Search Results (1,547)

Osteoarthritis (OA) is a chronic progressive joint disease characterized by cartilage degradation, subchondral bone remodeling, and synovial inflammation. This complex disorder arises from the interplay between mechanical stress and inflammatory processes, which is mediated by interconnected molecular signaling pathways. This review explores the dual roles of inflammatory and mechanical signaling in OA pathogenesis, focusing on crucial pathways such as NF-kB, JAK/STAT, and MAPK in inflammation, as well as Wnt/β-catenin, Integrin-FAK, and Hippo-YAP/TAZ in mechanotransduction. The interplay between these pathways highlights a vicious cycle wherein mechanical stress exacerbates inflammation, and inflammation weakens cartilage, increasing its vulnerability to mechanical damage. Additionally, we discuss emerging therapeutic strategies targeting these pathways, including inhibitors of cartilage-degrading enzymes, anti-inflammatory biologics, cell-based regenerative approaches, and non-pharmacological mechanical interventions. By dissecting the molecular mechanisms underlying OA, this review aims to provide insights into novel interventions that address both inflammatory and mechanical components of the disease, paving the way for precision medicine in OA management. Full article

Valued for their nutritional content, eggs have recently gained attention as a versatile biomaterial owing to their biocompatibility, biodegradability, and unique structural and biochemical composition. This review highlights the biomedical potential of various egg components—eggshell, eggshell membrane, egg white, and egg yolk—and their applications in bone grafting, tissue engineering, wound healing, drug delivery, and biosensors. Eggshells serve as a natural, calcium-rich source for bone tissue engineering and regenerative medicine. The eggshell membrane, with its antimicrobial and structural properties, offers promise as a wound healing scaffold. Egg white, known for its gelation and film-forming capabilities, is utilized in hydrogel-based systems for drug delivery and biosensing. Egg yolk, rich in lipids and immunoglobulin Y (IgY) antibodies, is being explored for diagnostic and therapeutic applications. This review critically examines the advantages and limitations of each egg-derived component and outlines current research gaps, offering insights into future directions for the development of egg-based biomaterials in biomedical engineering. Full article

Tissue-engineered scaffolds, particularly composite scaffolds composed of polymers combined with ceramics, bioactive glasses, or nanomaterials, play a vital role in regenerative medicine by providing structural and biological support for tissue repair. As scaffold designs grow increasingly complex, the need for non-invasive imaging modalities capable of monitoring scaffold integration, degradation, and tissue regeneration in real-time has become critical. This review summarizes current non-invasive imaging techniques used to evaluate tissue-engineered constructs, including optical methods such as near-infrared fluorescence imaging (NIR), optical coherence tomography (OCT), and photoacoustic imaging (PAI); magnetic resonance imaging (MRI); X-ray-based approaches like computed tomography (CT); and ultrasound-based modalities. It discusses the unique advantages and limitations of each modality. Finally, the review identifies major challenges—including limited imaging depth, resolution trade-offs, and regulatory hurdles—and proposes future directions to enhance translational readiness and clinical adoption of imaging-guided tissue engineering (TE). Emerging prospects such as multimodal platforms and artificial intelligence (AI) assisted image analysis hold promise for improving precision, scalability, and clinical relevance in scaffold monitoring. Full article

Cyclodextrins (CDs), cyclic oligosaccharides formed by α-1,4-glycosidic-bonded D-glucopyranose units, feature unique hydrophobic cavities and hydrophilic exteriors that enable molecular encapsulation via host–guest interactions. CDs form supramolecular host–guest complexes with diverse molecular entities, establishing their fundamental role in supramolecular chemistry. This review examines fabrication strategies for CD-based supramolecular hydrogels and their applications in tissue engineering and regenerative medicine, with focused analysis on wound healing, corneal regeneration, and bone repair. We critically analyze CD–guest molecular interaction mechanisms and innovative therapeutic implementations, highlighting the significant potential of CD hydrogels for tissue regeneration while addressing clinical translation challenges and future directions. Full article

Background: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold transformative potential for cardiovascular regenerative medicine, yet their clinical application is hindered by suboptimal mitochondrial maturation and metabolic inefficiencies. This systematic review evaluates targeted strategies for optimizing mitochondrial function, integrating metabolic preconditioning, substrate selection, and pathway modulation to enhance energy production and cellular resilience. Additionally, we examine the role of extracellular matrix stiffness and mechanical stimulation in mitochondrial adaptation, given their influence on metabolism and maturation. Methods: A comprehensive analysis of recent advancements in iPSC-CM maturation was conducted, focusing on metabolic interventions that enhance mitochondrial structure and function. Studies employing metabolic preconditioning, lipid and amino acid supplementation, and modulation of key signaling pathways, including PGC-1α, AMPK, and mTOR, were reviewed. Computational modeling approaches predicting optimal metabolic shifts were assessed, alongside insights into reactive oxygen species (ROS) signaling, calcium handling, and the impact of electrical pacing on energy metabolism. Results: Evidence indicates that metabolic preconditioning with fatty acids and oxidative phosphorylation enhancers improves mitochondrial architecture, cristae density, and ATP production. Substrate manipulation fosters a shift toward adult-like metabolism, while pathway modulation refines mitochondrial biogenesis. Computational models enhance precision, predicting interventions that best align iPSC-CM metabolism with native cardiomyocytes. The synergy between metabolic and biomechanical cues offers new avenues for accelerating maturation, bridging the gap between in vitro models and functional cardiac tissues. Conclusions: Strategic metabolic optimization is essential for overcoming mitochondrial immaturity in iPSC-CMs. By integrating biochemical engineering, predictive modeling, and biomechanical conditioning, a robust framework emerges for advancing iPSC-CM applications in regenerative therapy and disease modeling. These findings pave the way for more physiologically relevant cell models, addressing key translational challenges in cardiovascular medicine. Full article

Scaffolds are widely used in bioengineering, both as 3D native tissue-mimicking models for investigating mechanisms under physiological and pathological conditions and also as implantable agents in regenerative medicine. Histological approaches, mainly formalin-fixed paraffin-embedded (FFPE) and frozen sample sectioning, are commonly applied to evaluate cell distribution and tissue-like properties of scaffolds. However, standard histological processing is not always compatible with the materials that scaffolds are made of. Thus, some adaptations to protocols are required to obtain intact sections. In this review we discuss challenges related to the histological processing of scaffolds and solutions to overcome them. We sequentially cover processing steps of the three main histological techniques for sample preparation—cryomicrotomy, FFPE samples microtomy and vibrating microtomy. Furthermore, we highlight the critical considerations in choosing the most appropriate method based on scaffold composition, mechanical properties and the specific research question. The goal of this review is to provide practical guidance on choosing reliable histological evaluation of complex scaffold-based systems in tissue engineering research. Full article

Gene therapy is a groundbreaking strategy in regenerative medicine, enabling precise cellular behavior modulation for tissue repair. In situ nucleic acid delivery systems aim to directly deliver nucleic acids to target cells or tissues to realize localized genetic reprogramming and avoid issues like donor cell dependency and immune rejection. The key to success relies on biomaterial-engineered delivery platforms that ensure tissue-specific targeting and efficient intracellular transport. Viral vectors and non-viral carriers are strategically modified to enhance nucleic acid stability and cellular uptake, and integrate them into injectable or 3D-printed scaffolds. These scaffolds not only control nucleic acid release but also mimic native extracellular microenvironments to support stem cell recruitment and tissue regeneration. This review explores three key aspects: the mechanisms of gene editing in tissue repair; advancements in viral and non-viral vector engineering; and innovations in biomaterial scaffolds, including stimuli-responsive hydrogels and 3D-printed matrices. We evaluate scaffold fabrication methodologies, nucleic acid loading–release kinetics, and their biological impacts. Despite progress in spatiotemporal gene delivery control, challenges remain in balancing vector biocompatibility, manufacturing scalability, and long-term safety. Future research should focus on multifunctional “smart” scaffolds with CRISPR-based editing tools, multi-stimuli responsiveness, and patient-specific designs. This work systematically integrates the latest methodological advances, outlines actionable strategies for future investigations and advances clinical translation perspectives beyond the existing literature. Full article

This comprehensive review explores the expansive design space of network architectures and their significant impact on the mechanical and viscoelastic properties of hydrogel systems. By examining the intricate relationships between molecular structure, network connectivity, and resulting bulk properties, we provide critical insights into rational design strategies for tailoring hydrogel mechanics for specific applications. Recent advances in sequence-defined crosslinkers, dynamic covalent chemistries, and biomimetic approaches have significantly expanded the toolbox for creating hydrogels with precisely controlled viscoelasticity, stiffness, and stress relaxation behavior—properties that are crucial for biomedical applications, particularly in tissue engineering and regenerative medicine. Full article

Nanotechnology is revolutionizing medicine by enabling highly precise diagnostics, targeted therapies, and personalized healthcare solutions. This review explores the multifaceted applications of nanotechnology across medical fields such as oncology and infectious disease control. Engineered nanoparticles (NPs), such as liposomes, polymeric carriers, and carbon-based nanomaterials, enhance drug solubility, protect therapeutic agents from degradation, and enable site-specific delivery, thereby reducing toxicity to healthy tissues. In diagnostics, nanosensors and contrast agents provide ultra-sensitive detection of biomarkers, supporting early diagnosis and real-time monitoring. Nanotechnology also contributes to regenerative medicine, antimicrobial therapies, wearable devices, and theranostics, which integrate treatment and diagnosis into unified systems. Advanced innovations such as nanobots and smart nanosystems further extend these capabilities, enabling responsive drug delivery and minimally invasive interventions. Despite its immense potential, nanomedicine faces challenges, including biocompatibility, environmental safety, manufacturing scalability, and regulatory oversight. Addressing these issues is essential for clinical translation and public acceptance. In summary, nanotechnology offers transformative tools that are reshaping medical diagnostics, therapeutics, and disease prevention. Through continued research and interdisciplinary collaboration, it holds the potential to significantly enhance treatment outcomes, reduce healthcare costs, and usher in a new era of precise and personalized medicine. Full article

Cobalt is an essential trace element involved in key biological processes. It serves most notably as a component of vitamin B₁₂ (cobalamin) and a regulator of erythropoiesis. While cobalt deficiency can lead to disorders such as megaloblastic anemia, excess cobalt poses toxicological risks to the thyroid, cardiovascular, and hematopoietic systems. In recent years, cobalt ions (Co²⁺) have gained attention for their ability to mimic hypoxia and promote angiogenesis. This represents a crucial mechanism for tissue regeneration. Cobalt mediates this effect mainly by stabilizing hypoxia-inducible factor 1α (HIF-1α) under normoxic conditions, thereby upregulating angiogenic genes, including VEGF, FGF, and EPO. Experimental studies—from cell culture to animal models—have demonstrated cobalt-induced enhancement of endothelial proliferation, migration, and microvascular formation. Emerging evidence also indicates that Co²⁺-stimulated macrophages secrete integrin-β1-rich exosomes. These exosomes enhance endothelial motility and tubulogenesis independently of VEGF. Furthermore, cobalt-modified biomaterials have been developed to deliver cobalt ions in a controlled manner. Examples include cobalt-doped β-tricalcium phosphate or bioactive glasses. These materials support both angiogenesis and osteogenesis.This review summarizes current findings on cobalt’s role in angiogenesis. The emphasis is on its potential in cobalt-based biomaterials for tissue engineering and regenerative medicine. Full article

In the rapidly evolving field of biomedical engineering, hydrogels have emerged as highly versatile biomaterials that bridge biology and technology through their high water content, exceptional biocompatibility, and tunable mechanical properties. This review provides an integrated overview of both natural and synthetic hydrogels, examining their structural properties, fabrication methods, and broad biomedical applications, including drug delivery systems, tissue engineering, wound healing, and regenerative medicine. Natural hydrogels derived from sources such as alginate, gelatin, and chitosan are highlighted for their biodegradability and biocompatibility, though often limited by poor mechanical strength and batch variability. Conversely, synthetic hydrogels offer precise control over physical and chemical characteristics via advanced polymer chemistry, enabling customization for specific biomedical functions, yet may present challenges related to bioactivity and degradability. The review also explores intelligent hydrogel systems with stimuli-responsive and bioactive functionalities, emphasizing their role in next-generation healthcare solutions. In modern medicine, temperature-, pH-, enzyme-, light-, electric field-, magnetic field-, and glucose-responsive hydrogels are among the most promising “smart materials”. Their ability to respond to biological signals makes them uniquely suited for next-generation therapeutics, from responsive drug systems to adaptive tissue scaffolds. Key challenges such as scalability, clinical translation, and regulatory approval are discussed, underscoring the need for interdisciplinary collaboration and continued innovation. Overall, this review fosters a comprehensive understanding of hydrogel technologies and their transformative potential in enhancing patient care through advanced, adaptable, and responsive biomaterial systems. Full article

Extracellular vesicles (EVs) have emerged as promising acellular tools for modulating immune responses for tissue engineering applications. This study explores the potential of human fibroblast-derived EVs delivered within a three-dimensional (3D) injectable scaffold composed of polycaprolactone (PCL) nanofibers and collagen (PNCOL) to reprogram macrophage behavior and support scaffold integrity under inflammatory conditions. EVs were successfully isolated from human fibroblasts using ultracentrifugation and characterized for purity, size distribution and surface markers (CD63 and CD9). Macrophage-laden PNCOL scaffolds were prepared under three conditions: macrophage-only (MP), fibroblast co-encapsulated (F-MP), and EV-encapsulated (EV-MP) groups. Structural integrity was assessed via scanning electron microscopy and Masson’s trichrome staining, while immunomodulatory effects were evaluated through metabolic assays, gene expression profiling, and immunohistochemistry for macrophage polarization markers (CD80, CD206). When co-encapsulated with pro-inflammatory (M1) macrophages in PNCOL scaffolds, fibroblast-derived EVs preserved scaffold structure and significantly enhanced macrophage metabolic activity compared to the control (MP) and other experimental group (F-MP). The gene expression and immunohistochemistry data demonstrated substantial upregulation of anti-inflammatory markers (TGF-β, CD163, and CCL18) and surface protein CD206, indicating a phenotypic shift toward M2-like macrophages for EV-encapsulated scaffolds relative to the other groups. The findings of this study demonstrate that fibroblast-derived EVs integrated into injectable PCL–collagen scaffolds offer a viable, cell-free approach to modulate inflammation, preserve scaffold structure, and support regenerative healing. This strategy holds significant promise for advancing immuno-instructive platforms in regenerative medicine, particularly in settings where conventional cell therapies face limitations in survival, cost, or safety. Full article

Plant-derived vesicle-like nanoparticles (PDVLNs) are bioactive nanovesicles secreted by plant cells, emerging as a novel therapeutic tool for tissue repair and regeneration due to their low immunogenicity, intrinsic bioactivity, and potential as drug delivery carriers. This review examines PDVLNs’ biogenesis mechanisms, isolation techniques, and compositional diversity, emphasizing their roles in promoting essential regenerative processes—cell proliferation, differentiation, migration, immune modulation, and angiogenesis. We explore their therapeutic applications across multiple tissue types, including skin, bone, neural, liver, gastrointestinal, cardiovascular, and dental tissues, using both natural and engineered PDVLNs in various disease models. Compared to mammalian exosomes, PDVLNs offer advantages such as reduced immune rejection and ethical concerns, enhancing their sustainability and appeal for regenerative medicine. However, challenges in clinical translation, including scalability, standardization, and safety remain. This paper consolidates current knowledge on PDVLNs, highlighting their versatility and providing insights into engineering strategies to optimize efficacy, ultimately outlining future research directions to advance their clinical potential. Plant vesicle-like nanoparticles (PDVLNs) may become a new avenue for the treatment of tissue injury, promoting tissue repair and regeneration through their intrinsic bioactivity or as drug delivery carriers. In addition, PDVLNs can be engineered and modified to achieve better results. Full article

Tissue engineering enables autologous reconstruction of human tissues, addressing limitations in tissue availability and immune compatibility. Several tissue engineering techniques, such as self-assembly, rely on or benefit from extracellular matrix (ECM) secretion by fibroblasts to produce biomimetic scaffolds. Models have been developed for use in humans, such as skin and corneas. Ascorbic acid (vitamin C, AA) is essential for collagen biosynthesis. However, AA is chemically unstable in culture, with a half-life of 24 h, requiring freshly prepared AA with each change of medium. This study aims to demonstrate the functional equivalence of 2-phospho-L-ascorbate (2PAA), a stable form of AA, for tissue reconstruction. Dermal, vaginal, and bladder stroma were reconstructed by self-assembly using tissue-specific protocols. The tissues were cultured in a medium supplemented with either freshly prepared or frozen AA, or with 2PAA. Biochemical analyses were performed on the tissues to evaluate cell density and tissue composition, including collagen secretion and deposition. Histology and quantitative polarized light microscopy were used to evaluate tissue architecture, and mechanical evaluation was performed both by tensiometry and atomic force microscopy (AFM) to evaluate its macroscopic and cell-scale mechanical properties. The tissues produced by the three ascorbate conditions had similar collagen deposition, architecture, and mechanical properties in each organ-specific stroma. Mechanical characterization revealed tissue-specific differences, with tensile modulus values ranging from 1–5 MPa and AFM-derived apparent stiffness in the 1–2 kPa range, reflecting the nonlinear and scale-dependent behavior of the engineered stroma. The results demonstrate the possibility of substituting AA with 2PAA for tissue engineering. This protocol could significantly reduce the costs associated with tissue production by reducing preparation time and use of materials. This is a crucial factor for any scale-up activity. Full article

The One Health paradigm—recognizing the interconnected health of humans, animals, and the environment—promotes the development of sustainable technologies that enhance human health while minimizing ecological impact. In this context, bio-based hydrogels have emerged as a promising class of biomaterials for advanced medical applications. Produced through biotechnological methods such as genetic engineering and microbial fermentation, these hydrogels are composed of renewable and biocompatible materials, including recombinant collagen, elastin, silk fibroin, bacterial cellulose, xanthan gum, and hyaluronic acid. Their high water content, structural tunability, and biodegradability make them ideal candidates for various biomedical applications such as wound healing, tissue regeneration, and the design of extracellular matrix (ECM)-mimicking scaffolds. By offering controlled mechanical properties, biocompatibility, and the potential for minimally invasive administration, sustainable hydrogels represent a strategic innovation for regenerative medicine and therapeutic interventions. This review discusses the characteristics and medical applications of these hydrogels, highlighting their role in advancing sustainable healthcare solutions within the One Health framework. Full article