Search Results (1,505)

Myocardial infarction remains a leading cause of heart failure because current reperfusion therapies cannot prevent adverse ventricular remodeling or restore lost cardiomyocytes. Regenerative strategies based on stem cells and extracellular vesicles (EVs) have emerged as promising approaches; however, their clinical efficacy is limited by poor retention, rapid clearance, and the hostile post-infarction microenvironment. This narrative review critically examines the role of biomaterial-assisted delivery systems in enhancing stem cell and EV-based cardiac regeneration, with particular emphasis on the distinction between biomimetic and bioactive biomaterials, mechanisms of action, preclinical and clinical evidence, translational barriers, and emerging regenerative technologies. Current evidence demonstrates that injectable hydrogels, extracellular matrix-derived scaffolds, cardiac patches, conductive biomaterials, and multifunctional delivery platforms improve therapeutic retention, prolong paracrine signaling, and actively modulate inflammation, angiogenesis, fibrosis, and extracellular matrix remodeling, resulting in superior functional recovery compared with conventional delivery approaches in preclinical models. Nevertheless, robust clinical evidence remains limited because few biomaterial-assisted strategies have advanced beyond early-phase studies. Future progress will depend on integrating smart biomaterials with engineered extracellular vesicles, gene editing, and personalized regenerative approaches, together with standardized manufacturing, harmonized regulatory frameworks, and adequately powered clinical trials. Full article

The persistent shortage of donor organs and the inherent drawbacks of autologous grafts highlight the urgent need for advanced biomaterial scaffolds in regenerative medicine. Synthetic polymers and animal-derived matrices offer structural support, yet they frequently lack the biological complexity of native tissue or carry translational liabilities—xenogeneic antigens, pathogen transmission risk, and batch variability. This review positions the human placenta as a compelling, ethically sourced, and abundant reservoir for fully human, xeno-free biomaterials. We examine the placenta’s distinct anatomical compartments and their rich complement of extracellular matrix (ECM) proteins, growth factors, and bioactive cytokines. These components confer potent pro-angiogenic, anti-inflammatory, antimicrobial, and immunomodulatory properties, enabling precise direction of cellular behavior and tissue regeneration. We systematically assess recent advances in decellularization and the processing strategies required to preserve these bioactivities while eliminating immunogenic material. By integrating current tissue engineering applications with the regulatory and ethical frameworks shaping clinical translation, we argue that placenta-derived matrices are uniquely positioned to transcend the limitations of conventional scaffolds and serve as a robust platform for future regenerative therapies. Full article

Lignans and related neolignans are a diverse class of phenolic natural products with broad biological activities and great potential for pharmaceutical applications. This article summarizes representative subclasses of lignans and compares their antitumor and antioxidant properties from a structural and mechanistic perspective. Aryltetrahydronaphthalene lignans, represented by podophyllotoxin and its semi-synthetic derivatives, provide the clearest baseline for their mechanism of action by disrupting microtubules and inhibiting topoisomerase II. Other subclasses, including dibenzylbutyrolactone, arylnaphthalene, dibenzocyclooctadiene, furofuran lignans, glycosides, and bisphenolic neolignans, exhibit anticancer and redox-regulating effects. Future research should focus on linking structural diversity with validated molecular targets, pharmacokinetic properties, and in vivo efficacy to better define their translational potential. Full article

Acute and chronic wounds remain a major clinical burden, motivating the design of multilayer biomedical composite systems capable of combining structural support, antimicrobial protection, and controlled release of therapeutic agents within a single device. These architectures integrate natural and synthetic biomaterials, hydrogels, electrospun membranes, bioactive nanoparticles, and 3D-printed scaffolds to reproduce the multifunctionality of the native extracellular matrix. This review examines how layer-by-layer design and biomaterial selection govern mechanical strength, as well as bioactivity, and how these parameters can be tuned to the distinct phases of wound repair. Particular emphasis is placed on strategies for incorporating growth factors, antimicrobial agents, metal/metal-oxide nanoparticles to enhance re-epithelialization, angiogenesis, and infection control; emerging gene-based delivery strategies are also discussed. The main technologies and biomaterial combinations reported to date are compared, alongside a critical overview of their in vitro and in vivo performance. Reproducibility, scalability, and regulatory standardization remain the main barriers to clinical translation. We conclude by outlining priority research directions to advance multilayer composites from bench-scale prototypes toward approved wound-care products. Full article

Lichens are mutualistic symbiosis between a fungus (mycobiont) and an alga or cyanobacteria (photobiont), forming metabolically versatile holobionts capable of producing diverse secondary metabolites that facilitate their survival in extreme environments. Chrysothrix species, commonly known as “gold dust lichens,” are characterized by their vivid yellow thalli and their production of pulvinic acid derivatives, although their bioactive potential remains poorly explored. In this study, using organic chemistry techniques, we characterized the methanolic extract of Chrysothrix sp.—collected from the Paposo Fog Oasis in northern Chile, a unique coastal ecosystem sustained by persistent fog (“camanchacas”) within the Atacama Desert—and identified calycin as its major secondary metabolite through chromatographic purification and single-crystal X-ray diffraction. Antibacterial assays revealed that both the crude methanolic extract and purified calycin exhibited selective inhibitory activity against multidrug-resistant Gram-positive ESKAPE-E pathogens. Minimum Inhibitory Concentrations (MICs) ranged from 125 to 500 μg/mL, with the strongest effects observed against Enterococcus faecium (MDR, VRE) and Staphylococcus aureus (MDR, MRSA). No meaningful activity was detected against Gram-negative bacteria, consistent with the known permeability barrier conferred by the outer membrane. This work provides the first evidence of antibacterial activity for calycin isolated from Chrysothrix sp., highlighting the relevance of pulvinic acid derivatives as promising scaffolds for antimicrobial development. These findings highlight the potential of lichen-derived agents and alternative sources of antibacterial agents to address the global challenge of antimicrobial resistance. Full article

As the population ages, the demand for customizable, resorbable bone implants in tissue engineering has intensified, outstripping the limitations of traditional autografts and allografts. While silicate-based bioactive glasses dominate bioactive glass research, borate-based bioactive glasses (BBGs) present distinct biomimetic advantages due to their accelerated degradation kinetics and superior ion-release profiles. However, producing highly pure, homogeneous BBG powders tailored for additive manufacturing remains a severe bottleneck. This study reports the development of a highly efficient synthesis protocol and subsequent Digital Light Processing (DLP) 3D printing of BBG scaffolds. An aqueous-based precursor mixture was processed via spray drying and a customized multi-stage thermal pretreatment sequence up to 800 °C to mitigate material loss, minimize oxide evaporation, and completely eliminate carbonates. Subsequent “flash melting” at 1150 °C for 20 min yielded an amorphous, high-purity borate–phosphate glass network (68.1B₂O₃-3.8Na₂O-18.9CaO-4.9MgO-4.3P₂O₅, in wt%). Differential scanning calorimetry (DSC) revealed a glass transition temperature ($T_g$) of 625 °C, while in situ X-ray diffraction localized the onset of crystal nucleation between 706 °C and 723 °C. Following fine planetary milling to achieve a highly dense particle packing distribution (D_v50 = 5.4 µm, D_n50 = 0.6 µm), the optimized BBG powder was successfully loaded into an acrylate-based photosensitive slurry (51.2 wt% solid loading) to manufacture complex 3D biomimetic gyroid scaffolds via DLP. While the structural feasibility of printing high-resolution gyroid porous architectures is validated, post-printing evaluation highlighted a narrow thermal processing window; sintering at 660 °C optimized particle coalescence while minimizing microstructural de-densification caused by closed porosity expansion (which reaches 48.4% at 675 °C). This scalable synthesis-to-printing workflow offers a crucial steppingstone toward next-generation fully resorbable bone tissue scaffolds. Full article

Triple-negative breast cancer (TNBC) is the most clinically aggressive subtype of breast cancer, characterized by the absence of targetable hormone receptors and HER2 amplification, significantly constraining treatment choices. Estrogen Receptor Beta (ERβ) has emerged as a biologically relevant yet underutilized target in TNBC, with its re-expression linked to tumor suppression and improved prognosis, prompting the development of selective ERβ modulators as a precision therapeutic approach. We introduce ERβ-Score, an interpretable machine learning scoring system developed using a curated dataset of 1699 ERβ bioactive chemicals obtained from ChEMBL, characterized by 39 physicochemical and three-dimensional molecular descriptors. After implementing scaffold-disjoint train/test partitioning to avert structural data leakage, a Gradient Boosting Classifier, fine-tuned through Bayesian hyperparameter optimization, attained in five-fold cross-validation a Precision–Recall AUC (Area Under the Curve) of 0.891, a ROC-AUC (Receiver Operating Characteristic) of 0.888, a Matthews Correlation Coefficient of 0.664, an F1-score of 0.838, and a balanced accuracy of 0.831; on the scaffold-disjoint hold-out test set it attained a Precision–Recall AUC of 0.905, a ROC-AUC of 0.864, and a Matthews Correlation Coefficient of 0.578, indicating strong and balanced discrimination between active and inactive ERβ modulators. We note explicitly that this scaffold-disjoint hold-out constitutes internal validation, since it derives from the same curated ChEMBL workflow used for model development, and it is therefore reported throughout as scaffold-disjoint internal validation rather than as independent external validation. The applicability domain boundaries were established using a k-nearest-neighbor Tanimoto-similarity method with ECFP4 (Extended-Connectivity Fingerprint with a Diameter of 4) fingerprints, offering a quantitative confidence metric that identifies structurally new molecules beyond the model’s reliable prediction range. External validation against independent Tox21 ERβ bioassay data confirmed genuine, statistically significant predictive signal (ROC-AUC = 0.71) while revealing reduced sensitivity for structurally novel active compounds. The model was subsequently used for extensive virtual screening of natural product and drug-like compound libraries, with prioritized candidates undergoing structure-based molecular docking against the ERβ co-crystal structure (PDB: 7XWQ) using Smina, facilitating a comprehensive evaluation of hits based on both ligand and structural properties. To enhance accessibility, the complete pipeline was implemented as an open-access interactive web application utilizing Streamlit, enabling researchers to input any SMILES string and obtain, in real time, an activity prediction with a probability score, applicability domain classification, Lipinski drug-likeness assessment, interactive three-dimensional visualization of protein–ligand interactions, and on-demand docking within the ERβ active site. Full article

Plastic waste presents a persistent environmental burden, yet its constituent polymers represent structurally valuable chemical feedstocks. Mechanical recycling remains limited due to polymer degradation, additive contamination, and material downcycling, underscoring the need for alternative strategies. Chemical upcycling offers pathways to convert post-consumer plastics into higher-value monomers, functional chemicals, and bioactive or pharmaceutical precursors by exploiting inherent structural motifs such as aromatic rings, ester linkages, and heteroatom-containing backbones. Approaches such as catalytic depolymerization, molecular functionalization, microbial and enzymatic transformation, and scaffold repurposing enable the recovery of polymer-derived building blocks with improved functional value. Case studies illustrating the conversion of discarded plastics into advanced materials and biologically relevant small molecules demonstrate the potential of these approaches to stimulate innovation and expand sustainable chemical practices. Collectively, such developments align with green chemistry principles, support emerging circular chemical economies, and contribute to global sustainability priorities reflected in the United Nations Sustainable Development Goals. This review aims to outline the guiding principles of chemical upcycling and highlight the challenges in chemical design, encouraging the modern chemistry community to tap into the hidden potential of waste plastics. Full article

Chronic cutaneous ulcers pose a major clinical challenge due to persistent inflammation, impaired angiogenesis, and limited regenerative capacity, underscoring the need to develop bioactive scaffolds that mimic the extracellular matrix (ECM) and promote skin repair. In this study, electrospun Poly(ε-caprolactone) (PCL) scaffolds functionalized with 10% (PCLGLI10) and 20% (PCLGLI20) glycine were fabricated, physicochemically and mechanically characterized, and evaluated in combination with human Wharton’s jelly mesenchymal stromal cells (hWJ-MSCs). Glycine incorporation reduced fiber diameter to the nanoscale range (140–155 nm) and increased scaffold porosity (~71–72%) while preserving mechanical properties compatible with skin. FTIR and X-ray diffraction analyses confirmed glycine incorporation and a polymorphic transition from α- to γ-glycine during electrospinning. Cell viability remained above 95% in all scaffolds; however, PCLGLI10 significantly enhanced cell proliferation, metabolic activity, and the secretion of VEGF and HGF, mediators associated with angiogenesis and tissue repair. Furthermore, in a guinea pig full-thickness wound model, the PCLGLI10+hWJ-MSCs construct promoted a modulated inflammatory response and more organized collagen deposition. These findings support the potential of glycine-functionalized electrospun scaffolds as a promising strategy for chronic cutaneous ulcer regeneration. Full article

Three-dimensional (3D) bioprinting has emerged as a versatile biofabrication strategy that enables the precise, spatiotemporally controlled co-deposition of living cells, biomaterials, and bioactive agents, including growth factors, cytokines, and extracellular matrix (ECM) components, into geometrically defined 3D constructs. By translating digital design models derived from computed tomography (CT), magnetic resonance imaging (MRI), or computational modeling directly into physical tissue architectures, 3D bioprinting facilitates the assembly of hierarchically organized constructs that closely recapitulate the structural, mechanical, and functional characteristics of native tissues. The principal 3D bioprinting strategies are broadly classified into scaffold-based and scaffold-free approaches. Engineered bioinks, whether formulated as cell-laden natural, synthetic, or composite polymer hydrogels, tissue-derived decellularized ECM (dECM) components, or pure cellular spheroids and organoids, constitute the cornerstone of these biofabrication platforms. Scaffold-based 3D bioprinting comprises extrusion-based, droplet-based (inkjet and drop-on-demand), light-based vat photopolymerization (stereolithography and digital light processing), and laser-assisted bioprinting based on laser-induced forward transfer (LIFT). Each of these modalities imposes distinct constraints on bioink rheology, crosslinking mechanisms, spatial resolution, throughput, and post-printing cell viability; consequently, a specific 3D bioprinting strategy is selected according to the specific requirements of the target tissue application. Scaffold-free 3D bioprinting and bioassembly techniques, including the Kenzan method, aspiration-assisted bioprinting, magnetic bioprinting, and other field-directed tissue assembly approaches, enable the fabrication of spheroid- and organoid-based constructs without the necessity for exogenous biomaterial scaffolds. Because native tissues exhibit diversity in cellular composition, ECM architecture, mechanical properties, and physiological function, no individual bioprinting platform or bioink formulation serves as a universal 3D bioprinting solution. The engineering of biomimetic tissue constructs, therefore, requires the selection of application-tailored fabrication approaches. Under this biofabrication paradigm, 3D bioprinting has been applied across a wide range of tissue engineering targets, including skin, bone, cartilage, osteochondral interfaces, cardiac and vascular tissue, neural structures, ocular, dental, and adipose tissue. This review discusses recent advances in scaffold-based and scaffold-free 3D bioprinting applications for tissue engineering and regenerative medicine across diverse tissue systems. Full article

Osteomyelitis is a severe, progressive bone infection affecting approximately 21.8 per 100,000 individuals in the United States and remains a major challenge in orthopedic and reconstructive medicine. Staphylococcus aureus (S. aureus), responsible for nearly 75% of cases, is the most common causative pathogen. Current gold-standard management involves culture-directed antibiotic therapy administered for 4–6 weeks, often combined with surgical debridement and the use of antibiotic-loaded cement spacers. Despite these interventions, treatment frequently fails to achieve complete infection eradication, with recurrent or persistent disease reported in up to 40% of cases, contributing to chronic inflammation, impaired bone healing, and long-term functional deficits. These limitations highlight the need for therapeutic strategies that address infection control and bone regeneration. A narrative literature review was conducted to evaluate emerging tissue-engineered scaffold-based biomaterials as potential alternatives to conventional treatment. Emerging evidence suggests antimicrobial-loaded matrices, bioactive scaffolds, and stimuli-responsive biomaterials can provide localized drug delivery, structural support, and enhanced osteogenesis while improving infection control and osteointegration. Advances in targeted drug delivery, immunomodulatory biomaterials, and computational scaffold design further suggest opportunities for more effective therapies. These findings highlight the potential of scaffold-based biomaterials to improve osteomyelitis management, although further clinical studies are required. Full article

Tooth loss and bone resorption of the alveolar cavity caused by dental caries and periodontal disease remain major clinical challenges that compromise oral function. Tissue engineering approaches based on biocompatible scaffolds have emerged as promising strategies for bone regeneration; however, the influence of fabrication methods on scaffold performance remains unclear. This study developed hydroxyapatite/poly (lactic-coglycolic acid)/chitosan scaffolds (HAp/PLGA/CS) using freeze-drying and 3D-printing techniques and evaluated their physicochemical, biological, and biomechanical properties. The morphology, porosity, elemental composition, and mechanical properties of the scaffold were characterized, while the biocompatibility and osteogenic potential were evaluated using human dental pulp stem cells (hDPSCs). Finite element analysis (FEA) using COMSOL Multiphysics^® Version 6.2. was performed to evaluate scaffold behavior under simulated dental implant loading conditions. The 3D-printed scaffolds exhibited significantly higher cell viability than the freeze-dried scaffolds, reaching approximately 85% in the 50% filling group compared with 50% in the freeze-dried group. Microstructural analysis revealed interconnected hierarchical porosity, including macro-, micro-, and submicrometer scale pores. Although the 50% infill scaffold showed the highest cell viability, the 70% infill scaffold demonstrated the most favorable osteogenic profile, with enhanced expression of RUNX2 and OSX. Both types exhibited degradation profiles compatible with early bone regeneration. FEA simulations indicated that further mechanical optimization is required to improve load transfer and reduce deformation at the implant–scaffold interface. Overall, HAp/PLGA/CS scaffolds showed potential as experimental bioactive platforms for bone tissue engineering, with 3D-printed scaffolds providing greater architectural control and favorable early osteogenic responses. However, the translational relevance of these findings remains preliminary and requires validation through long-term degradation studies, in vivo bone regeneration and osseointegration models, cyclic mechanical testing, and implant fixation experiments. Full article

Introduction/Objectives: Temporomandibular joint osteoarthritis (TMJOA) causes pain, mandibular dysfunction, fibrocartilage degradation, and synovial inflammation. Current therapies are mainly palliative and limited by rapid intra-articular clearance and insufficient disease-modifying effects. This review summarizes injectable hydrogels for TMJOA as regenerative scaffolds, drug delivery systems, joint lubricants, and mechanical buffers. Methods: Relevant studies were identified from PubMed/MEDLINE, Web of Science and Google Scholar using terms related to TMJOA, injectable hydrogels, intra-articular delivery, tissue engineering, cartilage repair, lubrication, viscosupplementation and mechanical buffering. Studies were selected if they addressed hydrogel design, biological function, mechanical performance, biosafety or translational evaluation. Results: Injectable hydrogels have been investigated mainly as bioactive regenerative scaffolds and acellular functional biomaterials. Bioactive systems may regulate inflammation and oxidative stress, deliver cells, exosomes, drugs or growth factors, and support fibrocartilage repair. Acellular systems primarily aim to improve intra-articular retention, lubrication, viscoelastic adaptation and mechanical buffering. However, current evidence remains largely preclinical, with limited validation of long-term residence, degradation behavior, TMJ-specific mechanical performance, repeat dosing, biosafety and functional outcomes. Conclusions: Injectable hydrogels represent promising multifunctional platforms for TMJOA treatment. Cell-, exosome-, and growth factor-loaded systems show regenerative potential but face manufacturing, safety, regulatory, and long-term validation challenges. Acellular multifunctional hydrogels may be more feasible for near-term translation. Clinical Significance: Injectable hydrogels may provide minimally invasive, locally sustained treatment for TMJOA by integrating symptom control, microenvironment modulation, and mechanical adaptation. Full article

In this study, three formulations (F1, F2, and F3) were developed to fabricate hybrid scaffolds composed of chitosan (CS), polyvinylpyrrolidone (PVP), and polyvinyl alcohol (PVA), doped with curcumin (CUR) and silicon dioxide nanoparticles (NPs-SiO₂). Structural analysis of the scaffolds was performed using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). This analysis demonstrated that incorporating bioactive molecules, such as curcumin (CUR) and silicon dioxide nanoparticles (NPs-SiO₂), modified intermolecular interactions within the prepared scaffolds, thereby favoring the formation of more stable amorphous structures. This effect was most evident in scaffold formulation 3, which exhibited a more porous architecture with a uniform distribution of NPs-SiO₂. Furthermore, mechanical evaluation of the formulations revealed that F2 exhibited the highest elastic modulus (0.773 ± 0.177 MPa) and compressive strength (1.015 ± 0.012 MPa), while F3 showed a more balanced combination of flexibility, structural stability, and displacement capacity. All formulations achieved complete inhibition of the Gram-positive and Gram-negative bacterial strains evaluated under the same test conditions. In vitro studies demonstrated that F3 maintained cell viability above 80% in normal BHK-21 fibroblasts while exhibiting enhanced cytotoxicity toward HEp-2 tumor cells (IC₅₀ = 373.6 µg/mL). Additionally, subdermal implantation revealed the presence of trabeculae-like structures, osteocyte-like lacunae, and osteoblastic-like cells in F3, suggesting the initiation of osteogenic-type tissue organization. These findings identify F3 as the formulation with the most favorable balance of structural, mechanical, antimicrobial, and biological properties, supporting its potential application as a multifunctional scaffold for tissue regeneration. Full article

Current bone regeneration strategies face significant constraints, relying either on synthetic scaffolds with slow degradation that require biochemical supplements or on bioactive fillers. Recently, the focus has shifted towards functional natural biomaterials with inherent osteoinductive potential. This study presents a promising candidate based on a silica-containing plant-derived scaffold fabricated from rice straw, a sustainable resource with >20 wt.% silica. Morphological analyses revealed that the decellularised rice straw scaffold exhibits a unique surface pattern with a three-dimensional nanoarchitecture featuring parallel fibrillar protrusions and cellulosic spikes evenly distributed across the surface. Elemental mapping revealed abundant silicon, with minor traces of calcium and phosphorus, all of which are crucial components of bioactive minerals. The scaffold was highly biodegradable, with 81.7% weight loss after 90 days, attributed to its high water absorption (337%). The scaffold demonstrated excellent biocompatibility, maintaining MG63 cell viability and promoting robust adhesion and proliferation, with relative metabolic activity increasing from 105% at day 5 to 125% at day 7 relative to TCPS controls. Most remarkably, when seeded with adipose-derived human mesenchymal stem cells (hMSCs) in the absence of osteogenic medium, the scaffold induced significant biomineralisation. This osteoinductive capacity is attributed to its unique surface pattern, high roughness, and polar cellulosic substrate, together with bioactive silica that releases soluble silicon species. This work represents how agricultural waste can be upcycled for autonomous bone regeneration. Full article