Search Results (315)

Background/Objectives: Oncogenic KRAS drives ~30% of solid tumours, yet the only approved G12C-specific drugs benefit ≈ 13% of KRAS-mutant patients, leaving a major clinical gap. We sought mutation-agnostic natural ligands from Ziziphus lotus, whose stereochemically rich phenolics may overcome this limitation by occupying the SI/II (Switch I/Switch II) groove and locking KRAS in its inactive state. Methods: Phytochemical mining yielded five recurrent phenolics, such as (+)-catechin, hyperin, astragalin, eriodictyol, and the prenylated benzoate amorfrutin A, benchmarked against the covalent inhibitor sotorasib. An in silico cascade combined SI/II docking, multi-parameter ADME/T (Absorption, Distribution, Metabolism, Excretion, and Toxicity) filtering, and 100 ns explicit solvent molecular dynamics simulations. Pharmacokinetic modelling predicted oral absorption, Lipinski compliance, mutagenicity, and acute-toxicity class. Results: Hyperin and astragalin showed the strongest non-covalent affinities (−8.6 kcal mol⁻¹) by forging quadridentate hydrogen-bond networks that bridge the P-loop (Asp30/Glu31) to the α3-loop cleft (Asp119/Ala146). Catechin (−8.5 kcal mol⁻¹) balanced polar anchoring with entropic economy. ADME ranked amorfrutin A the highest for predicted oral absorption (93%) but highlighted lipophilic solubility limits; glycosylated flavonols breached Lipinski rules yet remained non-mutagenic with class-5 acute-toxicity liability. Molecular dynamics trajectories confirmed that hyperin clamps the SI/II groove, suppressing loop RMSF below 0.20 nm and maintaining backbone RMSD stability, whereas astragalin retains pocket residence with transient re-orientation. Conclusions: Hyperin emerges as a low-toxicity, mutation-agnostic scaffold that rigidifies inactive KRAS. Deglycosylation, nano-encapsulation, or soft fluorination could reconcile permeability with durable target engagement, advancing Z. lotus phenolics toward broad-spectrum KRAS therapeutics. Full article

The electrochemical conversion of CO₂ into high-purity Graphene NanoCarbon (GNC) materials provides a compelling path to address climate change while producing economically valuable nanomaterials. This work presents the progress and prospects of new large-scale syntheses of GNC allotropes via the C2CNT (CO₂ to Carbon Nano Technology) process. The C2CNT molten carbonate electrolysis technique enables the formation of Carbon NanoTubes (CNTs), Magnetic CNTs (MCNTs), Carbon Nano-Onions (CNOs), Carbon Nano-Scaffolds (CNSs), and Helical CNTs (HCNTs) directly from atmospheric or industrial CO₂. We discuss the morphology control enabled through variations in electrolyte composition, temperature, current density, and nucleation additives. We present results from scaled operations reaching up to 1000 tons/year CO₂ conversion and propose design approaches to reach megaton scales to support climate mitigation and GNC mass production. The products demonstrate high crystallinity, as evidenced by Raman, XRD, SEM, and TGA analyses, and offer promising applications in electronics, construction, catalysis, and medical sectors. Full article

In the context of critical challenges in curcumin-modified polyurethane synthesis—including limited curcumin bioavailability and suboptimal biodegradability/biocompatibility—a novel polyurethane material (Cur-PU) with good mechanical, shape memory, pH-responsive, and biocompatibility was synthesized via a one-pot, two-step synthetic protocol in which HO-PCL-OH served as the soft segment and curcumin was employed as the chain extender. The experimental results demonstrate that with the increase in Cur units, the crystallinity of the Cur-PU material decreases from 32.6% to 5.3% and that the intensities of the diffraction peaks at 2θ = 21.36°, 21.97°, and 23.72° in the XRD pattern gradually diminish. Concomitantly, tensile strength decreased from 35.5 MPa to 19.3 MPa, and Shore A hardness declined from 88 HA to 65 HA. These observations indicate that the sterically hindered benzene ring structure of Cur imposes restrictions on HO-PCL-OH crystallization, leading to lower crystallinity and retarded crystallization kinetics in Cur-PU. As a consequence, the material’s tensile strength and hardness are diminished. Except for the Cur-PU-3 sample, all other variants exhibited exceptional shape-memory functionality, with R_f and R_r exceeding 95%, as determined by three-point bending method. Analogous to pure curcumin solutions, Cur-PU solutions demonstrated pH-responsive chromatic transitions: upon addition of hydroxide ion (OH⁻) solutions at increasing concentrations, the solutions shifted from yellow-green to dark green and finally to orange-yellow, enabling sensitive pH detection across alkaline gradients. Hydrolytic degradation studies conducted over 15 weeks in air, UPW, and pH 6.0/8.0 phosphate buffer solutions revealed mass loss <2% for Cur-PU films. Surface morphological analysis showed progressive etching with the formation of micro-to-nano-scale pores, indicative of a surface-erosion degradation mechanism consistent with pure PCL. Biocompatibility assessments via L929 mouse fibroblast co-culture experiments demonstrated ≥90% cell viability after 72 h, while relative red blood cell hemolysis rates remained below 5%. Collectively, these findings establish Cur-PU as a biocompatible material with tunable mechanical properties, and pH responsiveness, underscoring its translational potential for biomedical applications such as drug delivery systems and tissue engineering scaffolds. Full article

Deoxyribonucleic acid (DNA) is not only a fundamental biological molecule but also a versatile material for constructing sensitive and specific biosensing platforms. Its ability to undergo sequence-specific hybridization via Watson–Crick base pairing enables both precise target recognition and the programmable construction of nanoscale structures. The demand for ultrasensitive detection increases in fields such as disease diagnostics, therapeutics, and other areas, and the inherent characteristics of DNA have driven the development of a wide range of signal amplification strategies. Among these, polymerase chain reaction (PCR), rolling circle amplification (RCA), and loop-mediated isothermal amplification (LAMP) represent powerful target-based methods that enzymatically increase the concentration of nucleic acid targets, thereby boosting detection sensitivity. In parallel, structure-based strategies leverage the nanoscale spatial programmability of DNA to construct functional architectures with high precision. DNA can be used as a scaffold, such as DNA nanostructures, to organize sensing elements and facilitate signal transduction. It can also function as a probe, like aptamers, to recognize targets with high affinity. These versatilities enable the creation of highly sophisticated sensing platforms that integrate molecular recognition and signal amplification. Driven by DNA nano-assembly capability, both target-based and structure-based approaches are driving the advancement of highly sensitive, selective, and adaptable diagnostic technologies. This review highlights recent developments in DNA nano-assembly-driven amplification strategies. Full article

The cryopreservation of three-dimensional (3D) biofabricated constructs is a key enabler for their clinical application in regenerative medicine. Unlike two-dimensional (2D) cultures, 3D systems such as encapsulated cell spheroids, molded hydrogels, and bioprinted tissues present specific challenges related to cryoprotectant (CPA) diffusion, thermal gradients, and ice formation during freezing and thawing. This review examines the current strategies for preserving 3D constructs, focusing on the role of biomaterials as cryoprotective matrices. Natural polymers (e.g., hyaluronic acid, alginate, chitosan), protein-based scaffolds (e.g., silk fibroin, sericin), and synthetic polymers (e.g., polyethylene glycol (PEG), polyvinyl alcohol (PVA)) are evaluated for their ability to support cell viability, structural integrity, and CPA transport. Special attention is given to cryoprotectant systems that are free of dimethyl sulfoxide (DMSO), and to the influence of hydrogel architecture on freezing outcomes. We have compared the efficacy and limitations of slow freezing and vitrification protocols and review innovative approaches such as temperature-controlled cryoprinting, nano-warming, and hybrid scaffolds with improved cryocompatibility. Additionally, we address the regulatory and manufacturing challenges associated with developing Good Manufacturing Practice (GMP)-compliant cryopreservation workflows. Overall, this review provides an integrated perspective on material-based strategies for 3D cryopreservation and identifies future directions to enable the long-term storage and clinical translation of engineered tissues. Full article

Due to its sarcoma-derived origin and the associated carcinogenic risks, as well as its lack of tissue-specific extracellular matrix biochemical cues, the use of the injectable gel scaffold Matrigel is generally restricted to research applications. Therefore, the development of new fully synthetic injectable gel scaffolds that exhibit performance comparable to Matrigel is a high priority. In this study, we developed a novel fully synthetic injectable gel scaffold by combining a biodegradable PLGA-PEG-PLGA copolymer, clay nanoparticle LAPONITE®, and L-arginine-loaded metal–organic frameworks (NU-1000) at the nano level. An aqueous solution of the developed hybrid scaffold (PLGA-PEG-PLGA/LAPONITE®/L-Arg@NU-1000) exhibited rapid sol–gel transition at body temperature following simple injection and formed a continuous bulk-sized gel, demonstrating good injectability. Long-term sustained slow release of L-arginine from the resultant gels can be achieved because NU-1000 is a suitable reservoir for L-arginine. PLGA-PEG-PLGA/LAPONITE®/L-Arg@NU-1000 hybrid gels exhibited good compatibility with and promoted the growth of human skeletal muscle satellite cells. Importantly, in vivo experiments using skeletal muscle injury model mice demonstrated that the tissue regeneration efficiency of PLGA-PEG-PLGA/LAPONITE®/L-Arg@NU-1000 gels is higher than that of Matrigel. Specifically, we judged the higher tissue regeneration efficacy of our gels by histological analysis, including MYH3 immunofluorescent staining, H&E staining, and Masson’s trichrome staining. Taken together, these data suggest that novel hybrid hydrogels could serve as injectable hydrogel scaffolds for in vivo tissue engineering and ultimately replace Matrigel. Full article

Electrospinning is a technique that enables the production of nano- and microfibrillar patterns that mimic the native extracellular matrix. However, these nanofibrous structures often lack mechanical properties suitable for reproducing the behavior of structurally complex tissues. Therefore, achieving more accurate and precise geometric structures be-comes a key challenge. In this context, additive manufacturing techniques such as 3D printing may allow for the development of tailored structures with highly controlled ar-chitecture and improved mechanical strength. However, in contrast with electrospinning, these techniques are commonly considered “low-resolution” techniques, unable to ma-nipulate structural details at the submicrometric scale. Hence, this review aims to intro-duce and discuss recent technological approaches based on combining these technologies for scaffold development in tissue engineering, detailing some distinct integration strate-gies correlating the outcomes to the benefits and drawbacks. Finally, a comprehensive analysis of the current state of the art in the registered intellectual property related to these integrated approaches will be proposed, assessing their distribution by geographic region and analyzing the main trends over time and future fallouts. Full article

Bioactive glass (BG) is a promising material known for its osteogenic, osteoinductive, antimicrobial, and angiogenic properties. For this reason, melt-quench-derived BG powders embedded into composite electrospun poly(ε-caprolactone) (PCL) mats represent an interesting option for the fabrication of bioactive scaffolds. However, incorporating BG into nano-/micro-fibers remains challenging. Our research focused on integrating two BG compositions into the mat structure: 45S5 and 45S5_MS (the former being a well-known, commercially available BG composition, and the latter a magnesium- and strontium-enriched composition based on 45S5). Both BG types were added at concentrations of 10 wt.% and 20 wt.%. A careful grinding process enabled effective dispersion of BG into a PCL solution, resulting in fibers ranging from 500 nm to 2 µm in diameter. The mats’ mechanical properties were not hindered by the inclusion of BG powder within the fibrous structure. Furthermore, our results indicate that BG powders were successfully incorporated into the scaffolds, not only preserving their properties but potentially enhancing their biological performance compared to unloaded PCL electrospun scaffolds. Our findings indicate proper cell differentiation and proliferation, supporting the potential of these devices for tissue regeneration applications. Full article

Despite the progress in cancer immunotherapy, therapeutic responses in solid tumors remain suboptimal due to the immunosuppressive nature of the tumor microenvironment (TME), limited immune cell infiltration, and inefficient delivery of immune-activating agents. Dendritic cell-based therapies possess strong immunological potential but face challenges in viability, standardization, and scalability. Likewise, exosomes and CAR-T cells are hindered by instability, production complexity, and limited efficacy in immune-excluded tumor settings. Objective: This study evaluates dendritic cell-derived vesicles (DC-Vesicles), embedded in a phospholipid-rich structural scaffold, as a multi-functional and scalable platform for immune modulation and therapeutic delivery. We aimed to assess their structural stability, immune marker preservation under clinical processing conditions, and potential to reprogram the TME. Methods and Results: DC-Vesicles were generated and analyzed using bottom-up proteomics via nanoLC–MS/MS on a timsTOF Pro 2 system under three conditions: fresh, concentrated, and cryopreserved. A consistent proteomic profile of over 400 proteins was identified, with cryopreserved samples retaining >90% of immune-relevant markers. Differential expression analysis confirmed stability of key immunological proteins such as HLA-A, QSOX1, ICAM1, NAMPT, TIGAR, and Galectin-9. No significant degradation was observed post-cryopreservation. Visualization through heatmaps, PCA, and volcano plots supported inter-condition consistency. In silico modeling suggested preserved capacity for M1 macrophage polarization and CD8⁺ T cell activation. Conclusions: DC-Vesicles demonstrate structural resilience and functional retention across storage conditions. Their cold-chain-independent compatibility, immune-targeting profile, and potential regulatory classification as Non-New Chemical Entities (NCEs) support their advancement as candidates for precision immunotherapy in resistant solid tumors. Full article

Severe skin damage poses a significant clinical challenge, as limited availability of skin donors, postoperative skin defects, and scarring often impair skin function. Traditional two-dimensional (2D) nanofibers exhibit small pore sizes that hinder cellular infiltration, unable to simulate the three-dimensional (3D) structure of the skin. To address these issues, we developed 3D porous nanofiber scaffolds composed of polycaprolactone–polylactic acid–mussel adhesive protein (PLGA-PCL-MAP) using low-temperature electrospinning combined with nano-spray technology. Meanwhile, this 3D scaffold features high porosity, enhanced water absorption, and improved air permeability. The incorporation of mussel adhesive protein (MAP) further increased the scaffold’s adhesive properties and biocompatibility. In vitro experiments demonstrated that the 3D nanofiber scaffolds significantly promoted the adhesion, proliferation, and migration of epidermal keratinocytes (HaCaTs) and human fibroblasts (HFBs), while providing ample space for inward cellular growth. Successful co-culture of HaCaT and HFBs within the scaffold revealed key functional outcomes: HaCaTs expressed keratinocyte differentiation markers CK10 and CK14, while HFBs actively secreted extracellular matrix components critical for wound healing, including collagen I, collagen III, and fibronectin. This skin substitute with a composite structure of epidermis and dermis based on three-dimensional nanofiber scaffolds can be used as an ideal skin replacement and is expected to be applied in wound repair in the future. Full article

In this study, poly(methyl methacrylate) (PMMA) nanofiber scaffolds reinforced with synthesized nano-hydroxyapatite (n-HA) were fabricated through electrospinning to enhance their potential for applications in bone tissue engineering. Sodium tripolyphosphate (STTP) was utilized as a surfactant to achieve a uniform distribution of particles and improve the structural integrity of the scaffolds. PMMA solutions were prepared at concentrations of the addition of STTP effectively stabilized n-HA dispersion, leading to enhanced fiber morphology, as confirmed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and transmission electron microscopy (TEM). The PMMA_10_HA_S nanofibers demonstrated a homogeneous fiber distribution with an average diameter of 345.40 ± 53.55 nm and a calcium content of 7.1%. Mechanical testing revealed that adding STTP enhanced the mechanical properties, with the n-HA-reinforced 10 wt.% PMMA nanofibers achieving a maximum tensile stress of 4.16 ± 2.13 MPa and an elongation of 7.1 ± 1.95%. Furthermore, cell cytotoxicity assays of different concentrations (25, 50, 75, and 100 mg/mL) using L929 fibroblast cells demonstrated no cytotoxic effect of PMMA_10_HA_S nanofibers. These findings, reinforced by STTP and n-HA, highlight the potential of PMMA_10_HA_S nanofiber scaffolds as promising candidates for bone tissue applications. Full article

Research on nano-sustained-release factors for bone tissue scaffolds has significantly promoted the precision and efficiency of bone-defect repair by integrating biomaterials science, nanotechnology, and regenerative medicine. Current research focuses on developing multifunctional scaffold materials and intelligent controlled-release systems to optimize the spatiotemporal release characteristics of growth factors, drugs, and genes. Nano slow-release bone scaffolds integrate nano slow-release factors, which are loaded with growth factors, drugs, genes, etc., with bone scaffolds, which can significantly improve the efficiency of bone repair. In addition, these drug-loading systems have also been extended to the fields of anti-infection and anti-tumor. However, the problem of heterotopic ossification caused by high doses has led to a shift in research towards a low-dose multi-factor synergistic strategy. Multiple Phase II clinical trials are currently ongoing, evaluating the efficacy and safety of nano-hydroxyapatite scaffolds. Despite significant progress, this field still faces a series of challenges: the immunity risks of the long-term retention of nanomaterials, the precise matching of multi-factor release kinetics, and the limitations of the large-scale production of personalized scaffolds. Future development directions in this area include the development of responsive sustained-release systems, biomimetic sequential release design, the more precise regeneration of injury sites through a combination of gene-editing technology and self-assembled nanomaterials, and precise drug loading and sustained release through microfluidic and bioprinting technologies to reduce the manufacturing cost of bone scaffolds. The progress of these bone scaffolds has gradually changed bone repair from morphology-matched filling regeneration to functional recovery, making the clinical transformation of bone scaffolds safer and more universal. Full article

Scaffolds play a crucial role in tissue engineering as regenerative templates. Fabricating scaffolds with good biocompatibility and appropriate mechanical properties remains a major challenge in this field. This study proposes a method for preparing multi-material scaffolds, enabling the 3D printing of collagen and thermoplastic elastomers at room temperature. Addressing the previous challenges such as the poor printability of pure collagen and the difficulty of maintaining structural integrity during multilayer printing, this research improved the printability of collagen by optimizing its concentration and pH value and completed the large-span printing of thermoplastic elastomer using a precise temperature-control system. The developed hybrid scaffold has an interconnected porous structure, which can support the adhesion and proliferation of fibroblasts. The scaffolds were further treated with different post-treatment methods, and it was proven that the neutralized and cross-linked collagen scaffold, which has both nano-fibers and a certain rigidity, can better support the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). The research results show that the collagen thermoplastic elastomer hybrid scaffold has significant clinical application potential in soft tissue and hard tissue regeneration, providing a versatile solution to meet the diverse needs of tissue engineering. Full article

Piezoelectric materials, due to their ability to generate an electric charge in response to mechanical deformation, are becoming increasingly attractive in the engineering of bone and neural tissues. This manuscript reports the effects of the addition of nanohydroxyapatite (nHA), introduction of gold nanoparticles (AuNPs) via sonochemical coating, and collector rotation speed on the formation of electroactive phases and biological properties in electrospun nanofiber scaffolds consisting of poly(vinylidene fluoride) (PVDF). FTIR, WAXS, DSC, and SEM results indicate that introduction of nHA increases the content of electroactive phases and fiber alignment. The collector rotational speed increases not only the fiber alignment but also the content of electroactive phases in PVDF and PVDF/nHA fibers. Increased fiber orientation and introduction of each of additives resulted in increased SFE and water uptake. In vitro tests conducted on MG-63 and hiPSC-NSC cells showed increased adhesion and cell proliferation. The results indicate that PVDF-based composites with nHA and AuNPs are promising candidates for the development of advanced scaffolds for bone and neural tissue engineering applications, combining electrical functionality and biological activity to support tissue regeneration. Full article

Background: Regeneration dentistry demonstrates significant challenges due to the complexity of different dental structures. This study aimed to investigate osteogenic differentiation of human pulp stem cells (hDPSCs) cultured on a 3D-printed poly lactic acid (PLA) scaffold coated with nano-hydroxyapatite (nHA) and naringin (NAR) as a model for a dental regenerative. Methods: PLA scaffolds were 3D printed into circular discs (10 × 1 mm) and coated with nHA, NAR, or both. Scaffolds were cultured with hDPTCs to identify cellular morphological changes and adhesion over incubation periods of 3, 7, and 21 days using SEM. Then, the osteogenic potential of PLA, PLA/nHA/NAR, or PLA scaffolds coated with MTA elutes (PLA/MTA scaffolds) were evaluated by measuring mineralized tissue deposition using calcium concentration assays and alizarin red staining (ARS). Also, immunofluorescence labelling of alkaline phosphatase (ALP) and dentine sialophosphoprotein (DSPP) within cultured cells were evaluated. Results: The highest cellular attachment was identified on the PLA/nHA/NAR scaffold, with morphological changes reflecting cellular differentiation. The highest calcium deposition and ARS were recognized in the PLA/nHA/NAR culture, with statistically significant difference (p < 0.05) compared to PLA/MTA. Also, ALP and DSPP markers showed statistically significantly higher (p < 0.05) immunoreactivity in cells cultured within PLA/nHA/NAR compared to PLA/MTA. Conclusions: The results confirm the osteogenic potential of PLA scaffolds coated with nHA/NAR for future animal and human investigations. Full article