Monitoring the levels of L-Tryptophan (L-Trp) in body fluids is crucial due to its significant role in metabolism and protein synthesis, which ultimately affects neurological health. Herein, we have developed a novel magneto-responsive electrochemical enantioselective sensor for the recognition of L-Trp based on oriented biochar derived from Loofah, Fe3O4 nanoparticles, and molecularly imprinted polydopamine (MIPDA) in xanthan hydrogel. The successful synthesis of these materials has been confirmed through physicochemical and electrochemical characterization. Various operational factors such as pH, response time, loading sample volume, and loading of active materials were optimized. As a result, the sensor exhibited an affordable linear range of 1.0-60.0 μM, with a desirable limit of detection of 0.44 μM. Furthermore, the proposed electrochemical sensor demonstrated good reproducibility and desirable selectivity for the determination of L-Trp, making it suitable for analyzing L-Trp levels in human plasma and serum samples. The development presented offers an appealing, easily accessible, and efficient strategy. It utilizes xanthan hydrogel to improve mass transfer and adhesion, biochar-stabilized Fe3O4 to facilitate magnetic orientation and accelerate mass transfer and sensitivity, and polydopamine MIP to enhance selectivity. This approach enables on-site evaluation of L-Trp levels, which holds significant value for healthcare monitoring and early detection of related conditions.

The monitoring of biomarkers in wound exudate is of great importance for wound care and treatment, and electrochemical biosensors with high sensitivity are potentially useful for this purpose. However, conventional electrochemical biosensors always suffer from severe biofouling when performed in the complex wound exudate. Herein, an antifouling electrochemical biosensor for the detection of involucrin in wound exudate was developed based on a wound dressing, oxidized bacterial cellulose (OxBC) and quaternized chitosan (QCS) composite hydrogel. The OxBC/QCS hydrogel was prepared using an in-situ chemical oxidation and physical blending method, and the proportion of OxBC and QCS was optimized to achieve electrical neutrality and enhanced hydrophilicity, therefore endowing the hydrogel with exceptional antifouling and antimicrobial properties. The involucrin antibody SY5 was covalently bound to the OxBC/QCS hydrogel to construct the biosensor, and it demonstrated a low limit of detection down to 0.45 pg mL-1 and a linear detection range from 1.0 pg mL-1 to 1.0 μg mL-1, and it was capable of detecting targets in wound exudate. Crucially, the unique antifouling and antimicrobial capability of the OxBC/QCS hydrogel not only extends its effective lifespan but also guarantees the sensing performance of the biosensor. The successful application of this wound dressing, OxBC/QCS hydrogel for involucrin detection in wound exudate demonstrates its promising potential in wound healing monitoring.

UNASSIGNED: First- (monomers), second- (pre-gelated), and third- (in situ gelating after injection) generation hydrogels were previously introduced to replace the vitreous body after vitrectomy surgery. In this study, we evaluated the surgical, optical, and viscoelastic properties of vitreous body replacement hydrogels before and after an accelerated aging protocol previously applied to intraocular implants.
UNASSIGNED: Measurements of injection force, removal speed using a clinically established vitrectomy setup, as well as evaluation of forward light scattering and viscoelastic properties before and after an accelerated aging protocol were conducted. Results were compared to porcine and human vitreous bodies, as well as currently clinically applied lighter- and heavier-than-water silicone oils.
UNASSIGNED: Removal speed of all tested hydrogels is substantially lower than the removal speed of porcine vitreous body (0.2 g/min vs. 2.7 g/min for the best performing hydrogel and porcine vitreous body, respectively). Forward light scattering in second-generation vitreous body replacement hydrogels was higher after the aging process than the straylight of the average 70-year-old vitreous body (9.4 vs. 5.5 deg2/sr, respectively). The viscoelastic properties of all hydrogels did not change in a clinically meaningful manner; however, trends toward greater stiffness and greater elasticity after aging were apparent.
UNASSIGNED: This study demonstrates surgical weaknesses of the hydrogels that need to be addressed before clinical use, especially low removal speed. Pre-linked hydrogels (second-generation) showed inferior performance regarding surgical properties compared to in situ gelating hydrogels (third-generation).
UNASSIGNED: This study highlights possible pitfalls regarding surgical and optical properties when applying vitreous replacement hydrogels clinically.

Failed skin wound healing, through delayed wound healing or wound dehiscence, is a global public health issue that imposes significant burdens on individuals and society. Although the application of growth factor is an effective method to improve the pace and quality of wound healing, the clinically approved factors are limited. Parathyroid hormone (PTH) demonstrates promising results in wound healing by promoting collagen deposition and cell migration, but its application is limited by potentially inhibitory effects when administered continuously and locally. Through partially replacing and repeating the amino acid domains of PTH(1-34), we previously designed a novel PTH analog, PTH(3-34)(29-34) or MY-1, and found that it avoided the inhibitory effects of PTH while retaining its positive functions. To evaluate its role in wound healing, MY-1 was encapsulated in liposomes and incorporated into the methacryloyl gelatin (GelMA) hydrogel, through which an injectable nanocomposite hydrogel (GelMA-MY@Lipo, or GML) was developed. In vitro studies revealed that the GML had similar properties in terms of the appearance, microstructure, functional groups, swelling, and degradation capacities as the GelMA hydrogel. In vitro drug release testing showed a relatively more sustainable release of MY-1, which was still detectable in vivo 9 days post-application. When the GML was topically applied to the wound areas of rat models, wound closure as well as tensile strength were improved. Further studies showed that the effects of GML on wound repair and tensile strength were closely related to the promotion of fibroblast migration to the wound area through the controlled release of MY-1. Mechanically, MY-1 enhanced fibroblast migration by activating PI3K/AKT signaling and its downstream molecule, Rac1, by which it increased fibroblast aggregation in the early stage and resulting in denser collagen deposition at a later time. Overall, these findings demonstrated that the nanocomposite hydrogel system promoted skin wound healing and increased tensile strength, thus offering new potential in the treatment of wound healing.

In this study, we use modified cationic nanocarriers as vehicles for the intracellular delivery of therapeutic siRNA. After developing nanocarrier formulations with appropriate pKa, size, swellability, and cytocompatibility, we investigated the importance of siRNA loading methods by studying the impact of the pH and time over which siRNA is loaded into the nanocarriers. We concentrate on diffusion-based loading in the presence and absence of electrostatic interactions. siRNA release kinetics were studied using samples prepared from nanocarriers loaded by both mechanisms. In addition, siRNA delivery was evaluated for two formulations. While previous studies were conducted with samples prepared by siRNA loading at low pH values, this research provides evidence that loading conditions of siRNA affect the release behavior. This study concludes that this concept could prove advantageous for eliciting prolonged intracellular release of nucleic acids and negatively charged molecules, effectively decreasing dose frequency and contributing to more effective therapies and improved patient outcomes. In addition, our findings could be leveraged for enhanced control over siRNA release kinetics, providing novel methods for the continued optimization of cationic nanoparticles in a wide array of RNA interference-based applications.

A bioinspired hydrogel composed of hyaluronic acid-graft-dopamine (HADA) and a designer peptide HGF-(RADA)4-DGDRGDS (HRR) was presented to enhance tissue integration following spinal cord injury (SCI). The HADA/HRR hydrogel manipulated the infiltration of PDGFRβ+ cells in a parallel pattern, transforming dense scars into an aligned fibrous substrate that guided axonal regrowth. Further incorporation of NT3 and curcumin promoted axonal regrowth and survival of interneurons at lesion borders, which served as relays for establishing heterogeneous axon connections in a target-specific manner. Notable improvements in motor, sensory, and bladder functions resulted in rats with complete spinal cord transection. The HADA/HRR + NT3/Cur hydrogel promoted V2a neuron accumulation in ventral spinal cord, facilitating the recovery of locomotor function. Meanwhile, the establishment of heterogeneous neural connections across the hemisected lesion of canines was documented in a target-specific manner via neuronal relays, significantly improving motor functions. Therefore, biomaterials can inspire beneficial biological activities for SCI repair.

OBJECTIVE: To evaluate using a biocellulose-based hydrogel as an adjuvant in the healing process of arterial ulcers.
METHODS: A prospective single group quasi-experimental study was carried out with chronic lower limb arterial ulcer patients. These patients received biocellulose-based hydrogel dressings and outpatient guidance on dressing and periodic reassessments. The primary outcomes were the ulcer-healing rate and product safety, which were assessed by ulcer area measured in photographic records of pre-treatment and posttreatment after 7, 30, and 60 days. Secondary outcomes were related to clinical assessment by the quality-of-life scores (SF-36 and EQ-5D) and pain, evaluated by the visual analogue scale (VAS).
RESULTS: Seventeen participants were included, and one of them was excluded. Six patients (37%) had complete wound healing, and all patients had a significant reduction in the ulcer area during follow-up (233.6mm2 versus 2.7mm2) and reduction on the score PUSH 3.0 (p < 0.0001). The analysis of the SF-36 and EQ-5D questionnaires showed a statistically significant improvement in almost all parameters analyzed and with a reduction of pain assessed by the VAS.
CONCLUSIONS: The biocellulose-based hydrogel was safe and showed a good perspective to promoting the necessary conditions to facilitate partial or complete healing of chronic arterial ulcers within a 60-day follow-up. Quality of life and pain were positively affected by the treatment.

Severe traumatic bleeding may lead to extremely high mortality rates, and early intervention to stop bleeding plays as a critical role in saving lives. However, rapid hemostasis in deep non-compressible trauma using a highly water-absorbent hydrogel, combined with strong tissue adhesion and bionic procoagulant mechanism, remains a challenge. In this study, a DNA hydrogel (DNAgel) network composed of natural nucleic acids with rapid water absorption, high swelling and instant tissue adhesion is reported, like a band-aid to physically stop bleeding. The excellent swelling behavior and robust mechanical performance, meanwhile, enable the DNAgel band-aid to fill the defect cavity and exert pressure on the bleeding vessels, thereby achieving compression hemostasis for deep tissue bleeding sites. The neutrophil extracellular traps (NETs)-inspired DNAgel network also acts as an artificial DNA scaffold for erythrocytes to adhere and aggregate, and activates platelets, promoting coagulation cascade in a bionic way. The DNAgel achieves lower blood loss than commercial gelatin sponge (GS) in male rat trauma models. In vivo evaluation in a full-thickness skin incision model also demonstrates the ability of DNAgel for promoting wound healing. Overall, the DNAgel band-aid with great hemostatic capacity is a promising candidate for rapid hemostasis and wound healing.

Despite recent advancements in peripheral nerve regeneration, the creation of nerve conduits with chemical and physical cues to enhance glial cell function and support axonal growth remains challenging. This study aimed to assess the impact of electrical stimulation (ES) using a conductive nerve conduit on sciatic nerve regeneration in a rat model with transection injury. The study involved the fabrication of conductive nerve conduits using silk fibroin and Au nanoparticles (AuNPs). Collagen hydrogel loaded with green fluorescent protein (GFP)-positive adipose-derived mesenchymal stem cells (ADSCs) served as the filling for the conduit. Both conductive and non-conductive conduits were applied with and without ES in rat models. Locomotor recovery was assessed using walking track analysis. Histological evaluations were performed using H&E, luxol fast blue staining and immunohistochemistry. Moreover, TEM analysis was conducted to distinguish various ultrastructural aspects of sciatic tissue. In the ES + conductive conduit group, higher S100 (p < 0.0001) and neurofilament (p < 0.001) expression was seen after 6 weeks. Ultrastructural evaluations showed that conductive scaffolds with ES minimized Wallerian degeneration. Furthermore, the conductive conduit with ES group demonstrated significantly increased myelin sheet thickness and decreased G. ratio compared to the autograft. Immunofluorescent images confirmed the presence of GFP-positive ADSCs by the 6th week. Locomotor recovery assessments revealed improved function in the conductive conduit with ES group compared to the control group and groups without ES. These results show that a Silk/AuNPs conduit filled with ADSC-seeded collagen hydrogel can function as a nerve conduit, aiding in the restoration of substantial gaps in the sciatic nerve with ES. Histological and locomotor evaluations indicated that ES had a greater impact on functional recovery compared to using a conductive conduit alone, although the use of conductive conduits did enhance the effects of ES.

The present study aims to develop and characterize a controlled-release delivery system for protein therapeutics in skeletal muscle regeneration following an acute injury. The therapeutic protein, a membrane-GPI anchored protein called Cripto, was immobilized in an injectable hydrogel delivery vehicle for local administration and sustained release. The hydrogel was made of poly(ethylene glycol)-fibrinogen (PEG-Fibrinogen, PF), in the form of injectable microspheres. The PF microspheres exhibited a spherical morphology with an average diameter of approximately 100 micrometers, and the Cripto protein was uniformly entrapped within them. The release rate of Cripto from the PF microspheres was controlled by tuning the crosslinking density of the hydrogel, which was varied by changing the concentration of poly(ethylene glycol) diacrylate (PEG-DA) crosslinker. In vitro experiments confirmed a sustained-release profile of Cripto from the PF microspheres for up to 27 days. The released Cripto was biologically active and promoted the in vitro proliferation of mouse myoblasts. The therapeutic effect of PF-mediated delivery of Cripto in vivo was tested in a cardiotoxin (CTX)-induced muscle injury model in mice. The Cripto caused an increase in the in vivo expression of the myogenic markers Pax7, the differentiation makers eMHC and Desmin, higher numbers of centro-nucleated myofibers and greater areas of regenerated muscle tissue. Collectively, these results establish the PF microspheres as a potential delivery system for the localized, sustained release of therapeutic proteins toward the accelerated repair of damaged muscle tissue following acute injuries.