Effect of Tannic Acid Concentrations on Temperature-Sensitive Sol-Gel Transition and Stability of Tannic Acid/Pluronic F127 Composite Hydrogels.

Recently, interest in polyphenol-containing composite adhesives for various biomedical applications has been growing. Tannic acid (TA) is a polyphenolic compound with advantageous properties, including antioxidant and antimicrobial properties. Additionally, TA contains multiple hydroxyl groups that exhibit biological activity by forming hydrogen bonds with proteins and biomacromolecules. Furthermore, TA-containing polymer composites exhibit excellent tissue adhesion properties. In this study, the gelation behavior and adhesion forces of TA/Pluronic F127 (TA/PluF) composite hydrogels were investigated by varying the TA and PluF concentrations. PluF (above 16 wt%) alone showed temperature-responsive gelation behavior because of the closely packed micelle aggregates. After the addition of a small amount of TA, the TA/PluF hydrogels showed thermosensitive behavior similar to that of PluF hydrogels. However, the TA/PluF hydrogels containing more than 10 wt% TA completely suppressed the thermo-responsive gelation kinetics of PluF, which may have been due to the hydrogen bonds between TA and PluF. In addition, TA/PluF hydrogels with 40 wt% TA showed excellent tissue adhesion properties and bursting pressure in porcine intestinal tissues. These results are expected to aid in understanding the use of mixtures of TA and thermosensitive block copolymers to fabricate adhesive hydrogels for versatile biomedical applications.

Hydrophilic/Hydrophobic Janus Nanofibers Containing Compound K for Cartilage Regeneration.

Introduction: Cartilage regeneration is a challenging issue due to poor regenerative properties of tissues. Electrospun nanofibers hold enormous potentials for treatments of cartilage defects. However, nanofibrous materials used for the treatment of cartilage defects often require physical and/or chemical modifications to promote the adhesion, proliferation, and differentiation of cells. Thus, it is highly desirable to improve their surface properties with functionality. We aim to design hydrophilic, adhesive, and compound K-loaded nanofibers for treatments of cartilage defects. Methods: Hydrophilic and adhesive compound K-containing polycaprolactone nanofibers (CK/PCL NFs) were prepared by coatings of gallic acid-conjugated chitosan (CHI-GA). Therapeutic effects of CHI-GA/CK/PCL NFs were assessed by the expression level of genes involved in the cartilage matrix degradation, inflammatory response, and lipid accumulations in the chondrocytes. In addition, Cartilage damage was evaluated by safranin O staining and immunohistochemistry of interleukin-1ß (IL-1ß) using OA animal models. To explore the pathway associated with therapeutic effects of CHI-GA/CK/PCL NFs, cell adhesion, phalloidin staining, and the expression level of integrins and peroxisome proliferator-activated receptor (PPARs) were evaluated. Results: CHI-GA-coated side of the PCL NFs showed hydrophilic and adhesive properties, whereas the unmodified opposite side remained hydrophobic. The expression levels of genes involved in the degradation of the cartilage matrix, inflammation, and lipogenesis were decreased in CHI-GA/CK/PCL NFs owing to the release of CK. In vivo implantation of CHI-GA/CK/PCL NFs into the cartilage reduced cartilage degradation induced by destabilization of the medial meniscus (DMM) surgery. Furthermore, the accumulation of lipid deposition and expression levels of IL-1ß was reduced through the upregulation of PPAR. Conclusion: CHI-GA/CK/PCL NFs were effective in the treatments of cartilage defects by inhibiting the expression levels of genes involved in cartilage degradation, inflammation, and lipogenesis as well as reducing lipid accumulation and the expression level of IL-1ß via increasing PPAR.

Bio-Inspired Self-Healing, Shear-Thinning, and Adhesive Gallic Acid-Conjugated Chitosan/Carbon Black Composite Hydrogels as Suture Support Materials.

The occurrence of leakage from anastomotic sites is a significant issue given its potential undesirable complications. The management of anastomotic leakage after gastrointestinal surgery is particularly crucial because it is directly associated with mortality and morbidity in patients. If adhesive materials could be used to support suturing in surgical procedures, many complications caused by leakage from the anastomosis sites could be prevented. In this study, we have developed self-healing, shear-thinning, tissue-adhesive, carbon-black-containing, gallic acid-conjugated chitosan (CB/Chi-gallol) hydrogels as sealing materials to be used with suturing. The addition of CB into Chi-gallol solution resulted in the formation of a crosslinked hydrogel with instantaneous solidification. In addition, these CB/Chi-gallol hydrogels showed enhancement of the elastic modulus (G') values with increased CB concentration. Furthermore, these hydrogels exhibited excellent self-healing, shear-thinning, and tissue-adhesive properties. Notably, the hydrogels successfully sealed the incision site with suturing, resulting in a significant increase in the bursting pressure. The proposed self-healing and adhesive hydrogels are potentially useful in versatile biomedical applications, particularly as suture support materials for surgical procedures.

Double-layer adhesives for preventing anastomotic leakage and reducing post-surgical adhesion.

Preventing anastomotic leakage (AL) and postoperative adhesions after gastrointestinal surgery is crucial for ensuring a favorable surgical prognosis. However, AL prevention using tissue adhesives can unintentionally lead to undesirable adhesion formation, while anti-adhesive agents may interfere with wound healing and contribute to AL. In this study, we have developed a double-layer patch, consisting of an adhesive layer on one side, utilizing gallic acid-conjugated chitosan (CHI-G), and an anti-adhesive layer on the opposite side, employing crosslinked hyaluronic acid (cHA). These CHI-G/cHA double-layer adhesives significantly prevented AL by forming physical barriers of CHI-G and reduced post-surgical adhesion at the anastomosis sites by the anti-adhesive layers of cHA. The bursting pressure (161.1 ± 21.6 mmHg) of double-layer adhesives-applied rat intestine at postoperative day 21 was far higher than those of the control (129.4 ± 5.7 mmHg) and the commercial anti-adhesives-applied group (120.8 ± 5.2 mmHg). In addition, adhesion score of double-layer adhesives-applied rat intestine was 3.6 ± 0.3 at postoperative day 21, which was similar to that of the commercial anti-adhesives-applied group (3.6 ± 0.3) and lower than that of the control group (4.9 ± 0.5). These findings indicate that the double-layer patch (CHI-G/cHA) has the potential to effectively prevent both postoperative adhesions and anastomotic leakage, offering a promising solution for gastrointestinal surgery.

The fate of fungal periprosthetic joint infection after total knee arthroplasty.

PURPOSE: To demonstrate the clinical outcomes of patients with fungal periprosthetic joint infections (PJIs) after two-stage exchange arthroplasty combined with antifungal therapy. METHODS: We retrospectively reviewed the outcomes of 41 patients with fungal PJIs after primary total knee arthroplasty (TKA) in a single centre from January 1999 to October 2017. During the first stage of resection arthroplasty, antifungal-impregnated cement spacers (AICSs) were implanted in all patients. After systemic antifungal treatment during the interval between the two surgeries, delayed reimplantation as part of a two-stage exchange protocol was performed when patients were clinically stable. We defined treatment success as a well-functioning arthroplasty without any signs of PJI after a minimum follow-up of two years without antimicrobial suppression. Successful treatment was confirmed by repeat negative cultures as well as a return of inflammatory markers to normal levels. RESULTS: The treatment success rate was 63.4% at the final follow-up. Thirty-six of 41 patients (87.8%) met the criteria for second-stage revision after confirmation of complete infection control. The mean prosthesis-free interval was 6.6 months (range, 2.0-30.0 months). During follow-up after two-stage exchange arthroplasty, ten patients (27.7% of 36 patients) unfortunately experienced recurrence or relapse of infection after an average of 31.3 months (range, 2.7-135.6 months). The rate of survivorship free from reinfection was 94.4% at six months, 84.8% at one year, and 73.6% at two years. Cox proportional hazard regression analysis demonstrated that the prosthesis-free interval (HR = 1.016, p = 0.037) and mean length of antifungal treatment (HR = 0.226, p = 0.046) were potential risk factors for failure. CONCLUSION: Fungal PJIs led to devastating clinical outcomes despite even two-stage revision arthroplasty with the use of AICSs and antifungal medications.

Carbon black-containing self-healing adhesive hydrogels for endoscopic tattooing.

Endoscopic tattooing with India ink is a popular method for identifying colonic lesions during minimally invasive surgery because it is highly challenging to localize lesions during laparoscopy. However, there is a perceived unmet need for the injection of India ink and carbon particle suspension due to various complications and inconstant durability during the perioperative period. In this study, carbon black-containing self-healing adhesive alginate/polyvinyl alcohol composite hydrogels were synthesized as endoscopic tattooing inks. Alginate (Alg) conjugated with phenylboronic acid (PBA) groups in the backbone was crosslinked with polyvinyl alcohol (PVA) because of the dynamic bonds between the phenylboronic acid in alginate and the cis-diol groups of PVA. The carbon black-incorporated Alg-PBA/PVA hydrogels exhibited self-healing and re-shapable properties, indicating that improved intraoperative localization could be achieved. In addition, the adhesive tattooing hydrogels were stably immobilized on the target regions in the intraperitoneal spaces. These carbon black-containing self-healing adhesive hydrogels are expected to be useful in various surgical procedures, including endoscopic tattooing.