, we demonstrated that bone marrow-derived antigen-presenting cells (APCs) from young mice (6-7 weeks) displayed significantly enhanced ovalbumin (OVA) peptide presentation compared to APCs from older mice (35-36 weeks). This age-dependent difference translated to significantly greater OVA-specific CD8+ T cell activation and increased cytotoxicity against B16-OVA cancer cells. These age-dependent differences are unique to our LNPoC and undetectable in traditional 2D cultures, confirming that our LNPoC was more effective than 2D cultures at recapitulating immunosenescence-mediated immune responses against cancer vaccines in vitro. The in vivo validation confirms these findings, as young mice demonstrated higher OVA-specific CD8+ T cell responses and smaller tumors than older mice. Our LNPoC is a valuable tool for assessing immunosenescence’s impact on cancer vaccines, potentially guiding more effective therapies for older adults.

Background: Embolization is a well-established treatment modality for liver cancer. However, traditional embolization agents are limited by inefficient delivery and aggregation in blood vessels. Novel shear-thinning hydrogels (STH) have been developed to address the need for safer and more effective local delivery of embolic agents and therapeutics. Objective: We aim to evaluate the efficacy of novel embolic agents such as STH using a human-relevant in vitro model that recapitulates human hepatocellular carcinoma capillary networks. Methods: A vascularized human liver-tumor-on-a-chip model was developed to assess embolic agent performance. The effects of drug-eluting STH (DESTH) on tumor cell viability, surface marker expression, vasculature morphology, and cytokine responses were evaluated. To study the effects of embolization on microvasculature morphology independent of the chemotherapy compound, we assessed the effect of different drug-free embolic agents on the vascular tumor microenvironment under flow conditions. Results: DESTH treatment induced tumor cell death, downregulated the expression of Epithelial Cell Adhesion Molecules (EpCAM) in HepG2, increased levels of cytokines such as Interleukin-4 (IL-4), Granulocyte-macrophage colony-stimulating factor (GM-CSF), and Vascular Endothelial Growth Factor (VEGF), and decreased albumin secretion. Furthermore, different embolic agents exert distinct effects on microvascular morphology, with STH causing complete regression of the microvascular networks. Conclusion: This vascularized liver tumor-on-a-chip model enables human-relevant, real-time assessment of embolic agent efficacy and vascular response, paving the way for the development of innovative and effective embolization therapies for liver cancer.

Smart biomaterials have significantly impacted human healthcare by advancing the development of medical devices designed to function within human tissue, mimicking the behavior of natural tissues. While the intelligence of biomaterials has evolved from inert to active over the past few decades, smart biomaterials take this a step further by making their surfaces or bulk respond based on interactions with surrounding tissues, imparting outcomes similar to natural tissue functions. This interaction with the surrounding tissue helps in creating stimuli-responsive biomaterials, which can be useful in tissue engineering, regenerative medicine, autonomous drug delivery, orthopedics, and much more. Traditionally, material engineering focused on refining the static properties of biomaterials to accommodate them within the body without evoking an immune response, which was a major obstacle to their unrestricted operation. This review highlights and explains various engineering approaches currently under research for developing stimuli-responsive biomaterials that tune their outcomes based on responses to bodily factors like temperature, pH, and ion concentration or external factors like magnetism, light, and conductivity. Applications in soft and hard tissue engineering, 4D printing, and scaffold design are also discussed. The advanced application of microfluidics, like organ-on-a-chip models, extensively benefits from the intrinsic smart properties of biomaterials, which are also discussed below. The review further elaborates on how smart biomaterial engineering could revolutionize biosensor applications, thereby improving patient care quality. We delineate the limitations and key challenges associated with biomaterials, providing insights into the path forward and outlining future directions for developing next-generation biomaterials that will facilitate clinical translation.

Glioblastoma (GBM) is an aggressive form of cancer, comprising ≈80% of malignant brain tumors. However, there are no effective treatments for GBM due to its heterogeneity and the presence of the blood‐brain barrier (BBB), which restricts the delivery of therapeutics to the brain. Despite in vitro models contributing to the understanding of GBM, conventional 2D models oversimplify the complex tumor microenvironment. Organ‐on‐a‐chip (OoC) models have emerged as promising platforms that recapitulate human tissue physiology, enabling disease modeling, drug screening, and personalized medicine. There is a sudden increase in GBM‐on‐a‐chip models that can significantly advance the knowledge of GBM etiology and revolutionize drug development by reducing animal testing and enhancing translation to the clinic. In this review, an overview of GBM‐on‐a‐chip models and their applications is reported for drug screening and discussed current challenges and potential future directions for GBM‐on‐a‐chip models.

Drug toxicity assays using conventional 2D static cultures and animal studies have limitations preventing the translation of potential drugs to the clinic. The recent development of organs‐on‐a‐chip platforms provides promising alternatives for drug toxicity/screening assays. However, most studies conducted with these platforms only utilize single endpoint results, which do not provide real‐time/ near real‐time information. Here, a versatile technology is presented that integrates a 3D liver‐on‐a‐chip with a label‐free photonic crystal‐total internal reflection (PC‐TIR) biosensor for rapid and continuous monitoring of the status of cells. This technology can detect drug‐induced liver toxicity by continuously monitoring the secretion rates and levels of albumin and glutathione S‐transferase α (GST‐α) of a 3D liver on‐a‐chip model treated with Doxorubicin. The PC‐TIR biosensor is based on a one‐step antibody functionalization with high specificity and a detection range of 21.7 ng mL⁻¹ to 7.83 x 10³ ng mL⁻¹ for albumin and 2.20 ng mL⁻¹ to 7.94 x 10² ng mL⁻¹ for GST‐α. This approach provides critical advantages for the early detection of drug toxicity and improved temporal resolution to capture transient drug effects. The proposed proof‐of‐concept study introduces a scalable and efficient plug‐in solution for organ‐on‐a‐chip technologies, advancing drug development and in vitro testing methods by enabling timely and accurate toxicity assessments.

Patient‐derived organoids (PDOs) developed ex vivo and in vitro are increasingly used for therapeutic screening. They provide a more physiologically relevant model for drug discovery and development compared to traditional cell lines. However, several challenges remain to be addressed to fully realize the potential of PDOs in therapeutic screening. This paper summarizes recent advancements in PDO development and the enhancement of PDO culture models. This is achieved by leveraging materials engineering and microfabrication technologies, including organs‐on‐a‐chip and droplet microfluidics. Additionally, this work discusses the application of PDOs in therapy screening to meet diverse requirements and overcome bottlenecks in cancer treatment. Furthermore, this work introduces tools for data processing and analysis of organoids, along with their microenvironment. These tools aim to achieve enhanced readouts. Finally, this work explores the challenges and future perspectives of using PDOs in drug development and personalized screening for cancer patients.