Hydrogel Barrier Research Articles

Biocompatible chitin-based Janus hydrogel membranes for periodontal repair

Periodontal defects caused by severe periodontitis are a widespread issue globally. Guided tissue regeneration (GTR) using barrier membranes for alveolar bone repair is a common clinical treatment. However, most commercially available collagen barrier membranes are expensive and lack the antibacterial properties essential for effective bone regeneration. Herein, we report a natural polysaccharide chitin hydrogel barrier membrane with a Janus structure (ChT-PDA-p-HAP), featuring high antibacterial and protein-repelling activity on the outer side and good osteogenesis ability on the inner side. This multifunctional membrane is fabricated though a three-step process: (i) dissolution and regeneration of chitin, (ii) co-deposition with polydopamine (PDA) and poly(sulfobetaine methacrylate) (pSBMA), and (iii) coating with gelatin-hydroxyapatite (gelatin-HAP). In vitro cell experiments demonstrated the membrane's high biocompatibility and significant osteogenic activity. In vivo implantation in rats with periodontal defects revealed that the cemento-enamel junction index of the ChT-PDA-p-HAP membrane (1.165 mm) was superior to that of the commercial Bio-Gide® membrane (1.350 mm). This work presents a method for fabricating a chitin-based Janus barrier membrane, potentially expanding the use of chitin in tissue engineering. Statement of significanceThis study introduces a Janus hydrogel membrane based on chitin, tailored for guided tissue regeneration in periodontal defects. By combining antibacterial properties and osteogenic capabilities in a single membrane, the ChT-PDA-p-HAP membrane represents a significant advancement over traditional collagen barriers. Its outer surface, enhanced by Cu2+ and PDA-pSBMA coatings, resists bacterial colonization and protein adhesion effectively, while the inner side, coated with gelatin-HAP, promotes robust bone formation. In vitro experiments demonstrate high biocompatibility and substantial osteogenic differentiation, while in vivo testing in rat models confirms good therapeutic efficacy compared to commercial membranes. This multifunctional approach not only utilizes chitin's abundant natural resource but also integrates simple coating techniques to enhance therapeutic outcomes in periodontal tissue engineering, offering promising avenues for broader biomedical applications.

Customizable Hydrogel Coating of ECM-Based Microtissues for Improved Cell Retention and Tissue Integrity.

Overcoming the oxygen diffusion limit of approximately 200 µm remains one of the most significant and intractable challenges to be overcome in tissue engineering. The fabrication of hydrogel microtissues and their assembly into larger structures may provide a solution, though these constructs are not without their own drawbacks; namely, these hydrogels are rapidly degraded in vivo, and cells delivered via microtissues are quickly expelled from the area of action. Here, we report the development of an easily customized protocol for creating a protective, biocompatible hydrogel barrier around microtissues. We show that calcium carbonate nanoparticles embedded within an ECM-based microtissue diffuse outwards and, when then exposed to a solution of alginate, can be used to generate a coated layer around the tissue. We further show that this technique can be fine-tuned by adjusting numerous parameters, granting us full control over the thickness of the hydrogel coating layer. The microtissues' protective hydrogel functioned as hypothesized in both in vitro and in vivo testing by preventing the cells inside the tissue from escaping and protecting the microdroplets against external degradation. This technology may provide microtissues with customized properties for use as sources of regenerative therapies.

Wet Tissue Interfacial Water Triggers Ultrafast In Situ Gelation of Sprayable Dry Powder for Postoperative Anti‐Adhesion

AbstractPostoperative adhesions complicate the majority of surgical procedures, imposing an excess medical burden. The segregation of injured tissue from healthy tissue is considered the optimal therapeutic strategy. However, achieving hemostasis while preventing adhesions in the immediate postoperative setting continues to pose a significant challenge. This paper presents the in situ formation of an asymmetrically adhesive hydrogel barrier via a sprayable dry powder (SDP) that enables interfacial water‐induced, ultra‐rapid gelation. Owing to SDP hydrophilicity and the interstitial spaces between particles, it can rapidly and efficiently absorb interfacial water, thereby facilitating smooth cross‐linking between material functional groups and tissue functional groups. In addition, SDP becomes less adhesive after gelation as a layer of interfacial water forms on the surface of the SDP hydrogel, enhancing its anti‐adhesion properties. Animal experiment outcomes demonstrate that SDP exhibits significant asymmetric adhesive properties before and after gelation, successfully preventing postoperative adhesions. As a result, SDP heralds a novel approach to the development of adhesives that can simultaneously mitigate adhesions and promptly arrest bleeding.

A Sprayable Janus Hydrogel as an Effective Bioadhesive for Gastrointestinal Perforation Repair

AbstractAdvancements in hydrogel bioadhesives for sealing gastrointestinal perforations (GP) face challenges due to weak mechanical properties, causing leakage, especially on uneven wound surfaces. Herein, a Janus hydrogel is introduced featuring a two‐step cross‐linking process, designed to serve as an efficient bioadhesive using a sprayable method. This Janus hydrogel formulation is achieved by modifying a photocurable hyaluronic acid hydrogel with dopamine (DA) and phenylboronic acid (PBA) groups, enabling reversible boronate ester bonds. These dynamic cross‐linking bonds facilitate shear‐thinning and self‐healing abilities, ensuring secure adhesion to complex wounds. A subsequent photocurable irreversible cross‐linking stage results in the formation of a hydrogel barrier with asymmetric adhesive properties, imparting inherent mechanical strength for postoperative anti‐adhesion. To enhance the clinical practicality of this hydrogel, an integrated sprayer device is further developed, enabling the efficient delivery of hydrogel at any angle and over long distances under minimally invasive conditions. Therefore, the HADP hydrogel, integrated with the sprayer device, successfully addressed the limitations associated with hydrogel bioadhesives in clinical applications concerning angles and terrains. This integrated approach presents a compelling solution for repairing gastrointestinal perforations in clinical settings. Moreover, it demonstrates significant potential for diverse applications in repairing complex wound surfaces.

Light-Operated Transient Unilateral Adhesive Hydrogel for Comprehensive Prevention of Postoperative Adhesions.

Dislocation of anti-adhesion materials, non-specific tissue adhesion, and the induction of secondary fibrinolysis disorders are the main challenges faced by postoperative anti-adhesion materials. Herein, a self-leveling transient unilateral adhesive hydrogel is custom-designed to conquer these challenges with a theoretically calculated and dual-step tailored gellan gum (GG) as the sole agent. First, the maximum gelation temperature of GG is lowered from 42-25°C through controlled perturbation of intra- and inter-molecular hydrogen bonds, which is achieved by employing the methacrylic anhydride as a "hydrogen bond's perturbator" to form methacrylate GG (MeGG). Second, the "self-leveling" injectability and wound shape adaptably are endowed by the formation of borate-diol complexed MeGG (BMeGG). Finally, the transient unilateral tissue-adhesive hydrogel (BMeGG-H) barrier is prepared through photo-controlled cross-linking of reactive alkenyl groups. This degradable hydrogel demonstrates favorable rheological properties, light-controlled unilateral adhesion properties, biocompatibility, anti-fibrin adhesion, and anti-cell adhesion properties in vitro. Comprehensive regulation of the fibrinolysis balance toward non-adhesion is conformed in a rat model after intra-abdominal surgery via anti-autoinflammatory response, intestinal wall integrity repair, and Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) balance adjustment. Notably, the 14th day anti-adhesion effective rate is 100%, indicating its significant potential in clinical applications for postoperative anti-adhesion.

A ROS-responsive and scavenging hydrogel for postoperative abdominal adhesion prevention

Postoperative abdominal adhesion (PAA) widely occurs after abdominal surgery, which often produces severe complications. However, there were still no satisfactory anti-adhesive products including barriers and anti-adhesive agents. Herein, we developed a ROS-responsive and scavenging hydrogel barrier, termed AHBC/PSC, wherein the monomer AHBC was synthesized by phenylboronic acid (PBA)-modified hyaluronic acid (HA-PBA) further grafted with adipic dihydrazide (ADH) and PBA-based chlorogenic acid (CGA) via ROS-sensitive borate ester bond, and the other monomer PSC was constructed by polyvinyl alcohol (PVA) grafted with sulfated betaine (SB) and p-hydroxybenzaldehyde (CHO). Further, the double crosslinked AHBC/PSC hydrogel was successfully fabricated between AHBC and PSC via forming dynamic covalent acylhydrazone bonds and borate ester bonds. Results showed that AHBC/PSC hydrogel had in situ gelation behavior, satisfactory mechanical properties (storage modulus of about 1 kPa and loss factor Tan δ of about 0.5), suitable wet tissue adhesion strength of about 2.3 kPa on rat abdominal wall, and good biocompatibility, achieving an ideal physical barrier. Particularly, CGA could be responsively released from the hydrogel by breakage of borate ester bonds between CGA and PBA based on high reactive oxygen species (ROS) levels of damaged tissue and exhibited great ROS scavenging capability to regulate inflammation and promote the polarization of macrophages from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. Moreover, the grafted SB as a zwitterionic group could reduce protein adsorption and fibroblast adhesion. Finally, the in vivo experiments revealed that AHBC/PSC hydrogel with good safety and in vivo retention behavior of about 2 weeks, effectively prevented PAA by regulating the inflammatory microenvironment and alleviating the fibrosis process. In brief, the versatile AHBC/PSC hydrogel would provide a more convenient and efficient approach for PAA prevention. Statement of significancePostoperative abdominal adhesion (PAA) widely occurs after surgery and is often accompanied by severe complications. Excessive inflammation and oxidative stress are very crucial for PAA formation. This study provides a ROS-responsive and scavenging hydrogel with suitable mechanical properties, good biocompatibility and biodegradability, and resistance to protein and fibroblast. The antioxidant and anti-inflammatory active ingredient could be responsively released from the hydrogel via triggering by the high ROS levels in the postoperative microenvironment thereby regulating the inflammatory balance. Finally, the hydrogel would effectively regulate the development process of PAA thereby achieving non-adhesion wound healing.

ROS-responsive sprayable hydrogel as ROS scavenger and GATA6+ macrophages trap for the prevention of postoperative abdominal adhesions

Postoperative abdominal adhesions are a common clinical problem after surgery and can cause many serious complications. Current most commonly used antiadhesion products are less effective due to their short residence time and focus primary on barrier function. Herein, we developed a sprayable hydrogel barrier (sHA-ADH/OHA-E) with self-regulated drug release based on ROS levels at the trauma site, to serve as a smart inflammatory microenvironment modulator and GATA6+ macrophages trap for non-adherent recovery from abdominal surgery. Sulfonated hyaluronic acid (HA) conjugates modified with adipic dihydrazide (sHA-ADH), and oxidized HA conjugates grafted with epigallocatechin-3-gallate (EGCG) via ROS-cleavable boronate bonds (OHA-E) were synthesized. sHA-ADH/OHA-E hydrogel was facilely fabricated within 5 s after simply mixing sHA-ADH and OHA-E through forming dynamic covalent acylhydrazones. With good biocompatibility, appropriate mechanical strength, tunable shear-thinning, self-healing, asymmetric adhesion, and reasonable in vivo retention time, sHA-ADH/OHA-E hydrogel meets the requirements of a perfect physical barrier. Intriguingly, sulfonic acid groups endowed the hydrogel with satisfactory anti-fibroblast and macrophage attachment capability, and were demonstrated for the first time to act as polyanion traps to prevent GATA6+ macrophages aggregation. Importantly, EGCG could be intelligently released by ROS triggering to alleviate oxidative stress and promote proinflammatory M1 macrophage polarize to antiinflammatory M2 phenotype. Further, the fibrinolytic system balance was restored to reduce fibrosis. Thanks to the above advantages, the sHA-ADH/OHA-E hydrogel exhibited excellent anti-adhesion effects in a rat sidewall defect–cecum abrasion model and is expected to be a promising and clinically translatable antiadhesion barrier.

Immunomodulatory melanin@Pt nanoparticle-reinforced adhesive hydrogels for healing diabetic oral ulcers

Oral ulcers may be addressed with various biomaterials infused with medications or cytokines. However, many patients derive little advantage from these substances due to inadequate adhesion, brief retention in the mouth, and diminished drug effectiveness. Here, we introduce a hydrogel patch (MPG3) consisting of a biopolymer matrix with light-activated adhesion features infused with platinum-decorated melanin nanoparticles that possess healing-promoting abilities. Initially, through straightforward local application, an adhesive hydrogel barrier forms over mucosal imperfections upon exposure to ultraviolet light. Following this, MPG3 exhibits outstanding oxygen production and reactive oxygen species elimination properties. These capabilities contribute to regulating the wound microenvironment, thereby expediting the wound's transition from the inflammatory to the proliferative stage. In rat models of oral ulcers, the MPG3 patch hastens recovery by modulating the inflammatory milieu of the damaged tissue and fostering expedited re-epithelialization and blood vessel formation. Conclusively, this light-activated adhesive hydrogel shows promise for swift wound healing and could revolutionize therapeutic approaches for treating clinical oral ulcers, especially in diabetic patients.

A rapid crosslinking injectable polygalacturonic acid barrier modified with zwitterion bottlebrush for preventing postoperative adhesion

Postoperation adhesion, as a worldwide problem, are often accompanied by serious complications and cause severe pain to patients, and traditional medicines and commercial anti-adhesion barriers have limited protective effects. So, we designed a novel injective, antifouling and photo-crosslinked polygalacturonic acid (PGA) hydrogel barrier composed of PGA methacrylate (PGAMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC) with excellent effect of covering the wound and preventing adhesion. The product termed, as PGAMA-MPC, enhanced hydration as expected with the introduction of abundant MPC, showing an obvious resistance to protein, cell, and microorganism. Simultaneously, as injectable medical materials, stable attachment to the wound and low invasiveness for tissue were provided by photo-crosslinking of PGAMA-MPC hydrogel during Minimally invasive surgery. In the rat model of cecal injury, the PGAMA-MPC hydrogel effectively prevented the postoperative peritoneal adhesion, showing an obvious protective effect within 7 d and the excellent ability to repair of cecum and abdominal wall after 14 d. Compared with the control group, the rats treated with PGAMA-MPC3 almost recovered to the level of the normal level. Furthermore, we found that PGAMA-MPC3 hydrogel significantly reduced the expression of inflammation and deposition of fibrin. The underlying mechanism of anti-adhesion was subsequently confirmed by analyzing the signaling pathway TGF-β1. The PGA-MPC3 hydrogel promoted fibrinolysis by blocking the activation of TGF-β1/Smad3 pathway. In conclusion, we developed an available polysaccharide hydrogel for rapid repair of peritoneum and prevention of postoperative adhesion, possessing an extensive application as medical materials.

Superwettable calcium ion exchanged carboxymethyl cellulose powder with self-gelation, tissue adhesion and bioabsorption for effective hemorrhage control

Water-soluble polymers can be used to develop self-gelling hemostatic powders, and powder wettability potentially plays the key role in determining their hemostatic efficacy. Herein, a superwettable calcium ion exchanged carboxymethyl cellulose (Ca-ex-CMC) powder is reported for effective hemorrhage control. Despite being water-soluble, Ca-ex-CMC powder can form a physically crosslinked hydrogel upon contact with water (self-gelation), and the rate of water permeating the hydrogel to achieve dissolution is extremely slow. With increased calcium content, Ca-ex-CMC powder shows not only improved procoagulant activity, but enhanced wettability which can facilitate the fusion of the powders with water, resulting in promoted water uptake and in-situ formation of strong hydrogel barriers with enhanced tissue adhesion. Applying Ca-ex-CMC powder to non-compressible (liver and tail) and massive (artery) hemorrhage wounds in rat and rabbit models can stanch bleeding instantly, because of complete sealing of the bleeding sites by enhanced in-situ self-gelation. Moreover, owing to water-solubility, Ca-ex-CMC powder shows outstanding bioabsorbability and histocompatibility after implantation into rabbit liver and gluteus. These findings not only support Ca-ex-CMC powder as a promising hemostatic agent for extensive application but identify the critical role of wettability in promoting hemostasis for self-gelling powders.

Enhanced Dural Repair Using Biodegradable Sealants Based on Photocurable Hyaluronic Acid.

Cerebrospinal fluid (CSF) leakage is a common complication of intradural surgery or incidental durotomy in neurosurgery. Dural suturing is a common method for durotomy repair, but this technique requires a long operation time and includes the risk of CSF leakage by incomplete sealing. Glue-type sealants are effective for watertight dural closure. However, unresolved shortcomings include insufficient sealing performance, poor biocompatibility, and excessive swelling. Here, a dural sealant using light-activated hyaluronic acid (HA) with multi-networks (HA photosealant) that provides fast sealing performance and high biocompatibility is reported. The HA photosealants form a watertight hydrogel barrier with multilength networks under low-energy visible light exposure (405nm, <1Jcm-2) for 5s and allow firm tissue adhesion on the wet dural surface. In a rabbit model of craniectomy and durotomy, HA photosealants exhibit the faster sealing performance of dural tears and enhance dural repair with accelerated bone formation compared to commercial surgical glues, with no degenerative changes, such as inflammation or necrosis, in histopathological evaluation. This biocompatible HA photosealant can be applied in a variety of clinical settings that require fast wound closure as a promising potential.

Enhanced air sparging for groundwater remediation using alginate gel-based removable hydraulic barriers

The objective of this study was to investigate the effect of a removable physical barrier on the air sparging performance using a lab-scale aquifer model was investigated. The barrier was installed in water-saturated porous media, prior to the air sparging, by injecting calcium chloride aqueous solution into the aquifer with pre-applied alginate solution. Changes in the air flow direction and air flux at the media surface during air sparging were evaluated. With a hydrogel barrier set at the center of the media, the airflow detoured the barrier resulting in a bimodal air flux distribution at the media surface. While employing two gel-formed barriers positioned away from the media's center, the airflow concentrated specifically on the gap between the barriers. The hydrogel was successfully removed using a sodium bicarbonate solution (1.0 mol/L). Using the hydrogel barrier, the performance of air sparging was significantly enhanced for removing contaminants [tetrachloroethene (PCE) and n-hexane mixture] due to increased air flux; 9.8% of PCE applied (7.8 g) was removed during 120 min air sprging for the gel barrier system whereas no PCE was removed for the control. Alginate gel did not show significant sorption capacity for PCE. It was stable in the contaminant up to 68 days with reasonable loss of its mass. Findings of this study present a promising option for air sparging process specifically targeting the contaminant source zone in the aquifer.

A Zwitterionic Hydrogel with Anti-Oxidative and Anti-Inflammatory Properties for the Prevention of Peritoneal Adhesion by Inhibiting Mesothelial-Mesenchymal Transition.

Postoperative peritoneal adhesion is a serious clinical complication. Various hydrogel barriers have been developed to prevent peritoneal adhesion. However, it remains a challenge to design a hydrogel with desirable physicochemical properties and bioactivities. In this study, a zwitterionic polysaccharide-based multifunctional hydrogel is developed using epigallocatechin-3-gallate (EGCG) to prevent postoperative abdominal adhesion. This hydrogel is simple to use and has desirable properties, such as excellent injectability, self-healing, and non-swelling properties. The hydrogel also has ultralow fouling capabilities, such as superior bactericidal performance, cell and protein adhesion, and low immunogenicity resistance. Moreover, the hydrogel exhibits good antioxidant activity, which is attributed to the integration of EGCG. Furthermore, the detailed mechanism from in vivo and in vitro experimental studies illustrates that hydrogel compositions can synergistically prevent adhesion formation through multiple pathways, including anti-inflammatory and antioxidant capabilities and inhibition effects on the mesothelial-mesenchymal transition (MMT) process induced by transforming growth factor (TGF-β). In summary, this zwitterionic multifunctional hydrogel has great potential to prevent postoperative adhesion formation in the clinical setting.

Chitooligosaccharide reconstitutes intestinal mucus layer to improve oral absorption of water-soluble drugs

Intestinal mucus is a complex natural hydrogel barrier with unique physical properties that impede the absorption of various oral drugs. Both washout from the upper water layer and the physical resistance of the mucus layer particularly affect bioavailability of, especially, highly water-soluble molecules. One potential strategy for designing pharmaceutical formulations is to add absorption enhancers (AEs). However, there are few reports of AEs that work on mucus and their underlying mechanisms, leading to imprecise application. In this study, we investigated chitooligosaccharide (COS) as a safe, low-cost, and effective oral drug AE. We revealed the hydrodynamic law of interaction between COS and the intestinal mucus layer, which was associated with absorption benefiting mucus structural reconstruction. Based on this, we designed a translational strategy to improve the bioavailability of a group of soluble oral drugs by drinking COS solution before administration. Moreover, this research is expected to expand its application scenario by reducing drug dosage such as avoiding gastro-intestinal irritation and slowing veterinary antibiotic resistance.

Agarose‐based hydrogels with tunable, charge‐selective permeability properties

AbstractPhysiologically, a hallmark of biological hydrogels is their ability to selectively trap diffusing molecules and particles. And indeed, there is now increasing interest in using selective hydrogel barriers for applications in biomedicine and medical engineering. However, when employing synthetic polymers to create hydrogels with selective permeabilities, controlling the type and strength of the ensuing filtration process is difficult. Here, we generate hybrid gels with adjustable selectivity profiles by mixing a series of (bio‐)macromolecules with agarose. Depending on the type and concentration of the incorporated macromolecules, those hybrid gels achieve a selective retardation of the diffusive translocation of either positively or negatively charged dextrans at both, acidic and neutral pH. Furthermore, we demonstrate three strategies that provide hydrogels with sequestered patches of both, cationic and anionic binding sites, thus creating symmetric charge (i.e., electrostatic bandpass) filters which still allow neutral molecules to pass. Moreover, such agarose matrices offer a high level of versatility as their permeability profiles can be tailored at will by integrating macromolecules with desired physico‐chemical properties. Thus, those agarose‐based hybrid gels may serve as a powerful platform to engineer adjustable and versatile materials for a broad range of future applications in the field of biomedical engineering.

Highly efficient bacteria-infected diabetic wound healing employing a melanin-reinforced biopolymer hydrogel

Owing to hyperglycemia-related metabolic abnormalities that cause oxidative stress, recurrent infections, and vascular lesions, the therapeutic management of diabetic wounds is still unsatisfactory. Herein, we present a hydrogel (GCM) wound dressing loaded with melanin nanoparticles in a polysaccharide matrix (biguanide chitosan and oxidized β-glucan) for efficient healing of bacterially infected diabetic wounds. By a simple local injection, a protective GCM hydrogel barrier is established over the wound to rapidly stop bleeding and neutralize inflammatory cytokines. Subsequently, the GCM hydrogel achieves an accelerated transfer from the inflammatory process to the healing phase of the wound because of its excellent photothermal antimicrobial and reactive oxygen species scavenging properties. Additionally, GCM hydrogel has a three-dimensional network structure that dramatically enhances cell proliferation, migration, and angiogenesis by creating favorable ecological conditions for cell survival. Notably, our GCM hydrogel can help treat a variety of bacteria-infected diabetic wounds like skin and oral ulcer wounds. Collectively, this work provides a new option for diabetic wound treatment.

An endoscopically compatible fast-gelation powder forms Janus-adhesive hydrogel barrier to prevent postoperative adhesions

Postoperative adhesions occur widely in various tissues, bringing the risk of secondary surgery and increased medical burden. Hydrogel barriers with Janus-adhesive ability can achieve physical isolation of adjacent tissues and are therefore considered an ideal solution. However, integrating endoscopic delivery convenience and viscoelastic Janus hydrogel formation remains a great challenge. Here, we present a report of the insitu formation of Janus-adhesive hydrogel barrier using a sprayable fast-Janus-gelation (FJG) powder. We first methacrylate the polysaccharide macromolecules to break the intermolecular hydrogen bonds and impart the ability of rapid hydration. FJG powder can rapidly absorb interfacial water and crosslink through borate ester bonds, forming a toughly adhesive viscoelastic hydrogel. The Janus barrier can be simply formed by further hydrating the upper powder with cationic solution. We construct rat models to demonstrate the antiadhesions efficiency of viscoelastic FJG hydrogels in organs with different motion modalities (e.g., intestine, heart, liver). We also developed a low-cost delivery device with a standardized surgical procedure and further validated the feasibility and effectiveness of FJG powder in minimally invasive surgery using a preclinical translational porcine model. Considering the advantages in terms of therapeutic efficacy, clinical convenience, and commercialization, our results reveal the great potential of Janus-gelation powder materials as a next-generation antiadhesions barrier.

Pump-less, recirculating organ-on-a-chip (rOoC) platform.

We developed a novel, pump-less directional flow recirculating organ-on-a-chip (rOoC) platform that creates controlled unidirectional gravity-driven flow by a combination of a 3D-tilting system and an optimized microfluidic layout. The rOoC platform was assembled utilizing a layer-to-layer fabrication technology based on thermoplastic materials. It features two organoid compartments supported by two independent perfusion channels and separated by a hydrogel barrier. We developed a computational model to predict wall shear stress values and then measured the flow rate in the microfluidic channels with micro-Particle-Image-Velocimetry (μPIV). The suitability of the rOoC for functional culture of endothelial cells was tested using HUVECs seeded in the perfusion channels. HUVECs aligned in response to the directional flow, formed a barrier and were able to sprout into the organoid compartments. Next, we demonstrated the viability of human stem-cell derived liver organoids in the organoid compartments. Finally, we show the possibility to circulate immune cells in the microfluidic channels that retain viability without being trapped or activated. The rOoC platform allows growing and connecting of two or more tissue or organ representations on-chip with the possibility of applying gradients, endothelial barriers, microvasculature and circulating cells independent of external tubing and support systems.

A novel intrauterine barrier for preventing the recurrence of IUA after TCRA procedure

Intrauterine adhesion (IUA) is the result of abnormal endometrium repair after trauma and infection that damages the basal layer of the endometrium, which is then replaced by scar tissue. In such instances, the endometrium partially or completely loses the ability to conceive the embryo. Even after surgery-based comprehensive treatment, a high rate of adhesion remains. A thin endometrium, poor blood supply, and poor function may also lead to refractory infertility, resulting in a poor reproductive prognosis even when the uterine cavity has been completely restored to normal. Therefore, two key points of postoperative management are the use of an intrauterine barrier to prevent re-adhesion and medicine to promote endometrial repair. However, there is currently no clinically applicable barrier that can meet the personalized dimensions of uterine cavity shape and size or effectively separate the wound wall. We have designed an intrauterine barrier that consists of a unique uterine-shaped, estrogen-release intrauterine device (IUD), which can be combined with an injectable, temperature-sensitive hydrogel. For this study, we will insert an estrogen-release IUD into the uterine cavity following transcervical resection of adhesion (TCRA) surgery, at the same time injecting 3–5 mL of liquid hydrogel at room temperature into the uterine cavity via the cervical channel. Due to its temperature sensitivity, the hydrogel will gradually solidify into a jellylike consistency, filling the uterine cavity with a solid barrier and completely preventing contact with the wounded wall to avoid the recurrence of adhesion. The estrogen-release IUD will be wrapped in the hydrogel barrier, which has many pores that allow sustainable estrogen release to promote endometrial regeneration and repair. This protocol can meet the needs of postoperative management of TCRA, but experimental and clinical studies are still needed to demonstrate its effectiveness. If patients in the study group have a lower adhesion recurrence and higher pregnancy rate compared to controls, our hypothesis will be confirmed that this barrier will prove a clinical application to help the functional repair of the endometrium and achieve a good reproductive prognosis.

Surgical treatment of large and complicated hiatal hernias with the new resorbable mesh with hydrogel barrier (Phasix™ ST): a preliminary study.

Evaluation of the efficacy and safety of the new monofilament fully resorbable mesh with hydrogel barrier (Phasix™ ST), for large and complex hiatal hernia repair. Between December 2017 and December 2020, 60 patients with large or complicated hiatal hernia were treated (40 robotic and 20 laparoscopic procedures). The mesh was placed after primary closure of the hiatal defect, in an onlay fashion around the esophagus, followed by 360o fundoplication. Follow-up at 3, 6, 12, 18, 24months from intervention included clinical evaluation and upper GI endoscopy. In cases of recurrence, radiologic survey and manometry were utilized. There were no conversions to open repair or significant postoperative incidents. Over a median follow-up of 21months (range 3-36), no recurrences or mesh related complications were observed. From our early experience, Phasix™ ST mesh seems to be safe and effective for the reinforcement of crural defects in large and complex hiatal hernia.