Advancements in hydrogel-based drug delivery systems for the treatment of inflammatory bowel disease: a review.

Inflammatory bowel disease (IBD) is a chronic disorder that affects millions of individuals worldwide. However, current drug therapies for IBD are plagued by significant side effects, low efficacy, and poor patient compliance. Consequently, there is an urgent need for novel therapeutic approaches to alleviate IBD. Hydrogels, three-dimensional networks of hydrophilic polymers with the ability to swell and retain water, have emerged as promising materials for drug delivery in the treatment of IBD due to their biocompatibility, tunability, and responsiveness to various stimuli. In this review, we summarize recent advancements in hydrogel-based drug delivery systems for the treatment of IBD. We first identify three pathophysiological alterations that need to be addressed in the current treatment of IBD: damage to the intestinal mucosal barrier, dysbiosis of intestinal flora, and activation of inflammatory signaling pathways leading to disequilibrium within the intestines. Subsequently, we discuss in depth the processes required to prepare hydrogel drug delivery systems, from the selection of hydrogel materials, types of drugs to be loaded, methods of drug loading and drug release mechanisms to key points in the preparation of hydrogel drug delivery systems. Additionally, we highlight the progress and impact of the hydrogel-based drug delivery system in IBD treatment through regulation of physical barrier immune responses, promotion of mucosal repair, and improvement of gut microbiota. In conclusion, we analyze the challenges of hydrogel-based drug delivery systems in clinical applications for IBD treatment, and propose potential solutions from our perspective.

In situ bioprinting of double network anti-digestive xanthan gum derived hydrogel scaffolds for the treatment of enterocutaneous fistulas.

The clinical treatment of enterocutaneous fistula is challenging and causes significant patient discomfort. Fibrin gel can be used to seal tubular enterocutaneous fistulas, but it has low strength and poor digestion resistance. Based on in situ bioprinting and the anti-digestive properties of xanthan gum (XG), we used carboxymethyl chitosan (CMC) and xanthan gum modified by grafted glycidyl methacrylate (GMA) and aldehyde (GCX) as the ink to print a double network hydrogel that exhibited high strength and an excellent anti-digestive performance. In addition, in vitro studies confirmed the biocompatibility, degradability, and self-healing of hydrogels. In our rabbit tubular enterocutaneous fistula model, the in situ printed hydrogel resisted corrosion due to the intestinal fluid and acted as a scaffold for intestinal mucosal cells to proliferate on its surface. To summarize, in situ bioprinting GCX/CMC double network hydrogel can effectively block tubular enterocutaneous fistulas and provide a stable scaffold for intestinal mucosal regeneration.

A click chemistry-mediated all-peptide cell printing hydrogel platform for diabetic wound healing.

High glucose-induced vascular endothelial injury is a major pathological factor involved in non-healing diabetic wounds. To interrupt this pathological process, we design an all-peptide printable hydrogel platform based on highly efficient and precise one-step click chemistry of thiolated γ-polyglutamic acid, glycidyl methacrylate-conjugated γ-polyglutamic acid, and thiolated arginine-glycine-aspartate sequences. Vascular endothelial growth factor 165-overexpressed human umbilical vein endothelial cells are printed using this platform, hence fabricating a living material with high cell viability and precise cell spatial distribution control. This cell-laden hydrogel platform accelerates the diabetic wound healing of rats based on the unabated vascular endothelial growth factor 165 release, which promotes angiogenesis and alleviates damages on vascular endothelial mitochondria, thereby reducing tissue hypoxia, downregulating inflammation, and facilitating extracellular matrix remodeling. Together, this study offers a promising strategy for fabricating tissue-friendly, high-efficient, and accurate 3D printed all-peptide hydrogel platform for cell delivery and self-renewable growth factor therapy.

Melt electrowriting-printed peritoneal scaffold prevents peritoneal adhesion and facilitates peritoneal repair.

Peritoneal adhesion is a critical issue after abdominal surgery. Cell-based methods for preventing peritoneal adhesion have not yet been fully investigated. Here, we constructed a highly biomimetic peritoneal scaffold by seeding mesothelial cells, the natural physiological barrier of the peritoneum, onto a melt electrowriting-printed scaffold. The scaffolds with the microfibers crossed at different angles (30°, 60°, and 90°) were screened based on mesothelial cell proliferation and orientation. Thirty degrees were more suitable for improving proliferation of mesothelial cells and cell growth in a single direction; therefore, the 30° peritoneal scaffold could better mimic the physiological structure of native peritoneum. Mechanistically, such a peritoneal scaffold was able to act as a barrier to prevent peritoneal resident macrophages from migrating to the site of the peritoneal lesion. In vivo mesothelial cell tracking using lentivirus technology confirmed that the peritoneal scaffold, compared to the scaffold without mesothelial cells, could prevent peritoneal adhesion and was directly involved in the repair of injured peritoneum. This study suggests that the peritoneal scaffolds can potentially prevent peritoneal adhesion, offering a new approach for clinical treatment.

Extracellular matrix bioink boosts stemness and facilitates transplantation of intestinal organoids as a biosafe Matrigel alternative.

Organoids hold inestimable therapeutic potential in regenerative medicine and are increasingly serving as an in vitro research platform. Still, their expanding applications are critically restricted by the canonical culture matrix and system. Synthesis of a suitable bioink of bioactivity, biosecurity, tunable stiffness, and printability to replace conventional matrices and fabricate customized culture systems remains challenging. Here, we envisaged a novel bioink formulation based on decellularized extracellular matrix (dECM) from porcine small intestinal submucosa for organoids bioprinting, which provides intestinal stem cells (ISCs) with niche-specific ECM content and biomimetic microstructure. Intestinal organoids cultured in the fabricated bioink exhibited robust generation as well as a distinct differentiation pattern and transcriptomic signature. This bioink established a new co-culture system able to study interaction between epithelial homeostasis and submucosal cells and promote organoids maturation after transplantation into the mesentery of immune-deficient NODSCID-gamma (NSG) mice. In summary, the development of such photo-responsive bioink has the potential to replace tumor-derived Matrigel and facilitate the application of organoids in translational medicine and disease modeling.

Mapping a Country Image from Global News Reports about COVID-19 Pandemic.

The outbreak of the coronavirus disease of 2019 (COVID-19) pandemic has infected hundreds of millions of people worldwide and caused millions of deaths. This study used media analysis and correlation analysis to elucidate the significant differences in the ways in which news reports from 228 countries discussed a specific country when covering the COVID-19 pandemic. Media reports analysed in this study were collected from the Global Database of Events, Language, and Tone project (GDELT). These differences were found to be deeply embedded in the economic, socio-political, and cultural contexts of different countries. The findings reinforced the hypothetical assumption in framing theory and promoted a measurable and upscaled use of framing theory into macro geography studies. This study highlights the urgent need of a geo-political examination of COVID-19 in the global context-an area with insufficient interest from interdisciplinary perspective beyond epidemiology. Further research can be of great value for the promotion of an effective international cooperation mechanism to curb the spread of COVID-19. Supplementary Information: The online version contains supplementary material available at 10.1007/s12061-022-09498-4.

Multifunctional hydrogel based on dopamine-modified hyaluronic acid, gelatin and silver nanoparticles for promoting abdominal wall defect repair.

Abdominal wall defects are often accompanied by severe infections and complications, creating a significant challenge for clinicians. There is an urgent need to develop a novel wound dressing that can effectively prevent intra-abdominal infection and promote the healing of defective abdominal walls. Based on a hydrogel dressing containing hyaluronic acid (HA) and gelatin (GT), herein we integrated dopamine with a catechol structure to enhance its antioxidant and adherent properties. HA is oxidized to form an aldehyde group, and subsequently grafted with dopamine. The dopamine-modified HA undergoes amidation reaction with GT at different concentrations. In addition, silver nanoparticles (AgNPs) were introduced to the hydrogel to enhance the antibacterial properties. The in vitro studies on GT/DA-HA demonstrated excellent physical and chemical properties, biodegradability, and biocompatibility. In a rat full-thickness skin defect model and a full-thickness abdominal wall defect model, the GT/DA-HA hydrogel could accelerate the healing process by improving wet adhesion, reducing wound inflammation, and promoting angiogenesis and formation of granulation tissues. The multifunctional hydrogel developed in this study shows great potential for treating full-thickness abdominal wall defects.

Multifunctional Electrospun Textiles for Wound Healing.

The novel multifunctional electrospun textiles were fabricated by incorporating sheet-like kaolinite and silver nanoparticles (AgNps) into a polyurethane (PU) textile by using electrostatic spinning to promote wound-healing process. Threedimensional network of PU electrospun textiles offered an appropriate framework for loading kaolinite nanosheets and AgNps. Moreover, the kaolinite nanosheets healed bleeding wounds by accelerating plasma absorption, increasing blood cell concentrations, and stimulating coagulation factors. Furthermore, the AgNps killed microbes by destroying the cell membrane, while the deleterious effects were controlled by incorporation into the electrospun textile. The therapeutic effects of multifunctional electrospun textile in treating full-thickness abdominal wall defect were explored. The wound healing process could be accelerated via the textile by restoring the abdominal physiological environment, reducing the inflammatory response, and promoting collagen deposition, angiogenesis, and epithelization.

Correction: A graphene hybrid supramolecular hydrogel with high stretchability, self-healable and photothermally responsive properties for wound healing.

[This corrects the article DOI: 10.1039/D0RA09106E.].

Responsive and self-healing structural color supramolecular hydrogel patch for diabetic wound treatment.

The treatment of diabetic wounds remains a great challenge for medical community. Here, we present a novel structural color supramolecular hydrogel patch for diabetic wound treatment. This hydrogel patch was created by using N-acryloyl glycinamide (NAGA) and 1-vinyl-1,2,4-triazole (VTZ) mixed supramolecular hydrogel as the inverse opal scaffold, and temperature responsive poly(N-isopropylacrylamide) (PNIPAM) hydrogel loaded with vascular endothelial cell growth factor (VEGF) as a filler. Supramolecular hydrogel renders hydrogel patch with superior mechanical properties, in which NAGA and VTZ also provide self-healing and antibacterial properties, respectively. Besides, as the existence of PNIPAM, the hydrogel patch was endowed with thermal-responsiveness property, which could release actives in response to temperature stimulus. Given these excellent performances, we have demonstrated that the supramolecular hydrogel patch could significantly enhance the wound healing process in diabetes rats by downregulating the expression of inflammatory factors, promoting collagen deposition and angiogenesis. Attractively, due to responsive optical property of inverse opal scaffold, the hydrogel patch could display color-sensing behavior that was suitable for the wound monitoring and management as well as guidance of clinical treatment. These distinctive features indicate that the presented hydrogel patches have huge potential values in biomedical fields.

Correction: Engineering an adhesive based on photosensitive polymer hydrogels and silver nanoparticles for wound healing.

Correction for 'Engineering an adhesive based on photosensitive polymer hydrogels and silver nanoparticles for wound healing' by Qinqing Tang et al., J. Mater. Chem. B, 2020, 8, 5756-5764, DOI: 10.1039/d0tb00726a.

Protein-Based Hybrid Responsive Microparticles for Wound Healing.

The in-depth development of biological materials, especially natural polymer materials, has injected strong vitality into clinical wound treatment. Here, a new type of controllable responsive microparticles composed of several natural polymer materials was presented for drug release and wound healing. These hybrid microparticles consisted of silk fibroin, gelatin, agarose, and black phosphorus quantum dots (BPQDs) and were loaded with growth factors and antibacterial peptides. Under near-infrared (NIR) irradiation, BPQDs could absorb the NIR light and increase the temperature of the microparticles to the melting point of gelatin. When the gelatin started to melt, the encapsulated drugs were gradually released because of the reversible phase transformation. Both in vitro and in vivo experiments have demonstrated that the BPQD-laden microparticles with a NIR-responsive feature could achieve the desired controllable release of growth factors to promote neovascularization formation. In addition, because antibacterial peptides were also mixed with the secondary hydrogel and encapsulated in the scaffolds, the microparticles are imparted with the antibacterial ability during storage and usage. These characteristics of BPQD-laden natural protein hybrid microparticles make them ideal for drug delivery and wound healing.

Metformin loaded porous particles with bio-microenvironment responsiveness for promoting tumor immunotherapy.

PD1/PD-L1 antibody blockade-based immunotherapy has been widely recognized in the field of cancer treatment; however, only a small number of cancer patients have been shown to respond well due to the PD1/PD-L1 antibody hydrolysis induced substandard immunotherapeutic efficacy and the low immunogenicity and immunosuppressive tumor microenvironment of the patients. Here, we present a novel tumor microenvironment (TME) responsive particle delivery system with a metformin-loaded chitosan (CS) inverse opal core and a manganese dioxide (MnO2) shell (denoted as CS-metformin@MnO2 particles) for inhibiting the PD-1/PD-L1 signaling pathway and promoting tumor immunotherapy. Benefiting from the interconnected porous structure of the inverse opal, metformin can be easily extensively loaded into the CS particles. With the coating of the TME responsive MnO2 shells, the particle delivery system was imparted with an intelligent "trigger" to prevent premature leaking of the drug until it reaches the tumor tissue. We have demonstrated that CS-metformin@MnO2 particles were able to promote the apoptosis of tumor cells through immunotherapeutic means both in vivo and in vitro. Specifically, the viability of tumor cells in the drug carrier-treated group was nearly 20% less than in the untreated group. In addition, the CS particles could serve as scaffolds for the regeneration of normal tissues and promote post-surgical wound healing due to their biocompatibility and antibacterial ability. These results make CS-metformin@MnO2 particles an excellent delivery system in tumor immunotherapy and post-surgical wound healing applications.

A graphene hybrid supramolecular hydrogel with high stretchability, self-healable and photothermally responsive properties for wound healing.

Wound healing is a ubiquitous healthcare problem in clinical wound management. In this paper, the fabrication of a graphene hybrid supramolecular hydrogel (GS hydrogel) for wound dressing applications is demonstrated. The hydrogel is composed of two components, including N-acryloyl glycinamide (NAGA) as the scaffold and graphene as the photothermally responsive active site for photothermal therapy. Based on the multiple hydrogen bonds between the dual amide motifs in the side chain of N-acryloyl glycinamide, the hydrogel exhibits high tensile strength (≈1.7 MPa), good stretchability (≈400%) and self-recoverability. In addition, the GS hydrogel shows excellent antibacterial activity towards methicillin-resistant Staphylococcus aureus (MRSA), benefiting from the addition of graphene that possesses great photothermal transition activity (≈85%). Significantly, in vivo animal experiments also demonstrated that the GS hydrogel effectively accelerates the wound healing processes by eradicating microbes, promoting collagen deposition and angiogenesis. In summary, this GS hydrogel demonstrates excellent mechanical performance, photothermal antimicrobial activity, and promotes skin tissue regeneration, and so has great application potential as a promising wound dressing material in clinical use.

Engineering an adhesive based on photosensitive polymer hydrogels and silver nanoparticles for wound healing.

Hemostasis, wound closure and prevention of infection are critical to wound healing after an injury. Skin adhesives have been used to seal incisions, thus aiding primary wound healing, as well as creating a barrier to microbes. We constructed a skin adhesive with antibacterial and hemostatic activities (AHAs) for wound management. The adhesive was made by using methacrylated hyaluronan-polyacrylamide (MHA-PAAm) hydrogels, integrated with silver nanoparticles (AgNPs) and bonded to gelatin. Because of the three-dimensional network structure of the hydrogels, nanoscale particles can be encapsulated into their voids; the AgNPs, through sustained delivery of silver ions, endow the adhesives with sustained broad-spectrum antibacterial activity. Furthermore, due to the introduction of MHA which can be crosslinked by visible light, the polyacrylamide hydrogel matrix can be formed through photo crosslinking. In addition, gelatin can be bonded to both the hydrogel matrix and host tissues because of the interaction between carboxyl and amino-moieties. Our animal studies demonstrated that the AHAs which possess tissue adhesive and antibacterial properties were easy to stretch, and were able to stop bleeding in rat tail amputation and liver injury models. AHAs enhance wound granulation tissue formation, vascular tissue formation, and collagen formation, as well as alleviate inflammation. These properties promoted wound closure in rat wound infection models, promising great potential for applying AHAs in clinical uses.

Antibacterial and angiogenic chitosan microneedle array patch for promoting wound healing.

A patch with the capability of avoiding wound infection and promoting tissue remolding is of great value for wound healing. In this paper, we develop a biomass chitosan microneedle array (CSMNA) patch integrated with smart responsive drug delivery for promoting wound healing. Chitosan possesses many outstanding features such as the natural antibacterial property and has been widely utilized for wound healing. Besides, the microstructure of microneedles enables the effective delivery of loaded drugs into the target area and avoids the excessive adhesion between the skin and the patch. Also, vascular endothelial growth factor (VEGF) is encapsulated in the micropores of CSMNA by temperature sensitive hydrogel. Therefore, the smart release of the drugs can be controllably realized via the temperature rising induced by the inflammation response at the site of wounds. It is demonstrated that the biomass CSMNA patch can promote inflammatory inhibition, collagen deposition, angiogenesis, and tissue regeneration during the wound closure. Thus, this versatile CSMNA patch is potentially valuable for wound healing in clinical applications.

Immunotherapeutic silk inverse opal particles for post-surgical tumor treatment.

Recurrence of malignant tumor after surgical resection is the main reason of cancer treatment failure. Here, a novel kind of silk inverse opal particles (SIOPs) for post-surgical tumor treatment is presented, and it is derived from colloid crystal bead templates by negatively replicating. Because of their abundant uniform nanopores, interconnected nanochannels and excellent biocompatibility, SIOPs could not only carry great amount of anti-tumor drugs for tumor therapy, but also could provide support for cell adhesion, proliferation and differentiation as the 3D spherical scaffolds which is beneficial to the tissue repair at resection sites. It is demonstrated that the antibody drugs could maintain their high biological activity without any influences during the preparation of SIOPs and these particles were able to enhance the therapeutic efficacy and promote tissue regeneration after surgical resection with their multifunctional features. These prominent properties indicate the great potentials of SIOPs as a promising strategy for efficient postoperative cancer therapy.

Hybrid material for open abdomen: saving the wound from intestinal fistula.

Treatment of an open abdomen (OA) wound combined with an intestinal fistula is a challenge in the clinic. Here, inspired by the antibacterial activity of graphene (G) and its derivatives, we present a hybrid patch based on the ability of graphene and polycaprolactone (PCL) to kill bacteria and save the cells in a wound. Benefiting from the antibacterial ability of graphene oxide (GO), cells could survive in the presence of bacteria. With the increased ability to protect cells, this patch accelerated wound healing in an OA and intestinal fistula wound model. Additionally, the sub-acute toxicity score showed no extra damage to organs. In conclusion, the employment of the hybrid material for an OA and an intestinal fistula wound healing is encouraging. A hybrid patch based on graphene oxide and polycaprolactone electrospun was generated for open abdomen and fistula wound. The application of the hybrid patch could save the cells from bacteria which contribute to accelerating wound healing.

[Status of diagnosis and management of acute appendicitis in 2017: a national multi-center retrospective study].

OBJECTIVE: To analyze the current status of diagnosis and management of acute appendicitis (AA) in China. METHODS: Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary. RESULTS: A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001). CONCLUSIONS: The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.