Search Results (266)

Long bone formation in vertebrates proceeds via endochondral ossification, a sequential process that begins with mesenchymal condensation, advances through cartilage anlage formation, and culminates in its replacement by mineralized bone. Recent advances in inducible lineage tracing and single-cell genomics have revealed that, rather than being a uniform event, mesenchymal condensation rapidly segregates into progenitor pools with distinct fates. Centrally located Sox9⁺/Fgfr3⁺ chondroprogenitors expand into the growth plate and metaphyseal stroma, peripheral Hes1⁺ boundary cells refine condensation via asymmetric division, and outer-layer Dlx5⁺ perichondrial cells generate the bone collar and cortical bone. Concurrently, dorsoventral polarity established by Wnt7a–Lmx1b and En1 ensures that dorsal progenitors retain positional identity throughout development. These lineage divergences integrate with signaling networks, including the Ihh–PTHrP, FGF, BMPs, and WNT/β-catenin networks, which impose temporal control over chondrocyte proliferation, hypertrophy, and vascular invasion. Perturbations in these programs, exemplified by mutations in Fgfr3, Sox9, and Dlx5, underlie region-specific skeletal dysplasias, such as achondroplasia, campomelic dysplasia, and split-hand/foot malformation, demonstrating the lasting impacts of embryonic patterning errors. Based on these insights, regenerative strategies are increasingly drawing upon developmental principles, with organoid cultures recapitulating ossification centers, biomimetic hydrogels engineered for spatiotemporal morphogen delivery, and stem cell- or exosome-based therapies harnessing developmental microRNA networks. By bridging developmental biology with biomaterials science, these approaches provide both a roadmap to unravel skeletal disorders and a blueprint for next-generation therapies to reconstruct functional bones with the precision of the embryonic blueprint. Full article

Biological decision-making under uncertainty relies on somatic markers, which are affective signals that bias choices without exhaustive computation. This study biomimetically translates the Somatic Marker Hypothesis (SMH) into synthetic somatic markers (SSMs), a minimal and interpretable evaluative mechanism that assigns a scalar valence to compressed environmental states in the high-dimensional discrete grid-world Pixelverse, without modelling subjective feelings. SSMs are implemented as a lightweight Python routine in which agents accumulate valence from experience and use a simple threshold rule (θ = −0.5) to decide whether to keep the current trajectory or reset the environment. In repeated simulations, agents perform few resets on average and spend a higher proportion of time in stable “good” configurations, indicating that non-trivial adaptive behaviour can emerge from a single evaluative dimension rather than explicit planning in this small stochastic grid-world. The main conclusion is that, in this minimalist 3 × 3 Pixelverse testbed, SMH-inspired SSMs provide an economical and transparent heuristic that can bias decision-making despite combinatorial state growth. Within this toy setting, they offer a conceptually grounded alternative and potential complement to more complex affective and optimisation model. However, their applicability to richer environments remains an open question for future research. The ethical implications of deploying such bio-inspired evaluative systems, including transparency, bias mitigation, and human oversight, are briefly outlined. Full article

Pharmaceuticals and personal care products (PPCPs) are emerging contaminants posing ecological risks in wastewater. Constructed wetlands (CWs) offer sustainable treatment through integrated biological processes. In this study, a biomimetic microbial CW reactor was developed using 30 L aquariums with porous media, aeration setups, and surface plants to simulate natural wetland conditions. This design combines enhanced microbial degradation strategies using fungal (Trametes versicolor), bacterial (Pseudomonas aeruginosa), and consortia degradation, integrating multiple biological pathways. Synthetic wastewater containing 100 mg/L of selected PPCPs, including caffeine, methylparaben, and trichlorocarbanilide (TCC), was used to evaluate the degradation potential of these microbial treatments. While caffeine and methylparaben were effectively targeted, TCC degradation was inconclusive due to solubility limitations in the selected solvent. Over three months, system stability, plant growth, and microbial biomass were monitored, and contaminant degradation was tracked using Nuclear Magnetic Resonance analysis. Results demonstrated that individual fungal and bacterial treatments achieved near-complete caffeine degradation (99–100%) within seven weeks, while the combined treatment accelerated this process to just four weeks. Methylparaben followed a similar trend, achieving complete degradation by the seventh week. This study highlights the potential of microbial CW systems fortified with targeted microbial consortia as a scalable solution for pollutant removal. Future work should refine microbial combinations and analytical methods to expand the range of treatable pollutants. Full article

The alveolar epithelium plays a critical role in respiratory function, facilitating air exchange and serving as a barrier against inhaled pathogens. Its unique three-dimensional architecture, in which epithelial cells grow on spherical alveolar structures, significantly increases the surface area-to-volume ratio for efficient gas exchange but poses challenges for in vitro reconstruction. Here, we present a biomimetic alveolar model based on gelatin methacryloyl (GelMA) hydrogel microspheres with precisely controlled sizes and composition fabricated via microfluidic technology. These microspheres function as micro-scaffolds for cell adhesion and growth, and an oxygen-permeable honeycomb microwell array facilitates the rapid assembly of cell-laden microspheres into physiologically relevant alveolar-like structures. Using this model, the effects of toxic gas exposure and pathogen infection, and demonstrated its potential use for both basic physiological studies and pathological applications, was investigated. This system recapitulates key features of the alveolar microenvironment and offers a versatile platform for respiratory research and drug screening. Full article

With the explosive growth of data across various fields, effective data preprocessing has become increasingly critical. Evolutionary and swarm intelligence algorithms have shown considerable potential in feature selection. However, their performance often deteriorates in large-scale problems, due to premature convergence and limited exploration ability. To address these limitations, this paper proposes an algorithm named IHBOFS, a biomimetics-inspired optimization framework that integrates multiple adaptive strategies to enhance performance and stability. The introduction of the Good Point Set and Elite Opposition-Based Learning mechanisms provides the population with a well-distributed and diverse initialization. Furthermore, adaptive exploitation–exploration balancing strategies are designed for each subpopulation, effectively mitigating premature convergence. Extensive ablation studies on the CEC2022 benchmark functions verify the effectiveness of these strategies. Considering the discrete nature of feature selection, IHBOFS is further extended with continuous-to-discrete mapping functions and applied to six real-world datasets. Comparative experiments against nine metaheuristic-based methods, including Harris Hawk Optimization (HHO) and Ant Colony Optimization (ACO), demonstrate that IHBOFS achieves an average classification accuracy of 92.57%, confirming its superiority and robustness in high-dimensional feature selection tasks. Full article

Achilles tendon injuries are among the most frequent and debilitating musculoskeletal conditions, often resulting in incomplete healing and functional deficits. Conventional repair techniques primarily restore structural continuity but rarely achieve full biomechanical or histological regeneration. Recent advances in tissue engineering have introduced innovative strategies combining biomimetic scaffolds, cellular therapy, growth factors, and mechanical loading to promote regenerative rather than fibrotic repair. This review summarises the current understanding of Achilles tendon biology and healing mechanisms, with a focus on the integration of stem cell technologies, scaffold design, and mechanobiological conditioning. Various scaffold systems, including natural, synthetic, hybrid, and hydrogel-based constructs, are evaluated for their biocompatibility, mechanical performance, and tenoinductive potential. Preclinical studies demonstrate that mesenchymal stem cell (MSC)-loaded scaffolds exhibit significantly enhanced biomechanical outcomes in tendon defect models, including improved tensile strength, organized collagen I deposition and aligned fibre architecture in repaired constructs. While preclinical results are promising, clinical translation remains limited by regulatory, economic, and methodological challenges. Future research should prioritise standardised protocols, long-term functional outcomes, and interdisciplinary collaboration. Full article

Salivary gland carcinomas (SGCs) are aggressive malignancies with limited treatment options, primarily due to the complexity of the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) remodel the extracellular matrix (ECM), enhance cancer cell stemness, and drive drug resistance. This study introduces a decellularized CAF-derived spheroid system as a biomimetic platform to study tumor–stromal interactions in SGC. Multicellular spheroids were generated by co-culturing Medical Research Council cell strain 5 (MRC-5) fibroblasts (fetal lung-derived) with A253 salivary gland cancer cells, producing distinct spatial architecture, with fibroblasts at the core and cancer cells at the periphery. Compared with A253-only spheroids, A253/MRC-5 spheroids exhibited enhanced proliferation and elevated expression of stemness markers (aldehyde dehydrogenase 1 [ALDH1], CD133, cytokeratin 19 [CK19]). MRC-5 spheroids displayed robust ECM and growth factor expression that persisted after decellularization. Decellularized spheroids retained biological activity, enabling A253 cells to develop invasive phenotypes, metabolic reprogramming, and stemness-associated signatures. Transcriptomic analysis revealed a transition from proliferative pathways to stress-adaptive survival programs, mirroring in vivo tumor behavior. Moreover, A253 cells cultured with decellularized fibroblast spheroids exhibited altered cisplatin sensitivity, highlighting the critical role of stromal ECM in therapeutic response. In conclusion, this study establishes decellularized CAF spheroids as a simplified yet biologically relevant TME-mimetic platform. By recapitulating tumor–stromal crosstalk without live co-culture, this system provides a powerful tool for mechanistic studies of salivary gland cancer, preclinical drug screening, and development of stroma-targeted therapies. Full article

Background and Objectives: Currently, the development of local drug delivery systems for the treatment of cancer patients is a pressing issue. Such systems allow for the targeted delivery of anticancer drugs directly to the tumor site, ensuring prolonged drug release or reducing the risk of recurrence after tumor removal, minimizing the impact on healthy tissues and thereby reducing the overall toxic load on the body. This work is devoted to evaluating the prospects of using scaffolds based on low-modulus titanium Ti-15Mo alloy with a biomimetic coating as a platform for the local administration of the cytostatic drug cisplatin into the patient’s body. Methods: Porous coatings were obtained by plasma electrolytic oxidation in an aqueous solution of sodium phosphate and calcium acetate with the addition of various components. The influence of coating parameters on the corrosion resistance of samples and on the antiproliferative effect of cisplatin-loaded scaffolds was evaluated. Human K562 hemoblastosis, HT116 intestinal cancer, and SKOV3 ovarian cancer cell lines were used as cell models. Results: It was shown that the addition of sodium phosphate (the PS type electrolyte) provides the formation of a coating with a developed system of interconnected pores characterized by an attractive combination of parameters: high porosity (17%), high pore size (3.9 μm), and considerable thickness (17.4 μm). This coating demonstrated the best corrosion resistance in a Ringer solution as compared to the other tested states. In addition, the PS coating loaded with cisplatin exhibited a pronounced cytotoxic effect on cancer cells. This effect was attributed to its ability to fix cisplatin on the surface, which slows down its release into the extracellular environment, increasing the time of its action, thereby contributing to a more effective (by more than 3 times) suppression of tumor cell proliferation compared to the action of the standard form of the drug in the form of a solution when changing the growth medium and subsequent incubation for 48 h. Conclusions: PS scaffolds made of low-modulus titanium alloy Ti-15Mo with a biomimetic surface in an electrolyte based on an aqueous solution of sodium phosphate and calcium acetate with the addition of sodium silicate can be used as an advanced platform for the local delivery of the cytostatic drug cisplatin, which makes them promising for application in orthopedic oncology. Full article

Background: Human adipose-derived mesenchymal stem cells (hADMSCs) are widely used in regenerative medicine due to their ability to proliferate and differentiate. Bone tissue engineering represents an innovative alternative to traditional grafts by combining biomimetic materials, stem cells, and bioactive factors to promote bone regeneration. Gellan gum (GG) is a promising scaffold material owing to its excellent biocompatibility and favorable physicochemical characteristics; however, chemical modifications such as methacrylation are necessary to enhance its mechanical strength and long-term stability. In this in vitro study, osteoprogenitor cells are cultured for 21 days on three 3D-printed GGMA-based scaffolds to evaluate their biological response: (i) neat GGMA, (ii) GGMA functionalized with hydroxyapatite (HAp), and (iii) GGMA functionalized with eumelanin derived from black soldier fly (BSF-Eumelanin). Methods: Cell adhesion, viability, proliferation and osteogenic differentiation are evaluated using MTT assays, histological staining (H&E and Alizarin Red S), alkaline phosphatase (ALP) activity, and gene expression analysis of key osteogenic markers. Results: Our results show that all GGMA-based scaffolds support cell adhesion, growth, and proliferation, while BSF-Eumelanin and HAp notably enhance osteogenic differentiation compared to neat GGMA. Conclusions: These findings highlight the potential of embedding bioactive factors into GGMA scaffolds to improve osteoconductive and osteoinductive performance, offering a promising strategy for bone repair. Full article

Non-union fractures represent a significant clinical challenge requiring innovative therapeutic approaches. Silk fibroin (SF) scaffolds have gained recognition as advantageous biomaterials for bone tissue engineering due to their biocompatibility and mechanical characteristics. This study investigated the biocompatibility and osteoinductive potential of SF scaffolds functionalized with hydroxyapatite (HA) and loaded with platelet growth factors (PGFs) using hematopoietic stem cells (HSCs). SF scaffolds were prepared and functionalized with HA through methanol impregnation, while PGFs were obtained from platelet lysate via apheresis procedures. HSCs were cultured on different experimental groups, namely SF, SF-HA, PGF, SF-PGF, and SF-HA-PGF, assessing biocompatibility through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Live/Dead staining, and cytoskeleton analysis over 7 days. Osteoinductive properties were evaluated using Alizarin Red staining for mineral matrix deposition at 14 and 21 days. The MTT assay revealed the biocompatibility of all the experimental groups. The Live/Dead assay confirmed high cell viability, while the cytoskeleton analysis revealed well-organized actin filaments comparable to controls. Alizarin Red staining showed that PGF alone promoted early mineral matrix deposition at day 14, while SF-HA, SF-PGF, and SF-HA-PGF groups demonstrated significantly enhanced mineralization at day 21 compared with SF alone. The combination of silk fibroin scaffolds with platelet growth factors alone or with hydroxyapatite and platelet growth factors creates a biomimetic environment that supports cell viability and induces the osteogenic differentiation of hemopoietic stem cells. These findings suggest significant potential for clinical translation in treating non-union fractures and bone defects. Full article

Decellularized extracellular matrix (dECM) scaffolds preserve native tissue structure and biochemical cues while minimizing immune responses, creating biomimetic templates that promote cell integration and tissue remodeling. This review examines the current state of dECM research, encompassing decellularization methods, scaffold quality evaluation assays, and tissue-specific applications across dermis, nerve, heart, lung, adipose, and placental ECMs. We analyze commercially available dECM products and ongoing clinical trials, while highlighting recent advances including 3D bioprinting and the integration of dECM with stem cells and growth factors. Despite these promising developments, several challenges continue to limit broader clinical translation: protocol standardization, residual immunogenicity, mechanical durability, and regulatory, manufacturing, and cost barriers. To address these limitations, we outline future directions focusing on patient-specific scaffolds, scalable bioprocessing, and integrated biofabrication strategies that will enable the development of safe and effective dECM-based therapies. Full article

Background/Objectives: Trophoblast cell surface antigen 2 (Trop2), a transmembrane glycoprotein overexpressed in a broad spectrum of epithelial malignancies but minimally expressed in normal tissues, has emerged as a clinically relevant prognostic biomarker and therapeutic target, particularly in breast cancer. This study aims to develop an enhanced way of targeting Trop2 expression in tumors and blocking it using extracellular vesicles (EVs) bioengineered to express a nanobody sequence against Trop2 (NB60 E). Methods: Here, a plasmid construct was designed to express the Trop2 sequence, NB60, flanked with HA tag and myc epitope and a PDGFR transmembrane domain in the C-terminal region, and was transfected into HEK293T cells for EVs isolation. The potency of NB60 E to knock down Trop2 in letrozole-resistant breast cancer cells (LTLT-Ca and MDA-MB-468 cells) was initially investigated. Thereafter, the effects of NB60 E on the cell viability and downstream signaling pathway of Trop2 via MTT assay and Western blotting were determined. Lastly, we also examined whether NB60 E treatment in Jurkat T cells affects IL-6, TNF-α, and IL-2 cytokine production by enzyme-linked immunosorbent assay (ELISA). Results: Results revealed treatment with NB60 E significantly reduced surface Trop2 expression across both cell lines by 23.5 ± 1.5% in MDA-MB-468, and 61.5 ± 1.5% in LTLT-Ca, relative to the HEK293T-derived control EVs (HEK293T E). NB60 E treatment resulted in a marked reduction in LTLT-Ca cell viability by 52.8 ± 0.9% at 48 h post-treatment. This was accompanied by downregulation of key oncogenic signaling molecules: phosphorylated ERK1/2 (p-ERK 1/2) decreased by 30 ± 4%, cyclin D1 by 67 ± 11%, phosphorylated STAT3 (p-STAT3) by 71.8 ± 1.6%, and vimentin by 40.8 ± 1.4%. ELISA analysis revealed significant decreases in IL-6 (−57.5 ± 1.5%, 7.4 ± 0.35 pg/mL) and TNF-α (−32.1 ± 0.3%, 6.1 ± 1.2 pg/mL) levels, coordinated by an increase in IL-2 secretion (22.1 ± 2.7%, 49.2 ± 1.1 pg/mL). Quantitative analysis showed marked reductions in the number of nodes (−45 ± 4.4%), junctions (−55 ± 3.5%), and branch points (−38 ± 1.2%), indicating suppression of angiogenic capacity. In vivo experiment using near-infrared Cy7 imaging demonstrated rapid and tumor-selective accumulation of NB60 E within 4 h post-administration, followed by efficient systemic clearance by 24 h. The in vivo results demonstrate the effectiveness of NB60 E in targeting Trop2-enriched tumors while being efficiently cleared from the system, thus minimizing off-target interactions with normal cells. Lastly, Trop2 expression in LTLT-Ca tumor xenografts revealed a significant reduction of 41.0 ± 4% following NB60 E treatment, confirming efficient targeted delivery. Conclusions: We present a first-in-field NB60 E-grafted EV therapy that precisely homes to Trop2-enriched breast cancers, silences multiple growth-and-invasion pathways, blocks angiogenesis, and rewires cytokine crosstalk, achieving potent antitumor effects with self-clearing, biomimetic carriers. Our results here show promising potential for the use of NB60 E as anti-cancer agents, not only for letrozole-resistant breast cancer but also for other Trop2-expressing cancers. Full article

Integrating bioluminescent organisms as passive lighting sources in the built environment is currently a hot topic. However, there are several limitations facing the implementation and up-scaling of these naturally bioluminescent organisms in the built environment on architectural and urban scales, such as the scale, sensitivity, enclosure, and difficulty of maintenance. Moreover, there are complex technicalities and operational aspects of conventional bioreactors that host these bioluminescent agents, especially in terms of managing their recharge and effluent, not to mention their high maintenance cost. The current work offers a sustainable, stand-alone, bioluminescent urban screen system employing Aliivibrio fischeri CECT 524 bioink on 3D-printed customized scaffolds as bioreceptive panel design based on a field-diffusion pattern to host the bioluminescent bacterial bioink. The field-diffusion pattern was employed thanks to its proven efficiency in entrapment of the various microbial cultures. Three different growth media were tested for culturing Aliivibrio fischeri CECT 524, including Luria Bertani Broth (LB), the Tryptone Soy Broth (TSB), and the standard Marine Broth (MB). The results revealed that the Marine Broth (MB) media achieved the highest bioluminescent intensity and duration. The maximum light emission typically in range of ~490 nm of blue–green light captured by a conventional reflex camera (human eye vision) was observed for 10 consecutive days in complete darkness after 3–10 s, at a room temperature of 25 °C. This was visible mainly at the thin curvilinear peaks of the 3D-printed field pattern. P1 achieved the highest performance in terms of visible blue–green light, and a duration of 10 days of active bioluminescence was achieved without the need for refilling, thanks to the high number of peaks and narrow wells at <0.5 cm of its field-diffusion pattern. This study proves the efficiency of this biomimetic pattern in terms of the bioreceptivity of the bioluminescent bacterial bioink. Furthermore, the proposed 3D-printed urban screens proved their economic sustainability in terms of affordability and their minimized production processes, in addition to their easy maintenance and recharge. These results qualify these 3D-printed bioluminescent urban screens for easy and decentralized adoption and application on an architectural and urban scale. Full article

Cell-mediated extracellular matrix (ECM) self-assembly provides a biologically relevant approach for developing near-physiological tissue-engineered constructs by utilizing stromal cells to secrete and assemble ECM components in the presence of ascorbic acid. Despite its unique advantages, this method often results in scaffolds with limited mechanical properties, depending on the cell type. This research aimed to enhance the mechanical properties of these constructs by culturing cells derived from various sources, including skin, bladder, urethra, vagina, and adipose tissue, on electrospun scaffolds composed of polycaprolactone and collagen (PCLCOL). The hybrid scaffolds were evaluated using various in vitro assays to assess their structural and functional properties. Results showed that different stromal cells could deposit ECM on the PCLCOL with distinct composition compared to the ECM that was self-assembled on tissue culture plates (TCP). Additionally, cells cultured on PCLCOL exhibited a different growth factor secretion profile compared to those on TCP. Mechanical testing demonstrated that the hybrid scaffolds exhibited high mechanical properties and superior manipulability. These findings suggest that PCLCOL could be a promising platform for developing biomimetic scaffolds that combine enhanced mechanical strength with integrated biological cues for tissue repair. Full article

Objective: Yttria-stabilized tetragonal zirconia polycrystal (Y-TZP), a variant of zirconia (ZrO₂), has attracted interest as a substitute for titanium in dental and orthopedic implants, valued for its biocompatibility and aesthetics that resemble natural teeth. However, its bioinert surface limits osseointegration, making surface modifications such as calcium phosphate (CaP) coatings highly relevant. Materials and methods: The review process adhered to the PRISMA guidelines. Electronic searches of PubMed, Scopus, Web of Science, Embase, and Cochrane Library (July 2025) identified studies evaluating CaP-coated zirconia implants. Eligible studies included in vitro, in vivo, and preclinical investigations with a control group. Data on coating type, deposition method, and biological outcomes were extracted and analyzed. Results: A total of 27 studies were analyzed, featuring different calcium phosphate (CaP) coatings including β-tricalcium phosphate (β-TCP), hydroxyapatite (HA), octacalcium phosphate (OCP), and various composites. These coatings were applied using diverse techniques such as RF magnetron sputtering, sol–gel processing, biomimetic methods, and laser-based approaches. In multiple investigations, calcium phosphate coatings enhanced osteoblast attachment, proliferation, alkaline phosphatase (ALP) expression, and bone-to-implant contact (BIC) relative to unmodified zirconia surfaces. Multifunctional coatings incorporating growth factors, antibiotics, or nanoparticles showed additional benefits. Conclusion: CaP coatings enhance the bioactivity of zirconia implants and represent a promising strategy to overcome their inertness. Further standardized approaches and long-term studies are essential to verify their translational relevance. Full article