Search Results (599)

The growing demand for sustainable materials has led to increased interest in biodegradable polymer fibers and nonwoven mats due to their eco-friendly characteristics and potential to reduce plastic pollution. This review highlights how mechanical properties influence the performance and suitability of biodegradable polymer fibers across diverse applications. This covers synthetic polymers such as polylactic acid (PLA), polyhydroxyalkanoates (PHAs), polycaprolactone (PCL), polyglycolic acid (PGA), and polyvinyl alcohol (PVA), as well as natural polymers including chitosan, collagen, cellulose, alginate, silk fibroin, and starch-based polymers. A range of fiber production methods is discussed, including electrospinning, centrifugal spinning, spunbonding, melt blowing, melt spinning, and wet spinning, with attention to how each technique influences tensile strength, elongation, and modulus. The review also addresses advances in composite fibers, nanoparticle incorporation, crosslinking methods, and post-processing strategies that improve mechanical behavior. In addition, mechanical testing techniques such as tensile test machine, atomic force microscopy, and dynamic mechanical analysis are examined to show how fabrication parameters influence fiber performance. This review examines the mechanical performance of biodegradable polymer fibers and fibrous mats, emphasizing their potential as sustainable alternatives to conventional materials in applications such as tissue engineering, drug delivery, medical implants, wound dressings, packaging, and filtration. Full article

Collagen implants in neurosurgery are widely used due to their biocompatibility, biodegradability, and ability to support tissue regeneration, but their mechanical properties, such as low tensile strength and susceptibility to enzymatic degradation, remain challenging. Current technologies are improving these implants through cross-linking, synthetic reinforcements, and advanced manufacturing techniques such as 3D bioprinting to improve durability and predictability. Industry 4.0 is contributing to this by automating production, using data analytics and machine learning to optimize implant properties and ensure quality control. In Industry 5.0, the focus is shifting to personalization, enabling the creation of patient-specific implants through human–machine collaboration and advanced biofabrication. eHealth integrates digital monitoring systems, enabling real-time tracking of implant healing and performance to inform personalized care. Despite progress, challenges such as cost, material property variability, and scalability for mass production remain. The future lies in smart biomaterials, AI-driven design, and precision biofabrication, which could mean the possibility of creating more effective, accessible, and patient-specific collagen implants. The aim of this article is to examine the current state and determine the prospects for the development of mechanical properties of collagen implant used in neurosurgery towards Industry 4.0/5.0, including ML model. Full article

Organoids and microphysiological systems (MPSs) have emerged as physiologically relevant platforms that recapitulate key structural and functional features of human organs, tissues, and microenvironments. As one of the essential components that define the success of these systems, hydrogels play the central role of providing a three-dimensional, biomimetic scaffold that supports cell viability, spatial organization, and dynamic signaling. Natural polymer-based hydrogels, derived from materials such as collagen, gelatin, hyaluronic acid, and alginate, offer favorable properties including biocompatibility, degradability, and an extracellular matrix-like architecture. This review presents recent advances in the design and application of such hydrogels, focusing on crosslinking strategies (physical, chemical, and hybrid), the viscoelastic characteristics, and stimuli-responsive behaviors. The influence of these materials on cellular processes, such as stemness maintenance, differentiation, and morphogenesis, is critically examined. Furthermore, the applications of organoid culture and dynamic MPS platforms are discussed, highlighting their roles in morphogen delivery, barrier formation, and vascularization. Current challenges and future perspectives toward achieving standardized, scalable, and translational hydrogel systems are also addressed. Full article

The extracellular matrix (ECM) is a collagen-based scaffold that provides structural support and regulates nutrient transport and cell signaling. ECM homeostasis depends on a dynamic balance between synthesis and degradation, the latter being primarily mediated by matrix metalloproteinases (MMPs). These enzymes are secreted as pro-forms and require activation to degrade ECM components. Their activity is modulated by tissue inhibitors of metalloproteinases (TIMPs). Aging disrupts this balance, leading to the accumulation of oxidized, cross-linked, and denatured matrix proteins, thereby impairing ECM function. Bruch’s membrane, a penta-laminated ECM structure in the eye, plays a critical role in supporting photoreceptor and retinal pigment epithelium (RPE) health. Its age-related thickening and decreased permeability are associated with impaired nutrient delivery and waste removal, contributing to the pathogenesis of age-related macular degeneration (AMD). In AMD, MMP dysfunction is characterized by the reduced activation and sequestration of MMPs, which further limits matrix turnover. This narrative review explores the structural and functional changes in Bruch’s membrane with aging, the role of MMPs in ECM degradation, and the relevance of these processes to AMD pathophysiology, highlighting emerging regulatory mechanisms and potential therapeutic targets. Full article

Chemokines are low-molecular-weight peptides classified as cytokines with chemotactic properties. The chemokine CXCL13 and its receptor CXCR5 play a significant role in cardiac remodeling, and their expression is markedly increased in experimental models of heart failure. Increased CXCL13 activity is associated with the expression of fibromodulin, a proteoglycan that binds and cross-links collagen fibers. The stressed heart undergoes intensive remodeling, including fibrosis. In our experiment, we investigated the effect of the most commonly used triple immunosuppressive regimens on the expression of the CXCR5 receptor, the chemokine CXCL13, and fibromodulin in rat heart tissue. For this purpose, we used Western blot analysis and ELISA. The study was started on 36 rats divided into 6 groups, which received drugs for a period of 6 months. Our results suggest that the chronic use of calcineurin inhibitors in combination with mycophenolate mofetil is a significant stress factor for the heart, leading to abnormal remodeling of the extracellular matrix. The use of rapamycin may alleviate the negative effects of immunosuppressive therapy on the heart. Our results are consistent with the results of our previous studies and provide a basis for further work aimed at understanding the pathophysiology of the development of changes in the heart with individual immunosuppressive regimens. Full article

Musculoskeletal (MSK) disorders remain a major global cause of disability, with diagnostic complexity arising from their heterogeneous presentation and multifactorial pathophysiology. Recent advances across imaging modalities, molecular biomarkers, artificial intelligence applications, and point-of-care technologies are fundamentally reshaping musculoskeletal diagnostics. This review offers a novel synthesis by unifying recent innovations across multiple diagnostic imaging modalities, such as CT, MRI, and ultrasound, with emerging biochemical, genetic, and digital technologies. While existing reviews typically focus on advances within a single modality or for specific MSK conditions, this paper integrates a broad spectrum of developments to highlight how use of multimodal diagnostic strategies in combination can improve disease detection, stratification, and clinical decision-making in real-world settings. Technological developments in imaging, including photon-counting detector computed tomography, quantitative magnetic resonance imaging, and four-dimensional computed tomography, have enhanced the ability to visualize structural and dynamic musculoskeletal abnormalities with greater precision. Molecular imaging and biochemical markers such as CTX-II (C-terminal cross-linked telopeptides of type II collagen) and PINP (procollagen type I N-propeptide) provide early, objective indicators of tissue degeneration and bone turnover, while genetic and epigenetic profiling can elucidate individual patterns of susceptibility. Point-of-care ultrasound and portable diagnostic devices have expanded real-time imaging and functional assessment capabilities across diverse clinical settings. Artificial intelligence and machine learning algorithms now automate image interpretation, predict clinical outcomes, and enhance clinical decision support, complementing conventional clinical evaluations. Wearable sensors and mobile health technologies extend continuous monitoring beyond traditional healthcare environments, generating real-world data critical for dynamic disease management. However, standardization of diagnostic protocols, rigorous validation of novel methodologies, and thoughtful integration of multimodal data remain essential for translating technological advances into improved patient outcomes. Despite these advances, several key limitations constrain widespread clinical adoption. Imaging modalities lack standardized acquisition protocols and reference values, making cross-site comparison and clinical interpretation difficult. AI-driven diagnostic tools often suffer from limited external validation and transparency (“black-box” models), impacting clinicians’ trust and hindering regulatory approval. Molecular markers like CTX-II and PINP, though promising, show variability due to diurnal fluctuations and comorbid conditions, complicating their use in routine monitoring. Integration of multimodal data, especially across imaging, omics, and wearable devices, remains technically and logistically complex, requiring robust data infrastructure and informatics expertise not yet widely available in MSK clinical practice. Furthermore, reimbursement models have not caught up with many of these innovations, limiting access in resource-constrained healthcare settings. As these fields converge, musculoskeletal diagnostics methods are poised to evolve into a more precise, personalized, and patient-centered discipline, driving meaningful improvements in musculoskeletal health worldwide. Full article

Background: Rundle’s curve describes the natural progression of disease as gradually worsening before reaching a peak and stabilizing. This study aimed to investigate whether Rundle’s curve could be applied to keratoconus over a five-year follow-up period. Methods: Longitudinal study. Patients with keratoconus who underwent Pentacam tomography imaging from the Australian Study of Keratoconus were included in this study. Patients who received surgical treatment for keratoconus were excluded. Latent class analysis was performed for five parameters: Kmean front, Kmean back, pachymetry pupil, pachymetry minimum and pachymetry apex. A total of 522 patients and 1041 eyes were included for analysis. Most parameters were stable. However, worsening keratoconus in a minority of patients (less than 5% of the population) was observed across the last year of follow-up. The patients that showed progression in the final year were younger in age and had higher baseline parameters. Results: This study suggests keratoconus does not conform to the classic Rundle’s curve of disease progression. Instead, keratoconus exhibits a distinct course characterized by an increased risk of progression among younger individuals and eyes with higher baseline parameter values. Conclusions: These findings underscore the importance of considering treatments that halt disease progression, such as corneal collagen crosslinking, particularly in this specific subgroup of patients. Full article

Background/Objectives: Keratoconus (KC) is a corneal ectatic disease, characterized by the progressive thinning of the cornea, myopia, and astigmatism, which lead to a decrease in visual acuity. Corneal collagen crosslinking (CXL) is an efficient method of stopping the progression of the disease. The objective of this study is to investigate the endothelial and biomechanical properties of the cornea in keratoconus patients, before and after undergoing corneal collagen crosslinking. Methods: A total of 66 eyes were diagnosed with progressive keratoconus and were recommended epi-off corneal crosslinking. Before the procedure, they were investigated with corneal topography (for minimum, maximum, average keratometry, and corneal astigmatism), specular microscopy (for the following endothelial cell parameters: number, density, surface, variability, and hexagonality), and an ocular response analyzer (for the following biomechanical parameters: corneal hysteresis and resistance factor). All measurements were repeated 1 month and 6 months after the intervention. Results: Several parameters differ according to the Amsler–Krumeich stage of keratoconus: in more advanced stages, patients present higher endothelial cell variability, a lower number of endothelial cells in the paracentral region of the cornea, lower CCT and CRF, and higher keratometry and astigmatism. Endothelial cell variability and number correlate with average keratometry, and there are also strong correlations between topography and CH and CRF. After CXL, the paracentral number of endothelial cells decreased; cell variability and average cell surface increased. Conclusions: More advanced keratoconus cases present with altered corneal biomechanics and topographical parameters, the endothelial layer also being affected proportional to the stage of the disease and also slightly affected after corneal collagen crosslinking. Full article

Background/Objectives: Bovine pericardial valve conduits (PVCs) are commonly used for right ventricular outflow tract reconstruction in both pediatric and adult patients. Calcification, particularly prevalent in children and young adults, is a leading cause of conduit failure and is affected by the chemical composition of the treated biomaterials. In this study, we aimed to compare the structural changes in diepoxy-treated (DE-PVCs) and glutaraldehyde-treated PVCs (GA-PVCs) and to identify factors contributing to tissue mineralization in a large animal model. Methods: Pulmonary artery replacement was performed in minipigs (33–88 kg) using twelve DE-PVCs and four GA-PVCs. After six months, the animals were euthanized, and the explanted PVCs underwent macroscopic and microscopic examination. Results: Large calcium deposits formed along conduit joining suture (CJS) lines in all PVCs, regardless of the cross-linking agent. Mineral clusters surrounded the multifilament braided thread, and its fibers were encrusted with hydroxyapatite crystals. In DE-PVCs, no mineralization occurred outside the suture lines, and they showed successful integration and graft vitalization with a uniform neointima and well-developed endothelial monolayer. GA-PVCs developed a rigid external capsule, foci of collagen fiber calcification within the walls, and neointimal hyperplasia with limited endothelial coverage. Conclusions: In PVCs, calcification predominantly occurs along the CJS lines, where the multifilament suture acts as a nucleation site for hydroxyapatite crystals. DE treatment prevents collagen mineralization, unlike GA, and offers better integration, reduced neointimal hyperplasia, and a well-developed endothelial layer. These findings suggest that DE-PVCs may be a superior option for pediatric cardiac surgery by reducing calcification and improving conduit durability. Overall, the results will help optimize PVC manufacturing strategies to lower the risk of conduit failure. Full article

The enzyme transglutaminase 2 (TG2) has an open conformation with transamidase activity which crosslinks matrix proteins contributing to fibrosis development. LDN-27219 promotes the closed conformation of TG2, which can enhance vasodilation, but its effects in renal tissue are unknown. We investigated whether LDN-27219 treatment affects albuminuria and markers of renal fibrosis as well as ex vivo vasodilatation. Male C57BL/6 mice (n = 48) underwent unilateral nephrectomy plus insertion of a deoxycorticosterone acetate pellet (DOCA group) or nephrectomy only (sham group). Both groups were randomized to intraperitoneal treatment with either LDN-27219 (8 mg/kg twice daily) or vehicle for 2 weeks. Urine albumin excretion was evaluated by metabolic cages. Kidney tissue fibrosis markers were assessed by qPCR and Western blotting, while the TG2 conformational state was evaluated using native gel electrophoresis. Collagen staining was performed using Picrosirius red and quantified under circularly polarized light. Mesenteric arteries were mounted in wire myographs for evaluation of vasorelaxation. DOCA mouse developed significant albuminuria (p < 0.001 vs. sham), but neither TG2 mRNA nor protein expression was upregulated in the kidney. However, the relative amount of TG2 in the closed conformation was higher in DOCA mice. LDN-27219 did not affect albuminuria, but LDN-27219-treated DOCA mice showed less urine production and less collagen staining than vehicle-treated DOCA mice. LDN-27219 did not affect TG2 mRNA or TG2 protein expression or mRNA of fibrosis markers. LDN-27219-treated mice had enhanced vasorelaxation to the nitric oxide donor sodium nitroprusside. In conclusion, LDN-27219 treatment in the one-kidney DOCA–salt model did not affect renal TG2 mRNA and protein expression or albuminuria but still exerted beneficial effects in terms of reduced kidney fibrosis and urine production in addition to enhanced vasodilatation. Full article

Background/Objectives: Preclinical models of liver fibrosis only partially mimic human disease processes. Particularly, traditional transforming growth factor beta 1 (TGFβ1)-induced hepatic stellate cell (HSC) models lack relevant processes, including hypoxia-induced pathways. Here, the ability of a hypoxia-mimicking compound (IOX2) to more accurately reflect the human fibrotic phenotype on a functional level was investigated. Methods: Human primary HSCs were stimulated (TGFβ1 +/− IOX2), and the cell viability and fibrotic phenotype were determined. The latter was assessed as protein levels of fibrosis markers—collagen, TIMP-1, and Fibronectin. Next-generation sequencing (NGS), differential expression analyses (DESeq2), and Ingenuity Pathway Analysis (IPA) were performed for mechanistic evaluation and biological annotation. Results: Stimulation with TGFβ1 + IOX2 significantly increased fibrotic marker levels. Also, fibrosis-related pathways were activated, and hypoxia-related genes and collagen modifications, such as crosslinking, increased dose-dependently. Comparative analysis with human fibrotic DEGs showed improved disease representation in the HSC model in the presence of IOX2. Conclusions: In conclusion, the HSC model better recapitulated liver fibrosis by IOX2 administration. Therefore, hypoxia-mimicking compounds hold promise for enhancing the translational value of in vitro fibrosis models, providing valuable insights in liver fibrosis pathogenesis and potential therapeutic strategies. Full article

Traumatic non-compressible hemorrhage and subsequent wound management remain critical challenges in military and civilian settings to this day. Cryogels have emerged as promising hemostatic materials for non-compressible hemorrhage due to their blood-triggered shape recovery. In this study, a biodegradable and mechanically resilient cryogel (CF/PD) was produced via cryopolymerization, employing methacrylated recombinant collagen as a macromolecular crosslinker alongside poly (ethylene glycol) diacrylate (PEGDA) and dopamine methacrylate (DMA). With its interpenetrating macro-porous structure and high hydrophilicity, the CF/PD rapidly absorbs blood and returns to its original shape within 1.5 s. In a rat liver defect model, CF/PD outperformed commercially available gelatin sponges, reducing hemostasis time by 74.4% and blood loss by 76.5%. Moreover, CF/PD cryogels facilitate in situ tissue regeneration by virtue of the bioactivity and degradability of recombinant collagen. This work establishes a bioactive recombinant collagen-driven cryogel platform, offering a transformative solution for managing non-compressible hemorrhage while enabling tissue regeneration. Full article

Hyaluronic acid (HA) is an unbranched polysaccharide particularly abundant in the extracellular matrix (ECM) of soft connective tissues. In humans, about 50% of the total HA in the organism is localized in the skin. HA plays an essential role in the hydration of the ECM, in the regulation of tissue homeostasis, in the resistance to mechanical stimuli/forces, and in the modulation of tissue regeneration. For these reasons, HA is widely used in regenerative medicine and cosmetics. In this study we used an innovative fluid dynamic system to investigate the effects of a cross-linked macrostructural HA formulation on dermal collagen of healthy human skin explants. The good preservation of skin explants provided by the bioreactor allowed applying refined high-resolution microscopy techniques to analyze in situ the HA-induced modifications on the ECM collagen fibrils up to 48 h from the application on the skin surface. Results demonstrated that this HA formulation, commercially proposed for subcutaneous injection, may act on dermal ECM also when applied transcutaneously, improving ECM hydration and modifying the organization of the collagen fibrils. These findings, obtained by the original combination of explanted human skin use with an advanced culture system and multiscale imaging techniques, are consistent with the volumizing and anti-aging effect of HA. Full article

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

Injectable biopolymer-based hydrogels have emerged as a powerful class of biomaterials designed for minimally invasive therapeutic strategies in modern medicine. These smart hydrogels, derived from natural biopolymers, such as alginate, chitosan, gelatin, hyaluronic acid, and collagen, offer unique advantages, including biocompatibility, biodegradability, and the ability to mimic the extracellular matrix. This review provides a comprehensive overview of recent advancements in the design, crosslinking mechanisms, and biofunctionality of injectable hydrogels tailored for targeted drug delivery and tissue regeneration. Special attention is given to their role in in situ gelling systems, cancer therapy, musculoskeletal repair, and neural regeneration. Challenges related to mechanical strength, degradation control, and clinical translation are also discussed, along with future perspectives for scalable manufacturing and regulatory approval. Full article