Search Results (563)

Poor vascularization is one of the basic obstacles to the regeneration of functioning tissues because an oxygen diffusion process and elimination of wastes are essential in preserving the grafts. Recently, biomaterials have allowed the invention of bioinspired polymer scaffolds and replicated the natural extracellular matrix (ECM) due to the mechanical tunability of the synthetic polymers with the biological signals of natural macromolecules. The review uses a mechanistic analysis of the strategies to improve angiogenesis by using surface topography modification, bioactive peptide incorporation and pre-vascularization. Another way to achieve complex, perfusable topologies is by using more sophisticated methods of fabrication, such as electrospinning, 3D/4D bioprinting, or microfluidics. Based on in vitro and in vivo results, we determine angiogenic effectiveness by using cellular assays and animal transfers, pointing towards the translational advances in patents and clinical uses of bone, cardiac, nervous, and skin tissues. In spite of the substantial improvements, large-scale production and high demands of the regulations still exist. The future directions include the incorporation of bioinspired designs and intelligent materials, nanotechnology, and AI-based optimization into developing patient-specific and adaptive scaffolds. The following innovations herald the advent of highly effective constructs that can be used to regenerate tissue and overcome the limitations of present tissue engineering therapies through the introduction of highly effective, vascularized constructs. Full article

The strategic recycling of fish processing byproducts as functional materials has attracted increasing attention for sustainable development and human health. In this study, we investigated the dermatological impact of chum salmon (Oncorhynchus keta) byproduct enzyme hydrolysates (OKPE) administered as a dietary supplement in mice. After eight weeks of OKPE administration, epidermal integrity was improved, as evidenced by a significant attenuation of transepidermal water loss (TEWL). These phenotypic improvements were associated with the regulation of aquaporin-mediated water transport, hyaluronan metabolism, and epidermal differentiation programs. Furthermore, OKPE intake promoted accelerated collagen biosynthesis. Amino acid profiling revealed that OKPE is uniquely enriched in residues essential for both natural moisturizing factor (NMF) synthesis and collagenous scaffold formation. Collectively, these findings suggest that OKPE has potential as a functional food ingredient for reinforcing the skin barrier and improving skin hydration. Full article

Hydrogel scaffolds have emerged as a central platform in tissue engineering due to their ability to mimic the extracellular matrix and support cellular functions. Among natural polymers, chitin and its derivative chitosan have emerged as valuable candidates for hydrogel scaffold development because of their biodegradability, compatibility with living tissues, and inherent biological functionality; however, their distinct and complementary roles in hydrogel scaffold design are often insufficiently differentiated in the literature. This review provides a comprehensive and mechanism-driven analysis of chitin- and chitosan-based hydrogel scaffolds, emphasising how their molecular structure governs network formation, mechanical performance, and biological functionality. Chitin is highlighted primarily as a structurally robust and crystalline component suitable for reinforcement. In contrast, chitosan serves as a versatile, soluble, and chemically reactive matrix enabling various crosslinking and functionalization strategies. Recent advances in physical, ionic, and covalent crosslinking as well as composite scaffold engineering, biofunctionalization, and emerging fabrication approaches such as injectable systems and three-dimensional bioprinting are systematically examined. The relationships between scaffold architecture, degradation behaviour, and cellular responses are discussed in key tissue engineering applications, including bone, cartilage, skin, and nerve regeneration. Importantly, this review introduces a unified structure–property–function framework that distinguishes the roles of chitin and chitosan within hydrogel systems and links crosslinking mechanisms to application-specific performance requirements, an aspect not comprehensively addressed in previous studies. Current challenges related to mechanical limitations, material variability, and clinical translation are critically evaluated, and future perspectives for the rational design of next-generation biomimetic hydrogel scaffolds are proposed. Full article

Chronic cutaneous wounds and traumatic skin injuries remain a major clinical challenge, characterized by dysregulated healing phases, high susceptibility to microbial infection, and suboptimal response to conventional therapies. Stem cell-derived exosomes (SC-Exos) have emerged as a paradigm-shifting, cell-free nanotherapeutic platform that harnesses the paracrine secretome of stem cells while avoiding the immunological and proliferative complications inherent to direct cell transplantation. Exosomes derived from diverse stem cell sources orchestrate multifactorial wound repair by modulating key cellular signaling cascades and transcriptomic programs that collectively regulate inflammation, angiogenesis, re-epithelialization, extracellular matrix (ECM) remodeling, and scar formation. Beyond their intrinsic regenerative capacity, SC Exos can be engineered using direct strategies (cargo loading, surface modification, biomaterial integration, and conjugation) and indirect approaches (genetic engineering, pretreatment, and preconditioning of parental cells), thereby enabling spatially controlled and temporally sustained exosome release at wound sites with enhanced bioavailability and therapeutic efficacy. In parallel, biomaterial-assisted delivery platforms, including hydrogels, scaffolds, and nanofibers, enhance exosome retention, stability, and controlled-release profiles within the wound microenvironment, thereby further potentiating tissue repair. This review provides a comprehensive overview of recent advances in SC Exos for wound healing and skin regeneration. We first summarize exosome biogenesis, molecular composition, and the distinctive characteristics of exosomes derived from different stem cell sources, along with preclinical evidence supporting their efficacy in cutaneous repair. We then critically examine exosome engineering strategies and biomaterial-integrated delivery systems that augment and fine-tune therapeutic outcomes. Finally, we discuss the current status of clinical trials of SC Exo-based therapies, key manufacturing and regulatory challenges, and future directions for translating these nanoscale, cell-free therapeutics into advanced, personalized wound management. Full article

Ultraviolet (UV) radiation is a main environmental factor responsible for skin damage, leading to oxidative stress, inflammation, and impairment of the skin barrier function. Furthermore, many components in sunscreen may accumulate in aquatic systems, causing environmental pollution. Therefore, the identification of novel natural bioactives that counteract these effects and can be useful as effective adjuvants in sunscreen formulations is of particular interest. Morin (1), a natural flavonoid, represents an attractive scaffold for modifications to enhance its biological activity. Herein, we aimed to investigate the effects of combining the flavonoid 1 and its derivative, morin semicarbazone (2), with the carotenoid fucoxanthin (FX) on UVB-exposed HaCaT keratinocytes. All compounds exhibited higher radical scavenging activity compared to Trolox. In this cell model, the phenolic–carotenoid combinations provided greater photoprotection than individual compounds, significantly enhancing cell viability and reducing necrosis, FX-2 emerged as the most potent combination, as evidenced by a marked reduction in reactive oxygen species (ROS) and malondialdehyde (MDA) levels, likely mediated through the activation of the nuclear factor erythroid 2-related factor 2/Heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Furthermore, the tested treatments exerted enhanced anti-inflammatory effects by significantly reducing interleukin-6 (IL-6), cyclooxygenase 2 (COX-2), and matrix metalloproteinase-9 (MMP-9) mediators, with FX-2 being the most active combination. In conclusion, our findings highlight the protective effects of the combinations of these phenolics with the carotenoid FX against UVB radiation and support their potential application as natural active ingredients in sunscreen formulations. Full article

The treatment of skin diseases remains a significant clinical challenge. Cellulose and its derivatives have emerged as research hotspots in skin-related applications due to their excellent biocompatibility, structural modifiability, and biomimetic properties. This review systematically summarizes the diverse construction forms of cellulose-based materials, including films, nanofibrous scaffolds, hydrogels, and aerogels, with a focus on smart responsive systems tailored to various microenvironmental conditions. Their application progresses in acute/chronic wound healing, bacterial infections, burns, scar prevention, immunomodulation, and smart wearable monitoring are highlighted. The underlying mechanisms involving anti-infection, pro-regeneration, microenvironment modulation, and sensing are analyzed, aiming to provide insights for further exploration of cellulose-based materials in skin disease therapy and even smart wearable devices. Full article

The fabrication of decellularized small intestinal submucosa (dSIS) requires a precise balance between effective cellular removal and the preservation of structural integrity. In this study, we compared four published dSIS protocols representing detergent-based, chaotropic-salt-based, and sequential ionic/alkaline–acidic strategies. Their performance was evaluated based on residual DNA, collagen preservation, surface ultrastructure, and mechanical properties. The best decellularization protocol demonstrated the lowest residual DNA levels, together with better collagen retention, scaffold architecture, and mechanical performance than the other methods tested. The selected decellularized scaffold was used in a murine acute wound model and showed good biocompatibility and integration with the surrounding tissue at 10 days after implantation. However, further extensive testing in murine models is essential before future scaling. Finally, this comparative study provides a practical framework for selecting dSIS preparation methods for skin repair applications. Full article

Cutaneous T-cell lymphoma (CTCL), primarily mycosis fungoides (MF) and Sézary syndrome (SS), has long been characterized as a neoplasm of mature memory T cells, based on monoclonal T-cell receptor (TCR) rearrangements and tissue-resident memory (TRM)/central memory (TCM) T-cell phenotypes. This review synthesizes converging population-genetic, multi-omic, and single-cell evidence to argue that this characterization is incomplete and that a progenitor-based model better accounts for the full spectrum of disease biology. We present evidence that initiating mutations arise in hematopoietic stem or early lymphoid progenitor survive thymic selection, and diversify after TCR assembly, resulting in branched evolution across both blood and skin. In SS, paired analyses reveal > 200 shared variants between CD34⁺ progenitors and Sézary cells, as well as signal-joint T-cell receptor excision circle (sjTREC) positivity, providing direct progenitor-level evidence. In MF, convergent signals, multiple malignant clonotypes per lesion, greater blood–skin than skin–skin clonotype overlap, and compartment-specific CNV subclones, implicate hematogenous seeding and reseeding. Population-scale lymphoid clonal hematopoiesis and lymphoid-pattern mosaic chromosomal alterations define a compatible antecedent state. Spatial single-cell atlases and trajectory analyses map site-conditioned programs in skin, including Th2-skewed cytokines, microbial responses, and UV signatures, that select and expand subclones and explain inter- and intra-patient heterogeneity. This framework reconciles mature immunophenotypes with upstream initiation and clarifies why compartment-focused therapies often reshape rather than eradicate disease. It yields testable predictions and actionable implications: trials should pair multicompartment cytoreduction with strategies that attenuate progenitor-derived reservoirs, restore immune balance, and repair skin barrier dysfunction. A progenitor-initiated, niche-adapted model provides a coherent scaffold for more durable control in CTCL. Full article

Solution electrospinning (SES) and melt electrowriting (MEW) are complementary fiber-based fabrication platforms extensively investigated in tissue engineering. SES generates fibers typically ranging from the nanometer to the low-micrometer scale, producing fibrous networks that mimic the native extracellular matrix (ECM) and support key cellular functions. MEW, by contrast, operates solvent-free and enables precise, layer-by-layer deposition of microfibers with well-controlled geometry, conferring the mechanical integrity and open-pore architecture that SES constructs inherently lack. Despite growing interest, the body of peer-reviewed literature reporting original hybrid SES–MEW fabrication and biological outcome data remains limited, with no comprehensive cross-tissue synthesis available to date. This narrative review examines the current state of SES–MEW hybrid strategies across five tissue engineering targets selected for their clinical relevance: skin, vascular grafts, bone, cartilage, cardiac valves, and skeletal muscle. For each application, the architectural rationale, the fabrication approach, and the in vitro and in vivo biological outcomes are discussed in an integrated manner, with attention to how the spatial organization of nano- and microfibers translates into tissue-specific functional responses. A comparative analysis across tissue types highlights both the versatility of hybrid constructs and their persistent limitations, including suture retention values that remain below clinically accepted thresholds in vascular applications, incomplete cellular infiltration through dense nanofibrous layers, and the absence of validated, reproducible scale-up protocols compatible with clinical-grade manufacturing. The review concludes by identifying the most critical open questions in the field, encompassing process standardization, regulatory classification, and the emerging role of machine learning in closed-loop MEW process optimization. This work aims to provide an evidence-based perspective on the current state of hybrid SES–MEW scaffold engineering and the key translational gaps limiting clinical application. Full article

Diabetic wounds are a common and severe complication of diabetes mellitus, characterized by delayed healing due to persistent inflammation, impaired angiogenesis, and cellular dysfunction. Conventional therapeutic approaches remain limited in efficacy. In recent years, exosomes have attracted considerable attention in wound healing and regenerative medicine because of their crucial role in intercellular communication and tissue repair. However, rapid clearance of exosomes in vivo greatly limits their therapeutic efficacy. To address this critical limitation, we engineered a decellularized extracellular matrix (dECM)-based hydrogel system functionalized with exosomes derived from skin-derived precursor cells (SKPs). This biomimetic scaffold was designed to serve as a local exosome-delivery platform at the wound site, with the aim of improving exosome utilization and augmenting their regenerative effects. Comprehensive in vitro characterization demonstrated that the exosome-loaded composite hydrogels exhibited robust pro-angiogenic activity, as evidenced by enhanced endothelial cell proliferation, migration, and tube formation. Moreover, the hydrogels displayed significant antibacterial effects against wound-relevant pathogens and potent reactive oxygen species (ROS)-scavenging capacity, thereby mitigating oxidative damage. Notably, the composite hydrogels also promoted the phenotypic polarization of macrophages toward the pro-regenerative M2 phenotype. In parallel, in vivo studies using a streptozotocin-induced diabetic rat wound model confirmed that treatment with the composite hydrogels significantly accelerated wound closure rates compared to control groups. Histological and immunohistochemical analyses revealed enhanced angiogenesis, as evidenced by increased CD31-positive microvessel density, as well as improved collagen deposition, re-epithelialization, and an attenuated local inflammatory microenvironment characterized by reduced pro-inflammatory cytokine expression and elevated M2 macrophage infiltration. Collectively, the SKPs exosome-loaded dECM based composite hydrogels developed in this study represent a potential therapeutic strategy for the treatment of diabetic wounds. Full article

Decellularized extracellular matrix (dECM) scaffolds derived from xenogeneic tissues represent promising biomaterials for tissue engineering. In this study, dECM scaffolds were developed and characterized from four ovine tissues—skin, tunica vaginalis, fascia lata, and pericardium—using a detergent-based decellularization protocol to evaluate decellularization efficiency and extracellular matrix (ECM) preservation. Decellularization was performed using a sequential detergent-based protocol with sodium dodecyl sulfate and Triton X-100. Decellularization efficacy and matrix preservation were evaluated through gross examination, histological analysis, scanning electron microscopy (SEM), and residual DNA quantification. Gross inspection revealed increased translucency and reduced pigmentation in decellularized tissues compared with native counterparts, indicating effective cellular removal while maintaining overall tissue architecture. Histological assessment confirmed the complete absence of nuclear and cytoplasmic material, alongside preservation of collagen-rich extracellular matrix organization. SEM analysis demonstrated well-maintained ultrastructural features, including aligned collagen fibers and porous ECM architecture, with complete removal of epithelial and stromal cellular elements. Quantitative analysis revealed approximately 94% reduction in residual DNA content across all decellularized tissues compared with native controls. This study demonstrated that the employed detergent-based protocol reliably produces structurally preserved, acellular scaffolds from multiple ovine tissues. The resulting biomaterials exhibit structural characteristics that support their potential use in tissue engineering applications, pending further functional validation. Full article

Elastic fibers are key components of the skin extracellular matrix and are essential for maintaining skin integrity and elasticity. During skin aging, particularly photoaging, elastic fiber integrity is progressively compromised by increased elastase activity and the downregulation of elastin and scaffold-related gene expression. Therefore, effective strategies to preserve elastic fiber function should address not only elastin synthesis but also enzymatic degradation and scaffold integrity. In this study, we investigated a multitarget approach to restoring the elastic fiber network by modulating elastin production, elastase activity, and scaffold protein expression. We found that Copper Tripeptide-1 enhanced elastin expression and secretion, ethyl ferulate inhibited elastase activity, and cedrol promoted scaffold-related gene expression and microfibrillar protein restoration in dermal fibroblasts. To assess the biological relevance of this approach, the combined treatment was evaluated using UV-damaged human skin biopsy samples. This combination effectively mitigated UV-induced elastic fiber disruption and significantly improved fiber architecture, as confirmed by immunofluorescence staining and scanning electron microscopy. These findings indicate that coordinated modulation of elastin production, proteolytic protection, and scaffold reinforcement is essential for maintaining elastic fiber integrity and represents a promising approach for preserving skin elasticity during aging. Full article

This study reports the development and characterization of hierarchical electrospun scaffolds based on poly (L-lactic acid) (PLA) and polyacrylonitrile (PAN) reinforced with calcium oxide (CaO) nanoparticles (18.5 ± 4.7 nm) for skin regeneration. Six configurations, including two five-layer multilayer systems (PLA/PAN/CaO and PAN/PLA/CaO), were evaluated to determine how composition and deposition sequence influence physicochemical, mechanical, and biological performance. FT-IR, XRD and DSC confirmed the successful integration of CaO, while thermal analysis evidenced an effect of chain mobility and interfacial interactions within multilayer systems. Cross-sectional SEM revealed the presence of both fibers with continuous interfaces. Nitrogen adsorption showed that CaO significantly increased the specific surface area (e.g., from 4.6 m²/g in neat PLA to 21.65 m²/g in PLA/CaO), with type IV isotherms indicating mesoporosity. Wettability assays demonstrated reduced contact angle in PLA (from 126.3° to 91.8°) and sequence-dependent surface properties in multilayers. Tensile testing confirmed that the multilayer architecture bridged the mechanical gap between compliant PLA and high-strength PAN, yielding intermediate moduli (~10–11 MPa) and balanced toughness. Antibacterial assays against S. aureus and E. coli showed that CaO significantly reduced bacterial viability, with PLA/PAN/CaO achieving the highest inhibition (up to 37.1%). In vitro HaCaT assays and in vivo implantation in BALB/c mice confirmed high cytocompatibility and biocompatibility. These findings demonstrate that multilayer electrospinning of PLA/PAN/CaO enables the design of structurally integrated, bioactive, and mechanically balanced scaffolds for advanced wound healing and dermal repair. Full article

Antimicrobial peptides (AMPs) have re-emerged as promising anti-infective agents, particularly against multidrug-resistant bacteria; however, their therapeutic development remains constrained by proteolytic degradation, host cell toxicity, and rapid systemic clearance. Rather than focusing solely on sequence discovery, recent efforts have shifted toward structural and supramolecular modification strategies aimed at improving stability, selectivity, and pharmacological performance. This review critically analyzes intramolecular modifications—including phosphorylation, glycosylation, acetylation, methylation, and backbone cyclization—that modulate peptide conformation and resistance to enzymatic degradation. In parallel, extramolecular approaches such as PEGylation, lipidation, and conjugation to antibiotics, siderophores, or antibodies are examined in the context of enhanced targeting and prolonged bioavailability. Particular emphasis is placed on localized delivery systems, including hydrogels, polymeric films, and nanofibrous scaffolds, which enable spatially controlled administration and mitigate systemic exposure. By integrating evidence from ex vivo and in vivo infection models, this work delineates the translational potential and remaining bottlenecks of chemically engineered AMP platforms for skin and soft tissue infections. Full article

Tissue engineering integrates concepts from medicine, biology, and engineering to create living constructs capable of repairing, replacing, or supporting damaged tissues. This multidisciplinary field relies on the interplay between biomaterials, cellular sources, and bioactive signaling to achieve functional tissue regeneration. This review provides a comprehensive overview of recent advances in scaffold design, highlighting natural, synthetic, and hybrid materials, as well as innovative fabrication techniques such as electrospinning, 3D bioprinting, and smart biomaterials. It discusses the role of stem cells and growth factors in directing regeneration and examines a wide range of clinical applications, including skin regeneration, cartilage repair, bone tissue engineering, dental and periodontal regeneration, nerve repair, cardiac tissue engineering, liver tissue models, and ophthalmic applications. Current challenges, such as immune responses, limited vascularization, scalability, and regulatory barriers, are addressed alongside emerging strategies aimed at improving clinical translation. By integrating diverse tissue types and engineering approaches within a unified framework, this review offers a broad yet detailed perspective on the current state and future directions of regenerative medicine. Full article