Gel Patch Research Articles

A Reconfigurable Proangiogenic Hydrogel Patch Enabling Minimally Invasive Drug Delivery.

Hydrogel is widely used for the sustained delivery of bioactive molecules that can treat various injuries, diseases, and tissue defects. However, inserting hydrogel implants without disrupting their functionality and microstructure often requires a large incision, leading to potential complications, such as infection, scarring, and pain. The gel implant is often manually rolled and inserted through a catheter for a minimally invasive delivery. However, success heavily depends on the user's skills, which can inadvertently damage the implant. To address this issue, we developed a reconfigurable hydrogel patch that can self-fold into a small tube and unfold spontaneously after implantation through a catheter. The hydrogel path was assembled by layering a drug-releasing poly(ethylene glycol) diacrylate (PEGDA) hydrogel sheet onto a PEGDA and polyethylenimine (PEI) hydrogel sheet, which rapidly swells and degrades homogeneously at controlled rates. The dynamics of the self-folding and unfolding process could be controlled by differences in the expansion ratio and elastic modulus between the two gel layers according to a mathematical model that closely matched experimental results. The unfolding process triggered a sustained release of the protein cargo. Specifically, the reconfigurable gel loaded with angiopoietin 1 significantly enhanced neovascularization, nearly doubling the vascular density compared to the control group following implantation through a tube with 15% smaller diameter than the original shape of the gel patch. This gel biopatch will be broadly useful for the minimally invasive delivery of a wide array of therapeutic molecules, potentially enhancing therapeutic outcomes.

Clinical Efficacy and Tolerability of a New Experimental Mucoadhesive Patch for Topical Anesthesia of Oral Mucosa in Pediatric Dentistry.

Background: The injection of local anesthetics is the procedure that still causes the most fear and anxiety in a dental session; to minimize this problem, we can use topical anesthesia. The aim of this study is to analyze the tolerability and the clinical efficacy in the control of pain, during the subsequent injection of the local anesthetic, of an experimental anesthetic patch with a new formulation, which was previously tested in gel formula. Methods: A total of 150 children, aged 4 to 9 years, were included in the study. Each patient was treated using three different pre-anesthesia methods (placebo gel, experimental gel, and experimental patch), according to a split-mouth procedure, within a week of each other. The injection pain was analyzed using the WBFPRS and FLACC scales. Patients' caregivers' satisfaction was recorded at the end of the procedures. The data were analyzed using one-way ANOVA-RM, Wilcoxon-Mann-Whitney, Mann-Whitney U, and χ2 tests. Results: In this study, significantly higher pain ratings were observed with the topical placebo gel and lower pain ratings were observed with the experimental patch. Conclusion: The use of the patch proved to be very effective in reducing pain both subjectively and objectively, in the absence of both local and systemic side effects, validating its use in the oral mucosa.

Intratumoral delivery of a highly active form of XCL1 enhances antitumor CTL responses through recruitment of CXCL9-expressing conventional type-1 dendritic cells.

Conventional type 1 dendritic cells (cDC1s) play a crucial role in antitumor immunity through the induction and activation of tumor-specific CD8+ cytotoxic T cells (CTLs). The chemokine XCL1 is a major chemotactic factor for cDC1s and its receptor XCR1 is selectively expressed on cDC1s. Here, we investigated the effect of intratumoral delivery of a highly active form of murine XCL1 (mXCL1-V21C/A59C) on cDC1-mediated antitumor immunity using a hydrophilic gel patch. The hydrophilic gel patch containing mXCL1-V21C/A59C increased cDC1 accumulation in the tumor masses and promoted their migration to the regional lymph nodes, resulting in enhanced induction of tumor-specific CTLs. Tumor-infiltrating cDC1s not only expressed XCR1 but also produced CXCL9, a ligand for CXCR3 which is highly expressed on CTLs and NK cells. Consequently, CTLs and NK cells were increased in the tumor masses of mice treated with mXCL1-V21C/A59C, while immunosuppressive cells such as monocyte-derived suppressive cells and regulatory T cells were decreased. We also confirmed that anti-CXCL9 treatment decreased the tumor infiltration of CTLs. The intratumoral delivery of mXCL1-V21C/A59C significantly decreased tumor growth and prolonged survival in E.G7-OVA and B16-F10 tumor-bearing mice. Furthermore, the antitumor effect of mXCL1-V21CA59C was enhanced in combination with anti-programmed cell death protein 1 treatment. Finally, using The Cancer Genome Atlas database, we found that XCL1 expression was positively correlated with tumor-infiltrating cDC1s and a better prognosis in melanoma patients. Collectively, our findings provide a novel therapeutic approach to enhance tumor-specific CTL responses through the selective recruitment of CXCL9-expressing cDC1s into the tumor masses.

Edible temperature-responsive-adhesive thermogalvanic hydrogel for self-powered multi-sited fatigue monitoring

An edible thermogalvanic gel patch with adaptive adhesion has been invented, which couples thermogalvanic and piezoresistive effects to acquire physiological signals, thereby achieving self-powered accurate surveillance of fatigue status.

Prediction and analysis of quality markers for Chuantieling gel patches based on HPLC fingerprinting and network pharmacology.

The Chuantieling gel patch (CGP), a traditional Chinese medicine compound, is an external treatment for asthma. It has shown remarkable effectiveness in alleviating asthma-related airway hyperresponsiveness and inflammation. Nevertheless, there is currently no information available regarding the analysis of quality markers for CGP, and there is a need for further improvement in quality control research. In this study, we developed an HPLC fingerprinting method for CGP and conducted a comprehensive methodological investigation. We assessed the similarity among 10 batches of CGP, identified common peaks, and quantified the content of seven major quality markers. Furthermore, we built a network pharmacology-based 'active ingredients-targets-pathways-diseases' network to forecast the potential mechanisms of action for the primary active components in asthma treatment. Our findings demonstrated that the developed CGP fingerprinting and content determination methods were consistent and trustworthy. We verified the existence of 25 shared peaks and successfully identified 7 chromatographic peaks, including sinigrin thiocyanate, ephedrine hydrochloride, methyleugenol, imperatorin, cinnamaldehyde, emodin, and 6-gingerol, using reference standards. The network pharmacology analysis suggested that these seven active components may target proteins such as STAT3 (signal transducer and activator of transcription 3), MAPK3 (mitogen-activated protein kinase 3), and TP53 (tumor protein P53) and influence various diseases through pathways including cancer pathways, hepatitis B, and PI3K-Akt (phosphoinositide 3-kinase-protein kinase B) signaling. This study provides insight into the complex multicomponent composition of CGP, and the predictive analysis through network pharmacology sets the stage for uncovering the mechanisms responsible for the therapeutic effects of CGP.

Thermogalvanic gel patch for self-powered human motion recognition enabled by photo-thermal-electric conversion

Quasi-solid-state electrolytes offer a cheap, leak-free, and scalable way to convert heat directly into electricity for wearable electronics. However, the limited temperature difference with the environment poses a challenge for the extensive application of thermoelectric gels. Currently, photo-thermal-electric (PTE) conversion is an environmentally-friendly technology to exploit the thermogalvanic effect of gels. Here, we report a smart light-driven flexible PTE gel for self-powered human motion monitoring. The whole structure takes advantage of the low thermal conductivity and high output power of poly(vinyl alcohol)/polydimethylsiloxane (PVA-PDMS) gels with Fe2+/3+ as a redox pair, together with the local surface plasmon resonance (LSPR) of Au nanoparticles (AuNPs)@SiO2-PDMS composite film. This enables simultaneous high thermogalvanic and photothermal performance, with an open circuit voltage of up to 12 mV and a short circuit current exceeding 1.25 A m−2 at a temperature difference of up to 9 °C under one sun. The PTE gel is fabricated into a proof-of-concept self-powered patch, which can actively distinguish human motions in real time by recognizing the switching of solar radiation stimulated by arm swing. This work provides thermogalvanic gels with a new opportunity in self-powered wearable sensing that may greatly promote the progress of intelligent medical electronics.

Neonatal Seizure Detection Using a Wearable Multi-Sensor System.

Neonatal seizure is an important clinical symptom of brain dysfunction, which is more common in infancy than in childhood. At present, video electroencephalogram (VEEG) technology is widely used in clinical practice. However, video electroencephalogram technology has several disadvantages. For example, the wires connecting the medical instruments may interfere with the infant's movement and the gel patch electrode or disk electrode commonly used to monitor EEG may cause skin allergies or even tears. For the above reasons, we developed a wearable multi-sensor platform for newborns to collect physiological and movement signals. In this study, we designed a second-generation multi-sensor platform and developed an automatic detection algorithm for neonatal seizures based on ECG, respiration and acceleration. Data for 38 neonates were recorded at the Children's Hospital of Fudan University in Shanghai. The total recording time was approximately 300 h. Four of the patients had seizures during data collection. The total recording time for the four patients was approximately 34 h, with 30 seizure episodes recorded. These data were evaluated by the algorithm. To evaluate the effectiveness of combining ECG, respiration and movement, we compared the performance of three types of seizure detectors. The first detector included features from ECG, respiration and acceleration records; the second detector incorporated features based on respiratory movement from respiration and acceleration records; and the third detector used only ECG-based features from ECG records. Our study illustrated that, compared with the detector utilizing individual modal features, multi-modal feature detectors could achieve favorable overall performance, reduce false alarm rates and give higher F-measures.

A semitransparent and tough wood-based adhesive gels with excellent adhesion both in air and underwater for emergency pipeline repair

The instant biomass-based adhesive gels have demonstrated promising potentials in various applications, including wound dressing, sensors, and underwater repair engineering. However, existing biomass-based gels usually have relatively poor mechanical and adhesion properties, and even lose their adhesion in wet conditions or underwater due to their inherent hydrophilicity, which remains a considerable challenge for its further application. Herein, we developed a semitransparent wood-based gel patch that can achieve instant and robust adhesion to various substrates both in air and underwater. In briefly, natural wood with porous channels was employed as the skeleton to enhance the mechanical strength of gels. Polymerizable ionic liquid (PIL) and acrylic acid (AA) were selected as the polymeric monomer and filled into the wood channels to synthesize gels by in-situ polymerization in the absence of chemical cross-linker agents. Abundant noncovalent bonds gave gels with superior adhesion to various substrates such as plastic, metal, polytetrafluoroethylene (PTFE), glass and wood. Additionally, the presence of C-F bond endowed the gels with low surface energy which could repel water molecules from the interface between gels and substrates, resulting in the outstanding underwater adhesion. The resultant wood-based gels displayed high tensile stress (6.10–9.34 MPa), which was 3.56–5.46 times higher than that of pure gels without the incorporation of wood. The maximum adhesion strength of gels could reach approximately 350 kPa in air and 345 kPa underwater. This work showed a promising application in emergency repair engineering of broken pipeline both in air and underwater.

Tough gel adhesive is an effective method for meniscal repair in a bovine cadaveric study

PurposeTo test tough gel adhesives to repair meniscus tears under relevant loading conditions and determine if they have adequate biomechanical properties to repair meniscus tears in a bovine cadaveric study.MethodsCyclic compression tests on 24 dissected bovine knees were performed. The tough gel adhesive was used either as an adhesive patch or as a coating bonded onto commercially available surgical sutures. Forty-eight menisci were tested in this study; 24 complete radial tears and 24 bucket-handle tears. After preconditioning, the specimens underwent 100 cycles of compression, (800 N/0.5 Hz) on an Instron© machine and the size of the gaps measured. One third of the menisci were repaired with pristine sutures, one third with adhesive patches, and one third with sutures coated in adhesive gel. The size of the gaps was compared after 100 and 500 cycles of compression.ResultsThe mean gap measured at the tear site without treatment was 6.46 mm (± 1.41 mm) for radial tears and 1.92 mm (± 0.65 mm) for bucket-handle tears. After treatment and 500 cycles of compression, the mean gap was 1.63 mm (± 1.41 mm) for pristine sutures, 1.50 mm (± 1.16 mm) for adhesive sutures and 2.06 mm (± 1.53 mm) for adhesive gel patches. There was no significant difference between treatments regardless of the type of tear. Also, the gaps for radial tears increased significantly with the number of compression cycles applied (p > 0.001).ConclusionFrom a biomechanical standpoint, the tough adhesive gel patch is as effective as suturing. In addition, it would allow the repair of non-suturable tears and thus broaden the indications for meniscus repair.Level of evidenceControlled laboratory study.

Self-Powered Respiratory Monitoring Strategy Based on Adaptive Dual-Network Thermogalvanic Hydrogels.

As a low-grade sustainable heat source, the breath waste heat exhaled by human bodies is always ignored, although producing a greater temperature than ambient. Converting this heat into electric energy for use as power sources or detecting signals is extremely important in cutting-edge wearable medicine. This heat-to-electricity conversion is possible with thermogalvanic hydrogels. However, challenges remain in their antifreezing and antidrying properties, significantly restricting the durability of thermogalvanic gels in practical applications. Herein, a dual-network poly(vinyl alcohol)/gelatin (PVA/GEL) gel thermogalvanic device with Fe(CN)63-/4- as a redox pair is developed, with an outstanding low-temperature durability and antidrying capacity. These features result from the use of a binary H2O/GL (glycerin) solvent to limit hydrogen bonding between water molecules. The prepared thermogalvanic gel patch is capable of easily converting physiological data into understandable electrical impulses using the temperature difference between the ambient environment and the heat produced by human breathing, realizing a simple self-powered respiratory monitoring strategy for the first time. Even below zero temperature, the gel patch-based mask can operate normally, implying it fits into low-temperature environments. This study sheds fresh light on the development of active wearable medical electronics that are powered by demic low-level heat.

Glucocorticosteroid and Silicone Gel During Patch Application Without Clinical Scar Improvement After Central Venous Catheter Removal: A Randomized Trial.

We studied whether glucocorticosteroid during patch occlusion has a beneficial effect on scar outcome in children and adolescents treated for cancer. A double-blinded placebo-controlled randomized clinical trial was performed. The main outcome was the Vancouver Scar Scale. Secondary outcomes were scar width and scar quality measured using the Patient and Observer Scar Assessment Scale. The patients were divided into an intervention groups and a control group. The intervention group was randomized into active and placebo group. The active treatment consisted of cream with glucocorticosteroid and fusidic acid. The placebo treatment consisted of cream with fusidic acid. Both groups received silicone gel patch after central venous catheter removal. The control group received no specific skin care. Assessment at 12 months showed that the intervention group had a significantly lower Vancouver Scar Scale and a smaller scar (0,1cm) compared with the control group ( P =0.00, P =0.02) but no benefit of glucocorticosteroid. The Patient and Observer Scar Assessment Scale showed no significant difference between the intervention and control groups ( P =0.84, P =0.36). Silicone gel sheet alone or in combination with application of glucocorticosteroid during sheet occlusion does not clinically improve scar outcome after removal of central venous catheter in children treated for neoplastic diseases.

Comparative study on in vivo and in vitro permeability of Huoxue Zhitong gel patch and microemulsion gel

This study aims to establish a method for determination of paeonol(Pae), eugenol(Eug), and piperine(Pip) content in receptor liquid and research on the permeability and pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The Franz diffusion experiment was conducted to assess the percutaneous permeability, and the microdialysis method was employed to assess pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The content of Pae, Eug, and Pip in receptor liquid in vitro and in vivo was determined by HPLC and UPLC-MS. The Q_n and J_(ss) of Pae, Eug, and Pip in the gel patch were significantly higher than those in the microemulsion gel, indicating that the drug release was faster in the gel patch. The C_(max), AUC_(0-760), and MRT of Pae, Eug, and Pip in the gel patch were higher than those in the microemulsion gel, indicating that the gel patch can promote the penetration and prolong the skin residence of the drug. The results of this study provide reference for improving the dosage form of Huoxue Zhitong patch.

Encapsulation of Commensal Skin Bacteria within Membrane‐in‐Gel Patches

AbstractThe commensal skin bacterium Staphylococcus epidermidis (S. epidermidis) provides a range of benefits to human hosts, contributing to skin equilibrium and good health, even though specific strains also act as pathogens if entering the host body. Therefore, skin‐applicable devices allowing to benefit from some factors secreted by S. epidermidis while keeping the bacteria at a desired location are important for the development of bacteriotherapeutical applications. Here, a membrane‐based gel patch is fabricated to trap S. epidermidis while keeping its metabolic activity. The pores of a track‐etched membrane are modified with layer‐by‐layer (LbL) multilayers to anchor bacteria, followed by coating the membrane with a thick layer of agarose gel, leading to a membrane‐in‐gel soft patch. LbL multilayers comprising antibacterial polycations are then deposited over the patch. By varying the multilayer composition, thickness and nature of the last layer, both probability of escape and metabolic activity of entrapped bacteria can be tuned. Poly(ethyleneimine)‐comprising multilayers prove to be particularly well‐suited for the fine control of bacterial escape and activity. These bacterial patches are thus complex living materials in which the living component is controlled by a careful combination of soft macromolecular components.

Study on Preparation Technology and Safety Evaluation of Hataagqi-19 Hydrogel Patch

Objectives: The study objective of the present study was to screen the dosage of matrix material and clarify the safety evaluation of Hataagqi-19 hydrogel patch. Methods: Single factor and orthogonal experiments were used to screen, and the best matrix ratio was screened out with peel strength, peel ability, viscosity, spread ability, uniformity, as evaluation indicators. Long term toxicity test was carried out in SD rats in order to test general conditions such as: body weight, food intake, electrocardiogram, blood, urine, and biochemical indicators, organ coefficients and histopathological changes. Moreover, skin allergic reaction tests were done to observe the allergic responce. Results: The ratio of the gel patch matrix is NP-700: aluminum glycolate: glycerol: carbomer = 6: 0.35: 35: 0.40; the ratio of azone and propylene glycol is 1: 1, and the total penetration enhancer dosage is 5%. Hataagqi-19 preparation had no obvious long-term toxicity or skin allergies. Conclusions: The Hataagqi-19 hydrogel patch prepared with the best ratio and transdermal agent showed good performance and safety. Furthermore, we did not observed toxic side effects, and the preparation process is feasible and reliable.

Adjuvant Activity of CpG-Oligonucleotide Administered Transcutaneously in Combination with Vaccination Using a Self-Dissolving Microneedle Patch in Mice.

In this study, we investigated the mechanism of transcutaneous adjuvant activity of the CpG-oligonucleotide (K3) in mice. Transcutaneous immunization (TCI) with an ovalbumin-loaded self-dissolving microneedle patch (OVA-sdMN) and K3-loaded hydrophilic gel patch (HG) increased OVA-specific Th2- and Th1-type IgG subclass antibody titers more rapidly and strongly than those after only OVA-sdMN administration. However, the antigen-specific proliferation of OVA-specific CD4+ T cells was similar between the OVA-only and the OVA+K3 groups. Population analysis of various immune cells in draining lymph nodes (dLNs) in the primary immune response revealed that the OVA+K3 combination doubled the number of dLN cells, with the most significant increase in B cells. Phenotypic analysis by flow cytometry revealed that B-cell activation and maturation were promoted in the OVA+K3 group, suggesting that direct B-cell activation by K3 largely contributed to the rapid increase in antigen-specific antibody titer in TCI. In the secondary immune response, a significant increase in effector T cells and effector memory T cells, and an increase in memory B cells were observed in the OVA+K3 group compared with that in the OVA-only group. Thus, K3, as a transcutaneous adjuvant, can promote the memory differentiation of T and B cells.

Patients satisfaction and life improvement after use of silicone gel patch in painful hypertrophic surgical wounds in upper limb

Patients satisfaction and life improvement after use of silicone gel patch in painful hypertrophic surgical wounds in upper limb

Preliminary Results of a Reverse Thermal Gel Patch for Fetal Ovine Myelomeningocele Repair

BackgroundPrenatal surgical closure of Myelomeningocele (MMC) is considered part of the current age armamentarium. Clinical data has demonstrated the need for innovative patches to maximize the benefits and decrease the risks of this approach. Our team has developed a minimally invasive reverse thermal gel (RTG) patch with cellular scaffolding properties. Here, we demonstrate the initial gross and microscopic histological effects of this RTG patch in the fetal ovine model of MMC. Materials and MethodsA fetal ovine MMC defect was created at 68-75 days gestation, RTG patch application or untreated at 100-103 days, and harvest at 135-140 days. The RTG was applied to the defect and secured in place with an overlay sealant. Defect areas underwent gross and microscopic analysis for inflammation and skin development. Brains were analyzed for hindbrain herniation and hydrocephalus. ResultsThe untreated fetus (n = 1) demonstrated an open defect lacking tissue coverage, evidence of spinal cord injury, increased caspase-3, Iba1 and GFAP in spinal cord tissues, and hindbrain herniation and ventricular dilation. RTG treated fetuses (n = 3) demonstrated defect healing with well-organized dermal and epidermal layers throughout the entire healed tissue area overlaying the defect with minimal inflammation, reduced caspase-3, Iba1 and GFAP in spinal cord tissues, and no hindbrain herniation or ventricular dilation. ConclusionAn RTG patch applied to MMC defects in fetal sheep promoted skin coverage over the defect, was associated with minimal inflammation of the spinal cord tissues and prevented brain abnormalities. The present findings provide exciting results for future comprehensive radiological, functional, and mechanistic evaluation of the RTG.

A study of the mucoadhesive patches loaded with mangosteen peel extract in periodontitis

ObjectiveThe treatment of periodontitis with scaling and root planing has a good prognosis. However, periodontitis may also exacerbate. The mucoadhesive patch is one of the distribution systems of topical drugs, which is not irritable to the mucosa and eventually increases permeability. Based on phytochemical screening, mangosteen peel extract has an active ingredient with high anti-inflammatory and antibacterial properties. This study aims to understand the potential of a mucoadhesive patch loaded with mangosteen peel extract to inhibit alveolar bone damage in periodontitis. MethodsThis experimental laboratory research was conducted using 27 Wistar rats divided into three groups: the positive control group (0.7% tetracycline gel application), negative control group (mucoadhesive patch application), and experimental group (mucoadhesive patch loaded with mangosteen peel extract application). Rats were administered 1 × 109 colony-forming unit as much as 200 μL of Actinobacillus actinomycetemcomitans bacteria three times at 2-day intervals. Tetracycline gel and mucoadhesive patch application were administered for 1 h/day for 3 days. Three rats from each group were sacrificed on days 3, 5, and 7 after the application. The lower jaw was dissected for histopathological examination using haematoxylin and eosin staining to determine the number of osteoclasts and osteoblasts. ResultsThe mucoadhesive patches loaded with mangosteen peel extract significantly reduced the number of osteoclasts and increased the number of osteoblasts in all groups (p < 0.05). ConclusionThe mucoadhesive patches loaded with mangosteen peel extract can prevent alveolar bone damage in periodontitis by inhibiting the number of osteoclasts and increasing the number of osteoblasts.

Wearable Electronics Based on the Gel Thermogalvanic Electrolyte for Self-Powered Human Health Monitoring.

There is always a temperature difference of more than 10 degrees between the human body, as a sustainable heat source, and the ambient temperature. Converting body heat into electricity that in turn is used to drive personal medical electronics is of significance in smart wearable medicine. To avoid the frangibility and complex preparation of traditional thermoelectric materials, we fabricated a gel electrolyte-based thermogalvanic generator with Fe3+/Fe2+ as a redox pair, which presents not only moderate thermoelectric performance but also excellent flexibility. With a micropore-widespread polyvinylidene fluoride diaphragm implanted in the gel, a thermal barrier was created between the two halves, effectively improving the Seebeck coefficient by reducing its thermal conductivity. Considering the superior temperature response of the gel, a self-powered body temperature monitoring system was established by conformally affixing it to the forehead. Meanwhile, the gel patch with a high specific heat capacity can effectively cool down fever patients. This work may offer a new train of thought for exploiting self-powered wearable medical electronics by scavenging low-grade body heat.

Formulation development and evaluation of nimesulide transdermal gel patch system

Formulation development and evaluation of nimesulide transdermal gel patch system