Search Results (187)

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

Type I collagen is a major protein in animals, and its hydrolyzed products, collagen peptides, have wide-ranging applications. This article reviews collagen peptides’ preparation methods, biological activities, and application progress in the fields of food, cosmetics, and medicine. By employing various extraction and hydrolysis methods, collagen peptides with different molecular weights can be obtained, and their biological activities are closely related to their molecular weight and amino acid sequence. Studies have revealed that collagen peptides possess a variety of biological activities, including antioxidant, hematopoietic promotion, osteogenic differentiation promotion, antihypertensive, and anti-diabetic effects. In the food industry, their antioxidant and hypoglycemic properties have opened new avenues for the development of healthy foods; in the cosmetics field, the moisturizing, anti-aging, and repair functions of collagen peptides are favored by consumers; in the medical field, collagen peptides are used in wound dressings, drug carriers, and tissue engineering scaffolds. Looking to the future, the development of green and efficient preparation technologies for collagen peptides and in-depth research into the relationship between their structure and function will be important research directions. The multifunctional properties of collagen peptides provide a broad prospect for their further application in the health industry. Full article

Since the mid-19th century, researchers have explored the potential of bio-based polymeric materials for diverse applications, with particular promise in medicine. This review provides a focused and detailed examination of natural and synthetic biopolymers relevant to tissue engineering and biomedical applications. It emphasizes the structural diversity, functional characteristics, and processing strategies of major classes of biopolymers, including polysaccharides (e.g., hyaluronic acid, alginate, chitosan, bacterial cellulose) and proteins (e.g., collagen, silk fibroin, albumin), as well as synthetic biodegradable polymers such as polycaprolactone, polylactic acid, and polyhydroxybutyrate. The central aim of this manuscript is to elucidate how intrinsic properties—such as molecular weight, crystallinity, water retention, and bioactivity—affect the performance of biopolymers in biomedical contexts, particularly in drug delivery, wound healing, and scaffold-based tissue regeneration. This review also highlights recent advancements in polymer functionalization, composite formation, and fabrication techniques (e.g., electrospinning, bioprinting), which have expanded the application potential of these materials. By offering a comparative analysis of structure–property–function relationships across a diverse range of biopolymers, this review provides a comprehensive reference for selecting and engineering materials tailored to specific biomedical challenges. It also identifies key limitations, such as production scalability and mechanical performance, and suggests future directions for developing clinically viable and environmentally sustainable biomaterial platforms. 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

Background/Objectives: Although the nanocomposite of poly(L-lactic acid) with graphene oxide (PLLA-GO) shows promise for tissue engineering, its specific bioactive interactions with diverse cell lineages during early tissue regeneration remain unclear. This study comprehensively investigated the in vitro multifaceted biocompatibility of PLLA-GO using human fibroblasts (FN1 cells), murine mesenchymal stem cells (mBMSCs), and human umbilical vein endothelial cells (HUVECs). Methods: Morphological analyses were performed using optical and scanning electron microscopy, while proliferation dynamics were assessed via CFSE staining. Cell cycle progression was evaluated using flow cytometry, mitochondrial activity was examined through TMRE staining, and inflammatory cytokine profiling was performed via Cytometric Bead Array (CBA). Results: PLLA-GO exhibited primary biocompatibility across all evaluated cell lines, characterized by efficient adhesion and proliferation. However, significant cell-type-dependent modulations were observed. The FN1 cells exhibited proliferative adaptation but induced accelerated scaffold degradation, as evidenced by a substantial increase in cellular debris (5.93% control vs. 34.38% PLLA-GO; p = 0.03). mBMSCs showed a transient initial proliferative response and a significant 21.66% increase in TNF-α production (179.67 pg/mL vs. 147.68 pg/mL in control; p = 0.03). HUVECs demonstrated heightened mitochondrial sensitivity, exhibiting a 32.19% reduction in mitochondrial electrical potential (97.07% control vs. 65.82% PLLA-GO; p ≤ 0.05), alongside reductions in pro-inflammatory cytokines TNF-α (8.73%) and IL-6 (12.47%). Conclusions: The PLLA-GO processing method is crucial for its properties and subsequent cellular interactions. Therefore, rigorous and specific preclinical evaluations—considering both cellular contexts and fabrication—are indispensable to ensure the safety and therapeutic potential of PLLA-GO in tissue engineering and regenerative medicine. Full article

Cell technologies have provided promising tools for modulating the properties of multipotent mesenchymal stem/stromal cells (MSCs) to meet the needs of cell therapy as well as tissue engineering and regenerative medicine (TERM). Ex vivo preconditioning is directed at enhancing the engraftment of MSCs and activating their secretory activity, primarily the production of soluble mediators. The present review aims to highlight the underestimated effect of the most accepted preconditioning approaches on the modification of the important set of insoluble molecules secreted by MSCs into extracellular space—the extracellular matrix (ECM). A thorough review of the published literature was performed, with particular emphasis on ECM-related data. The analysis of data on ECM changes showed that most of the applied preconditioning methods—hypoxia, inflammatory priming, pharmacological agents, 3D culture, and scaffolds—generally stimulate ECM production, increase the deposition of growth factors, promote alignment, and increase ECM stiffness. There are already preliminary results demonstrating the successful application of preconditioned ECM for promoting angiogenesis, targeted stromal lineage differentiation, and other therapeutic goals. The prospects for further research in this area are discussed. Full article

Secondary osteonecrosis (ON) is a common complication in paediatric cancer survivors. Combining multipotent mesenchymal stromal cells (MSCs) with core decompression surgery halts disease progression and stimulates bone regeneration. However, the success of advanced therapy medicinal products (ATMPs) requires versatile “off-the-shelf” tissue engineering products (TEPs). This study evaluated the safety and efficacy of TEPs loaded with allogeneic MSCs from Wharton’s jelly (WJ-MSCs) in a large-animal model of bone regeneration to support a paediatric investigational plan for ON patients. WJ-MSC-laden fibrin-based hydrogels combined with a synthetic bone substitute (PRO-DENSE^TM) were tested in 16 juvenile sheep (8 males and 8 females) distributed in four experimental groups. Each animal received four cylindrical bone defects in the femoral and tibial epiphyses and was assessed at 6 and 12 weeks. Safety was confirmed, and bone regeneration was observed across all groups. A combination of WJ-MSCs with PRO-DENSE^TM led to improved histological scores, osteogenesis, and construct integration. Trabecular bone volume also increased more in cellular groups over time. However, effects were inconsistent across groups, reflecting the variability seen in clinical trials and highlighting the significant impact of factors such as immunogenetic compatibility, MSC batch potency, and interaction with the recipient’s microenvironment on the therapeutic effectiveness and successful clinical translation of allogeneic ATMPs. Full article

The ester of caffeic acid with α-hydroxydihydrocaffeic acid, named rosmarinic acid (α-o-caffeoyl-3,4-dihydroxyphenyllactic acid; RA) can occur as oligomeric molecules, or in free, esterified, and glycosidic forms. Although it is commonly found among the members of the plants from the Lamiaceae (mints) and Boraginaceae (borages) families, only certain plant species produce a comparatively high concentration of RA. This valuable bioactive compound exhibits anti-cancer, anti-angiogenic, antioxidant, anti-inflammatory, antiviral, and antimicrobial properties, among others. As it is difficult to obtain high quantities of RA from natural sources, and since chemical manufacturing is costly and challenging, various biotechnological methods have recently been investigated to boost RA production. Plant cell tissue culture has been used to promote RA production in various plant species, particularly medicinal ones, with elicitation being the most commonly used technique. This review explores the main steps involved in RA biosynthesis in plants, including the molecular mechanisms and physiological alterations underlying its function, along with the primary mechanisms of RA accumulation in response to elicitation. Recent progress in synthetic biology-based RA synthesis, as well as metabolic engineering techniques to enhance the industrial production of this valuable bioactive constituent, are also discussed. Full article

Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan widely recognised for its biocompatibility, biodegradability, and unique viscoelastic properties. Its structural versatility enables the formation of hydrogels with tuneable physicochemical characteristics, making it a valuable biomaterial in drug delivery and regenerative medicine. This review outlines HA properties, gel-forming approaches, and modern medicine and bioengineering applications. It provides a comprehensive overview of advances in HA production strategies, including microbial fermentation, animal tissue extraction, and production in vitro. Particular attention is given to gel-forming mechanisms, emphasising physical and chemical crosslinking methods like carbodiimide crosslinking, radical polymerisation, and enzymatic crosslinking. Advances in HA-based drug delivery systems and applications of HA-based materials in tissue engineering are also discussed, focusing on HA-based hydrogels with conjugates and combinations with compounds like collagen, alginate, and chitosan. Full article

Ginger (Zingiber officinale Roscoe), valued both for its medicinal and culinary uses, can be adversely affected by abiotic stresses such as high temperature and drought, which can impact its growth and development. The HSP90 gene family has been recognized as a crucial element for enhancing heat and drought resistance in plants. Nevertheless, no studies have yet reported on the HSP90 gene family in ginger. This study investigates the HSP90 gene family in ginger and its crucial role in the plant’s responses to abiotic stresses. A total of 11 ZoHSP90 members were identified in the ginger genome, and these genes were unevenly distributed across five chromosomes. Bioinformatics analyses revealed that the HSP90 proteins in ginger vary in size, ranging from 306 to 886 amino acids. These proteins are predominantly located in the cytoplasm, endoplasmic reticulum, and mitochondria. Notably, ten conserved motifs were identified, with variations in motif distribution correlating with phylogenetic relationships among the genes. Furthermore, the gene structure analysis indicated differences in exon numbers, which may reflect specialized regulatory mechanisms and functional differentiation among the ZoHSP90 genes. Cis-acting elements within the promoter regions of the ZoHSP90 genes were identified, and their involvement in stress responses and hormonal signaling pathways was revealed. These elements are critical for regulating gene expression patterns in response to environmental stimuli, such as methyl jasmonate, salicylic acid, and abscisic acid. The presence of these elements indicates that ZoHSP90 genes play significant regulatory roles in plant adaptation to environmental changes. Expression profiling of the ZoHSP90 genes under various abiotic stress conditions demonstrated tissue specificity and dynamic regulation. Different ZoHSP90 genes exhibited distinct expression patterns in response to low-temperature, drought, high-temperature, and salt stresses. This suggests that the HSP90 gene family in ginger possesses both conserved functions and species-specific adaptations to optimize stress responses. Overall, this research provides valuable insights into the molecular functions of the HSP90 gene family in ginger and lays the groundwork for future studies aimed at enhancing crop resilience through genetic engineering. The findings contribute to a deeper understanding of plant adaptability to environmental stressors, which is crucial for improving agricultural productivity in the face of climate change. Full article

Carbon nanomaterials that include different forms such as graphene, carbon nanotubes, fullerenes, graphite, nanodiamonds, carbon nanocones, amorphous carbon, as well as porous carbon, are quite distinguished by their unique structural, electrical, and mechanical properties. This plays a major role in making them pivotal in various medical applications. The synthesis methods used for such nanomaterials, including techniques such as chemical vapor deposition (CVD), arc discharge, laser ablation, and plasma-enhanced chemical vapor deposition (PECVD), are able to offer very precise control over material purity, particle size, and scalability, enabling for nanomaterials catered for different specific applications. These materials have been explored in a range of different systems, which include drug-delivery systems, biosensors, tissue engineering, as well as advanced imaging techniques such as MRI and fluorescence imaging. Recent advancements, including green synthesis strategies and novel innovative approaches like ultrasonic cavitation, have improved both the precision as well as the scalability of carbon nanomaterial production. Despite challenges like biocompatibility and environmental concerns, these nanomaterials hold immense promise in revolutionizing personalized medicine, diagnostics, and regenerative therapies. Many of these applications are currently positioned at Technology Readiness Levels (TRLs) 3–4, with some systems advancing toward preclinical validation, highlighting their emerging translational potential in clinical settings. This review is specific in evaluating synthesis techniques of different carbon nanomaterials and establishing their modified properties for use in biomedicine. It focuses on how these techniques establish biocompatibility, scalability, and performance for use in medicines such as drug delivery, imaging, and tissue engineering. The implications of nanostructure behavior in biological environments are further discussed, with emphasis on applications in imaging, drug delivery, and biosensing. Full article

The mammary gland is a modified sweat gland responsible for milk production. It is affected by diseases that reduce animals’ quality of life, consequently leading to economic losses in livestock. With advancements in tissue bioengineering and regenerative medicine, studying the extracellular matrix (ECM) of the bovine mammary gland can improve our understanding of its physiology and the processes that affect it. This knowledge could also enable the development of sustainable therapeutic alternatives for both the dairy production chain and human oncology research. A common approach in regenerative medicine is decellularization, a process that removes all cells from tissue while preserving its architecture and ECM components for subsequent recellularization. The success of recellularization depends on obtaining immunologically compatible scaffolds and using appropriate cell culture sources and methods to ensure tissue functionality. However, tissue culture technology still faces challenges due to specific requirements and high costs. Here, we review the literature on biomaterials and tissue engineering, providing an overview of the ECM of the bovine mammary gland and advances in its bioengineering, with a focus on regenerative medicine for bovine species. The methodology employed consists of a structured search of scientific databases, including PubMed, Google Scholar, and SciELO, using specific keywords related to tissue engineering and the bovine mammary gland. The selection criteria prioritized peer-reviewed articles published between 2002 and 2025 that demonstrated scientific relevance and contributed to the understanding of bovine mammary gland bioengineering. Although research on this topic has advanced, vascularization, tissue maturation, and scalability remain key barriers to widespread application and economic viability. Full article

Digital light processing (DLP) technology stands out as a groundbreaking method in the field of biomedical engineering that enables the production of highly precise structures using photopolymerizable materials. Smart materials such as shape memory polymers, hydrogels, and nanocomposites are used as ideal materials for personalized medicine applications thanks to their properties such as superior mechanical strength, biocompatibility, and sensitivity to environmental stimuli in DLP technology. The integration of these materials with DLP enables the production of functional and complex structures, especially in areas such as bone and soft tissue engineering, drug delivery, and biosensor production. However, limited material diversity, scalability problems in production processes, and technical difficulties in optimizing bioprinting parameters are among the main obstacles in this field. This study systematically examines the role of smart biomaterials in DLP-based bioprinting processes. It addresses the innovative applications of these materials in tissue engineering and regenerative medicine. It also comprehensively evaluates its contributions to biomedical applications and discusses future research areas to overcome current limitations. Full article

Aloe Vera (Aloe barbadensis Miller), a historically revered medicinal plant, has garnered great scientific attention due to its polysaccharide-rich bioactive compounds with significant therapeutic potential. This review examines the role of Aloe Vera polysaccharides as therapeutic agents in biomedical applications, highlighting their benefits as well as the risks. Traditionally recognized for its anti-inflammatory and antimicrobial effects, which are very important in wound healing, the Aloe Vera relies on its polysaccharides, which confer immunomodulatory, antioxidant, and tissue-regenerative properties. These compounds have shown promise in various applications, including skin repair, tissue engineering scaffolds, and antiviral therapies, with their delivery being facilitated via gels, thin films, or oral formulations. This review explores also their mechanisms of action and applications in modern medicine, including in the development of topical gels, dietary supplements, and innovative delivery systems such as thin films and scaffolds. Despite the promising benefits, the review addresses the possible side effects too, including allergic reactions, gastrointestinal disorders, and drug interactions, emphasizing the importance of understanding these risks for their safe clinical use. Assessing both the advantages and challenges of Aloe Vera polysaccharide medical use, this review contributes to the ongoing dialog regarding the integration of natural products into therapeutic practices, ultimately supporting informed decisions regarding their clinical application. Full article

Hydrogel particles are essential in biological applications because of their distinctive capacity to retain water and encapsulate active molecules within their three-dimensional structure. Typical particle sizes range from nanometers (10–500 nm) to micrometers (1–500 µm), depending on the specific application and method of preparation. These characteristics render them optimal carriers for the administration of active compounds, facilitating the regulated and prolonged release of pharmaceuticals, including anticancer agents, antibiotics, and therapeutic proteins. Hydrogel particles can exhibit various morphologies, including spherical, rod-shaped, disk-shaped, and core–shell structures. Each shape offers distinct advantages, such as improved circulation time, targeted drug delivery, or enhanced cellular uptake. Additionally, hydrogel particles can be engineered to respond to various stimuli, such as temperature, pH, light, magnetic fields, and biochemical signals. Furthermore, their biocompatibility and capacity to acclimate to many biological conditions make them appropriate for sophisticated applications, including gene treatments, tissue regeneration, and cell therapies. Microfluidics has transformed the creation of hydrogel particles, providing precise control over their dimensions, morphology, and stability. This technique facilitates reproducible and highly efficient production, reducing reagent waste and optimizing drug encapsulation. The integration of microfluidics with hydrogels provides opportunities for the advancement of creative and effective solutions in contemporary medicine. Full article