Research on triamcinolone-loaded thermosensitive chitosan hydrogels for preventing esophageal stricture induced by endoscopic submucosal dissection.

Early-stage esophageal cancer is primarily treated by endoscopic submucosal dissection (ESD). However, extensive mucosal dissection creates a significant risk of postoperative esophageal stricture. Clinically, postoperative stricture can be prevented by glucocorticoids; however, there are drawbacks to both systemic and local administration of glucocorticoids, and improving drug administration methods is crucial. In this study, we developed a chitosan-based thermosensitive hydrogel for triamcinolone (TA) delivery. Our results indicated that the hydrogel remains liquid at low temperatures and can be injected into the esophageal wound site through an endoscopic biopsy channel. Upon reaching body temperature, the hydrogel undergoes spontaneous gelation and firmly adheres to the wound surface. The liquid phase enables convenient and precise delivery, while the gel phase achieves remarkable adhesion, tensile strength, and resistance to degradation. Moreover, the hydrogel exhibited an extended release duration of >10 days when loaded with a 10 mg dose. In vitro studies revealed that the hydrogel suppresses the proliferation and fibrogenesis of human scar fibroblasts (HKF). In a rat skin dermal defect model, the hydrogel attenuated keloid formation during the healing process. Consequently, the chitosan-based thermosensitive hydrogel developed in this study for triamcinolone delivery may be an effective tool for preventing post-ESD esophageal stricture.

Polyvinyl-alcohol, chitosan and graphene-oxide composed conductive hydrogel for electrically controlled fluorescein sodium transdermal release.

Accurate and controlled release of drug molecules is crucial for transdermal drug delivery. Electricity, as an adjustable parameter, offers the potential for precise and controllable drug delivery. However, challenges exist in selecting the appropriate drug carrier, electrical parameters, and release model to achieve controlled electronic drug release. To overcome these challenges, this study designed a functional hydrogel using polyvinyl alcohol, chitosan, and graphene oxide as components that can conduct electricity, and constructed a drug transdermal release model using fluorescein sodium salt with proper electrical parameters. The results demonstrated that the hydrogel system exhibited low cytotoxicity, good conductivity, and desirable drug delivery characteristics. The study also integrated the effects of drug release and tissue repair promotion under electrical stimulation. Cell growth was enhanced under low voltage direct current pulses, promoting cell migration and the release of VEGF and FGF. Furthermore, the permeability of fluorescein sodium salt in the hydrogel increased with direct current stimulation. These findings suggest that the carbohydrate polymers hydrogel could serve as a drug carrier for controlled release, and electrical stimulation offers new possibilities for functional drug delivery and transdermal therapy.

Nanocomposite hydrogel based on chitosan/laponite for sealing and repairing tracheoesophageal fistula.

Tracheoesophageal fistula (TEF) is an abnormal connection between the trachea and esophagus that severely impairs quality of life. Current treatment options have limitations, including conservative treatment, surgical repair, and esophageal stent implantation. Here, we introduced laponite (LP) nano-clay to improve chitosan-based hydrogels' rheological properties and mechanical properties and developed an endoscopically injectable nanocomposite shear-thinning hydrogel to seal and repair fistulas as an innovative material for the treatment of TEF. Excellent injectability, rheological properties, mechanical strength, self-healing, biodegradability, biocompatibility, and tissue repair characterize the new hydrogel. The introduction of LP nano-clay improves the gel kinetics problem of hydrogels to realize the sol-gel transition immediately after injection, avoiding gel flow to non-target sites. The addition of LA nano-clay can significantly improve the rheological properties and mechanical strength of hydrogels, and hydrogel with LP content of 3 % shows better comprehensive performance. The nanocomposite hydrogel also shows good cytocompatibility and can promote wound repair by promoting the migration of HEEC cells and the secretion of VEGF and FGF. These findings suggest that this nanocomposite hydrogel is a promising biomaterial for TEF treatment.

Construction of Microfluidic Chip Structure for Cell Migration Studies in Bioactive Ceramics.

Cell migration is an essential bioactive ceramics property and critical for bone induction, clinical application, and mechanism research. Standardized cell migration detection methods have many limitations, including a lack of dynamic fluid circulation and the inability to simulate cell behavior in vivo. Microfluidic chip technology, which mimics the human microenvironment and provides controlled dynamic fluid cycling, has the potential to solve these questions and generate reliable models of cell migration in vitro. In this study, a microfluidic chip is reconstructed to integrate the bioactive ceramic into the microfluidic chip structure to constitute a ceramic microbridge microfluidic chip system. Migration differences in the chip system are measured. By combining conventional detection methods with new biotechnology to analyze the causes of cell migration differences, it is found that the concentration gradients of ions and proteins adsorbed on the microbridge materials are directly related to the occurrence of cell migration behavior, which is consistent with previous reports and demonstrates the effectiveness of the microfluidic chip model. This model provides in vivo environment simulation and controllability of input and output conditions superior to standardized cell migration detection methods. The microfluidic chip system provides a new approach to studying and evaluating bioactive ceramics.

A chitosan-optimized polyethyleneimine/polyacrylic acid multifunctional hydrogel for reducing the risk of ulcerative arterial bleeding.

Ulcerative arterial bleeding is characterized by sudden onset, rapid disease development, and high mortality, which is a great challenge for clinicians to treat, specially bleeding in areas where endoscopic operation is difficult, or in the case of diffuse bleeding, tumor bleeding, and recurrent bleeding. Herein, we proposed a novel treatment strategy using biomaterials to protect the wound and isolate the erosion of digestive tract contents to prevent arterial bleeding in advance. By introducing chitosan to construct multihydrogen-bonding and an electrostatic interaction system, we developed polyethyleneimine/polyacrylic acid/chitosan (PEI/PAA/CS) multifunctional hydrogel. The new hydrogel is characterized by ultrafast gelation, strong tissue adhesion, gastric acid resistance, burst resistance, biocompatibility, hemostasis, and tissue repair. The addition of CS significantly improved the tissue adhesion, biocompatibility, hemostasis, and tissue repair ability of the hydrogel. The PEI/PAA/CS hydrogel could adhere to the ulcer surface and form a protective layer on the wound to prevent arterial bleeding. Importantly, the PEI/PAA/CS hydrogel also has the ability to stop bleeding and promote wound repair, which has been demonstrated in a variety of hemorrhage models in rats and rabbits. All of these factors indicate that the PEI/PAA/CS hydrogel is a promising biomaterial for reducing the risk of ulcerative arterial bleeding.

Design and validation of performance-oriented injectable chitosan thermosensitive hydrogels for endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) is a challenging procedure. The use of biomaterials to improve the operator's convenience (operating affinity) has received little attention. We prepared two thermosensitive hydrogels, lactobionic acid-modified chitosan/chitosan/ß-glycerophosphate thermosensitive hydrogel (hydrogel 1) and its lyophilized powders (hydrogel 2), characterized their physicochemical properties and evaluated their performance in ESD experiments on large animals, by comparing with the commonly used normal saline (NS) and glycerin fructose (GF). These hydrogels showed good low-temperature fluidity; their viscosities at 4 °C were 92.2 mPa.s and 26.9 mPa.s, respectively. The hydrogels provided significantly better viscoelastic properties than NS and GF. The relaxation moduli of hydrogels were higher than those of NS and GF when the strains were 1 %, 5 %, and 10 %. The hydrogels can be maintained for seven days, even at pH 1, after which they degrade entirely. In pig model experiments, we performed submucosal injection and ESD procedures in the stomach and esophagus. The cushion height produced by the hydrogels was higher than those of NS and GF 30 min after injection. The ESD operation time for hydrogels was significantly shorter. Postoperative wound observation and histological analysis showed that the hydrogels promoted wound healing. The two hydrogels differed in fluidity, viscoelasticity, and other properties, which makes it possible to select the hydrogels according to the size and location of the lesion during ESD operation, and hydrogel 2 may be more suitable for use in lengthier procedures. In general, the hydrogels showed good performance, facilitated the intraoperative operation of ESD, shorten the operation time and promoted wound healing, which is of great significance for reducing the complications and reducing the threshold of ESD operation and further promoting the popularity of ESD.

Vanillin enhances the antibacterial and antioxidant properties of polyvinyl alcohol-chitosan hydrogel dressings.

Wound management requires the preparation of controllable, safe and effective dressings to isolate the wound from the external environment. Currently, widely used commercial dressings focus on the isolation effect rather than an environment conducive to wound healing. To provide the dressing with beneficial properties such as wetting and antioxidant and antibacterial activity, this study used polyvinyl alcohol (PVA) hydrogel as the base material and introduced chitosan (CS) and vanillin (V) to design a PVA/CS/V three-phase hydrogel dressing. The dressings were prepared using a freeze-thaw cycle to achieve properties. We conducted a comparative analysis of PVA/V and PVA/CS two-phase hydrogels. The PVA/CS/V (PCV) hydrogel dressing maintaining an elastic modulus at >5 kPa at 15-40 °C. An in vitro antibacterial assay showed the potent antibacterial ability of hydrogels against gram-positive and -negative bacteria, and cells in some PCV groups showed higher activity. The antioxidant results showed that PCV hydrogel had a potent scavenging effect on DPPH, ABTS+, and PTIO free radical. The antibacterial and antioxidant properties of three-phase hydrogel showed the best performance in all experimental groups. These results suggest that PCV hydrogel has value in commercial applications due to its simple preparation process and excellent biological properties.

Chitosan thermosensitive hydrogels based on lyophilizate powders demonstrate significant potential for clinical use in endoscopic submucosal dissection procedures.

The goal of this study was to develop intraoperative biomaterials for use in endoscopic submucosal dissection (ESD) procedures that are stable during storage, easy to use, and effective in clinical practice. Therefore, injectable thermosensitive hydrogels were developed based on lactobionic acid-modified chitosan/chitosan/ß-glycerophosphate (CSLA/CS/GP) hydrogel lyophilizate powders, and their properties were compared with original hydrogels that had not been freeze-dried. The results indicated that the lyophilizate powders retained their thermosensitive properties, and gels could be formed within 5 min at 37 °C. Compared to the original hydrogels, the injectability of the hydrogels derived from lyophilizate powders increased significantly. These novel materials maintained their original porous network lamellar structure but exhibited improved mechanical strength and tissue adhesion. Their application with L929 and GES-1 cells revealed that the lyophilizate powder hydrogels demonstrated good cytocompatibility and clearly protected the cells in an acidic environment. The results of submucosal injection experiments involving porcine stomach tissue indicated that the heights of the cushions created by CSLA/CS/GP lyophilizate powder hydrogels lasted longer than those generated with normal saline. The thermosensitive hydrogels based on lyophilizate powders may contribute to practical clinical applications involving ESD, and may also have potential value for other applications in the digestive tract.

Lactobionic acid-modified chitosan thermosensitive hydrogels that lift lesions and promote repair in endoscopic submucosal dissection.

To develop a biomaterial to lift the lesion and promote wound healing in endoscopic submucosal dissection (ESD), we used lactobionic acid (LA) to improve the water solubility of chitosan (CS) and prepared a new three-phase hydrogel system with lactobionic acid-modified chitosan/chitosan/ß-glycerophosphate (CSLA/CS/GP). The results indicated that the hydrogel retains temperature-sensitive properties, and CSLA obviously improved the low-temperature fluidity of the hydrogel precursor solution, enabling injection of the hydrogel by endoscopic needle. The mechanical strength and bio-adhesion of the hydrogels were also improved by the addition of CSLA and the hydrogels could be maintained in acidic environment for a few days and exhibit greater protection of cells. The CSLA/CS/GP hydrogels show good cytocompatibility. The heights of cushions elevated by CSLA/CS/GP hydrogels remained ∼ 60 % 2 h post-injection in porcine stomach models. Given the unique characteristics of these materials, the CSLA/CS/GP thermo-sensitive hydrogel is a promising intraoperative biomaterial in ESD.

Evaluating platelet activation related to the degradation products of biomaterials using molecular markers.

Increasing numbers of biodegradable medical devices may be used in the circulatory system. The effects of the released degradation products from these medical devices on the blood may be gradual and cumulative. When they reach critical levels, they may cause thrombosis and other complications. For this reason, it is important to evaluate the blood compatibility of degradation products for quality control and development of these devices. In the present study, we evaluated the degradation products of four biodegradable materials (collagen, polylactic acid, calcium phosphate ceramics, and magnesium) using platelet activation molecular markers that are associated with thrombosis. We found that the degradation products activate platelets to a certain extent, and that the degradation products produced during various degradation time periods activate platelets to varying degrees. This platelet activation occurs via several mechanisms, most of which are associated with the physicochemical properties of the degradation products, including ion concentration, pH, molecular microstructure, and molecular weight. Our findings not only provide a clearer understanding of the effects of degradation products from blood-contacting biodegradable devices, but also provide material for screening of degradation behavior so as to improve quality control for these devices.

Feasibility study of use of rabbit blood to evaluate platelet activation by medical devices.

It is important to ascertain platelet responses to blood-contacting medical devices as part of a complete hemocompatibility evaluation. Nevertheless, researchers often face the problem of insufficient quantities of human blood for evaluation of platelet activation by actual medical devices. If animal blood can replace human blood to evaluate platelet activation by medical devices, testing will be smoother and will aid for quality control of related products. Therefore, in this study, we exposed representative biomaterials to human blood, rabbit blood and mouse blood, and evaluated similarities and differences in platelet activation among the three types of blood by measuring various molecular markers. We found that rabbit blood and human blood had considerable similarity in terms of platelet activation, while mouse blood and human blood showed considerable differences. Therefore, rabbit blood may replace human blood for platelet function testing.