Search Results (328)

Ischemia–reperfusion (I/R) injury is a complex pathological process underlying numerous acute organ failures and is a significant cause of morbidity and mortality in diseases such as myocardial infarction, stroke, thrombosis, and organ transplantation. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have demonstrated considerable therapeutic potential, but their broad tropism and general repair signaling may limit their efficacy. This review addresses the emerging paradigm of using organ-specific EVs for the treatment of I/R injury in the respective organs. We summarize the existing studies performed on experimental animals showing that these native EVs could possess tissue tropism and carry a specialized cargo of proteins, miRNAs, and lipids tailored to the unique regenerative needs of their organ of origin, enabling them to precisely modulate key processes, including inflammation, apoptosis, oxidative stress, and angiogenesis. However, their clinical translation faces challenges related to scalable production, standardization, and the dualistic nature of their effects, which can be either protective or detrimental, depending on the cellular source and pathophysiological context. Future developments need to focus on overcoming these obstacles through rigorous isolation protocols, engineering strategies such as cargo enrichment and hybrid vesicle creation, and validation in large-animal models. Overall, organ-specific EVs offer a novel, cell-free therapeutic strategy with the potential to significantly improve outcomes in I/R injury. Full article

(1) Background: The extracellular matrix (ECM) is a natural scaffold for cells, creating a three-dimensional architecture composed of fibrous proteins (mainly collagen) and proteoglycans, which are synthesized by resident cells. In this study, a physiological hypoxic environment was utilized to enhance ECM production by human mesenchymal stem cells (hMSCs), a process relevant to tissue engineering and regenerative medicine. (2) Methods: hMSCs were treated with deferoxamine (DFO), a pharmaceutical hypoxia-mimetic agent that induces cellular responses similar to low-oxygen conditions through stabilization of hypoxia inducible factor-1α (HIF-1α). The time points 0 h 24 h, 3 h 24 h, and 24 h 24 h refer to DFO being added immediately after cell seeding (before cells adhesion), 3 h after cell seeding (during initial cells attachment), and 24 h after cell seeding (after focal adhesions formation and actin organization), respectively, to evaluate the influence of cell adhesion on ECM deposition. hMSCs incubated in culture media were subsequently exposed to DFO for 24 h. Samples were then subjected to cell viability tests, scanning electron microscopy (SEM), atomic force microscopy (AFM) and laser scanning confocal microscopy (CLSM) assessments. (3) Results: Viability tests indicated that DFO concentrations in the range of 0–300 µM were non-toxic over 24 h. The presence of collagen fibers in the DFO-derived ECM was confirmed with anti-collagen antibodies under CLSM. Increased ECM secretion was observed under the following conditions: 3 μM DFO (24 h 24 h), 100 μM DFO (0 h 24 h) and 300 μM DFO (3 h 24 h). SEM and AFM images revealed the morphology of various stages of collagen formation with both collagen fibrils and fibers identified. (4) Conclusions: Our preliminary study demonstrated enhanced ECM secretion by hMSC treated with DFO at concentrations of 3, 100, and 300 µM within a short cultivation period of 24–48 h without significant affecting cell viability. By mimicking physiological processes, it may be possible to stimulate endogenous tissue regeneration, for example, at an injury site. Full article

In recent years, apatite-based materials have garnered significant interest, particularly for applications in tissue engineering. Apatite is most commonly employed as a coating for metallic implants, as a component in composite materials, and as scaffolds for bone and dental tissue regeneration. Among its various forms, hydroxyapatite (HAP) is the most widely used, owing to its natural occurrence in human and animal hard tissues. An emerging area of research involves the use of fluoride-substituted apatite, particularly fluorapatite (FAP), which can serve as a direct fluoride source at the implant site, potentially offering several biological and therapeutic advantages. However, substituting HAP with FAP may lead to unforeseen changes in material behavior due to the differing physicochemical properties of these two calcium phosphate phases. This study investigates the effects of replacing hydroxyapatite with fluorapatite in ceramic–polymer composite materials incorporating β-1,3-glucan as a bioactive polymeric binder. The β-1,3-glucan polysaccharide was selected for its proven biocompatibility, biodegradability, and ability to form stable hydrogels that promote cellular interactions. Nitrogen adsorption analysis revealed that FAP/glucan composites had a significantly lower specific surface area (0.5 m²/g) and total pore volume (0.002 cm³/g) compared to HAP/glucan composites (14.15 m²/g and 0.03 cm³/g, respectively), indicating enhanced ceramic–polymer interactions in fluoride-containing systems. Optical profilometry measurements showed statistically significant differences in profile parameters (e.g., Rp: 134 μm for HAP/glucan vs. 352 μm for FAP/glucan), although average roughness (Ra) remained similar (34.1 vs. 27.6 μm, respectively). Microscopic evaluation showed that FAP/glucan composites had smaller particle sizes (1 μm) than their HAP counterparts (2 μm), despite larger primary crystal sizes in FAP, as confirmed by TEM. XRD analysis indicated structural differences between the apatites, with FAP exhibiting a reduced unit cell volume (524.6 ų) compared to HAP (528.2 ų), due to substitution of hydroxyl groups with fluoride ions. Spectroscopic analyses (FTIR, Raman, ³¹P NMR) confirmed chemical shifts associated with fluorine incorporation and revealed distinct ceramic–polymer interfacial behaviors, including an upfield shift of PO₄³⁻ bands (964 cm⁻¹ in FAP vs. 961 cm⁻¹ in HAP) and OH vibration shifts (3537 cm⁻¹ in FAP vs. 3573 cm⁻¹ in HAP). The glucan polymer showed different hydrogen bonding patterns when combined with FAP versus HAP, as evidenced by shifts in polymer-specific bands at 888 cm⁻¹ and 1157 cm⁻¹, demonstrating that fluoride substitution significantly influences ceramic–polymer interactions in these bioactive composite systems. Full article

A subset of chondrocytes in various human cartilage tissues, including neoplastic, regenerative, and normal cartilage, expresses α-smooth muscle actin (α-SMA), a protein typically found in smooth muscle cells. These α-SMA-containing chondrocytes, termed myochondrocytes and myochondroblasts, may play important roles in cartilage physiology, regeneration, and structural integrity, particularly in auricular and articular cartilage. This review synthesizes current knowledge regarding the terminology, distribution, and biological significance of these cells across normal, osteoarthritic, transplanted, and neoplastic cartilage. We summarize key findings from immunohistochemical studies using markers such as S-100, α-SMA, and SOX9, along with ultrastructural confirmation of myofilament bundles via electron microscopy. Current evidence suggests that myochondrocytes exhibit enhanced regenerative potential and contribute to matrix remodeling. Furthermore, their presence reflects the inherent cellular heterogeneity of cartilage, potentially arising from transdifferentiation processes involving fibroblasts, mesenchymal stem cells, or chondroblasts. Finally, TGF-β1 and PDGF-BB are identified as a critical modulator of α-SMA expression and chondrocyte phenotype. A deeper understanding of nature and function of myochondrocytes and myochondroblasts may improve interpretations of cartilage pathology and inform strategies for tissue engineering and cartilage repair. This review highlights the need for further investigation into the molecular regulation and functional roles of these cells in both physiological and pathological contexts. Full article

Over the past decade, cellular immunotherapy has emerged as a transformative strategy for non-small cell lung cancer (NSCLC), with dendritic-cell (DC) vaccines, T-cell vaccines, and natural killer (NK)-cell therapies demonstrating distinct mechanisms and clinical potential. DC vaccines capitalize on antigen presentation to prime tumor-specific T-cell responses, showing excellent safety profiles limited mainly to injection-site reactions and flu-like symptoms. While monotherapy has shown limited efficacy, combinations with checkpoint inhibitors or chemotherapy enhance immune activation and survival outcomes. Recent innovations, including neoantigen-loaded, mRNA-electroporated, and exosome-pulsed DCs, demonstrate improved immunogenicity and personalized approaches. T-cell vaccines, designed to activate cytotoxic CD8+ T-cell responses, have been tested across multiple platforms, including peptide-based (MAGE-A3), viral vector (TG4010/MUC1), and mRNA (CV9201/92) formulations. While the phase III MAGRIT trial presented no disease-free survival (DFS) benefit with adjuvant MAGE-A3 vaccination, the TG4010 vaccine improved progression-free survival (PFS; HR 0.66) and overall survival (OS; HR 0.67) in MUC1-positive NSCLC when combined with chemotherapy. Current strategies focus on personalized neoantigen vaccines and KRAS-targeted approaches (e.g., ELI-002), with ongoing phase III trials evaluating their potential in resectable NSCLC. NK-cell therapies have also shown promise, with early trials establishing the feasibility of autologous and allogeneic infusions, while engineered CAR-NK cells enhance tumor-specific targeting. Combination strategies with checkpoint inhibitors significantly improve response rates and PFS, revealing synergies between innate and adaptive immunity. Recent advances include cytokine-enhanced, memory-like NK cells to overcome immunosuppression and “off-the-shelf” products for broader clinical use. Together, these cellular immunotherapies represent a versatile and evolving frontier in NSCLC treatment, with ongoing research optimizing combinations, delivery platforms, and patient selection to maximize therapeutic benefit. Full article

Immunoregulation is an emerging treatment strategy to promote wound healing by modulating the local immune system at the wound site. In this study, an extracellular matrix biomimetic and polysaccharide-based hydrogel was engineered to regulate the wound immune environment through Michael-type addition between maleimidyl pullulan and chitosan modified with hydroxyproline. The proposed hydrogel exhibited favorable injectable and self-healing properties, which facilitated the full coverage of irregularly shaped wounds. A natural polyphenol, epigallocatechin-3-gallate (EGCG), was incorporated into hydrogels, which thereby exhibited excellent biocompatibility, good reactive oxygen species (ROS) scavenging ability, anti-inflammatory activity, and antibacterial properties against S. aureus and E. coli. Furthermore, evaluations of a full-thickness skin defect mice model showed that the hydrogel with EGCG effectively alleviated the inflammatory response by reducing pro-inflammatory cellular infiltration and down-regulating the inflammatory cytokine TNF-α, while up-regulating anti-inflammatory cytokine IL-10. Notably, a faster wound healing rate was also achieved by the better promotion effect of the hydrogel on increasing the formation of re-epithelialization, granulation tissue generation, collagen deposition, and angiogenesis. Therefore, our immunoregulatory strategy showed great potential in the design of biomaterials for wound management. Full article

The rapid shift toward electric vehicles (EVs) has underscored the critical importance of battery pack crashworthiness, creating a demand for lightweight, energy-absorbing protective systems. This review systematically explores bio-inspired cellular structures as promising solutions for improving the impact resistance of EV battery packs. Inspired by natural geometries, these designs exhibit superior energy absorption, controlled deformation behavior, and high structural efficiency compared to conventional configurations. A comprehensive analysis of experimental, numerical, and theoretical studies published up to mid-2025 was conducted, with emphasis on design strategies, optimization techniques, and performance under diverse loading conditions. Findings show that auxetic, honeycomb, and hierarchical multi-cell architectures can markedly enhance specific energy absorption and deformation control, with improvements often exceeding 100% over traditional structures. Finite element analyses highlight their ability to achieve controlled deformation and efficient energy dissipation, while optimization strategies, including machine learning, genetic algorithms, and multi-objective approaches, enable effective trade-offs between energy absorption, weight reduction, and manufacturability. Persistent challenges remain in structural optimization, overreliance on numerical simulations with limited experimental validation, and narrow focus on a few bio-inspired geometries and thermo-electro-mechanical coupling, for which engineering solutions are proposed. The review concludes with future research directions focused on geometric optimization, multi-physics modeling, and industrial integration strategies. Collectively, this work provides a comprehensive framework for advancing next-generation crashworthy battery pack designs that integrate safety, performance, and sustainability in electric mobility. Full article

This review emphasizes the latest developments in bioprinted scaffolds in tissue engineering, with a focus on their biomimetic applications. The accelerated pace of development of 3D bioprinting technologies has transformed the ability to fabricate scaffolds with the potential to replicate the structure and function of native tissues. Bioprinting methods such as inkjet, extrusion-based, laser-assisted, and digital light processing (DLP) approaches have the potential to fabricate complex, multi-material structures with high precision in geometry, material composition, and cellular microenvironments. Incorporating biomimetic design principles to replicate the mechanical and biological behaviors of native tissues has been of major research interest. Scaffold geometries that support cell adhesion, growth, and differentiation essential for tissue regeneration are mainly of particular interest. The review also deals with the development of bioink, with an emphasis on the utilization of natural, synthetic, and composite materials for enhanced scaffold stability, printability, and biocompatibility. Rheological characteristics, cell viability, and the utilization of stimuli-responsive bioinks are also discussed in detail. Their utilization in bone, cartilage, skin, neural, and cardiovascular tissue engineering demonstrates the versatility of bioprinted scaffolds. Despite the significant advancements, there are still challenges that include achieving efficient vascularization, long-term integration with host tissues, and scalability. The review concludes by underlining future trends such as 4D bioprinting, artificial intelligence-augmented scaffold design, and the regulatory and ethical implications involved in clinical translation. By considering these challenges in detail, this review provides insight into the future of bioprinted scaffolds in regenerative medicine. Full article

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of certain hematologic malignancies, yet its success in solid tumors has been limited by antigen heterogeneity, an immunosuppressive tumor microenvironment, and barriers to cell trafficking and persistence. To expand the reach of cellular immunotherapy, multiple immune cell types—γδ T cells, invariant NKT cells, virus-specific T cells, natural killer (ΝΚ) cells, and myeloid effectors such as macrophages and dendritic cells—are now being explored as alternative or complementary CAR platforms. Each lineage brings unique advantages, such as the innate cytotoxicity and safety profile of CAR NK cells, the tissue infiltration and microenvironment-modulating capacity of CAR macrophages, or the MHC-independent recognition offered by γδ T cells. Recent advances in pharmacological strategies, synthetic biology, and artificial intelligence provide additional opportunities to overcome barriers and optimize CAR design and manufacturing scale-up. Here, we review the state of the art in engineering diverse immune cells for solid tumor therapy, highlight safety considerations across autologous, allogeneic, and in vivo CAR cell therapy approaches, and provide our perspective on which platforms might best address current unmet clinical needs. Collectively, these developments lay the foundation for next-generation strategies to achieve durable immunotherapy responses in solid tumors. Full article

Polymers and polymer composites offer versatile possibilities for engineering the physico-chemical properties of materials on micro- and macroscopic scales. This review provides an overview of polymeric and polymer-decorated particles that can serve as drug-delivery vectors: linear polymers, star polymers, diblock-copolymer micelles, polymer-grafted nanoparticles, polymersomes, stealth liposomes, microgels, and biomolecular condensates. The physico-chemical interactions between the delivery vectors and biological cells range from chemical interactions on the molecular scale to deformation energies on the particle scale. The focus of this review is on the structure and elastic properties of these particles, as well as their circulation in blood and cellular uptake. Furthermore, the effects of polymer decoration in vivo (e.g., of glycosylated plasma membranes, cortical cytoskeletal networks, and naturally occurring condensates) on drug delivery are discussed. Full article

Cellular immunotherapy has emerged as a transformative approach in oncology, revolutionizing cancer treatment paradigms. Since the groundbreaking development of induced pluripotent stem cells (iPSCs) by Yamanaka in 2008, significant progress has been made in generating various iPSCs-derived immunocytes, including T cells, dendritic cells, macrophages, natural killer (NK) cells, and B cells. These engineered immune cells offer unprecedented opportunities for personalized cancer therapy as they can be derived from patients’ own cells to minimize immune rejection. In addition, various new techniques are being used for the induction and amplification of iPSCs-derived immunocytes, such as small-molecule techniques, 3D culture systems, nanotechnology, and animal models for the in vivo amplification of immunocytes. Of course, challenges remain in improving immunocyte characteristics. Targeting efficiency needs enhancement to better distinguish tumor cells from healthy tissue, while biological activity must be optimized for sustained antitumor effects. Safety concerns, particularly regarding potential off-target effects and cytokine release syndrome, require further investigation. The immunosuppressive nature of tumor microenvironment also poses significant hurdles for solid tumor treatment. Ongoing clinical trials are exploring the therapeutic potential of iPSCs-derived immunocytes, with researchers investigating combination therapies and genetic modifications to overcome current limitations. Full article

Plants are frequently exposed to a range of abiotic stresses, including drought, salinity, extreme temperatures, and heavy metals, that severely impair their growth and productivity. Among the adaptive mechanisms that plants have evolved, the accumulation of glycine betaine (GB), a naturally occurring, zwitterionic, and chemically stable osmoprotectant, has been widely recognized as a key strategy for stress tolerance. In higher plants, GB is primarily synthesized via the two-step oxidation of choline, catalyzed by choline monooxygenase (CMO) and betaine aldehyde dehydrogenase (BADH). GB contributes to cellular homeostasis by modulating osmotic balance, regulating ion flux, scavenging reactive oxygen species (ROS), enhancing antioxidant defense systems, and stabilizing proteins and membrane structures. Both exogenous application of GB and genetic engineering approaches aimed at enhancing endogenous GB biosynthesis have been shown to significantly improve plant tolerance to a variety of abiotic stresses. In this review, we provide a comprehensive overview of recent advances in the understanding of GB biosynthesis, its regulatory mechanisms, and its multifaceted roles in plant stress responses. We also highlight emerging prospects for leveraging GB-centered strategies to enhance crop resilience in challenging environmental conditions. Full article

Two-dimensional cell culture systems lack the ability to replicate the complex, three-dimensional (3D) architecture and cellular microenvironments found in vivo. Multicellular spheroids (MCSs) present a promising alternative, with the ability to mimic native cell–cell and cell–matrix interactions and provide 3D architectures similar to in vivo conditions. These factors are critical for various biomedical applications, including cancer research, tissue engineering, and drug discovery and development. Polymeric materials such as hydrogels, solid scaffolds, and ultra-low attachment surfaces serve as versatile platforms for 3D cell culture, offering tailored biochemical and mechanical cues to support cellular organization. This review article focuses on the structure–property relationships of polymeric biomaterials that influence MCS formation, growth, and functionality. Specifically, we highlight their physicochemical properties and their influence on spheroid formation using key natural polymers, including collagen, hyaluronic acid, chitosan, and synthetic polymers like poly(lactic-co-glycolic acid) and poly(N-isopropylacrylamide) as examples. Despite recent advances, several challenges persist, including spheroid loss during media changes, limited viability or function in long-term cultures, and difficulties in scaling for high-throughput applications. Importantly, the development of MCS platforms also supports the 3R principle (Replacement, Reduction, and Refinement) by offering ethical and physiologically relevant alternatives to animal testing. This review emphasizes the need for innovative biomaterials and methodologies to overcome these limitations, ultimately advancing the utility of MCSs in biomedical research. Full article

Healing large bone defects remains challenging. Gelatin scaffolds are biocompatible and biodegradable, but lack osteoinductive activity. Plant-derived exosomes carry miRNAs, growth factors, and proteins that modulate osteogenesis, but free exosomes suffer from poor stability, limited targeting, and low bioavailability in vivo. We developed a 3D GelMA hydrogel loaded with Epimedium-derived exosomes (“GelMA@Exo”) to improve exosome retention, stability, and sustained release. Its effects on MC3T3-E1 preosteoblasts—including proliferation, osteogenic differentiation, migration, and senescence—were evaluated via in vitro assays. Angiogenic potential was assessed using HUVECs. Underlying mechanisms were examined at transcriptomic and protein levels to elucidate GelMA@Exo’s therapeutic osteogenesis actions. GelMA@Exo exhibited sustained exosome release, enhancing exosome retention and cellular uptake. In vitro, GelMA@Exo markedly boosted MC3T3-E1 proliferation, migration, and mineralized nodule formation, while reducing senescence markers and promoting angiogenesis in HUVECs. Mechanistically, GelMA@Exo upregulated key osteogenic markers (RUNX2, TGF-β1, Osterix, COL1A1, ALPL) and activated the PI3K/Akt pathway. Transcriptomic data confirmed global upregulation of osteogenesis-related genes and bone-regeneration pathways. This study presents a GelMA hydrogel functionalized with plant-derived exosomes, which synergistically provides osteoinductive stimuli and structural support. The GelMA@Exo platform offers a versatile strategy for localized delivery of natural bioactive molecules and a promising approach for bone tissue engineering. Our findings provide strong experimental evidence for the translational potential of plant-derived exosomes in regenerative medicine. Full article

The paradigm-shift idea of murburn concept is no hypothesis but developed directly from fundamental facts of cellular/ecological existence. Murburn involves spontaneous and stochastic interactions (mediated by murzymes) amongst the molecules and unbound ions of cells. It leads to effective charge separation (ECS) and formation/recruitment of diffusible reactive species (DRS, like radicals whose reactions enable ATP-synthesis and thermogenesis) and emission of radiations (UV/Vis to ELF). These processes also lead to a chemo-electromagnetic matrix (CEM), ascertaining that living cell/organism react/function as a coherent unit. Murburn concept propounds the true utility of oxygen: generating DRS (with catalytic and electrical properties) on the way to becoming water, the life solvent, and ultimately also leading to phase-based macroscopic homeostatic outcomes. Such a layout enables cells to become simple chemical engines (SCEs) with powering, coherence, homeostasis, electro-mechanical and sensing–response (PCHEMS; life’s short-term “intelligence”) abilities. In the current review, we discuss the coacervate nature of cells and dwell upon the ways and contexts in which various radiations (either incident or endogenously generated) could interact in the new scheme of cellular function. Presenting comparative evidence/arguments and listing of systems with murburn models, we argue that the new perceptions explain life processes better and urge the community to urgently adopt murburn bioenergetics and adapt to its views. Further, we touch upon some distinct scientific and sociological contexts with respect to the outreach of murburn concept. It is envisaged that greater awareness of murburn could enhance the longevity and quality of life and afford better approaches to therapies. Full article