Biomimetic Hydrogel Research Articles

Biomimetic Resveratrol-Loaded Sericin Hydrogel: Augmented Antimicrobial and Wound Healing Potential in Animal Model

The development and advances in designing effective wound healing is a challenge encountered for ages. Recent studies have utilized sericin as an excellent wound healing biomaterial owing to properties such as inexpensive, naturally occurring, easily accessible, biocompatible, non-immunogenic and biodegradable. In the present research an attempt has been made to develop an efficient wound dressing with a blend composed of resveratrol incorporated into a hydrogel of chitosan, sericin and PVA (Polyvinyl Alcohol). The incorporation of sericin and resveratrol in a hydrogel is a novel amalgamation, combined with the unique antibacterial, antioxidant, and anti-inflammatory properties of chitosan, projected to create a synergistic effect that significantly accelerates wound healing. The selected hydrogels exhibited a porous network, in vitro release of 72.18±1.23 % and suitable spreadability. Furthermore, the antimicrobial studies viz. agar diffusion, broth dilution and biofilm formation assay revealed significant potential of the hydrogel which was comparable to the marketed formulations (Betadine®). Additionally, the in vivo studies in wound excision model demonstrated significantly higher wound closure in animal groups treated with F2 gel when compared with toxic groups, and other treatment groups. Further the histopathological studies give auxiliary evidence of accelerated wound healing in terms of rapid reepithelization and collagen formation. The study showed that the prepared hydrogel can be a promising wound dressing for treating wounds.

Silkworm cocoon bionic design in wound dressings: A novel hydrogel with self-healing and antimicrobial properties

Hydrogels with rapid wound-healing capabilities and antimicrobial effects are gaining significant interest in related fields. Nonetheless, developing a multifunctional hydrogel wound dressing with injectable self-assembling, self-healing, antimicrobial properties, and efficient skin wound-healing capabilities remained a formidable challenge. In this experiment, we drew inspiration from silkworm cocoons' natural formation and protective mechanisms, employing a novel physical cross-linking method to create an injectable and self-healing quaternary hydrogel successfully. The hydrogel is based on a matrix of silk fibroin/silk sericin (SF/SS), with 1,2-dimyristoyl-sn-glycero-3-phosphate sodium salt (DMPG) serving as a physical cross-linking agent to form the hydrogel network structure, and the incorporation of silver nanoparticles (AgNPs) further enhances its antimicrobial capabilities. Our biomimetic hydrogel, which replicated the chemical properties of silkworm cocoons, demonstrated excellent hydrophilicity with a water contact angle that ranged from 37 to 52°. Its tensile and compressive resistance was approximately four times greater than that of a pure SF hydrogel, and its swelling performance was about three times higher than that of a pure SF hydrogel. Furthermore, the hydrogel exhibited an impressive bacterial inhibition rate of over 98 % in bacterial growth and inhibition experiments, which provided a solid foundation for accelerating wound healing. Likewise, experiments with mice and histological analyses revealed that on day 7, the expression of TNF-α and IL-1β in the wound tissues treated with the SF/SS/AgNPs hydrogel was significantly reduced by >25 % compared to the blank control group. This reduction indicates that the hydrogel could decrease the production of inflammatory cytokines, potentially aiding in the acceleration of wound healing and mitigation of inflammation-related adverse reactions. By day 14, the wounds were healed mainly, with the wound area reduced by 17 % compared to that of the blank group. This demonstrates the significant potential of this cocoon-mimetic hydrogel in accelerating wound healing and providing wound protection.

Biomimetic hydrogel evaporator with excellent salt-rejection performance via edge-preferential crystallization and ion-transport effects

Solar steam generation has been considered a compellent desalination technology due to its environmental friendliness and sustainability, while interfacial salt crystallization and low freshwater yield are two serious issues that constrain its widespread application. In this work, inspired by lotus seedpod, a biomimetic evaporator containing conductive hydrogel was fabricated through 3D printing. The printed evaporator has excellent solar absorption, good mechanical properties, high water capture ability, and reduced vaporization enthalpy, which are exactly desired by good evaporators. Furthermore, the vertical micro-channels and networks inside hydrogel promote the transport of ions from the interface to bulk seawater, and the constructed edge petals drive salt ions to crystallize at the edges, both of these strategies suppress the salt crystallization and ensure long-term continuous operation of the evaporator in concentrated (25 wt%) seawater. Due to these positive effects, the evaporator can achieve 2.413 and 1.889 kg·m−2·h−1 steam yield under one sun in pure water and concentrated (25 wt%) seawater, which is much higher than the 2D evaporator and competitive among the reported evaporators. This work paves the road for the practical utilization of hydrogel in solar desalination.

Prussian Blue Nanohybridized Multicellular Spheroids as Composite Engraftment for Antioxidant Bone Regeneration and Photoacoustic Tomography.

Regulating the complex microenvironment after tooth extraction to promote alveolar bone regeneration is a pressing challenge for restorative dentistry. In this study, through modulating the mechanical properties of the cellular matrix, we guided various types of cells by self-organizing to form multicellular spheroids (MCSs) and hybridized MCSs with Prussian Blue nanoparticles (PBNPs) in the process. The constructed Prussian Blue nanohybridized multicellular spheroids (PBNPs@MCSs) with empowered antioxidant functions effectively reduced cell apoptosis under peroxidative conditions and exhibited enhanced ability to regulate the microenvironment and promote bone repair both in vitro and in vivo. In addition, the PBNPs@MCSs exhibited enhanced photoacoustic imaging ability to trace low doses of PBNPs. Therefore, the constructed PBNPs@MCSs based on the biomimetic hydrogel can be used as a form of an engraftment building block, with a greater potential for pro-bone repair application in the complex microenvironment of the oral cavity.

Preparation and properties of biomimetic bone repair hydrogel with sandwich structure.

One of the critical factors that determines the biological properties of scaffolds is their structure. Due to the mechanical and structural discrepancies between the target bone and implants, the poor internal architecture design and difficulty in degradation of conventional bone implants may cause several adverse outcomes. To date, many scaffolds, such as 3-D printed sandwich structures, have been successfully developed for the repair of bone defects; however, the steps of these methods are complex and costly. Hydrogels have emerged as a unique scaffold material for repairing bone defects because of their good biocompatibility and excellent physicochemical properties. However, studies exploring bioinspired hydrogel scaffolds with hierarchical structures are scarce. More efforts are needed to incorporate bioinspired structures into hydrogel scaffolds to achieve optimal osteogenic properties. In this study, we developed a low-cost and easily available hydrogel matrix that mimicked the natural structure of the bone's porous sandwich to promote new bone growth and tissue integration. A comprehensive evaluation was conducted on the microstructure, swelling rate, and mechanical properties of this hydrogel. Furthermore, a 3D finite element analysis was employed to model the structure-property relationship. The results indicate that the sandwich-structured hydrogel is a promising scaffold material for bone injury repair, exhibiting enhanced compressive stress, elastic modulus, energy storage modulus, and superior force transmission.

Magneto-Enzymatic Microgels for Precise Hydrogel Sculpturing.

The inclusion of hollow channels in tissue-engineered hydrogels is crucial for mimicking the natural physiological conditions and facilitating the delivery of nutrients and oxygen to cells. Although bio-fabrication techniques provide diverse strategies to create these channels, many require sophisticated equipment and time-consuming protocols. Herein, collagenase, a degrading agent for methacrylated gelatin hydrogels, and magnetic nanoparticles (MNPs) are combined and processed into enzymatically active spherical structures using a straightforward oil bath emulsion methodology. The generated microgels are then used to microfabricate channels within biomimetic hydrogels via a novel sculpturing approach that relied on the precise coupling of protein-enzyme pairs (for controlled local degradation) and magnetic actuation (for directional control). Results show that the sculpting velocity can be tailored by adjusting the magnetic field intensity or concentration of MNPs within the microgels. Additionally, varying the magnetic field position or microgel size generated diverse trajectories and channels of different widths. This innovative technology improves the viability of encapsulated cells through enhanced medium transport, outperforming non-sculpted hydrogels and offering new perspectives for hydrogel vascularization and drug/biomolecule administration. Ultimately, this novel concept can help design fully controlled channels in hydrogels or soft materials, even those with complex tortuosity, in a single wireless top-down biocompatible step.

Engineering a 3D Biomimetic Peptides Functionalized-Polyethylene Glycol Hydrogel Model Cocultured with Endothelial Cells and Astrocytes: Enhancing In Vitro Blood-Brain Barrier Biomimicry.

The blood-brain barrier (BBB) poses a significant challenge for drug delivery and is linked to various neurovascular disorders. In vitro BBB models provide a tool to investigate drug permeation across the BBB and the barrier's response to external injury events. Yet, existing models lack fidelity in replicating the BBB's complexity, hindering a comprehensive understanding of its functions. This study introduces a three-dimensional (3D) model using polyethylene glycol (PEG) hydrogels modified with biomimetic peptides that represent recognition sequences of key proteins in the brain. Hydrogels were functionalized with recognition sequences for laminin (IKVAV) and fibronectin peptides (RGD) and chemically cross-linked with matrix metalloprotease-sensitive peptides (MMPs) to mimic the extracellular matrix of the BBB. Astrocytes and endothelial cells were seeded within and on the surface of the hydrogels, respectively. The barrier integrity was assessed through different tests including transendothelial electrical resistance (TEER), the permeability of sodium fluorescence (Na-F), the permeability of Evan's blue bound to albumin (EBA), and the expression of zonula occluden-1 (ZO-1) in seeded endothelial cells. Hydrogels with a combination of RGD and IKVAV peptides displayed superior performance, exhibiting significantly higher TEER values (55.33 ± 1.47 Ω·cm2) at day 5 compared to other 2D controls including HAECs-monoculture and HAECs-cocultured with NHAs seeded on well inserts and 3D controls including RGD hydrogel and RGD-IKVAV monoculture with HAECs and RGD hydrogel cocultured with HAECs and NHAs. The designed 3D system resulted in the lowest Evan's blue permeability at 120 min (0.215 ± 0.055 μg/mL) compared to controls. ZO-1 expression was significantly higher and formed a relatively larger network in the functionalized hydrogel cocultured with astrocytes and endothelial cells compared to the controls. Thus, the designed 3D model effectively recapitulates the main BBB structure and function in vitro and is expected to contribute to a deeper understanding of pathological CNS angiogenesis and the development of effective CNS medications.

Injectable Biomimetic Hydrogel Constructs for Cell-Based Menopausal Hormone Therapy with Reduced Breast Cancer Potential.

Hormone replacement therapy (HRT) has been a primary method in menopausal women and patients with ablated ovaries, but safety has been a concern. Cell-based HRT has emerged as an alternative approach without side effects causing pharmaceutical HRT via 3-dimensionally engineered constructs layering ovarian hormone-producing cells. In this study, we applied micro-sized ovarian cell-laden hydrogel beads as an approach to cell-based HRT using a minimally invasive method in the menopausal rat model. Here, we constructed GC/TC-laden microbeads (GTBs; GC, granulosa cell; TC, theca cell) that allow crosstalk between endocrine cells, encapsulating multiple beads for the figuration of the original ovary. We assessed the ovarian hormone production function of GTB through invitro culture for 90 days. We applied it to a menopausal rat model and confirmed that GTB-injected rats restored their endocrine function, leading to the regeneration of the thinned endometrium and the maintenance of regular estrous cycles in some individuals. Additionally, it was observed to alleviate menopausal symptoms, including body weight gain and osteoporosis. Notably, the GTB-injected rats did not show mammary gland hyperplasia observed in the pharmaceutical HRT groups and exhibited fewer p53- and KI67-positive and an increase in phosphatase and tensin homolog-positive mammary gland epithelial cells compared to pharmaceutical hormone-treated rats. These results suggest that GTB-based HRT could present a lower risk of breast cancer compared to conventional pharmaceutical-HRT use. Our study highlights the potential of cell-based HRT using an injectable artificial ovary, offering a safer alternative for women requiring HRT.

Polyvinyl alcohol /chitosan biomimetic hydrogel enhanced by MXene for excellent electromagnetic shielding and pressure sensing

Traditional electromagnetic shielding materials are difficult to realize practical applications due to excessive fillers, poor mechanical properties, and difficulty in preservation, etc. Hydrogel is a biomaterial with good biocompatibility and sustainability, which not only can overcome the aforementioned issues, but its biomimetic hierarchical porous structure also enables multifunctional applications. In this paper, a honeycomb-like unidirectional porous wall structured hydrogel is prepared by a simple freeze-thaw cycle and salting out method. Polyvinyl alcohol (PVA) and chitosan (CS) form a double cross-linked network (DN) enhanced by MXene, resulting in excellent mechanical and flexibility. Due to the synergistic effects of MXene, water, Fe3O4, abundant interfaces and micrometer porous wall structure, the electromagnetic shielding performance is enhanced. EMI SE increases by 30.7 dB as the MXene concentration increases from 0 to 1.5 wt%, and EMI SE increases from 7.9 to 66.7 dB as the water content increases from 0 to 76 %. Besides this, we encapsulate the hydrogel into a simple sensor, the signal response is rapid, the response /recovery time is 50/100 ms respectively, and it exhibits good sensitivity (0.0187 kPa−1). Different signals are generated based on variations in pressure, which holds significant importance for the development of wearable flexible sensors and information encoding.

A nanozyme-functionalized bilayer hydrogel scaffold for modulating the inflammatory microenvironment to promote osteochondral regeneration

BackgroundThe incidence of osteochondral defects caused by trauma, arthritis or tumours is increasing annually, but progress has not been made in terms of treatment methods. Due to the heterogeneous structure and biological characteristics of cartilage and subchondral bone, the integration of osteochondral repair is still a challenge.ResultsIn the present study, a novel bilayer hydrogel scaffold was designed based on anatomical characteristics to imitate superficial cartilage and subchondral bone. The scaffold showed favourable biocompatibility, and the addition of an antioxidant nanozyme (LiMn2O4) promoted reactive oxygen species (ROS) scavenging by upregulating antioxidant proteins. The cartilage layer effectively protects against chondrocyte degradation in the inflammatory microenvironment. Subchondral bionic hydrogel scaffolds promote osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) by regulating the AMPK pathway in vitro. Finally, an in vivo rat preclinical osteochondral defect model confirmed that the bilayer hydrogel scaffold efficiently promoted cartilage and subchondral bone regeneration.ConclusionsIn general, our biomimetic hydrogel scaffold with the ability to regulate the inflammatory microenvironment can effectively repair osteochondral defects. This strategy provides a promising method for regenerating tissues with heterogeneous structures and biological characteristics.Graphical abstract

Visible light photo-crosslinking of biomimetic gelatin-hyaluronic acid hydrogels for adipose tissue engineering

Tissue engineering (TE) of adipose tissue (AT) is a promising strategy that can provide 3D constructs to be used for in vitro modelling, overcoming the limitations of 2D cell cultures by closely replicating the complex breast tissue extracellular matrix (ECM), cell-cell, and cell-ECM interactions. However, the challenge in developing 3D constructs of AT resides in designing artificial matrices that can mimic the structural properties of native AT and support adipocytes biological functions. Herein, we developed photocrosslinkable hydrogels by employing gelatin methacrylate (GelMA) and hyaluronic acid methacrylate (HAMA) to mimic the collagenous and glycosaminoglycan components of AT microenvironment, respectively. The physico-mechanical properties of the hydrogels were tuned to target AT biomimetic properties by varying the hydrogel formulation (with or without hyaluronic acid), and the amount of photoinitiator (ruthenium/sodium persulfate) used to crosslink the hydrogels via visible light. The physical and mechanical properties of the developed hydrogels were tuned by varying the material formulation and the photoinitiator concentration. Preadipocytes were encapsulated inside the hydrogels and differentiated into mature adipocytes. Findings enlightened that HAMA addition in hybrid hydrogels boosted an increased lipid accumulation. The engineered biomimetic adipocyte-based constructs resulted promising as scaffolds or 3D in vitro models of AT.

Injectable Tissue Adhesive Microgel Composite Containing Antifibrotic Drug for Vocal Fold Scarring.

Vocal fold (VF) scarring, a complex problem in laryngology, results from injury and inflammation of the layered architecture of the VFs. The resultant voice hoarseness, for which successful therapeutic options are currently limited, affects the patient's quality of life. A promising strategy to reverse this disorder is the use of antifibrotic drugs. The present study proposes a novel microbead-embedded injectable hydrogel that can sustain the release of the anti-fibrotic drug pirfenidone (PFD) for vocal fold scarring. Microbeads were developed using sodium alginate and gelatin, which were further embedded into a biomimetic and tissue adhesive gellan gum (GG) hydrogel. The microbead-embedded hydrogel exhibited improved injectability, viscoelasticity, tissue adhesiveness, degradability, and swelling compared to the hydrogel without beads. Additionally, the bead-embedded hydrogel could sustain the release of the PFD for a week. In vitro studies showed that the drug-loaded hydrogel could reduce the migration and proliferation of fibroblast cells in a dose-dependent manner. In summary, this study demonstrates the potential of a PFD-loaded injectable hydrogel with enhanced viscoelastic and tissue-adhesive properties for vocal fold scarring applications.

Biomimetic kartogenin containing κ-carrageenan hydrogel for nucleus pulposus regeneration

Intervertebral disc degeneration is a clinical disease that reduces the quality of patient's life. The degeneration usually initiates in the nucleus pulposus (NP), hence the use of hydrogels represents a promising therapeutic approach. However, the viscoelastic nature of hydrogel and its ability to provide biomimetic architecture and biochemical cues influence the regeneration capability. This study focused on tuning the physical nature of a glycosaminoglycan hydrogel (κ-carrageenan) as well as the release kinetics of a chondrogenic factor (kartogenin - KGN) through physical cross-linking. For this, κ-carrageenan was cross linked with 2.5 % and 5 % potassium chloride (KCl) for 15 and 30 min and loaded with KGN molecule at 50 μM and 100 μM. The tight network structure with low water retention and degradation property was seen in hydrogel cross-linked with increased KCl concentration and time. However, optimal degradation along with NP mimicking viscoelastic nature was exhibited by 5 wt% KCl treated hydrogel (H3 hydrogel). All hydrogel groups exhibited burst KGN release at 24 h followed by a sustained release for 5 days. However, hydrogel cross-linked with 5 wt% KCl enhanced chondrogenic differentiation, mainly at lower KGN dose. In summary, this study shows the potential application of biomimetic KGN laden carrageenan hydrogel in NP regeneration.

Stepwise co-assembled biomimetic hydrogel with antibacterial, angiogenesis, and tissue regeneration acceleration for diabetic wound healing

Bacterial infections and inadequate tissue regeneration capacity are prevalent issues in diabetic wounds, impeding the healing process. To solve these problems, a biomimetic hydrogel combined with bacterial cellulose (BC), recombinant human collagen type III (RHC), and ε-poly-L-Lysine (EPL) is fabricated by stepwise co-assembly technology. Owing to the RHC and EPL modifications of BC, the biomimetic hydrogel exhibited antibacterial effects and promoted fibroblast proliferation and angiogenesis, which accelerated the healing of diabetic wounds. Biomimetic hydrogels exhibit good mechanical properties and excellent water absorption, that can protect wounds and provide a moist environment. In addition, in vitro studies have shown that the hydrogels exhibit excellent antibacterial activity and biocompatibility. In vivo studies on diabetic wound healing have shown that biomimetic hydrogels can promote angiogenesis, accelerate collagen deposition, and re-epithelialize wound sites to promote wound healing. This study provides a new and promising strategy for the treatment of diabetic wounds.

Self-growing biomimetic functional hydrogel particles for conformance control in tight reservoir fracture network

Hydraulic fracturing is gradually becoming a common approach for enhancing the oil production from tight reservoirs. Blocking agents such as soft particle systems are necessary as a means of conformance control to mitigate the side effect of reservoir heterogeneity due to hydraulic fracturing. In this work, a novel technique based on the mussel biomimetic concept is proposed to generate self-growing biomimetic functional hydrogel particles (SG-BFHPs). The fracture conformance control capacity of the products is evaluated, and the results show that multi-scale (0.5–3.0 mm) SG-BFHPs can cohere and grow at the reservoir condition, and the median agglomerated particle size can increase by 20–25 times. High flow resistance (Frr = 10.7–11.8), facilitated by the higher adhesion between the biomimetic particles and the pore walls, can be established by SG-BFHPs while maintaining a good injectivity. In the single-fracture model, the increased oil recovery by SG-BFHPs is about 12.2 %, and in the matrix-fracture model can be increased from 9.2 %–13.5 % to 25.8 %–28.8 %. AFM experiments show that SG-BFHPs have stronger adhesion between particles or rock surface than conventional hydrogel particles. After conformance control of SG-BFHPs, the particles are distributed in an irregular structure in the fractures and adsorbed on the fracture wall under the effect of inter-particle cohesion and adhesion, which can realize fracture channel adjustment by the particle self-growing. The SG-BFHPs studied in this paper provide valuable insights for the development of dispersed particle gel, which is of great significance in improving oil recovery in tight reservoirs.

"Coir Raincoat"-Boosted Biomimetic Hydrogel for Efficient Solar Desalination and Wastewater Purification.

Solar-driven interfacial evaporation is an efficient method for purifying contaminated or saline water. Nonetheless, the suboptimal design of the structure and composition still necessitates a compromise between evaporation rate and service life. Therefore, achieving efficient production of clean water remains a key challenge. Here, a biomimetic dictyophora hydrogel based on loofah/carbonized sucrose@ZIF-8/polyvinyl alcohol is demonstrated, which can serve as an independent solar evaporator for clean water recovery. This special structural design achieves effective thermal positioning and minimal heat loss, while reducing the actual enthalpy of water evaporation. The evaporator achieves a pure water evaporation rate of 3.88kg m-2 h-1 and a solar-vapor conversion efficiency of 97.16% under 1 sun irradiation. In comparison, the wastewater evaporation rate of the evaporator with ZIF-8 remains at 3.85kg m-2 h-1 for 30 days, which is 16.3% higher than the light irradiation without ZIF-8. Equally important, the evaporator also showcases the capability to cleanse water from diverse sources of contaminants, including those with small molecules, oil, heavy metal ions, and bacteria, greatly improving the lifespan of the evaporator.

Design and evaluation of a bilayered dermal/hypodermal 3D model using a biomimetic hydrogel formulation

Due to the limitations of the current skin wound treatments, it is highly valuable to have a wound healing formulation that mimics the extracellular matrix (ECM) and mechanical properties of natural skin tissue. Here, a novel biomimetic hydrogel formulation has been developed based on a mixture of Agarose-Collagen Type I (AC) combined with skin ECM-related components: Dermatan sulfate (DS), Hyaluronic acid (HA), and Elastin (EL) for its application in skin tissue engineering (TE). Different formulations were designed by combining AC hydrogels with DS, HA, and EL. Cell viability, hemocompatibility, physicochemical, mechanical, and wound healing properties were investigated. Finally, a bilayered hydrogel loaded with fibroblasts and mesenchymal stromal cells was developed using the Ag-Col I-DS-HA-EL (ACDHE) formulation. The ACDHE hydrogel displayed the best in vitro results and acceptable physicochemical properties. Also, it behaved mechanically close to human native skin and exhibited good cytocompatibility. Environmental scanning electron microscopy (ESEM) analysis revealed a porous microstructure that allows the maintenance of cell growth and ECM-like structure production. These findings demonstrate the potential of the ACDHE hydrogel formulation for applications such as an injectable hydrogel or a bioink to create cell-laden structures for skin TE.

Biomimetic Hydrogel Strategies for Cancer Therapy.

Recent developments in biomimetic hydrogel research have expanded the scope of biomedical technologies that can be used to model, diagnose, and treat a wide range of medical conditions. Cancer presents one of the most intractable challenges in this arena due to the surreptitious mechanisms that it employs to evade detection and treatment. In order to address these challenges, biomimetic design principles can be adapted to beat cancer at its own game. Biomimetic design strategies are inspired by natural biological systems and offer promising opportunities for developing life-changing methods to model, detect, diagnose, treat, and cure various types of static and metastatic cancers. In particular, focusing on the cellular and subcellular phenomena that serve as fundamental drivers for the peculiar behavioral traits of cancer can provide rich insights into eradicating cancer in all of its manifestations. This review highlights promising developments in biomimetic nanocomposite hydrogels that contribute to cancer therapies via enhanced drug delivery strategies and modeling cancer mechanobiology phenomena in relation to metastasis and synergistic sensing systems. Creative efforts to amplify biomimetic design research to advance the development of more effective cancer therapies will be discussed in alignment with international collaborative goals to cure cancer.

Red-light-excited TiO2/Bi2S3 heterojunction nanotubes and photoelectric hydrogels mediate epidermal-neural network reconstruction in deep burns

Inspired by the strong light absorption of carbon nanotubes, we propose a fabrication approach involving one-dimensional TiO2/Bi2S3 QDs nanotubes (TBNTs) with visible red-light excitable photoelectric properties. By integrating the construction of heterojunctions, quantum confinement effects, and morphological modifications, the photocurrent reached 9.22 µA/cm2 which is 66 times greater than that of TiO2 nanotubes (TNTs). Then, a red light-responsive photoelectroactive hydrogel dressing (TBCHA) was developed by embedding TBNTs into a collagen/hyaluronic acid-based biomimetic extracellular matrix hydrogel with good biocompatibility, aiming to promote wound healing and skin function restoration. This approach is primarily grounded in the recognized significance of electrical stimulation in modulating nerve function and immune responses. Severe burns are often accompanied by extensive damage to epithelial-neural networks, leading to a loss of excitatory function and difficulty in spontaneous healing, while conventional dressings inadequately address the critical need for nerve reinnervation. Furthermore, we highlight the remarkable ability of the TBCHA photoelectric hydrogel to promote the reinnervation of nerve endings, facilitate the repair of skin substructures, and modulate immune responses in a deep burn model. This hydrogel not only underpins wound closure and collagen synthesis but also advances vascular reformation, immune modulation, and neural restoration. This photoelectric-based therapy offers a robust solution for the comprehensive repair of deep burns and functional tissue regeneration. Statement of significanceWe explore the fabrication of 1D TiO2/Bi2S3 nanotubes with visible red-light excitability and high photoelectric conversion properties. By integrating heterojunctions, quantum absorption effects, and morphological modifications, the photocurrent of TiO2/Bi2S3 nanotubes could reach 9.22 µA/cm², which is 66 times greater than that of TiO2 nanotubes under 625 nm illumination. The efficient red-light excitability solves the problem of poor biosafety and low tissue penetration caused by shortwave excitation. Furthermore, we highlight the remarkable ability of the TiO2/Bi2S3 nanotubes integrated photoelectric hydrogel in promoting the reinnervation of nerve endings and modulating immune responses. This work proposes an emerging therapeutic strategy of remote, passive electrical stimulation, offering a robust boost for repairing deep burn wounds.

Developing a Biomimetic 3D Neointimal Layer as a Prothrombotic Substrate for a Humanized In Vitro Model of Atherothrombosis.

Acute cardiovascular events result from clots caused by the rupture and erosion of atherosclerotic plaques. This paper aimed to produce a functional biomimetic hydrogel of the neointimal layer of the atherosclerotic plaque that can support thrombogenesis upon exposure to human blood. A biomimetic hydrogel of the neointima was produced by culturing THP-1-derived foam cells within 3D collagen hydrogels in the presence or absence of atorvastatin. Prothrombin time and platelet aggregation onset were measured after exposure of the neointimal models to platelet-poor plasma and washed platelet suspensions prepared from blood of healthy, medication-free volunteers. Activity of the extrinsic coagulation pathway was measured using the fluorogenic substrate SN-17. Foam cell formation was observed following preincubation of the neointimal biomimetic hydrogels with oxidized LDL, and this was inhibited by pretreatment with atorvastatin. The neointimal biomimetic hydrogel was able to trigger platelet aggregation and blood coagulation upon exposure to human blood products. Atorvastatin pretreatment of the neointimal biomimetic layer significantly reduced its pro-aggregatory and pro-coagulant properties. In the future, this 3D neointimal biomimetic hydrogel can be incorporated as an additional layer within our current thrombus-on-a-chip model to permit the study of atherosclerosis development and the screening of anti-thrombotic drugs as an alternative to current animal models.