Search Results (91)

Machine learning is reshaping gel-based additive manufacturing by enabling accelerated material design and predictive process optimization. This review provides a comprehensive overview of recent progress in applying machine learning across gel formulation development, printability prediction, and real-time process control. The integration of algorithms such as neural networks, random forests, and support vector machines allows accurate modeling of gel properties, including rheology, elasticity, swelling, and viscoelasticity, from compositional and processing data. Advances in data-driven formulation and closed-loop robotics are moving gel printing from trial and error toward autonomous and efficient material discovery. Despite these advances, challenges remain regarding data sparsity, model robustness, and integration with commercial printing systems. The review results highlight the value of open-source datasets, standardized protocols, and robust validation practices to ensure reproducibility and reliability in both research and clinical environments. Looking ahead, combining multimodal sensing, generative design, and automated experimentation will further accelerate discoveries and enable new possibilities in tissue engineering, biomedical devices, soft robotics, and sustainable materials manufacturing. Full article

The topical application of curcumin can act directly on the tissue, but there are problems related to solubility and permeation. Bigels combine hydrogels and organogels to enhance the release and transport of bioactives through the skin. The aim of this study was to develop bigels for the topical delivery of curcumin. Employing a rheology test, it was found that all bigels showed a solid-like behavior structure (G′ > G″) with stiffness increasing with higher organogel content. The principle of time–temperature superposition (TTS) was used to generate master curves. Microscopy revealed a morphological structure that depended on the organogel/hydrogel ratio. The bigels exhibited a pH compatible with that of human skin, and the curcumin content met the standards for uniform dosage. Thermal characterization showed the presence of three peaks in coconut oil bigels and two peaks in castor oil bigels. Bigels with a 45% castor oil organogel/55% hydrogel ratio exhibited a longer controlled release of curcumin, while bigels with coconut oil showed a faster release. The release data were fitted to mathematical models indicating non-Fickian release. The permeability of curcumin through Strat-M membranes was investigated, and greater permeation was observed with increasing organogel content. The developed bigels could be a promising option for the topical delivery of curcumin. Full article

This study developed electrosprayed deferoxamine (DFO)-loaded poly(lactic-co-glycolic acid) microspheres (DFO-MS) combined with a sucrose acetate isobutyrate (SAIB) depot (DFO-MS@SAIB) for bone-defect repair, targeting the coordinated regulation of angiogenesis and osteogenesis in vascularized bone regeneration—where new blood vessels support functional bone integration. In vitro/in vivo evaluations confirmed its dual pro-angiogenic and pro-osteogenic effects via HIF-1α pathway activation. Background/Objectives: Emerging evidence underscores the indispensability of vascularization in bone-defect repair, a clinical challenge exacerbated by limited intrinsic healing capacity. While autologous grafts and growth-factor-based strategies remain mainstream, their utility is constrained by donor-site morbidity, transient bioactivity, and poor spatiotemporal control over angiogenic–osteogenic coupling. Here, we leveraged DFO, a hypoxia-mimetic HIF-1α stabilizer with angiogenic potential, to engineer an injectable DFO-MS@SAIB depot. This system was designed to achieve sustained DFO release, thereby synchronizing vascular network formation with mineralized tissue regeneration in critical-sized defects. Methods: DFO-MS were fabricated via electrospraying and combined with SAIB (DFO-MS@S) to form an injectable sustained-release depot. Their physicochemical properties, including morphology, encapsulation efficiency, degradation, release kinetics, and rheology, were systematically characterized. In vitro, the angiogenic capacity of HUVECs co-cultured with DFO-MS was evaluated; conditioned HUVECs were then co-cultured with BMSCs to assess the BMSCs’ cytocompatibility and osteogenic differentiation. In vivo bone regeneration in a rat calvarial defect model was evaluated using micro-CT, histology, and immunohistochemistry. Results: The DFO-MS@SAIB system achieved sustained DFO release, stimulating HUVEC proliferation, migration, and tubulogenesis. In a Transwell co-culture model, pretreated HUVECs promoted BMSC migration and osteogenic differentiation via paracrine signaling involving endothelial-secreted factors (e.g., VEGF). HIF-1α pathway activation upregulated osteogenic markers (ALP, Col1a1, OCN), while in vivo experiments demonstrated enhanced vascularized bone regeneration, with significantly increased bone volume/total volume (BV/TV) and new bone area compared with controls. Conclusion: The DFO-MS@SAIB system promotes bone regeneration via sustained deferoxamine release and HIF-1α-mediated signaling. Its angiogenesis–osteogenesis coupling effect facilitates vascularized bone regeneration, thereby offering a translatable strategy for critical-sized bone-defect repair. Full article

Coronary artery disease (CAD) and peripheral artery disease (PAD) are associated with increased blood viscosity, which contributes to vascular inflammation and impaired microcirculation. Blood viscosity plays a crucial role in disease progression, influencing endothelial function and tissue perfusion. Sarpogrelate hydrochloride, a serotonin receptor antagonist, has antiplatelet and vasodilatory properties that may improve microvascular function and blood rheology. This randomized, parallel-group, open-label, single-center, phase IV clinical trial enrolled 68 patients with both CAD and PAD. The participants were randomized in a 1:1 ratio to receive either aspirin monotherapy (100 mg) or aspirin (100 mg) plus sarpogrelate (300 mg) for 12 weeks. The primary outcome was the change in blood viscosity from baseline to week 12, assessed using the scanning capillary technique. Secondary outcomes included erythrocyte deformability, flow-mediated dilation (FMD), and tissue oxygen delivery index (tODI), which collectively provide insights into microvascular function and oxygen transport efficiency. Elevated blood viscosity is a key factor in cardiovascular disease progression, yet conventional antiplatelet therapy has shown limited effects on hemorheology. Sarpogrelate, by targeting serotonin-mediated pathways, may enhance microcirculatory function and optimize vascular health. These effects could lead to better oxygen delivery and overall vascular health, thereby optimizing cardiovascular outcomes. By integrating hemorheological and vascular markers, this study aims to provide evidence on the potential benefits of combination therapy. Findings could inform optimized antiplatelet strategies to improve vascular health and reduce cardiovascular risk in patients with CAD and PAD. Full article

Royal jelly and medical grade honey are traditionally used in treating wounds and infections, although their effectiveness is often variable and insufficient. To overcome their limitations, we created novel amphiphiles by modifying the main reparative and antimicrobial components, queen bee acid (hda) and 10-hydroxyl-decanoic acid (hdaa), through peptide bonding with specific tripeptides. Our molecular design incorporated amphiphile targets as being biocompatible in wound healing, biodegradable, non-toxic, hydrogelable, prohealing, and antimicrobial. The amphiphilic molecules were designed in a hda(hdaa)-aa1-aa2-aa3 structural model with rational selection criteria for each moiety, prepared via Rink/Fmoc-tBu-based solid-phase peptide synthesis, and structurally verified by NMR and LC–MS/MS. We tested several amphiphiles among those containing moieties of hda or hdaa and isoleucine–leucine–aspartate (ILD-amidated) or IL-lysine (ILK-NH₂). These tests were conducted to evaluate their prohealing and antimicrobial hydrogel properties. Our observation of their hydrogelation and hydrogel-rheology showed that they can form hydrogels with stable elastic moduli and injectable shear-thinning properties, which are suitable for cell and tissue repair and regeneration. Our disc-diffusion assay demonstrated that hdaa-ILK-NH₂ markedly inhibited Staphylococcus aureus. Future research is needed to comprehensively evaluate the prohealing and antimicrobial properties of these novel molecules modified from hda and hdaa with tripeptides. Full article

Background: Vascular complications, following the application of non-permanent, hyaluronic acid-based tissue fillers are a rare but very serious and rapidly progressive disorder that can, in extreme cases, lead to skin necrosis, blindness, or a stroke. Interest in aesthetic procedures is constantly growing, so awareness and knowledge of the correct and comprehensive treatment of complications are important. The human face is an area characterised by complex innervation and vascularisation. There are high-risk areas in which the application of fillers should be carried out with particular care using appropriate techniques and instruments, as well as preparations with specific rheology. The aetiopathogenesis of vascular complications is complex—involving partial or complete vessel occlusion, the presence of local inflammation in the affected tissues, and potential arteriospasm of the vessels supplying the area, resulting in tissue dysperfusion and ischaemia. Methods: In this article, the case of a patient who developed signs of a vascular compromise on the forehead area after improperly administering filler in the glabellar and nasal areas is presented. Result: The diagnostic and therapeutic management applied, including above all high doses of hyaluronidase, Doppler ultrasound diagnostics, and general medications, as well as a complementary treatment of the distant effects of the complication, i.e., erythema and tissue loss in the forehead area, by autologous injection procedures and laser therapy, resulted in a full recovery and a very good aesthetic result. Conclusions: This case proves that complications after aesthetic medicine procedures, including vascular complications are possible. Education of patients and doctors, proper diagnosis, and initiation of appropriate treatment at an early stage of the problem can bring very good therapeutic results for the patient. Full article

Background/Objectives: Exsanguination is a leading cause of preventable death in military and civilian settings due to extensive blood loss and hemorrhagic shock, which trigger systemic effects such as impaired tissue perfusion, hypoxia, inflammation, and multi-organ dysfunction. Standard resuscitation restores blood volume but fails to address critical aspects of hemorrhagic shock, including inflammation, coagulopathy, and reperfusion injury. To address these limitations, novel phospholipid nanoparticle (PNP)-based resuscitative fluids, VBI-S and VBI-1, were developed to modulate nitric oxide (NO) levels, improving hemodynamic stability, tissue oxygenation, and reducing inflammatory injury. This study assessed the potential of novel phospholipid nanoparticle fluids, VBI-S and VBI-1, as resuscitative agents for severe hemorrhagic shock by evaluating their ability to regulate nitric oxide, restore blood pressure, and mitigate ischemia–reperfusion injury. Methods: This study involved two phases with Sprague Dawley rats (n = 6 per group). Phase one, lasting 4 h, included four groups: blood, Ringer’s lactate, VBI-S, and VBI-1. Phase two, lasting 12 h, comprised sham, blood, and VBI-1 groups. Under anesthesia, one femoral artery was catheterized for blood pressure monitoring, and blood withdrawal from the other induced apnea. Reanimation was performed using an intra-arterial infusion of shed blood, Ringer’s lactate, VBI-S, or VBI-1. Tissue samples were analyzed histologically and for oxidative DNA damage via immunofluorescence. Chemiluminescence and rheology assessed nitric oxide interactions and viscosity. Data were analyzed using ANOVA. Results: VBI-1 and shed blood increased mean arterial pressure (MAP) from <10 mmHg to survivable levels sustained for 12 h, with VBI-1 showing significantly higher MAP at 3–4 h. Rats treated with Ringer’s lactate died within 30 min. Histology revealed reduced organ damage in VBI-1-treated rats compared to shed blood. Immunohistochemistry indicated significantly less oxidative DNA damage (p < 0.001) in VBI-1-treated rats. VBI-1 exhibited superior viscosity and nitric oxide binding. Conclusions: VBI-1 demonstrates strong potential as a resuscitative fluid, offering blood pressure restoration, reduced oxidative damage, and enhanced tissue perfusion, with significant implications for use in resource-limited and pre-hospital settings. Full article

Tissue spheroids are self-organised 3D cellular aggregates that serve as a versatile platform in tissue engineering. While numerous high-throughput methods exist to characterise the cellular function of tissue spheroids, equivalent techniques for the mechanical characterisation are still lacking. In this review, we focus on tissue fusion— a simple, fast, and inexpensive method to characterise the rheology of tissue spheroids. We begin by discussing the implications of tissue rheology in development and disease, followed by a detailed explanation of how the phenomenon of arrested coalescence can be used to explore the rheology of tissue spheroids. Finally, we present different theoretical models that, when combined with experimental data, allow us to extract rheological information. Full article

Background/Objectives: Histopathological examination enables visualization of morphological changes in cells and tissues. In recent years, there has been increasing interest in assessing the mechanical properties of tissues that cannot be determined by standard histopathological examinations. Mechanobiology is crucial in human physiology and holds promise for uncovering new diagnostic markers for disease processes such as carcinogenesis and inflammation. In this study, we concentrated on measuring the mechanical properties of appendix biopsy specimens to identify potential mechanomarkers of inflammation. Appendix tissues provided the opportunity to measure mechanical properties both with an atomic force microscope and a shear rheometer. Methods: The atomic force microscope AFM—NanoWizard 4 BioScience JPK/Bruker was used for the evaluation of the elastic modulus (i.e., Young’s modulus) of appendix tissues. Young’s modulus was derived from the Hertz-Sneddon model applied to force-indentation curves. The rheological properties of macroscopic samples were measured on a parallel-plate, strain-controlled shear rheometer Anton Paar MCR302. Results: The data collected suggest that elasticity, expressed as Young’s modulus and the storage modulus, could be considered a marker indicating appendix tissue inflammation. Young’s modulus of inflamed appendix tissues was found to be significantly lower than that of healthy ones, with an average reduction of 67%. Furthermore, it was observed that inflamed appendix tissues, in comparison to healthy ones, respond differently under varying axial and shear stresses, enabling their identification. Conclusions: Our findings suggest that the specific mechanical properties of inflamed vermiform appendices could serve as novel mechanomarkers for the early detection and monitoring of appendicitis. Full article

This study explored extrusion-based 3D bioprinting as a method for depositing cell-laden bio-ink to create well-defined scaffolds for tissue regeneration. Natural hydrogels, known for their biocompatibility and low cell toxicity, were favored for bio-ink formulation in this process. However, their limited mechanical strength poses a challenge to maintaining structural integrity. To address this, the rheological properties of hybrid hydrogels containing cellulose-derived nanofiber (TONFC) at concentrations between 0.5% and 1.0%, along with alginate and gelatin at levels between 2% and 5%, were tested in this study. A total of eight formulations was created by adjusting the proportions of alginate, TO-NFC, and gelatin, resulting in a combined solid content of 8%. Various rheological properties, such as the flow behavior, recovery rate, and linear viscoelastic range, were analyzed. Bi-layer scaffolds were 3D printed with various compositions and the shape fidelity was investigated. Human mesenchymal stem cells (hMSCs) were mixed to prepare bio-ink and cell survivability was observed after 7 incubation days. The ability to control 3D printability and the favorable survival of cells make nanofiber-infused alginate–gelatin a promising option for creating precisely shaped scaffolds using the 3D bio-printing process. Full article

Skin bioprinting has the potential to revolutionize treatment approaches for injuries and surgical procedures, while also providing a valuable platform for assessing and screening cosmetic and pharmaceutical products. This technology offers key advantages, including flexibility and reproducibility, which enable the creation of complex, multilayered scaffolds that closely mimic the intricate microenvironment of native skin tissue. The development of an ideal hydrogel is critical for the successful bioprinting of these scaffolds with incorporated cells. In this study, we used a hydrogel formulation developed in our laboratory to fabricate a 3D-bioprinted skin model. The hydrogel composition was carefully selected based on its high compatibility with human skin cells, incorporating alginate, methyl cellulose, and nanofibrillated cellulose. One of the critical challenges in this process, particularly for its commercialization and large-scale production, is ensuring consistency with minimal batch-to-batch variations. To address this, we explored methods with which to preserve the physicochemical properties of the hydrogels, with a focus on freezing techniques. We validated the pre-frozen hydrogels’ printability, rheology, and mechanical and surface properties. Our results revealed that extended freezing times significantly reduced the viscosity of the formulations due to ice crystal formation, leading to a redistribution of the polymer chains. This reduction in viscosity resulted in a more challenging extrusion and increased macro- and microporosity of the hydrogels, as confirmed by nanoCT imaging. The increased porosity led to greater water uptake, swelling, compromised scaffold integrity, and altered degradation kinetics. The insights gained from this study lay a solid foundation for advancing the development of an in vitro skin model with promising applications in preclinical and clinical research. Full article

Hyaluronic acid (HA) fillers are widely used in esthetic medicine and are categorized into biphasic and monophasic types based on their manufacturing processes. To evaluate the quality of these fillers, it is essential to understand their rheological properties, which reflect their viscoelastic nature. Rheology, the study of material deformation and flow, reveals how fillers behave under stress, combining properties of solids and liquids. This study explores the fundamental principles of elasticity and viscosity, rooted in Hooke’s law of elasticity and Newton’s law of viscosity, to explain the complex behavior of viscoelastic substances like HA fillers. The distinction between biphasic and monophasic fillers lies in their chemical cross-linking processes, which impact their molecular weight, structure, and ultimately, their clinical performance. Biphasic fillers with minimal cross-linking rely on natural molecular entanglements, exhibiting lower modification efficiency and greater elasticity. Conversely, monophasic fillers, which undergo extensive chemical cross-linking, demonstrate higher modification efficiency, firmer texture, and enhanced resistance to enzymatic degradation. The study emphasizes the importance of thoroughly removing residual cross-linking agents to ensure filler safety. Understanding these rheological characteristics aids clinicians in selecting appropriate fillers based on injection sites, tissue conditions, and desired outcomes, balancing viscoelastic properties and safety for optimal esthetic results. Full article

In this work, physically crosslinked injectable hydrogels based on carrageenan, locust bean gum, and gelatin, and mechanically nano-reinforced with green graphene oxide (GO), were developed to address the challenge of finding materials with a good balance between injectability and mechanical properties. The effect of GO content on the rheological and mechanical properties, injectability, swelling behavior, and biocompatibility of the nanocomposite hydrogels was studied. The hydrogels’ morphology, assessed by FE-SEM, showed a homogeneous porous architecture separated by thin walls for all the GO loadings investigated. The rheology measurements evidence that G′ > G″ over the whole frequency range, indicating the dominant elastic nature of the hydrogels and the difference between G′ over G″ depends on the GO content. The GO incorporation into the biopolymer network enhanced the mechanical properties (ca. 20%) without appreciable change in the injectability of the nanocomposite hydrogels, demonstrating the success of the approach described in this work. In addition, the injectable hydrogels with GO loadings ≤0.05% w/v exhibit negligible toxicity for 3T3-L1 fibroblasts. However, it is noted that loadings over 0.25% w/v may affect the cell proliferation rate. Therefore, the nano-reinforced injectable hybrid hydrogels reported here, developed with a fully sustainable approach, have a promising future as potential materials for use in tissue repair. Full article

Skin wounds often form scar tissue during healing. Early intervention with tissue-engineered materials and cell therapies may promote scar-free healing. Exosomes and extracellular vesicles (EV) secreted by mesenchymal stromal cells (MSC) are believed to have high regenerative capacity. EV bioactivity is preserved after lyophilization and storage to enable use in remote and typically resource-constrained environments. We developed a bioprinted bandage containing reconstituted EVs that can be fabricated at the point-of-need. An alginate/carboxymethyl cellulose (CMC) biomaterial ink was prepared, and printability and mechanical properties were assessed with rheology and compression testing. Three-dimensional printed constructs were evaluated for Young’s modulus relative to infill density and crosslinking to yield material with stiffness suitable for use as a wound dressing. We purified EVs from human MSC-conditioned media and characterized them with nanoparticle tracking analysis and mass spectroscopy, which gave a peak size of 118 nm and identification of known EV proteins. Fluorescently labeled EVs were mixed to form bio-ink and bioprinted to characterize EV release. EV bandages were bioprinted on both a commercial laboratory bioprinter and a custom ruggedized 3D printer with bioprinting capabilities, and lyophilized EVs, biomaterial ink, and thermoplastic filament were deployed to an austere Arctic environment and bioprinted. This work demonstrates that EVs can be bioprinted with an alginate/CMC hydrogel and released over time when in contact with a skin-like substitute. The technology is suitable for operational medical applications, notably in resource-limited locations, including large-scale natural disasters, humanitarian crises, and combat zones. Full article

Gelatin-based photo-crosslinkable hydrogels are promising scaffold materials to serve regenerative medicine. They are widely applicable in additive manufacturing, which allows for the production of various scaffold microarchitectures in line with the anatomical requirements of the organ to be replaced or tissue defect to be treated. Upon their in vivo utilization, the main bottleneck is to monitor cell colonization along with their degradation (rate). In order to enable non-invasive visualization, labeling with MRI-active components like N-(2,2-difluoroethyl)acrylamide (DFEA) provides a promising approach. Herein, we report on the development of a gelatin-methacryloyl-aminoethyl-methacrylate-based biomaterial ink in combination with DFEA, applicable in digital light processing-based additive manufacturing towards bone tissue regeneration. The fabricated hydrogel constructs show excellent shape fidelity in line with the printing resolution, as DFEA acts as a small molecular crosslinker in the system. The constructs exhibit high stiffness (E = 36.9 ± 4.1 kPa, evaluated via oscillatory rheology), suitable to serve bone regeneration and excellent MRI visualization capacity. Moreover, in combination with adipose tissue-derived stem cells (ASCs), the 3D-printed constructs show biocompatibility, and upon 4 weeks of culture, the ASCs express the osteogenic differentiation marker Ca²⁺. Full article