Search Results (1,759)

Background: Effective regenerative therapeutics for acute and chronic wounds remain a critical unmet need in biomedicine. Objectives: This study aimed to develop novel collagen–cerium oxide nanoparticle hydrogels designed to enhance cellular metabolism, proliferation, and antioxidant/antimutagenic activity, accelerating wound regeneration in vivo. Methods: Collagen–nanocerium composites were synthesized by combining a collagen extract with cerium oxide nanoparticles at defined concentrations. In vitro assays using human fibroblasts identified two formulations that enhanced proliferation and metabolic activity by 42–50%. FTIR spectroscopy confirmed chemical interactions within the composite matrix. Toxicity, antioxidant, and antigenotoxic effects were evaluated using Escherichia coli MG1655 lux-biosensors to assess their general toxicity, antioxidant and pro-oxidant activities, and antigenotoxic and promutagenic effects. In vivo efficacy was tested in Wistar rats with full-thickness skin wounds. Treated groups were compared to untreated controls and Dexpanthenol-treated positive controls. On days 3, 7, and 14, healing was assessed clinically, histologically, and morphometrically. Results: Biosensor analysis demonstrated non-toxicity and antigenotoxic activity of the nanocomposites, reduced DNA damage by up to 45%, providing 31–49% protection against H₂O₂ and 15–23% against O₂⁻ radicals. The animal study results demonstrated significantly accelerated healing with both nanocomposites versus control and comparison groups, evidenced by improved tissue regeneration, reduced inflammation, and increased fibroblast infiltration. Conclusions: The developed hydrogels exhibit promising pharmacological profiles, including antioxidant, antimutagenic, anti-inflammatory, and pro-regenerative effects validated across in vitro and in vivo models. Full article

Fabricating breast tumor models that mimic the natural breast tissue-like microenvironment (normal or cancerous) both physically and bio-metabolically, despite extended research, is still a challenge. A native-mimicking breast tumor model is the demand since complex biophysiological mechanisms in the native breast tissue hinder deciphering the root causes of cancer initiation and progression. Hydrogels, which mimic the natural extracellular matrix (ECM), are increasingly demanded for various biomedical applications, including tissue engineering and tumor modeling. Their biomimetic 3D network structures have demonstrated significant potential to enhance the breast tumor model, treatment, and recovery. Additionally, 3D tumor organoids cultivated within hydrogels maintain the physical and genetic traits of native tumors, offering valuable platforms for personalized medicine and therapy response evaluation. Hydrogels are broadly classified into static and dynamic hydrogels. Static hydrogels, however, are inert to external stimuli and do not actively participate in biological processes or provide scaffolding systems. Dynamic hydrogels, on the other hand, adapt and respond to the surrounding microenvironment or even create new microenvironments according to physiological cues. Dynamic hydrogels typically involve reversible molecular interactions—through covalent or non-covalent bonds—enabling the fabrication of hydrogels tailored to meet the mechanical and physiological properties of target tissues. Although both static and dynamic hydrogels can be advanced by incorporating active nanomaterials, their combinations with dynamic hydrogels provide enhanced functionalities compared to static hydrogels. Further, engineered hydrogels with adipogenic and angiogenic properties support tissue integration and regeneration. Hydrogels also serve as efficient delivery systems for chemotherapeutic and immunotherapeutic agents, enabling localized, sustained release at tumor sites. This approach enhances therapeutic efficacy while minimizing systemic side effects, supporting ongoing research into hydrogel-based breast cancer therapies and reconstructive solutions. This review summarizes the roles of dynamic hydrogels in breast tumor models. Furthermore, this paper discusses the advantages of integrating nanoparticles with dynamic hydrogels for drug delivery, cancer treatment, and other biomedical applications, alongside the challenges and future perspectives. Full article

Periodontitis, a prevalent chronic infectious disease triggered by oral biofilm microbiota, results in progressive destruction of periodontal supporting tissues, and conventional treatments have limited therapeutic effects on it. Hydrogels, due to their excellent biocompatibility, three-dimensional extracellular matrix-like structure, and localized sustained-release properties, can provide support for cell attachment, promote cell proliferation and differentiation, and improve drug utilization efficiency, showing great promise for applications in treating periodontitis as well as promoting periodontal tissue regeneration. This article first introduces the limitations of current periodontitis treatments and the unique advantages of hydrogels in periodontitis treatment and periodontal tissue regeneration, and then provides an overview of the classifications of hydrogels, the active substances they can load, and the characteristics and functions of these active substances. Subsequently, the article introduces the latest advances in the application of several common natural polymer hydrogels in periodontal tissue regeneration. Finally, the article discusses the current limitations of hydrogels in terms of structure and properties, and proposes potential solutions and future development directions in periodontal tissue regeneration. Full article

Tenascin-C (TNC) is a complex extracellular matrix (ECM) protein that plays a critical role in regulating cellular adhesion, motility, proliferation, and inflammation through its interaction with Toll-like receptor 4 (TLR4) and other receptors. The upregulation of TNC is associated with inflammatory responses, autoimmune disorders, and neoplastic conditions during both physiological and pathological tissue remodeling. In the central nervous system (CNS), TNC contributes to neuroinflammatory processes by modulating the function of immune cells and the secretion of pro-inflammatory mediators, thereby playing a pivotal role in the initiation and progression of neuroinflammatory diseases. TNC is expressed in astrocytes, neural progenitor cells, and various neuronal populations within both developing and mature CNS regions. It regulates neuronal migration and axonal guidance during neurogenesis, facilitating synaptic plasticity and CNS regeneration. Furthermore, TNC enhances neuroplasticity through interactions with receptor families, such as integrins, to establish the molecular connections necessary for cell communication and signal transduction. This review investigates the mechanistic properties of TNC, focusing on its spatiotemporal expression, molecular interactions with receptors, and its role in neurological disorders, in addition to its modulatory capacity in neuroplastic processes. Additionally, this review delves into recent research advancements with respect to neuroinflammation involving TNC, along with therapeutic strategies targeting TNC. Full article

In the early 1990s, the decline of textile manufacturing due to various factors resulted in the abandonment of industrial sites previously utilized in Yazd. This study examines the regeneration of industrial heritage through place branding in a developing country, utilizing a case study approach. The objective is to design a framework for the development of a branding strategy aimed at the regeneration of industrial heritage sites in Yazd. By integrating both quantitative and qualitative methodologies, this study utilizes SWOT analysis through focus group discussions in conjunction with the Delphi method. Furthermore, in the strategy development process, the expert panel technique is employed to formulate Weihrich’s TOWS matrix. The findings indicate that the risk of textile heritage sites remaining unknown to tourists, as well as the potential for enhancing the identity of Yazd, received the highest mean scores. In contrast, the results indicate that the lowest mean scores were associated with the factors of multiple non-official brands in Yazd and the presence of basic tourist infrastructure. This study presents a comprehensive framework for the integration of place branding into industrial heritage regeneration initiatives, grounded in original empirical data, and offers valuable insights for policymakers, heritage managers, and urban planners. Full article

Alginate-hydroxyapatite (AL) scaffolds modified with fibronectin (FN) or bioactive glass (BGMS10) have recently been characterized for their physicochemical properties and proposed as promising candidates for bone regeneration. Here, we present their first systematic biological evaluation, focusing on adhesion, proliferation, osteogenic differentiation, and in vivo host response. We compared FN-, BG-, and unmodified AL scaffolds using an immortalized mesenchymal stromal cell line (M-SOD) and primary human bone marrow-derived (BM-MSCs) and adipose-derived stromal cells (ASCs). FN scaffolds enhanced initial adhesion across all cell types and supported proliferation in M-SODs, but primary BM-MSCs and ASCs showed minimal expansion, regardless of scaffold type. BG scaffolds promoted expression of late-stage osteogenic markers in BM-MSCs, consistent with their ion release profile, but had limited impact on ASCs. In vivo subcutaneous implantation of acellular scaffolds in nude mice revealed robust host cell infiltration and extracellular matrix deposition across all scaffold types, confirming biocompatibility and integration. However, vascularization remained limited and did not differ substantially between formulations. Together, these findings highlight a critical discrepancy between immortalized and primary stromal cell responses to scaffold cues, underscoring the choice of cell source when evaluating the biocompatibility of a novel scaffold. At the same time, the effective in vivo integration observed across scaffold types emphasizes the importance of host tissue responses for translational evaluation of functional biomaterials. Full article

Fluoroquinolones, one of the most frequently used antibiotics, despite their wide spectrum of beneficial activity, are linked to serious adverse effects such as tendinopathies. Tendon injuries connected to the use of the group of drugs frequently affect the Achilles tendon—an anatomical structure, crucial to the proper mobility of lower limb, that is made of collagen fibers and extracellular matrix (ECM). Fluoroquinolones derive and decrease collagen and proteoglycans synthesis; they also disturb tendon regeneration by downregulating activity of metalloproteinases, enzymes essential for the proper collagen remodeling, especially after injuries. The exact way in which fluoroquinolones affect all these processes is not clearly known. However, some studies present that the chemical properties of fluorine such as electronegativity and ability to chelate di- and trivalent metal ions are one of the possible explanations for the problem. Our review summarizes various concepts of fluoroquinolones’ impact on the Achilles tendon structure, particularly collagen type I. What is more, it emphasizes the risk factors for more frequent Achilles tendon damage and presents the potential preventive strategies associated with the usage of the antioxidants. Full article

Intervertebral disc degeneration is a leading cause of chronic back pain, with existing treatments focusing on symptom management rather than true tissue repair. Cellular therapies—such as platelet-rich plasma (PRP), autologous chondrocytes, and mesenchymal stem cells (MSCs)—have emerged as promising strategies for disc regeneration. In this study, fifteen New Zealand white rabbits underwent fluoroscopy-guided needle puncture of the L4-L5 discs and were allocated to receive PRP alone, PRP-chondrocytes, or PRP-MSCs eight weeks later, while the L3-L4 disc served as a healthy internal control. At 16 weeks post-injury, histological scoring revealed significant improvements in annular integrity, cellularity, and matrix composition in all treated groups compared with untreated lesions, with the greatest gains observed in the PRP-chondrocytes arm, intermediate effects with PRP-MSCs, and more modest changes with PRP alone. Complementary RT-qPCR analysis of COL2A1 and COL10A1 expression confirmed a shift toward a more regenerative phenotype, marked by enhanced COL2A1 and reduced COL10A1 levels, which was most pronounced in the PRP-chondrocytes arm. Despite these advances, none of the interventions fully restored the healthy disc architecture, underscoring the complexity of disc repair. These findings support the potential of combining PRP with chondrocytes or MSCs for intervertebral disc regeneration and demonstrate the need for further optimization of cell doses, PRP formulations, and delivery protocols before clinical translation. Full article

Impaired bone regeneration and wound healing represent a major clinical and socioeconomic challenge for our aging and multimorbid population. Fracture and wound healing share many common features, with transforming growth factor beta (TGF-β) being a key regulator of inflammation, angiogenesis, fibroblast activation, and matrix remodeling. The dysregulation of TGF-β signaling is a hallmark of chronic wounds, excessive scar formation, and fracture non-union. Extracellular matrix protein 1 (ECM1) plays a crucial role in the activation of latent TGF-β. As a protein of the extracellular matrix, ECM1 offers ideal conditions for the biofunctionalization of bone implants or wound patches. Its mode of action has been studied mainly in fibrosis models of the liver or heart, where TGF-β acts as a driver of the disease. The controlled knock-out or overexpression of ECM1 either promoted or improved fibrosis development. In this review, we discuss how these findings can be applied to the biofunctionalization of implants to support bone and wound healing, considering the impact of TGF-β on the different healing phases. Full article

Background/Objectives: Osteoarthritis (OA) is a prevalent age-related degenerative joint disease causing cartilage damage, leading to a debilitating lifestyle. However, there are currently no drugs on the market that promote cartilage repair, and advanced cases often require arthroplasty. Increasing evidence suggests that exosomes, the smallest extracellular vesicles (30–150 nm) secreted by all cell types, are involved in the pathological process of OA and play a crucial and complex role in its progression. This review aims to provide in-depth insights into exosome biology, isolation techniques, their role in OA pathophysiology, and their clinical therapeutic potential. Methods: We systematically reviewed studies published since 2020 on exosomes in OA, focusing on their biological properties, isolation techniques, pathological roles, and therapeutic applications. Results: Exosomes derived from synovial fluid, chondrocytes, synoviocytes, and mesenchymal stem cells regulate key processes in OA progression, including inflammation, apoptosis, extracellular matrix degradation, and regeneration. Various cell-derived exosomes show therapeutic potential for cartilage damage/OA. However, their mechanisms of action have not been fully investigated. Moreover, emerging methodologies, such as utilizing novel materials for exosome delivery, potentially facilitate the development of more effective and personalized therapeutic interventions. Conclusions: Exosomes exert dual roles in OA pathogenesis and therapy. Although challenges remain regarding their sources, dosage, delivery, and standardization, exosome-based strategies represent a promising cell-free therapeutic approach with potential applications in personalized and precision medicine. Full article

As life expectancy continues to increase, age-related disorders are becoming more prevalent. Among these, vascular complications resulting from chronic inflammation are particularly concerning, as they impair angiogenesis and hinder tissue repair, both processes that heavily rely on a well-structured extracellular matrix (ECM). In this context, MicroMatrix^® UBM Particulate, a skin substitute composed of collagen, laminin, and proteoglycans, appears to offer properties conducive to tissue regeneration. The aim of this study was to evaluate the regenerative potential of MicroMatrix^® combined with the Secretome of human Dental Pulp Stem Cells (hDPSC-S), using the medicinal leech Hirudo verbana, a well-established model for studying wound healing, angiogenesis, and tissue regeneration. Adult leeches were injected with MicroMatrix^® either suspended in FBS-free medium (CTRL) or supplemented with hDPSC-S. 1-week post-treatment, the animals were sacrificed and subjected to morphological and immunohistochemical analyses. Our findings revealed that MicroMatrix^® successfully integrated into the leech body wall. Notably, when supplemented with hDPSC-S, there was a marked increase in cell infiltration, including telocytes and Hematopoietic Precursor Stem Cells, along with a significantly higher vessel density compared to CTRL. These results support the effectiveness of the cell-free device composed of MicroMatrix^® and hDPSC-S, highlighting its potential as a promising strategy for regenerative therapies aimed at treating complex wounds with poor vascularization. Full article

Peptides are widely used in cosmetic formulations to stimulate extracellular matrix (ECM) synthesis, while silybin (a flavonolignan from Silybum marianum) offers retinol-like benefits through antioxidant and photoprotective activity. This study evaluated a novel anti-aging cream combining seven bioactive peptides with silybin to assess synergistic effects on ECM regeneration and clinical skin rejuvenation. In vitro assays in human dermal fibroblasts and keratinocytes revealed that the formulation rapidly upregulated gene and protein expression of collagen types I, III, IV, and XVII and lysyl oxidase (LOX) within 4–16 h. Ex-vivo, ultraviolet (UV)-damaged skin explants treated with the peptide–silybin complex showed enhanced recovery of collagen, elastic fibers, and LOX versus untreated controls. A 56-day clinical study (n = 31) demonstrated significant improvements in wrinkle area and volume, elasticity (+12.5%), firmness (+20.7%), and dermal density (+78%, all p < 0.001). No adverse effects were reported, and over 80% of participants noted improved skin texture and firmness. These findings highlight a novel synergy between peptides and silybin, with rapid ECM activation and clinical efficacy. To our knowledge, this is the first evidence of a cosmetic peptide formulation significantly upregulating LOX expression, suggesting a new mechanism for strengthening dermal architecture and improving skin resilience. Future studies should elucidate the mechanisms underlying these effects and assess whether other botanicals confer complementary benefits when combined with peptide blends. Full article

Background: The treatment of wounds remains a significant clinical challenge, particularly in chronic and infected wounds, where delayed healing often results in complications. Recent advances in biomaterials have highlighted the potential of polymer-based scaffolds as promising platforms for wound management due to their ability to mimic the extracellular matrix, support tissue regeneration, and provide a moist environment conducive to healing. Objectives: This review aims to provide a comprehensive overview of the recent progress in the design and application of polymer-based scaffolds loaded with essential oil (EO) components, emphasizing their role in promoting effective wound healing. Methods: Relevant literature on polymeric scaffolds and EO-based bioactive agents was systematically reviewed, focusing on studies that investigated the biological activities, fabrication techniques, and therapeutic performance of EO-loaded scaffolds in wound management. Results: Findings from recent studies indicate that EO components, particularly monoterpenoids such as thymol, carvacrol, and eugenol, exhibit remarkable antimicrobial, anti-inflammatory, antioxidant, and analgesic properties that accelerate wound healing. When incorporated into polymer matrices, these components enhance scaffold biocompatibility, antimicrobial efficacy, and tissue regeneration capacity through synergistic interactions. Conclusions: The integration of essential oil components into polymeric scaffolds represents a promising strategy for developing multifunctional wound dressings. Such systems combine the structural advantages of polymers with the therapeutic benefits of EOs, offering an effective platform for accelerating healing and preventing wound infections. Full article

Hydrogel scaffolds have emerged as pivotal materials in regenerative medicine due to their biocompatibility, tunable mechanical properties, and ability to mimic the extracellular matrix. However, conventional fabrication techniques often lack the precision required to create complex architectures, limiting their effectiveness in tissue engineering. This review explores advanced laser-based fabrication methods, such as two-photon polymerization, laser-induced forward transfer, selective laser sintering/melting, and laser direct writing, which offer unparalleled resolution and control over scaffold geometry. These techniques enable the production of intricate 3D structures tailored to specific clinical needs, from vascular networks to patient-specific implants. We analyze the principles, advantages, and limitations of each method, highlighting their biomedical applications and the challenges of scalability, material compatibility, and cost. By bridging the gap between laboratory research and clinical implementation, laser-based technologies hold significant promise for advancing personalized medicine and tissue regeneration. Full article

Background/Objectives: Gingival tissue deficiencies present significant treatment challenges. We investigated three xenogeneic collagen scaffolds—Fibro-Gide, FibroMATRIX, and Mucoderm—with and without human gingival MSCs for soft tissue augmentation. Methods: The study assessed scaffold properties (mechanical properties and micro-CT structure), cytocompatibility, ex vivo vascular growth stimulation (CAM-test), and in vivo effects in rabbit model. Results: All scaffolds were cytocompatible and maintained MSC viability via extract and contact cytotoxicity tests. Fibro-Gide showed the highest porosity at 78.5%, followed by FibroMATRIX at 64.3%, while Mucoderm had the lowest porosity at 33.2%. Mucoderm exhibited the greatest stiffness due to its dense structure, contrasting with the more similar mechanical properties of Fibro-Gide and FibroMATRIX. In an ex vivo HET-Cam model of the angiogenic response, Fibro-Gide exhibited reduced blood vessel length and blood flow rate compared to FibroMATRIX and Mucoderm. In vivo, Mucoderm resorbed completely, FibroMATRIX demonstrated optimal partial degradation, and Fibro-Gide retained most of its collagen structure. Conclusions: The FibroMATRIX with MSCs combination showed particularly promising results for enhancing tissue thickness and vascularization, suggesting this approach could significantly improve gingival regeneration outcomes. Full article