Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide and impose a substantial clinical and socioeconomic burden. Despite advances in medical, interventional, and surgical treatments, considerable residual cardiovascular risk persists, highlighting the need for effective and sustainable therapeutic approaches. Milk-derived extracellular vesicles (MDEVs) are heterogeneous lipid-bilayer vesicles present in human and bovine milk and have attracted increasing interest as potential orally administered biological nanocarriers. MDEVs carry diverse bioactive cargo, including proteins, lipids, messenger RNAs, microRNAs, and long non-coding RNAs, while their membrane-associated components may contribute to gastrointestinal stability, cargo protection, and interactions with intestinal cells. Emerging preclinical evidence suggests that MDEVs may influence inflammatory responses, oxidative stress, myocardial fibrosis, angiogenesis, and gut–heart axis signaling. However, direct evidence from cardiovascular disease models remains limited, and several proposed mechanisms are supported primarily by studies conducted in intestinal, metabolic, oncological, or other non-cardiovascular settings. MDEVs can also be engineered to carry nucleic acids, peptides, proteins, and small-molecule drugs or to introduce tissue-targeting properties. Nevertheless, their systemic absorption, biodistribution, cardiovascular tissue accumulation, and long-term safety after oral administration remain insufficiently defined. Moreover, milk source, processing conditions, isolation methods, co-isolated non-vesicular components, cargo composition, dose metrics, administration routes, and disease models may substantially affect the reported biological effects. Continued advances in purification, standardized characterization, rigorous biodistribution analysis, safety assessment, and scalable manufacturing are therefore required to determine the translational potential of MDEVs in cardiovascular therapy.
Adipose tissue is a vital component in both regenerative medicine and cultivated meat, yet the selection of the cellular starting material remains an underexplored determinant of adipose construct performance in bioprinting. This mini-review explores next-generation adipose tissue engineering, emphasizing bioprinting functional fat with adipocytes at the intersection of these two fields. While current adipose bioprinting strategies predominantly rely on adipose-derived stem or stromal cells for their expandability and manufacturability, mature adipocytes (ACs) and microfat emerge as alternative cell sources with distinct advantages in functional fidelity, metabolic relevance, and immediate tissue-like behavior. However, these approaches impose fundamentally different biological and engineering constraints that directly influence biofabrication strategy, biomaterial design, and translational potential. This mini review offers a structured comparison of mature adipocyte-, progenitor-, and microtissue-based strategies, highlighting features that influence biofabrication and applicability. Scalability is identified as a major bottleneck in translation, with a focus on process robustness, batch-to-batch reproducibility, and manufacturing concepts relevant to preclinical test systems, clinical applications, and large-scale cultivated meat (CM) production. By proposing a cell-source-guided framework for adipose bioprinting, this mini review aims to provide a practical decision-making perspective for developing next-generation adipose constructs.
The Notch signaling pathway is pivotal in joint homeostasis and the pathogenesis of osteoarthritis (OA). Under physiological conditions, transient or physiological Notch signaling maintains cartilage matrix synthesis to preserve joint function. Under pathological conditions, persistent or excessive activation of Notch signaling suppresses the expression of chondrogenic genes and induces the production of catabolic factors, thereby driving OA progression. From a cellular perspective, the Notch signaling pathway exerts crucial regulatory role in the functions of various resident cell types within the joint. For instance, it regulates the differentiation and maturation of chondrocytes, influences the chondrogenic differentiation process of mesenchymal stem cells (MSCs), and modulates the phenotype of fibroblast-like synoviocytes (FLSs). At the level of the extracellular cartilage microenvironment, the Notch signaling pathway participates in extracellular matrix (ECM) homeostasis imbalance and inflammatory factor activation in OA by regulating the expression of downstream genes. Furthermore, Notch controls chondrocyte hypertrophic degeneration through extensive molecular crosstalk with the TGF-β/BMP, Wnt/β-catenin, NF-κB, and Hippo-YAP pathways. Beyond cartilage, Notch plays a crucial role in promoting neurovascular invasion at the osteochondral junction and abnormal subchondral bone remodeling, which directly contributes to joint pain and structural failure. Many Notch-targeted approaches, such as pharmacological inhibitors, RNA-based therapies, and molecular interventions targeting ligands and downstream effectors, have been investigated because existing treatments are unable to stop the progression of OA. Simultaneously, stem cell-based approaches use precise Notch modulation to improve cartilage repair and chondrogenic differentiation. However, systemic administration of small-molecule inhibitors raises concerns about off-target effects and delivery inefficiency in avascular cartilage, while conventional stem cell injections frequently encounter problems like phenotypic instability and limited durability. In conclusion, in-depth studies on the Notch signaling pathway in OA not only clarify the pathogenesis of OA but also lay a theoretical and experimental foundation for the development of innovative therapeutic strategies.
There is a strong need to quantify skin mechanical properties for flap design in plastic surgery, such as syndactyly reconstruction. Quantitative measurement of skin mechanical properties enables more accurate surgical planning, thereby improving surgical outcomes and reducing complications. Although a large number of methods and devices have been proposed, nearly none of them have been applied in surgical practice. We therefore conducted a comprehensive narrative review of the literature published from 1969 to the present on in vivo skin mechanical property measurement. To identify the factors limiting clinical application, studies using suction, indentation, torsion, stretching, non-contact, and computational approaches were screened and categorized based on their underlying mechanical assumptions and boundary conditions. Three fundamental paradoxes limiting clinical translation were identified: (1) conventional engineering characterization requires destructive testing, which is incompatible with preserving intact skin for surgery; (2) in vivo measurements inevitably capture surrounding tissue boundary constraints rather than intrinsic skin mechanics; and (3) engineering analyses depend on stress-based parameters and skin thickness, whereas thickness is rarely considered in clinical flap planning. Furthermore, inverse numerical models, such as finite element analysis, rely on idealized assumptions that may not fully reflect complex, patient-specific surgical conditions. Rather than attempting to identify a universally accurate conventional measurement device, this review proposes a novel paradigm shift: combining non-invasive microstructural imaging with computer vision and machine learning to predict mechanical transition thresholds (e.g., collagen alignment and tangent modulus) directly from unstretched tissue, with the goal of enabling patient-specific, computational surgical flap planning.
IntroductionInvestigating the stress distribution generated by orthodontic forces within the periodontal ligament (PDL) is critical for quantifying mechanical stimuli, correlating them with subsequent histological responses, and ultimately identifying evidence-based optimal force levels. This study aimed to evaluate the combined biomechanical effects of alveolar bone height loss, tooth movement type, and alveolar bone density on the initial retraction of the maxillary central incisor, and to quantify the weighting of each factor on PDL stress.MethodsA three-dimensional (3D) finite element model of the maxilla, dentition, PDL, and orthodontic appliances was constructed based on cone-beam computed tomography (CBCT) data. Eighty experimental conditions were established by combining five levels of alveolar bone height loss (0–4 mm), four tooth movement types, and four alveolar bone density levels (simulated via cortical bone Young’s modulus: 12,500–27,500 MPa). A 1 N bilateral retraction force was applied. The initial displacements of the crown and root and the maximum PDL von Mises stress were calculated. Multiple linear regression was used to quantify the factor contributions.ResultsAlveolar bone height loss significantly increased both tooth displacement and PDL stress. Uncontrolled and controlled tipping resulted in greater sagittal retraction and root intrusion, whereas bodily and controlled root movements were associated with more distolingual rotation. However, bone density affected displacement but had no significant effect on PDL stress. The regression model (R2 = 0.80) revealed that tooth movement types exerted the strongest influence on PDL stress, followed by alveolar bone height loss (β = 0.535, p < 0.05). All conditions, except for 4 mm bone loss combined with uncontrolled tipping, exhibited PDL stresses below the 0.026 MPa safety threshold.ConclusionThese findings provided novel quantitative biomechanical evidence regarding the combined effects of these variables and could guide individualized force control strategies and the development of AI-assisted orthodontic decision-making systems.
Periodontitis is a chronic inflammatory oral disease characterized by irreversible alveolar bone resorption, which severely impairs oral health and even leads to tooth loss. Clinical bone augmentation therapy for alveolar bone defects mainly relies on exogenous bone substitute materials. However, traditional materials are prone to implantation failure due to the persistent inflammatory microenvironment and bacterial infection in the periodontal area. The addition of antibiotics to improve antibacterial properties not only induces bacterial resistance but also causes systemic toxic and side effects, making it difficult to meet clinical treatment needs. This review focuses on the core demand for bone substitute materials in periodontitis treatment to simultaneously achieve antibacterial, anti-inflammatory, and osteogenic functions—an essential characteristic that distinguishes such materials from conventional antibacterial drugs and single-function bone graft materials. We systematically elaborate on multiple interrelated inflammatory signaling pathways (e.g., RANKL/RANK/OPG, cGAS-STING, NF-κB, JAK-STAT, MAPK, PI3K/AKT, HIF-1, TGF-β/SMAD, Wnt/β-catenin, Hippo) and inflammasome mechanisms involved in periodontitis-associated alveolar bone resorption, exploring potential targets for screening excellent anti-inflammatory and osteogenic active molecules. On this basis, we summarize modification strategies for bioceramic bone tissue-engineered substitutes, including incorporating metal ions (Ag, Cu, Sr, Mn, Mg, Zn, etc.) and natural anti-inflammatory molecules into the material matrix to enhance their multifunctional properties while maintaining favorable physical and biological characteristics. We also discuss structural and functional optimization of composites via surface morphology modification, photothermal, and photodynamic coating construction to improve adaptability to the periodontal inflammatory microenvironment. These reconstructed multifunctional composite bioceramic materials integrate antibacterial, anti-inflammatory, and osteogenic functions, eliminating periodontal bacterial infection, alleviating local chronic inflammation, and actively promoting osteoblast differentiation and alveolar bone defect repair, thereby perfectly matching the pathological characteristics of periodontitis. This review clarifies the core design concept of multifunctional integration for bioceramic bone tissue-engineered substitutes in periodontitis treatment and provides a theoretical basis and technical reference for developing novel bone graft materials with clinical transformation potential.
Terpenoids (isoprenoids) constitute one of the largest and most structurally diverse families of natural products with application ranging from flavors, pharmaceuticals to biofuels. Conventional extraction from plants is often limited by low yields, seasonal variability, and environmental constraints; whereas, chemical synthesis requires toxic chemicals and energy-intensive processes. Consequently, microbial cell factories have emerged as sustainable and industrially scalable alternatives for terpenoid biosynthesis. Different microorganisms possess distinct physiological and metabolic advantages, including efficient precursor supply, tolerance to toxic products, internal storage for hydrophobic compounds, utilization of renewable carbon sources, and compatibility with complex biosynthetic pathways. Furthermore, several microbial hosts have strains with Generally Recognized as Safe (GRAS) status, making them attractive candidates for food and nutraceutical applications, although their regulatory acceptance ultimately depends on the production strain, genetic modifications, manufacturing process, product, and intended use. In addition, photosynthetic cyanobacteria offer a promising platform for direct conversion of CO2 into terpenoids, providing opportunities for more resource-efficient and sustainable biomanufacturing. Therefore, strategic host selection is a crucial step in designing efficient microbial platforms for terpenoid production. The present review provides a host-centric perspective by comparing conventional and emerging microbial cell factories, highlighting their physiological strengths, product spectrum, industrial applicability, and strategic considerations for sustainable and application-specific terpenoid biomanufacturing.
Biopharmaceuticals are the originating products of biotechnology, an area of increased focus for strategic U.S. leadership. The discovery, development, and manufacturing of biopharmaceuticals create large amounts of data, which is then managed and preserved for business and regulatory purposes. In accordance with the resource-based view management framework, this data is a resource which, when combined with the right capabilities, is foundational to building a company’s competitive market advantage. Big Data Capabilities to acquire, analyze, curate, store, and use data for targeted purposes across the entire biopharmaceutical manufacturing lifecycle are key to realizing business value from big data collections. This paper describes these capabilities in relation to recent advances in biopharmaceutical manufacturing and the benefits these capabilities can help realize. We argue that developing shared capabilities benefits both individual businesses, who can adopt and adapt them to establish their own strategy and competitive advantage, as well as the entire industry, which advances biopharmaceutical science through shared knowledge and collaboration. This paper was derived from extensive material collected from biopharmaceutical manufacturing industry subject matter experts gathered by the Big Data Program of the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL).
BackgroundThe use of autologous growth factors, such as those contained in Hypoxia-Preconditioned Serum (HPS) and Platelet-Rich Plasma (PRP), represents a promising strategy to enhance regenerative processes in injured nerves. As an initial in vitro study, we investigated the effects of these secretomes on the neuroblastoma cell line N2a.MethodsHPS and PRP were first compared with normal serum (NS) using a protein microarray to detect neurologically related growth factors. Subsequently, N2a cells were cultured with three different secretome concentrations (0.1%, 1%, and 10%) for up to 96 h and analyzed for proliferation (cell counting), viability (Alamar Blue), cytotoxicity (LDH assay), combined proliferation and migration (scratch assay), and neurite outgrowth.ResultsMicroarray analysis identified 30 neurotrophic, regulatory, and inflammatory factors in both HPS and PRP. Compared with PRP, HPS contained significantly higher levels of BDNF, CNTF, and VEGF-A, as well as the regulatory factors IL-6, TGF-β, and LIF. Several neurodegeneration-associated markers, including FAS, TNF-α, and IL-8, were also elevated in HPS. Proliferation and migration were most strongly stimulated by the 1% concentration of HPS and PRP, which also maintained high viability and low cytotoxicity. After 96 h, both PRP and HPS markedly enhanced neurite outgrowth by increasing total neurite count, neurite length, neurite-covered area, and branching points. PRP-0.1% and -1% produced the strongest effects, with up to 1.7-fold higher values across assessed parameters than the negative control, whereas HPS-0.1% increased these parameters by up to 1.4-fold. Further analyses demonstrated that these effects occurred alongside marked cell proliferation. Although the proportion of neurite-bearing cells (NBCs) declined over time because total cell expansion outpaced the increase in NBCs, normalization of neurite parameters to NBCs revealed up to 1.7-fold increases in neurite count, neurite length, neurite-covered area, and branching points per NBC, with the strongest effects observed in HPS-0.1% and PRP-0.1%.ConclusionHPS and PRP promoted expansion of the neurite network while enhancing neurite elaboration of NBCs despite pronounced proliferative effects. These findings identify HPS and PRP as biologically active secretomes with potential to support neuronal structural remodeling, warranting investigation in primary neuronal cultures and in vivo models of peripheral nerve regeneration.
IntroductionMidstance is a key instant in running, marking the transition from braking phase to propulsion phase. Despite its significance for stability and force transmission, a standard identification method of midstance instant is lacking, leading to inconsistent data interpretations. This study aimed to systematically compare different midstance instant identification methods and to highlight how they affect trunk and lower-limb kinematics in both able-bodied sprinters and sprinters with lower limb amputation.Methods22 able-bodied athletes, 4 athletes with unilateral transtibial and 4 athletes with unilateral transfemoral amputation performed two maximal 60-m sprints on an instrumented track. Kinematic and kinetic data were recorded using 10 infrared cameras and 9 embedded force platforms. Seven methods were considered, including kinematic and kinetic approaches. Sagittal absolute angles of trunk, thigh, and shank segments, as well as the hip, knee and ankle joints were extracted at the instants identified by each method. Both temporal differences and corresponding body postures at the detected instants were evaluated across methods and against the theoretical midpoint of stance (50%). Differences were assessed using either one-way repeated measures ANOVA or Friedman tests, depending on data normality, followed by Bonferroni post-hoc comparisons when appropriate.ResultsInstants identified as midstance consistently preceded the temporal midpoint of the stance phase across methods considering both able-bodied and athletes with lower-limb amputation. Kinematic methods showed limited consistency, identifying different instants within the stance phase. Their agreement with kinetic-based methods was only partial and depended on both the identification method and the athlete group. Consequently, midstance identified with different methods reflected distinct body postures within the stance phase. This resulted in significant variations in segment and joint angles, potentially leading to different biomechanical interpretations of sprinting.DiscussionSince the present findings suggest that method performance may differ across able-bodied athletes, athletes with transtibial amputation, and athletes with transfemoral amputation, researchers and practitioners should carefully consider the choice of method, clearly disclose it and ensure its consistent application.
IntroductionSuccessfully managing bl eeding bone defects relies on biomaterials capable of promoting early hemostasis alongside osteogenesis. While 3D-printed hydroxyapatite (3DP-HA) scaffolds possess osteoconductivity, their clinical utility can be limited by poor blood stability and inadequate initial hemostatic properties. To address these challenges, this preliminary study investigates the surface modification of 3DP-HA scaffolds using carboxymethyl cellulose (CMC) and its calcium-crosslinked derivative (CMC–Ca).Materials and methodsScaffolds were coated with either 1% or 2% CMC, or a CMC–Ca complex at varying formulations (1:1, 1:2, and 2:1). Total porosity and mean pore diameter were evaluated via micro-computed tomography (micro-CT). Surface morphology and elemental properties were characterized via scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Early in vitro hemostatic tendencies were evaluated through blood absorption and whole-blood clotting index (BCI) assays. Preliminary cytocompatibility and early osteogenic response were assessed by observing cell attachment via SEM and measuring alkaline phosphatase (ALP) activity at Day 7 using a human fetal osteoblast cell line (hFOB 1.19).ResultsAll modified formulations maintained total porosity ranging from 54.08% to 61.85%. Blood absorption capacity was comparable among all groups without statistically significant differences. For the in vitro clotting assay, the 2:1 CMC–Ca formulation exhibited a lower blood clotting index value than the other scaffold groups, suggesting a favorable initial coagulation response under the tested conditions. In vitro biological assays provided early descriptive evidence that the coatings permitted cell attachment and spreading by Day 7. Furthermore, ALP activity remained comparable across all groups, indicating that the surface modifications did not inherently suppress early-stage osteogenic signaling at the investigated time point.ConclusionThis preliminary study demonstrates that surface-modified 3DP-HA scaffolds maintained macro-porosity while the addition of CMC and CMC–Ca coatings provided early indications of in vitro hemostatic potential and early osteogenic compatibility. In particular, the 2:1 CMC–Ca formulation showed a positive initial blood clotting tendency without descriptive impairment of osteoblastic function. While further comprehensive, higher-powered quantification and mechanistic assays are required, these initial results offer a potential baseline strategy for developing surface-modified bone grafts.
ObjectiveTillaux-Chaput fractures are avulsion fractures involving the tibial insertion of the anterior inferior tibiofibular ligament. Inadequate fixation may result in distal tibiofibular syndesmotic instability and post-traumatic ankle arthritis. Conventional fixation methods, such as cannulated screws and suture anchor fixation, exhibit inherent limitations in the management of small or comminuted fragments. This study aimed to compare the biomechanical performance of cannulated screw fixation, suture anchor fixation, and a newly developed distal tibiofibular locking plate system for Tillaux-Chaput fractures using finite element analysis.MethodsComputed tomography data from a healthy adult male ankle were used to reconstruct a three-dimensional finite element model consisting of the tibia, fibula, and talus. A Tillaux-Chaput fracture was simulated at the anterolateral distal tibia. Four fixation models were established: cannulated screw fixation, suture anchor fixation, and two configurations of the novel locking plate system. Five physiological loading conditions were simulated, including plantar flexion, dorsiflexion, internal rotation, external rotation, and single-leg standing. The maximum von Mises stress and total displacement of both the fracture fragment and fixation devices were evaluated.ResultsAcross all loading conditions, the novel locking plate configurations exhibited lower peak stress and displacement of the fracture fragment than both cannulated screw and suture anchor fixation. The plate-2 fixation demonstrated the most favorable overall performance, with fracture fragment stress ranging from 2.28 to 4.70 MPa under non-standing conditions and 4.63 MPa during single-leg standing. Under internal and external rotation, the cannulated screw model showed the highest fragment stress, reaching 30.72 and 29.42 MPa, respectively. During single-leg standing, the suture anchor fixation showed the highest fragment stress of 43.19 MPa. The locking plate models also exhibited a more uniform stress distribution and better control of fragment displacement, particularly under torsional loading.ConclusionThe novel distal tibiofibular locking plate system provided superior biomechanical stability compared with cannulated screw and suture anchor fixation in this finite element model of Tillaux-Chaput fracture. By combining plate support, locking screw fixation, and suture-assisted reinforcement, this system may offer a promising fixation strategy for small and comminuted Tillaux-Chaput fragments.
Sericin protein is derived from silk cocoons from silkworms. Sericin functions as a glue to bond the two fibroin filaments together in the silk cocoon. It is a hydrophilic, hot water-soluble macromolecular glycoprotein. In the silk industry, sericin is usually removed and discarded as waste during the degumming process of silk yarn or fabrics, often by boiling with soap water. Besides being readily available and inexpensive, sericin is biocompatible and biodegradable. In recent times, sericin has received considerable attention due to its numerous versatile properties and potential applications in various areas, including cosmetics, pharmaceuticals, food, sustained drug delivery, and the fabrication of functional biomaterials, particularly in the biomedical field. Sericin, as a biomaterial with biocompatibility, immune-compatibility, biodegradability, anti-inflammatory, antibacterial, antioxidant, and photoprotective properties, has been identified as a potential biomaterial. This review aims to outline and contextualize recent advancements in sericin research, with a special focus on tissue engineering applications. These include insight into sericin gene expression in the silkworm (Ser1 to Ser6) and the use of sericin as a biomaterial in various forms, such as films, fibers, sponges, gels, and bio-coatings for implants, as well as micro/nano vehicles for targeted delivery systems. Although sericin is mainly described as a waste-derived biomaterial, this review attempts to integrate sericin gene diversity, extraction strategies, and structure–function relationships to identify the key determinants of its translational potential for tissue engineering applications.
Molecular stabilisation of mRNA is central to the development of therapeutics. Stabilisation is gained through modifications that cause mRNA to resist degradation, evade immune recognition, and prolong expression. These modifications introduce degrees of biological orthogonality, which, in this context, is the extent to which a molecule becomes invisible to the natural systems that would otherwise process or eliminate it. We propose that orthogonality provides a framework for understanding biosecurity risks across the spectrum of synthetic nucleic acid modification, from current mRNA therapeutics to mirror life. We develop this framework through a five-stage continuum from engineered mRNA to fully orthogonal mirror-life systems, using the 2024 scientific moratorium that was recommended for mirror life as a biosecurity governance endpoint. Across this spectrum, there is an increasing degree to which engineered genetic material can resist degradation and evade immune recognition, and a threshold at which this genetic material could be replicated. mRNA has minimal biosecurity issues because it is detectable, immunologically decomposable and unable to replicate, whereas mirror life would be highly undetectable, minimally decomposable, and replicable. Orthogonality, however, does not appear only at these extremes, and we suggest that biosecurity-relevant risks can accumulate progressively as we engineer greater orthogonality. Orthogonality should be a significant factor in designing biosecurity governance, alongside sequence screening and product-level assessments. We suggest a trajectory-focused oversight that monitors, across research programmes, the properties that turn orthogonality into risk and triggers staged reviews as they advance. The properties in question are persistence, reflected in half-life extension, nuclease resistance, and environmental persistence, along with invisibility to recognition and surveillance and the capacity for autonomous replication.
Amended Engineered Soil (AES), a functional substrate incorporating biomass-derived straw fiber, has been applied for the ecological restoration of degraded slopes. However, how AES affects the coordinated responses of substrate structure, root development, and rhizosphere microbiome assembly during early-stage restoration remains unclear. In this study, AES and Conventional Engineered Soil (CES) were compared during a 90-day slope restoration experiment using Lolium perenne as the target species. Compared with CES, AES substantially improved substrate moisture and nutrient conditions, with water content increasing from approximately 10.4%–16.6% and available phosphorus increasing more than fivefold. AES also promoted the formation of large water-stable aggregates, indicating improved structural stability of the reconstructed substrate. These changes were accompanied by marked improvements in vegetation establishment, including a 18.4% increase in plant height, more than 40% increase in dry biomass, and a pronounced increase in root length. Root tensile strength was also enhanced, suggesting greater belowground reinforcement. AES significantly increased bacterial richness and Shannon diversity, whereas the fungal response was mainly reflected in increased richness rather than diversity. Correlation analysis further showed close associations among substrate nutrient conditions, plant growth, root reinforcement, and microbial diversity. These findings suggest that AES promotes early-stage slope restoration through the coordinated improvement of substrate quality, vegetation establishment, root development, and rhizosphere microbial communities, while providing a sustainable pathway for biomass resource utilization.
IntroductionMaintaining appropriate foot-ground contact is important for walker-assisted lower-limb exoskeleton training. Excessive plantar loading may increase initial-contact impact and actuator load, whereas excessive unloading may reduce frictional contact and contact stability. Passive spring support can provide impact buffering, but it cannot adjust the support working point according to gait phase or plantar-pressure feedback.MethodsThis study proposes a multi-zone plantar-pressure-guided position control method for the support-force adjustment plate of a walker-assisted lower-limb exoskeleton. The system combines a fixed-stiffness spring with a vertical screw-driven adjustment plate. Total plantar pressure was obtained by fusing signals from 18 pressure cells on each instrumented foot and served as the main feedback variable. Regional plantar pressures and the center of pressure supported gait-phase recognition and contact-state estimation. A phase-related plantar-pressure target band was used as an engineering constraint to maintain stable foot-ground contact. Experiments involved three healthy male participants under no-spring, passive-spring, and proposed-control conditions during low-speed frame-assisted walking.Results and discussionIn the proposed-control condition, peak total plantar pressure was 0.687±0.015 BW, 21.2% lower than in the no-spring condition and 6.7% lower than in the passive-spring condition. Relative to the no-spring condition, the loading rate decreased from 9.02±0.53 to 2.56±0.07 BW/s, and the initial-contact impact impulse decreased from 0.143±0.009 to 0.064±0.002 BW⋅s. Hip-knee actuator electrical energy decreased from 38.95±2.20 to 27.24±1.54 J/gait cycle. After vertical-axis actuator energy was included, measured total actuator electrical energy was 30.60±1.68 J/gait cycle and remained lower than in both comparison conditions. These preliminary results suggest that plantar-pressure feedback can regulate support-plate position, attenuate contact impact, and reduce measured robotic actuator effort during low-speed walker-assisted walking.
BackgroundThe development of new hydrogels with antimicrobial, biocompatible, and controlled drug-release properties remains a significant challenge for wound-healing applications. The present study primarily focused on the development of PBC/κ-carrageenan composite hydrogels using two different types of probiotic bacterial cellulose (PBC) named as PBC_LP and PBC_PP, which have not been reported previously.MethodsIn this study, two distinct types of probiotic bacterial cellulose (PBC) were synthesized and designated as (PBC_LP) and (PBC_PP). The synthesis of these two distinct types of PBC was accomplished via in situ co-culture of Komagataeibacter xylinus with Lactiplantibacillus plantarum (previously Lactobacillus plantarum) and Pediococcus pentosaceus, separately. “PBC_LP” and “PBC_PP”-based hydrogels were developed by mixing PBCs with κ-Carrageenan using physical and potassium-ion-mediated ionic crosslinking methodologies. The bacterial cellulose (BC)-based hydrogel was selected as a control group for the experimental investigation.ResultsStructural characterization by FTIR and XRD confirmed successful integration of BC as well as PBC with κ-Carrageenan through physical and ionic interactions. SEM analysis revealed highly porous, interconnected three-dimensional architectures, which are favourable for biomedical applications. The hydrogels exhibited high porosity, high equilibrium liquid content (>95%), and rapid swelling within 30 min. Ionic crosslinking has been demonstrated to enhance gel fraction and rheological stability, while reducing pore size, porosity, and swelling behavior. Rheological analysis demonstrated stable viscoelastic gel-like behavior and shear-thinning properties, suitable for injectable or adaptable wound-healing materials. In vitro cytocompatibility studies using BALB/3T3 fibroblast cells demonstrated favourable cell viability, particularly for non-crosslinked PBC-based hydrogels, indicating favourable cellular interactions and proliferation. Furthermore, the hydrogels exhibited efficient uptake and a biphasic release profile for Betadine and Gentian Violet, with crosslinked systems showing a more controlled release profile. Importantly, PBC-containing hydrogels exhibited inhibitory activity against Escherichia coli, Staphylococcus aureus, and Candida albicans, which was further enhanced upon loading with antimicrobial agents.ConclusionThe PBC/κ-Carrageenan hydrogels developed in this study exhibit a combination of advantageous structural, biological, rheological, antimicrobial, and controlled-release properties. This underscores their potential as multifunctional wound-healing and antimicrobial-delivery systems, making the hydrogel a potential candidate for tissue-engineering and wound-healing applications after in vivo and clinical studies in future work.
IntroductionFor lower-limb exoskeletons to provide continuous position-reference assistance based on wearer state, the state of human–exoskeleton coupling must be sensed and translated into executable motor commands. However, when prediction outputs are directly fed into low-level controllers without further processing, command discontinuities and increased human–exoskeleton interaction torque may occur because of sensor noise or gait-phase transitions. Multisource information fusion and short-horizon gait prediction are therefore regarded as effective means of addressing this problem.MethodsIn this study, a prediction-driven position-reference control method based on multisource information fusion and a CNN-BiLSTM-GTN model is proposed. Surface electromyography (sEMG), inertial measurement unit (IMU) signals, plantar pressure, joint angles and angular velocities, and human–exoskeleton interaction torques are synchronously collected and organized as sliding-window inputs. In the developed CNN-BiLSTM-GTN model, local dynamic feature extraction by convolutional neural networks, temporal dependency modelling by bidirectional long short-term memory networks, and hip–knee synergistic coupling representation by a graph transformation network are integrated to enable accurate short-term prediction of hip and knee joint-angle trajectories. To make the predicted angles executable, a prediction-driven position-reference assistive strategy is designed. The predicted rolling position references are corrected using measured joint states, gait phase, plantar support state, and interaction torque, thereby generating smooth and bounded joint angle commands.ResultsExperimental results show that the proposed model achieved higher prediction accuracy than the evaluated prediction baselines. The closed-loop experiment further showed that the predicted trajectories could be converted into continuous and bounded position commands with stable tracking.DiscussionDuring the evaluated trials, the measured interaction torques remained below the predefined controller intervention threshold.
Orthopaedic surgical outcomes remain variable due to the poorly characterised, patient-specific post-surgical mechanical and physiological environment of implants and tissues. Differences in anatomy, alignment, neuromuscular function, and movement govern surgical-site loading and the tissue-level environment that drive healing. Coupled neuromusculoskeletal-finite element analysis (NMSK-FEA) workflows link these factors to the tissue-level mechanical and physiological environment, enabling preoperative evaluation of surgical strategies. This paper outlines current methodological considerations for the development and application of coupled NMSK-FEA workflows in orthopaedic biomechanics and identifies key priorities for their translation into clinically useful decision-support tools. We discuss methodological considerations and rationale for creating personalised MSK and NMSK models, patient-specific FEA geometry and material definition, transfer of NMSK outputs into FEA motion, loading, and boundary conditions, and selection of clinically relevant output measures. The workflow enforces NMSK and FEA parameter and boundary condition constraints to generate physiologically plausible outputs. Case studies of anterior cruciate ligament reconstruction and proximal femoral osteotomy are presented as methodological exemplars to illustrate how these NMSK-FEA workflow recommendations can be operationalised. These examples of NMSK-FEA workflows used in clinical cases show that mechanically optimal solutions can differ substantially between patients, thereby reinforcing the need for personalised biomechanical assessment. This paper presents practical recommendations for standardising and validating workflows and communicating key findings in a format that supports clinical decision making, laying the groundwork for prospective clinical validation. Together, these recommendations help move orthopaedic surgery planning beyond population averages towards patient-specific decision support at the point of care.
