Search Results (8,810)

Myostatin (Mstn), a well-characterized member of the transforming growth factor-β (TGF-β) superfamily, serves as a key negative regulator of skeletal muscle mass. Its overactivation is closely associated with the pathogenesis of various musculoskeletal and metabolic disorders. Over the past decades, inhibiting Mstn has emerged as a promising therapeutic strategy to promote muscle growth. A range of Mstn-targeted inhibitors has been developed, yielding encouraging preclinical and clinical outcomes. These include small molecules, monoclonal antibodies, peptibodies, and gene therapy-based approaches. This review summarizes the biological structure and function of Mstn, provides a comprehensive overview of recent advances in Mstn-targeted therapeutics, and offers critical insights into future directions for drug development and clinical translation. Full article

Peripheral nerve injuries involving critical-sized gaps remain a major clinical challenge. Although autologous nerve grafting is considered the gold standard for peripheral nerve repair, its clinical application is limited by the availability of donor nerve tissue and the risk of donor-site morbidity, including sensory deficits and functional impairment. Therefore, nerve guidance conduits (NGCs) have emerged as a promising alternative when combined with bioactive modulation strategies. In this study, we evaluated bisvinyl sulfonemethyl (BVSM)-crosslinked gelatin conduits integrated with electrical stimulation (ES) at different frequencies (0, 2, 20, and 200 Hz) in a rat sciatic nerve defect model over a 4-week recovery period (n = 10 per group). Structural regeneration was assessed by morphometric analysis, electrophysiology, macrophage infiltration, CGRP immunoreactivity, retrograde Fluorogold tracing, quantitative PCR of growth factors and inflammatory cytokines, and behavioral testing. Among all stimulation paradigms, low-frequency ES at 2 Hz produced the most pronounced regenerative effects. The 2 Hz group demonstrated significantly greater axon number, axonal density, and regenerated nerve area compared with control and high-frequency groups (p < 0.05). Electrophysiological assessments revealed improved nerve conduction velocity, higher MAP amplitudes, and shorter latencies. Enhanced macrophage recruitment and elevated CGRP expression were observed, suggesting coordinated neuroimmune and neurochemical activation. Gene expression analysis indicated upregulation of neurotrophic factors and balanced inflammatory cytokine responses under low-frequency stimulation. In contrast, high-frequency stimulation (200 Hz) failed to enhance overall regeneration and showed reduced axonal metrics, suggesting possible overstimulation-associated suppression. Collectively, these findings demonstrate that BVSM-crosslinked conduits provide a stable and biocompatible regenerative scaffold, and that appropriately tuned low-frequency electrical stimulation (2 Hz) optimally enhances structural, molecular, and functional recovery. The integration of material engineering with bioelectrical modulation represents a promising strategy for next-generation bioelectronic interfaces in peripheral nerve repair. Full article

As natural nanoscale intercellular messengers, exosomes exhibit considerable potential in modulating inflammation, angiogenesis, immunoregulation, and tissue remodeling, making them attractive candidates for regenerative medicine. However, their clinical translation remains limited by rapid systemic clearance, nonspecific biodistribution, insufficient lesion retention, and functional attenuation in hostile pathological microenvironments. In this review, we propose that biomaterial engineering should evolve from providing passive exosome carriers to constructing active regulatory platforms capable of precise spatiotemporal control. We summarize engineering strategies along two complementary dimensions. In the temporal dimension, biomaterials can enable sustained, sequential, or microenvironment-responsive release to match the dynamic phases of tissue repair. In the spatial dimension, biomaterials can improve local retention, tissue anchoring, structural guidance, endogenous cell recruitment, and lesion-specific delivery. Using cutaneous wound healing, osteochondral regeneration, myocardial repair, and neural regeneration as representative examples, we further analyze these strategies through a “clinical challenge–engineering strategy–biological mechanism” framework, with particular attention to how engineered systems influence key signaling pathways such as PI3K/Akt, Wnt/β-catenin, NF-κB, and PTEN/PI3K/Akt/mTOR. We also discuss translational barriers, including exosome heterogeneity, safety concerns inherited from parental cells, large-scale GMP-compliant manufacturing, product standardization, storage stability, and regulatory classification of exosome–biomaterial hybrids. Finally, we highlight emerging directions, including multi-mechanism combinational systems, closed-loop responsive platforms, and artificial intelligence-assisted design for personalized exosome therapeutics. This review provides a design-oriented framework to accelerate the bench-to-bedside development of biomaterial-enabled precision exosome therapy. Full article

Extrusion-based bioprinting faces significant challenges in achieving the shape fidelity and internal porosity necessary for cell viability, often hindered by subjective assessment methods. This study investigated the relationship between rheological properties and print quality using a natural polymer biomaterial ink composed of 12% gelatin, 5% alginate, and 1% carboxymethylcellulose. We conducted a comparative analysis between traditional pneumatic systems and screw-driven volumetric extrusion, utilizing a suite of quantitative metrics: Spreading Ratio (SR), Printability Index (P_r), Uniformity Ratio (UF), Collapse Angle (θ), and evaluated porosity. Our results demonstrate that the screw-driven system’s positive displacement mechanism provides superior control over filament morphology by enabling precise volumetric modulation. While the pneumatic system exhibited a high SR of 1.82 and the lowest porosity at 59.92%, the screw-driven system allowed for “under-extrusion” to compensate for viscoelastic die swell. Reducing the flow rate to 50% in the screw system lowered the SR to 1.09, nearly matching the nozzle diameter, and increased porosity to 76.46%. Furthermore, the screw-driven system achieved an ideal P_r of 1.0, whereas the pneumatic system produced distorted, rounded pores with a P_r of 1.57. The findings indicate that screw-driven extruders can decouple line complex rheology from the printing process, allowing for finer spatial resolution and better pore interconnectivity. Full article

Ovarian tissue cryopreservation is the primary fertility preservation strategy for prepubertal girls and patients requiring urgent gonadotoxic therapy. However, the risk of reintroducing malignant cells has prompted the development of safer alternatives, including follicle isolation followed by three-dimensional scaffold encapsulation for transplantation. Fibrin is a promising biomaterial for bioengineered ovary construction, although its ability to support early human follicle maintenance remains unclear. Follicles isolated from cryopreserved ovarian tissues of six patients were encapsulated within fibrin scaffolds of graded concentrations (high, medium, low). After 7 days of in vitro culture, follicle survival and diameter change were quantified. A total of 282 follicles (45.4 ± 10.1 µm) were embedded into fibrin scaffolds. After culture, 237 viable follicles were detected, yielding an overall survival of 84%. Follicle diameter increased to 58.8 ± 12.0 µm. Follicle survival rates were comparable across groups, while mean follicle diameter was 56.3 ± 12.5 µm (high), 61.9 ± 13.4 µm (medium), and 57.4 ± 9.3 µm (low). Follicles cultured in medium-concentration fibrin demonstrated significantly larger diameters compared with both high and low groups (p < 0.05), with no difference between high and low groups. Fibrin-based bioprosthetic ovary scaffolds support short-term in vitro maintenance of isolated human follicles, preserving spherical morphology and granulosa cell layer integrity. Medium-concentration fibrin was associated with greater follicle diameter expansion compared with higher and lower concentrations, indicating that scaffold composition influences early morphometric changes during in vitro follicle culture. Full article

Wound-healing and skin regeneration are the focus of intensive research, driven by a rapidly expanding global market and the growing clinical demand for more effective interventions engineered to actively direct and enhance tissue regeneration. Recent advances in biomaterial engineering and 3D bioprinting have accelerated the development of highly customized, functional constructs mimicking native tissue. Together, these innovations are reshaping therapeutic strategies and expanding the translational potential of next-generation skin substitutes. This review presents an overview of the evolution of material printing technologies and the different categories of 3D bioprinting techniques and processing methods, followed by an evaluation of the properties of natural biomaterials as bioinks for skin wound-healing and their application in skin tissue engineering. Moreover, we provide a comprehensive global market analysis, with consideration of costs, benefits, and a SWOT analysis to identify the full potential of this technology for the development of novel skin wound-healing products. Recommendations and future perspectives are provided to guide researchers, clinicians, and industry partners on the current state and potential of adopting 3D bioprinting with natural biomaterials for effective wound-healing therapies. Full article

The high mortality rate from microbial infections underscores the need to discover new antimicrobials. This work produced antibacterial Chitosan biofilms with and without the incorporation of the ethanolic extract of Libidibia ferrea stem bark and its ethyl acetate and aqueous fractions. The extract and fractions were subjected to FTIR and ¹H NMR analysis. The biofilms were characterized by FTIR, scanning electron microscopy, thermogravimetry, and differential scanning calorimetry analysis. The ¹H NMR and FTIR data, as well as the colorimetric quantification of total phenolics, demonstrated the presence of phenolic compounds. Staphylococcus aureus and Bacillus cereus were the most susceptible bacteria for Chitosan/L. ferrea biofilms and fractions (growth inhibition zones values in the range of 10.8 ± 0.1 to 14.0 ± 0.1 mm, and minimum inhibitory or bactericidal concentration, MIC or MBC values of the fractions were in the range of 125 to 250 µg mL⁻¹. Only the fractions inhibited Pseudomonas aeruginosa (MIC = 250 µg mL⁻¹). Chitosan/L. ferrea biofilms exhibited efficient interactions between chitosan functional groups and secondary metabolites, good thermal stability, and increased rigidity in mechanical tests. This study reinforces the pharmacological potential of biodegradable Chitosan/L. ferrea biofilms as antibacterial agents biofilms. Full article

Pelvic organ prolapse (POP) is a common benign gynecological disorder that substantially affects quality of life, particularly in aging female populations. Current management strategies, including standardized vaginal pessaries and synthetic surgical meshes, are often limited by poor anatomical adaptability, mechanical mismatch with native pelvic tissues, and long-term safety concerns. These limitations have driven increasing interest in personalized and biomechanically compatible therapeutic solutions. Three-dimensional (3D) printing, also known as additive manufacturing, has emerged as a promising bioengineering technology to address these unmet clinical needs. By enabling layer-by-layer fabrication directly from digital models, 3D printing allows for precise control over device geometry, mechanical properties, and material composition, facilitating patient-specific design. This narrative review summarizes recent progress in 3D printing for POP management across three major application domains: (i) next-generation meshes based on biodegradable polymers, elastomeric materials, natural biomaterials, and hydrogel systems; (ii) customized vaginal pessaries tailored to individual pelvic anatomy using imaging-assisted workflows; and (iii) imaging-based pelvic models and prototype devices for surgical planning, education, and exploratory assessment. Overall, existing studies demonstrate that 3D printing enables improved biomechanical compatibility, enhanced tissue integration, and multifunctional device design, including drug delivery capability. Although current evidence is largely pre-clinical or based on pilot studies, additive manufacturing holds strong potential to advance POP management toward safer, personalized, and functionally optimized clinical solutions. Full article

Bone tissue plays a vital role in the human body and possesses intrinsic self-repair mechanisms; however, large defects or pathological fractures may exceed its natural healing capacity. Bone tissue engineering provides promising strategies to restore bone integrity through the use of scaffolds, growth factors, and stem cells. While calcium phosphate (CaP)-based ceramics, such as hydroxyapatite (HAp) and tricalcium phosphate (TCP), represent the current benchmark, their limitations, including slow degradation (HAp) and limited osteoinductivity (TCP), have driven the development of alternative biomaterials. In this context, magnesium phosphate (MgP)-based materials have gained increasing attention due to their tunable resorption rate, improved biodegradability, and ability to stimulate osteogenesis and angiogenesis through the release of magnesium (Mg²⁺) ions. This study reports on composite scaffolds based on electrospun poly(ε-caprolactone) (PCL) fibres coated with MgP layers doped with lithium (Li) and zinc (Zn), designed to mimic the nanofibrous architecture of the extracellular matrix. Lithium and zinc were selected due to their known ability to modulate cellular response, with lithium promoting osteogenic activity and zinc contributing to improved cell proliferation and antibacterial potential. The phosphate phases obtained by coprecipitation were deposited onto the PCL fibres using Matrix-Assisted Pulsed Laser Evaporation (MAPLE), enabling controlled surface functionalization. Following thermal treatment, the formation of the crystalline magnesium pyrophosphate (Mg₂P₂O₇) phase was confirmed by chemical and structural characterization. The combination of a slowly degrading PCL matrix, providing sustained structural support, and a bioactive MgP coating, enabling rapid and controlled ion release, results in improved scaffold performance in terms of biocompatibility, biodegradability, and bioactivity. While the slow degradation rate of PCL ensures mechanical stability over an extended period, the surface-deposited MgP phase allows immediate interaction with the biological environment, facilitating faster ion release and enhancing cell–material interactions. These findings highlight the potential of the developed composites as promising candidates for trabecular bone regeneration and as viable alternatives to conventional CaP-based scaffolds in regenerative medicine. Full article

The progression of chronic bone diseases is intricately linked to dysregulated macrophage polarisation. However, a comprehensive understanding of the complex interplay between macrophage polarisation and metabolic reprogramming in the context of bone disorders remains elusive. Thus, this review conducted a systematic search of major databases, including PubMed, using combinations of keywords such as “macrophage polarisation,” “immunometabolism,” “metabolic reprogramming,” and “chronic bone diseases” (including “osteoporosis,” “osteoarthritis,” and “periodontitis”). Inclusion criteria prioritised original research published within the last five years to capture recent advances. Diverging from previous reviews constrained by the classical M1/M2 dichotomy, this article aims to delineate the heterogeneity and functional plasticity of macrophages within the bone microenvironment, emphasising metabolic reprogramming as a central mechanism driving the dynamic behaviour of macrophages across various skeletal pathologies. Furthermore, this review highlights the pivotal roles of specific metabolites—such as succinate, itaconate, and citrate—within the osseous microenvironment, underscoring their influence on macrophage phenotypic transitions and the regulation of bone metabolic homeostasis. Finally, this article envisages innovative therapeutic strategies targeting the “metabolism–immunity axis,” encompassing the design of nano-delivery systems to modulate macrophage metabolism, the utilisation of engineered extracellular vesicles, the development of immunometabolism-modulating biomaterials, and the exploration of naturally occurring bioactive molecules. Based on these findings, the present work proposes the “metabolism–immunity–skeleton” axis as a theoretical framework, thereby establishing a robust foundation for the development of precision metabolic immunotherapy tailored to a spectrum of chronic bone diseases. Full article

Fibrin gel, a protein-based polymer naturally generated during coagulation, has garnered attention in the biomedical field for applications such as fibrin glue, due to its specific physical and biological properties. Despite it, low mechanical strength and rapid degradation limited its utilization for biomedical applications. This study presents a reproducible protocol for the synthesis of pure fibrin hydrogels, aimed at achieving predictable structural properties through the precise calibration of fibrinogen and thrombin concentrations. By examining the mechanical and morphological characteristics, as well as the relationship between reagent concentrations and structural integrity, this research assesses impacts on swelling behavior, water absorption, and overall stability. Through a comprehensive analytical approach, we identified an optimal formulation, specifically 2.25 mg/mL fibrinogen and 1.375 U/mL thrombin, that effectively balances structural integrity with high cytocompatibility. The results demonstrate that this calibrated approach ensures high procedural reproducibility and a well-defined hydrogel architecture without the need for exogenous chemical cross-linkers. This work provides a robust methodological framework to overcome the common lack of reproducibility in fibrin-based hydrogel studies, positioning these materials as highly reliable candidates for advanced 3D in vitro models and biomedical applications. Full article

Deposits of insoluble protein plaques, which are mostly composed of fibrils from disease-specific amyloid proteins, are histological markers of various human disorders. These range from non-neuropathic amyloidosis such as light chain amyloidosis or type II diabetes to well-known neuro-degenerative diseases such as Alzheimer’s Disease and Parkinson’s Disease. There are indications that these types of fibrillar suprastructures display biological activity distinct from the individual fibrils they are composed of. Yet, little is known about the mechanisms underlying the assembly of fibrillar suprastructures. An understanding of secondary fibril self-assembly into mesoscopic and macroscopic suprastructures is also critical for their application as novel biomaterial. The paucity of experimental data and theoretical models on fibrillar supra-assembly likely relates to the experimental and conceptual challenges in following this type of assembly on multiple length- and timescales, and in characterizing the distinct morphologies formed. Here, we report that the amyloid dye thioflavin T (ThT) is augmented during self-assembly of isolated lysozyme fibrils. We provide evidence that this augmentation of ThT fluorescence results from the unquenching of fibril-bound ThT during fibril binding. Combining ThT fluorescence, optical density, and fluorescence quenching kinetics with optical and electron microscopy, we propose that fibril self-assembly is driven by a transition from reaction-limited ordered assembly to diffusion-limited random cross-linking of fibrils. Full article

As the most abundant natural polymer on Earth, cellulose offers distinct advantages including renewability, biocompatibility, and modifiability. Among its various morphologies, spherical cellulose hydrogels (SCHs) represent a particularly versatile form ranging from micrometer to millimeter scales. They possess a unique hydrophilic 3D network, excellent flowability, high specific surface area, and outstanding mechanical stability, demonstrating great potential for biomedical applications. This mini-review highlights the primary bottom-up fabrication strategies for SCHs, including dripping, spraying, emulsion, and microfluidics, and the mechanisms by which different fabrication processes regulate their size, morphology, and structure are elucidated. On this basis, the recent advancements in SCHs across key biomedical domains, specifically in chromatographic separation, controlled drug delivery, tissue engineering, and wound healing, are discussed. Finally, the current challenges and future directions in this field are summarized and predicted, aiming to provide a reference for the development and application of high-performance cellulose-based biomaterials. Full article

Lignocellulose represents an abundant repository of renewable carbon. Derived from various plant sources, it holds tremendous potential as a renewable and sustainable feedstock for the production of valuable chemicals and fuels. However, its solid fermentable compounds, cellulose and hemicellulose, are embedded within complex lignin structures and are therefore poorly accessible to microbial conversion. This paper describes an artificial rumen reactor (ARR) that uses anaerobic microbes from the cattle rumen to increase the release of fermentable carbon from recalcitrant biomass. We outline the development of an ARR for the efficient conversion of lignocellulosic grass into volatile fatty acids (VFAs), which are valuable precursors for the production of a range of bioproducts, including biofuels, biomaterials, and biochemicals. The ARR, a 4-L bioreactor equipped with a ceramic filtration unit, has been optimised and was operated for extended periods of continuous VFA production. Across distinct short- and long-term observation periods, and independent of the cow from which the rumen microbes originated, the bioreactor demonstrated the ability to sustain VFA production, indicating robustness and stability. At an input of 60–80 g dry grass d⁻¹, the system produced approximately 6 mol VFA per kg of dry matter input (DMI). The decoupling of the Solid Retention Time (SRT; 10 days) and the Liquid Retention Time (LRT; 0.5 days) prevented inhibition of the VFA production. The VFA profile was dominated by acetic and propionic acids, comprising 68% and 19%, respectively, with butyric acid and minor VFAs accounting for the remainder. The application of low oxygen levels (<10%) in the reactor via limited aeration did not affect the VFA yield or its profile. Full article

Background/Objectives: The growing prevalence of obesity necessitates innovative gut-targeted material strategies to modulate diet-associated metabolic dysfunction. This study investigates a spray-dried konjac glucomannan–montmorillonite (KGM-MMT) hybrid designed to integrate fermentable polysaccharide properties with luminal lipid-adsorptive clay functions within a single micro-engineered formulation. Methods: In HFD-fed mice treated for 42 days with 2% w/w KGM-MMT, cumulative body weight gain was attenuated by 7.6%, with an AUC of 5094 ± 52.95, compared to 5513 ± 81.35 in HFD controls (p < 0.0001). Results: Serum IL-6 concentrations were reduced by 97% (p = 0.0002), while blood glucose decreased by 46% (p < 0.0001); these effects were greater than those observed with MMT (24%, p = 0.0271) and KGM (16%, ns). Gut microbiota profiling demonstrated a significant 6.2-log₂-fold increase in Lactobacillaceae (p = 0.023) and a 2.4-log₂-fold increase in Enterococcaceae (p = 0.015) following KGM-MMT treatment. Functional shifts inferred from 16S rRNA gene-based prediction indicated a 1.9-fold increase in short-chain fatty acid-related pathways and a 5.4-fold increase in bile acid deconjugation pathways. Conclusions: Although the KGM-MMT hybrid did not consistently outperform its individual components across all endpoints, it consolidated complementary KGM- and MMT-associated effects within a single dosage form. These findings support spray-dried KGM-MMT as a gut-targeted biomaterial strategy that integrates multiple luminal and microbiota-associated functions within a single formulation. Future studies should define dose–response relationships, validate microbiota-derived functional predictions using higher-resolution approaches, and assess durability and safety under longer-term exposure. Full article