Effective tissue adhesion under wet and dynamic physiological conditions remains a major challenge in wound management and tissue repair. Conventional tissue adhesives often suffer from limited biocompatibility, inadequate wet adhesion, or lack of degradability, restricting their broader clinical use. In recent years, biobased adhesive hydrogels have emerged as promising alternatives owing to their intrinsic biocompatibility, tunable mechanical properties, and capability to achieve robust adhesion in complex biological environments. In addition to being passive sealants, recent developments have made these materials smartly responsive to various stimuli (pH, temperature, light, magnetic field, ultrasound), achieving multifunctional and on-demand treatment performance. This review summarizes recent advances in biobased adhesive hydrogels, with emphasis on material design strategies, interfacial adhesion mechanisms, evaluation methodologies, and representative biomedical applications. Particular attention is given to how biobased materials address the challenges of wet-tissue adhesion, mechanical mismatch, and dynamic tissue interfaces. Finally, current limitations and future development directions are discussed, including translational challenges, minimally invasive applications, and the integration of multifunctionality with clinical practicality. This review aims to provide guidance for the rational design and clinical translation of next-generation biobased adhesive hydrogels.
Background: The development of small-diameter vascular grafts poses a significant challenge in tissue engineering. Despite advances in biofabrication, current vessel mimics lack remodelling and regenerative capabilities. Here, we sought to fabricate patient-specific bioengineered vessels using induced pluripotent stem cells (iPSCs) and functionalised biodegradable scaffolds to produce patient-specific bioengineered vessels. Methods: Human iPSCs were differentiated into mesenchymal stem cells (iMSCs) using SB431542, a TGF-β1 pathway inhibitor. iMSCs were further differentiated into vascular smooth muscle cells (VSMCs) with PDGF-BB and TGF-β1. Human bone marrow derived mesenchymal stem cells (hBM-MSC) from a commercial source were used for optimising differentiation protocols and quality control of iMSCs. Electrospun poly-L-lactide (PLLA) scaffolds coated with silk fibroin were developed for cell adhesion and growth. Both hBM-MSCs and iMSCs were seeded on these scaffolds for in-scaffold differentiation into VSMCs. The cell-laden scaffolds were rolled into tubular structures to scaffolds with ~3 mm inner diameters and ~20 mm in length. Results: Over 34-36 days, iPSCs were differentiated into cells with fibroblast-like morphology (iMSCs) expressing MSC markers CD73, CD90, and CD105, confirmed via immunofluorescence and flow cytometry. Thereafter, hBM-MSCs and iMSCs were successfully differentiating into VSMCs by supplementing media with PDGF-BB and TGF-β1 media over 9 days. Differentiated VSMCs expressed of α-SMA, CNN1, SM22, and MYH-11. Silk fibroin-coated PLLA scaffolds enhanced MSC adhesion and proliferation compared to uncoated scaffolds. The engineered tubular grafts displayed VSMC markers and mechanical properties akin to autologous coronary artery bypass grafting (CABG) grafts. Conclusion: This study developed a versatile method to fabricate tissue-engineered blood vessels using stem cells and silk fibroin-coated scaffolds. The resulting grafts exhibited tunica media-like structures and mechanical properties comparable to autografts used in CABG, showing strong potential for clinical application. ### Competing Interest Statement The authors have declared no competing interest.
Wearable electronics can achieve high-fidelity monitoring of pulse waveforms on the body surface enabling early diagnosis of cardiovascular diseases (CVDs). Textile-based wearable devices offer advantages in terms of high permeability and comfort. However, knitted strain sensors struggle to capture small-range deformation signals due to stress dissipation during friction and slip of yarns within the textiles. They are optimized for mechanical adaptability and adhesive capability. In this work, the stitch configurations of knitted structure are adjusted to optimize the energy dissipation ratio during deformation and waveform fitting performance. These electric-mechanical results enabled the selection of the most suitable knitted structure for the clinical diagnosis. On the other hand, the sensor's adhesion is optimized with respect to electrical-force-strain coupling and energy transfer efficiency at the interface between skin and sensor. The balance between the storage modulus and loss modulus are adjusted via the crosslinking degree of the polyacrylamide (PAAm) hydrogel network. As a result, the optimized knitted sensor enables stable collection of pulse waveforms from the radial and dorsalis pedis arteries. In human patient evaluations, the knitting-based strain sensor can distinguish patients with different potential CVD risks through extracted characteristic indicators.
The programmable materials have attracted attention for its groundbreaking functionalities across diverse applications, especially the curl-fiber reinforced composites inspired from collagen fibers. In this work, a novel helix-tubular composite (HTC) is developed through an integrated braiding-knitting fabrication approach. Experimental analyses demonstrate that the mechanical properties of HTC can be directionally optimized through parameterization of secondary conformational architecture and coupling states. Remarkably, HTC manifests triphasic nonlinear mechanical behavior analogous to native ligamentous tissues. This biomimetic response originates from synergistic interactions between the stiff helix conformation (the stiff conformation) and highly stretchable tubular conformation (the stretchable conformation). Furthermore, cyclic tensile evaluations reveal exceptional fatigue resistance exceeding thousands of cycles. This durability substantiates the composite’s potential for replicating the multifunctional mechanical behavior of biological tendons and ligaments. These findings establish a methodological framework for engineering advanced materials with spatially programmable mechanical properties through conformational coupling.
The growing demand for sustainable air filtration media has sparked interest in replacing traditional non-biodegradable filters with biodegradable materials. In this paper, a strategy was developed to regulate the fibre morphology of poly(L-lactic acid) (PLLA)/ poly(D-lactic acid) (PDLA) electrospun membranes by manipulating the molecular weights of the fibres. The strategy involved plasticisation of short PDLA chains and selective solvent-polymer interactions, which induced swelling and recrystallisation of the polymer chains to introduce a porous structure into the fibres and increase the tensile toughness of the fibrous membranes by 79 %. The porous fibres enlarged the specific surface area of the membranes and increased the PM0.3 (particulate matter with a diameter of less than 0.3 μm) removal with a filtration efficiency (η) from around 86 % to over 97 %. In addition, the exclusive stereocomplex-crystallites in the porous fibre membranes enabled the fibres to maintain high filtration efficiencies during continuous filtration at a relatively high temperature of 150 °C. Enhanced toughness, excellent fine particle capture, and outstanding thermal stability make porous PLLA/PDLA fibrous membranes a biodegradable alternative to currently high temperature air filtration materials.
The development of small-diameter vascular grafts remains a major challenge in tissue engineering due to limited remodelling and regenerative capabilities. While strides have been made on the biofabrication of vessel mimics, little clinical translation success has been achieved to treat coronary artery disease (CAD). This study aimed to fabricate patient-specific bioengineered vessels using induced pluripotent stem cells (iPSCs) and functionalised biodegradable scaffolds. Human iPSCs were differentiated into mesenchymal stem cells (iMSCs) using SB431542, then further into vascular smooth muscle cells (VSMCs) with PDGF-BB and TGF-β1. Human bone marrow-derived MSCs (hBM-MSCs) were used to optimise differentiation protocols. Electrospun poly-L-lactide (PLLA) scaffolds coated with silk fibroin improved cell adhesion and proliferation. Both hBM-MSCs and iMSCs were seeded on these scaffolds for in-scaffold VSMC differentiation. The resulting cell-laden scaffolds were rolled into tubular structures (~3 mm inner diameter, ~20 mm length). Over 34–36 days, iPSCs differentiated into iMSCs expressing MSC markers (CD73, CD90, CD105), followed by successful VSMC differentiation within 9 days, confirmed by α-SMA, CNN1, SM22 , and MYH-11 expression. Silk fibroin-coated PLLA scaffolds enhanced MSC adhesion and proliferation compared to uncoated scaffolds. The engineered tubular grafts displayed VSMC markers and mechanical properties akin to autologous coronary artery bypass grafts (CABGs). This study developed a versatile method to fabricate tissue-engineered blood vessels using stem cells and silk fibroin-coated scaffolds. The resulting grafts exhibited tunica media-like structures and mechanical properties comparable to autografts used in CABG, showing strong potential for clinical application.
The transport of nanoparticles in polymer networks has critical implications in biology and medicine, especially through thermophoresis in response to temperature gradients. This study presents a single-particle energy-conserving dissipative particle dynamics (seDPD) method by integrating a single-particle model into the energy-conserving DPD model to simulate the mesoscopic thermophoretic behavior of nanoparticles in polymer matrices. We first validate the newly developed seDPD model through comparisons with analytical solutions for nanoparticle viscosity, thermal diffusivity, and hydrodynamic drag and then demonstrate the effectiveness of the seDPD model in capturing thermophoretic forces induced by temperature gradients. The results show that nanoparticles driven by the Soret forces exhibit unique transport characteristics, such as drift velocity and diffusivity, leading to a significant acceleration of nanoparticle diffusion in the polymer network, which has been known as the giant acceleration of diffusion. Quantifying how nanoparticles move in flexible polymer networks sheds light on the interaction dynamics of nanoparticles within polymer networks, providing insight into nanoparticle behavior in complex environments that could be leveraged in various applications from drug delivery to material design.
Due to the intrinsic non-invasive nature, cost-effectiveness, high safety, and real-time capabilities, besides diagnostic imaging, ultrasound as a typical mechanical wave has been extensively developed as a physical tool for versatile biomedical applications. Especially, the prosperity of nanotechnology and nanomedicine invigorates the landscape of ultrasound-based medicine. The unprecedented surge in research enthusiasm and dedicated efforts have led to a mass of multifunctional micro-/nanosystems being applied in ultrasound biomedicine, facilitating precise diagnosis, effective treatment, and personalized theranostics. The effective deployment of versatile ultrasound-based micro-/nanosystems in biomedical applications is rooted in a profound understanding of the relationship among composition, structure, property, bioactivity, application, and performance. In this comprehensive review, we elaborate on the general principles regarding the design, synthesis, functionalization, and optimization of ultrasound-based micro-/nanosystems for abundant biomedical applications. In particular, recent advancements in ultrasound-based micro-/nanosystems for diagnostic imaging are meticulously summarized. Furthermore, we systematically elucidate state-of-the-art studies concerning recent progress in ultrasound-based micro-/nanosystems for therapeutic applications targeting various pathological abnormalities including cancer, bacterial infection, brain diseases, cardiovascular diseases, and metabolic diseases. Finally, we conclude and provide an outlook on this research field with an in-depth discussion of the challenges faced and future developments for further extensive clinical translation and application.
Clinical cognitive advancement within the Alzheimer’s disease (AD) continuum is intimately connected with sustained accumulation of tau protein pathology. The biological brain age and its gap show great potential for pathological risk and disease severity. In the present study, we applied multivariable linear support vector regression to train a normative brain age prediction model using tau brain images. We further assessed the predicted biological brain age and its gap for patients within the AD continuum. In the AD continuum, evaluated pathologic tau binding was found in the inferior temporal, parietal-temporal junction, precuneus/posterior cingulate, dorsal frontal, occipital, and inferior-medial temporal cortices. The biological brain age gaps of patients within the AD continuum were notably higher than those of the normal controls (p < 0.0001). Significant positive correlations were observed between the brain age gap and global tau protein accumulation levels for mild cognitive impairment (r = 0.726, p < 0.001), AD (r = 0.845, p < 0.001), and AD continuum (r = 0.797, p < 0.001). The pathologic tau-based age gap was significantly linked to neuropsychological scores. The proposed pathologic tau-based biological brain age model could track the tau protein accumulation trajectory of cognitive impairment and further provide a comprehensive quantification index for the tau accumulation risk.
Electrospun fibre has shown great potential in tissue engineering and regenerative medicine due to its high specific surface area and extracellular matrix-mimicking structure. However, fabricating an electrospun fibrous scaffold with controllable complex 3D macroscopic configuration remains a challenge. In the present study, a novel method was designed to transform 2D electrospun poly (L-lactic acid) (PLLA) fibrous membrane to tubular PLLA fibrous scaffolds with 3D complex but tailored configuration. The electrospun PLLA fibrous membrane was rolled around a designed mould and then treated with acetone. Treated vascular grafts’ length, diameter, and shape can be tailored by the mould parameters. Moreover, treated vascular grafts achieve favourable mechanical properties (Young’s modulus = 155 MPa, tensile stress = 8.79 MPa and radial force = 2.2 N) and the mechanical properties could be engineered on demand. In addition, treated vascular grafts kept their initial structure and size during long-term in vitro experiments once they were formed. In addition, with the acetone-induced recrystallization of PLLA, pristine solid PLLA fibres were changed to hierarchical porous PLLA fibres with ultra-high specific surface area (28.9 m2/g) and wettability (water contact angle = 101.32°), which has positive effects on cell adhesion and proliferation ability. A7r5 in vitro experiment shows that the proliferation rate of treated vascular grafts increased 153% at day 4 and 170.6% at day 7 compared with pristine vascular grafts.
Integrated diagnostic and therapeutic dressings are desirable to relieve diabetic patients who often suffer from diabetic foot ulcers (DFUs) and peripheral vascular diseases (PVDs). However, it is highly difficult to monitor the pulse waves with fidelity under wet environments and connect the waveforms to diseases through a small strain sensor. Additionally, immobilizing MXenzyme to regulate spatially heterogeneous levels of reactive oxygen species (ROS) and applying active intervention to enhance ulcer healing on a single structure remain a complex task. To address these issues, we designed a multiscale wearable dressing comprising a knitted all-textile sensing array for quantitatively investigating the pulse wave toward PVD diagnosis. MXenzyme was loaded onto the dressing to provide multiple enzyme mimics for anti-inflammatory activities and deliver electrical stimulation to promote wound growth. In mice, we demonstrate that high and uniform expression of the vascular endothelial growth factor (VEGF) is observed only in the group undergoing dual mediation with electrical stimulation and MXenzyme. This observation indicates that the engineered wound dressing has the capability to accelerate healing in DFU. In human patient evaluations, the engineered dressing distinguishes vascular compliance and pulse period, enabling the diagnosis of arteriosclerosis and return blockage, two typical PVDs. The designed and engineered multiscale dressing achieves the purpose of integrating diagnostic peripheral vessel health monitoring and ulcer healing therapeutics for satisfying the practical clinical requirements of geriatric patients.
Wearable photothermal materials can capture light energy in nature and convert it into heat energy, which is critical for flexible outdoor sports. However, the conventional flexible photothermal membranes with low specific surface area restrict the maximum photothermal capability, and loose structure of electrospun membrane limits durability of wearable materials. Here, an ultrathin nanostructure candle soot/ multi-walled carbon nanotubes / poly (l-lactic acid) (CS/MWCNTs/PLLA) photothermal membrane is first prepared via solvent-induced recrystallization. The white blood cell membrane-like nanowrinkles with high specific surface area are achieved for the first time and exhibit optimal light absorption. The solvent-induced recrystallization also enables the membrane to realize large strength and durability. Meanwhile, the membranes also show two-sided heterochromatic features and transparency in thick and thin situations, respectively, suggesting outstanding fashionability. Nanowrinkled photothermal membranes by novel solvent-induced recrystallization show high flexibility, fashionability, strength, and photothermal characteristics, which have huge potential for outdoor warmth.
Large bone defects, often resulting from trauma and disease, present significant clinical challenges. Electrospun fibrous scaffolds closely resembling the morphology and structure of natural ECM are highly interested in bone tissue engineering. However, the traditional electrospun fibrous scaffold has some limitations, including lacking interconnected macropores and behaving as a 2D scaffold. To address these challenges, a sponge-like electrospun poly(L-lactic acid) (PLLA)/polycaprolactone (PCL) fibrous scaffold has been developed by an innovative and convenient method (i.e., electrospinning, homogenization, progen leaching and shaping). The resulting scaffold exhibited a highly porous structure (overall porosity = 85.9 %) with interconnected, regular macropores, mimicking the natural extracellular matrix. Moreover, the incorporation of bioactive glass (BG) particles improved the hydrophilicity (water contact angle = 79.7 degrees) and biocompatibility and promoted osteoblast cell growth. In-vitro 10-day experiment revealed that the scaffolds led to high cell viability. The increment of the proliferation rates was 195.4 % at day 7 and 281.6 % at day 10. More importantly, Saos-2 cells could grow, proliferate, and infiltrate into the scaffold. Therefore, this 3D PLLA/PCL with BG sponge holds great promise for bone defect repair in tissue engineering applications.
Bacteria-initiated cancer therapy has been demonstrated high therapeutic efficacy against cancer. However, the undesired therapeutic efficacy and induced systematic inflammation storm compromise the therapeutic effect and outcome. Herein, a thermally-activated living nanomedicine composed of reactive biohybrid (designated as Sa@FeS) is rationally designed and engineered for enhancing hydrogen sulfide (H2S)-combined chemodynamic oncotherapy by biomineralizing ferrous sulfide nanoparticles (FeS NPs) onto the surface of a Salmonella typhimurium strain (Sa) without reducing bacterial activity. Ascribed to the deep penetration capability of Sa, FeS NPs facilitate photothermally-enhanced catalytic Fenton reaction of decomposing endogenous H2O2 into cytotoxic hydroxyl radicals deep in tumor tissues upon near infrared irradiation. Meanwhile, Sa bacteria maintain sustained H2S release within tumor for achieving H2S-induced intracellular acidosis that favors the generation of reactive oxygen species synergistically. Of note, the thermally-triggered all-in-one strategy effectively inhibits bacterial viability, thus reducing the risk of systematic inflammation storm and ensuring biosafety. Therefore, the engineered nano-bacteria living system exerts the thermally-enhanced nanocatalytic and gas therapies to effectively eradicate tumors, providing a distinct paradigm for the combination of synthetic biology and nanomedicine in tumor therapy.
Electrospinning technology for fabricating nanofiber films and the Hummer method for synthesizing graphene oxide (GO), along with subsequent reduction, have been significantly advanced, demonstrating immense potential for large-scale industrial applications. Nanofibrous films loaded with reduced graphene oxide (rGO) have been widely explored for their applications in electromagnetic shielding, the biomedical fields, and pollutant adsorption. However, fragile mechanical performance of electrospun fibers with limited surface post-treatment methods has somewhat hindered their further industrial development. In response to this challenge, we propose a dual-regulation strategy involving post-treatment to form porous nanofiber films and the controlled flake size of rGO for surface coating during preparation. This approach aims to achieve poly(l-lactic acid) (PLLA)/rGO electrospun fibrous films with enhanced mechanical properties. It offers a roadmap for the continued application and standardized production of fibrous films loaded with rGO.
Flexible electrochemical sensors can adhere to any bendable surface with conformal contact, enabling continuous data monitoring without compromising the surface's dynamics. Among various materials that have been explored for flexible electronics, metal-organic frameworks (MOFs) exhibit dynamic responses to physical and chemical signals, offering new opportunities for flexible electrochemical sensing technologies. This review aims to explore the role of electrocatalysis in MOF films specifically designed for flexible electrochemical sensing applications, with a focus on their design, fabrication techniques, and applications. We systematically categorize the design and fabrication techniques used in preparing MOF films, including in situ growth, layer-by-layer assembly, and polymer-assisted strategies. The implications of MOF-based flexible electrochemical sensors are examined in the context of wearable devices, environmental monitoring, and healthcare diagnostics. Future research is anticipated to shift from traditional microcrystalline powder synthesis to MOF thin-film deposition, which is expected to not only enhance the performance of MOFs in flexible electronics but also improve sensing efficiency and reliability, paving the way for more robust and versatile sensor technologies.
Electromagnetic interference shielding and thermal management by wearable devices show great poten-tial in emerging digital healthcare. Conventional metal films implementing the functions must sacrifice either flexibility or permeability, which is far from optimal in practical applications. In this work, an ultra-thin (15 mu m), flexible, and porous Cu/PLLA fibrous membrane is developed by depositing copper particles on the polymer substrate. With novel acetone & heat treatment procedure, the membrane is considerably stronger while maintaining the porous fibre structure. Its fantastic breathability and super high electrical conductivity (9471.8130 S/cm) enable the composites to have fast electrical heating char-acteristics and excellent thermal conductivity for effective thermal management. Meanwhile, the porous polymer substrate structure greatly enhances the diffusion of conductive substances and increases the electromagnetic interference shielding effectiveness of the membranes (7797.98 dB cm2/g at the H band and 8072.73 dB cm2/g at the Ku band respectively). The composites present high flexibility, breathability, and strength with the functions of thermal management and electromagnetic shielding, showing great potential for future portable electronic devices and wearable integrated garments. (c) 2023 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science & Technology.
Hierarchical porous poly(l-lactic acid) PLLA@TiO2 fibrous membranes have been successfully fabricated by a facile electrospinning/post-treatment method. The unique blossoming porous structure created by inducing the crystallization of PLLA chains in acetone post-treatment increases the specific surface area and exposes the TiO2 nanoparticles (NPs) on the fiber surface. The porous PLLA@TiO2-0.1 membrane using a PLLA:TiO2 weight ratio of 1:5 achieves the highest photocatalytic efficiency. Methylene blue (MB) is used to observe the removal of contaminants and evidence stable removal kinetics over five cycles under the same conditions. Intriguingly, there is a sine functional relationship between the hydrophobic PLLA@TiO2 membranes measured by the water contact angle (WCA) and the removal kinetic constants k fitted by the experimental data on photocatalytic degradation, which can be used to investigate the mechanism between hydrophobicity and photocatalytic degradation of the membranes. Due to their excellent photocatalytic degradation efficiency, recycling, and stability, porous PLLA@TiO2 fibrous membranes have promising application prospects in photocatalytic water treatment.