Injectable antimicrobial hydrogels with antimicrobial peptide and sanguinarine controlled release ability for preventing bacterial infections.

The emergence of antibiotic resistant bacteria represents a significant and common clinical problem worldwide as infections are becoming increasingly common. It is urgent to broaden the sources of biomaterials that can prevent both bacterial infection and antibiotic resistance. In this work, oxidized sodium alginate/aminated hyaluronic acid (OSA/AHA) hydrogel with various proportions was developed based on Schiff base reaction. Herein, polydopamine (PDA)-Bmkn2 nanoparticle and sanguinarine were incorporated into hydrogels to enhance antibacterial properties. The prepared PDA-Bmkn2 nanoparticles, with uniform particle size and good dispersion, could serve as a delivery system for Bmkn2. The prepared hydrogels showed appropriate swelling ratio, extremely good mechanical strengths and improved biodegradability. Meanwhile, the Bmkn2 and sanguinarine were released from the hydrogels in a sustainable manner. Furthermore, OSA/AHA/sanguinarine/PDA-Bmkn2 hydrogel (less than 10 µg/mL BmKn2 and 0.2 µg/mL sanguinarine) had excellent biocompatibility. Antibacterial experiments confirmed that OSA/AHA/sanguinarine/PDA-Bmkn2 hydrogel had effective antimicrobial activity on Escherichia coli and Staphylococcus aureus. Therefore, the prepared injectable hydrogels with good biocompatibility and excellent synergistic antibacterial activity promise great potential for preventing localized bacterial infections.

Bioprinting of a Blue Light-Cross-Linked Biodegradable Hydrogel Encapsulating Amniotic Mesenchymal Stem Cells for Intrauterine Adhesion Prevention.

Intrauterine adhesion (IUA) is a common and prevailing complication after uterine surgery, which can lead to clinical symptoms such as a low menstrual volume, amenorrhea, periodic lower abdominal pain, infertility, and so on. Placing a three-dimensional printing hydrogel between the injured site and the adjacent tissue is considered to be a physical barrier to prevent adhesion, which can isolate the damaged area during the healing process. In this work, a tissue hydrogel with various proportions of a methacrylated gelatin (GelMA) and methacrylated collagen (ColMA) composite hydrogel loaded with amniotic mesenchymal stem cells (AMSCs) was constructed by using three-dimensional biological printing technology. Compared with the single GelMA hydrogel, the composite antiadhesion hydrogel (GelMA/ColMA) showed an appropriate swelling ratio, enhanced mechanical properties, and impressive stability. Meanwhile, the microstructure of the GelMA/ColMA composite hydrogel showed a denser and interconnected microporous structure. In addition, the cytotoxicity study indicated that the GelMA/ColMA hydrogel has a cytocompatibility nature toward AMSCs. Finally, the fabrication of stem cell encapsulation hydrogels was studied, and the cells could be released continuously for more than 7 days with the normal cell function. The results of in vivo experiments indicated that the GelMA/ColMA/hAMSC (human amnion mesenchymal stem cell) hydrogel can prevent cavity adhesion in a rat IUA model. Therefore, bioprinting a biodegradable hydrogel cross-linked by blue light has satisfactory anticavity adhesion effects with excellent physical properties and biocompatibility, which could be used as a preventive barrier for intrauterine adhesion.

A Smart Multifunctional Nanoparticle for Enhanced Near-Infrared Image-Guided Photothermal Therapy Against Gastric Cancer.

BACKGROUND: Surgery is considered to be a potentially curative approach for gastric cancer. However, most cases are diagnosed at a very advanced stage for the lack of typical symptoms in the initial stage, which makes it difficult to completely surgical resect of tumors. Early diagnosis and precise personalized intervention are urgent issues to be solved for improving the prognosis of gastric cancer. Herein, we developed an RGD-modified ROS-responsive multifunctional nanosystem for near-infrared (NIR) imaging and photothermal therapy (PTT) against gastric cancer. METHODS: Firstly, the amphiphilic polymer was synthesized by bromination reaction and nucleophilic substitution reaction of carboxymethyl chitosan (CMCh) and 4-hydroxymethyl-pinacol phenylborate (BAPE). Then, it was used to encapsulate indocyanine green (ICG) and modified with RGD to form a smart multifunctional nanoparticle targeted to gastric cancer (CMCh-BAPE-RGD@ICG). The characteristics were determined, and the targeting capacity and biosafety were evaluated both in vitro and in vivo. Furthermore, CMCh-BAPE-RGD@ICG mediated photothermal therapy (PTT) effect was studied using gastric cancer cells (SGC7901) and SGC7901 tumor model. RESULTS: The nanoparticle exhibited suitable size (≈ 120 nm), improved aqueous stability, ROS-responsive drug release, excellent photothermal conversion efficiency, enhanced cellular uptake, and targeting capacity to tumors. Remarkably, in vivo studies suggested that CMCh-BAPE-RGD@ICG could accurately illustrate the location and margin of the SGC7901 tumor through NIR imaging in comparison with non-targeted nanoparticles. Moreover, the antitumor activity of CMCh-BAPE-RGD@ICG-mediated PTT could effectively suppress tumor growth by inducing necrosis and apoptosis in cancer cells. Additionally, CMCh-BAPE-RGD@ICG demonstrated excellent biosafety both in vitro and in vivo. CONCLUSION: Overall, our study provides a biocompatible theranostic nanoparticle with enhanced tumor-targeting ability and accumulation to realize NIR image-guided PTT in gastric cancer.

Preparation of biocompatible wound dressings with long-term antimicrobial activity through covalent bonding of antibiotic agents to natural polymers.

Wound dressings with long-term antimicrobial activity are highly desired for treatment of chronic wound infections. Herein, the sustained antimicrobial wound dressings were developed by using antibiotic agents, ciprofloxacin HCL (CIP) and gentamicin sulfate (GS), covalent bonding to natural polymer matrix composites, carboxymethyl chitosan (CMC) and collagen (COL). By amide bond formation between antibiotic agents and polymer chains, two antimicrobial wound dressings CMC-COL-CIP and CMC-COL-GS were prepared. The presented wound dressings exhibited high water absorption capacity, excellent water vapor transmission rate (WVTR), appropriate mechanical properties, and impressive stability. Cytocompatibility of the dressings was demonstrated by in vitro human skin fibroblast (HSF) cells culture study. The results of in vitro and in vivo studies indicated that the two antimicrobial wound dressings have effective antimicrobial activity and prolonged antimicrobial period. Furthermore, the antimicrobial dressings could promote the wound healing, reepithelialization, collagen deposition, and angiogenesis. It also displays superiority wound healing effects compared to commercially available silver-based dressings (Aguacel Ag). This work indicates that the prepared antimicrobial wound dressings have great potential application in chronic wound healing, such as severe wound cure and diabetic foot ulcers.

Transglutaminase-catalyzed preparation of crosslinked carboxymethyl chitosan/carboxymethyl cellulose/collagen composite membrane for postsurgical peritoneal adhesion prevention.

Peritoneal adhesion is a general complication following pelvic and abdominal surgery, which may lead to chronic abdominal pain, bowel obstruction, organ injury, and female infertility. Biodegradable polymer membranes have been suggested as physical barriers to prevent peritoneum adhesion. In this work, a transglutaminase (TGase)-catalyzed crosslinked carboxymethyl chitosan/carboxymethyl cellulose/collagen (CMCS/CMCL/COL) composite anti-adhesion membrane with various proportions of CMCS, CMCL, and COL (40/40/20, 35/35/30, 25/25/50) was developed. After crosslinking by TGase, the composite anti-adhesion membranes shown enhanced mechanical properties and improved biodegradability. Meanwhile, the high cytocompatibility of anti-adhesion membranes was proved by in vitro cell culture study. Moreover, the anti-adhesion membrane with the proportion of 25/25/50 was implanted between the artificially defected cecum and peritoneal wall in rats and following by general observation, histological examination, and inflammatory factors assay. The results indicated that the anti-adhesion membrane can significantly prevent peritoneal adhesion with negligible immunogenicity. Therefore, the composite membrane crosslinked by TGase had satisfactory anti-adhesive effects with high biocompatibility and low antigenicity, which could be used as a preventive barrier for peritoneal adhesion.