Abalone-Inspired Adhesive and Photo-Responsive Microparticle Delivery Systems for Periodontal Drug Therapy.

Antibiotics provide promising strategies for treating periodontitis, while their delivery and controllable release with desired oral retention remain challenging. Here, inspired by the unique suction-cup structures of abalones, a novel adhesive and photo-responsive microparticle (MP) delivery system is developed to treat periodontitis through microfluidic electrospray technology. Such MPs are generated by quickly ionic cross-linking of sodium alginate together with photo-curing of poly(ethylene glycol) diacrylate of the distorted microfluidic droplets during their high-speed dropping into calcium chloride solution. Attributing to their unique concave structures, the abalone-inspired MPs exhibit desired underwater adhesion ability and stability under running water. In addition, due to the loading of antibiotics minocycline hydrochloride and near-infrared (NIR)-responsive black phosphorus during their fabrication, the resultant MPs can not only eradicate bacteria directly, but also realize a controllable and effective drug release upon NIR irradiation. Based on these features, it is demonstrated from in vivo periodontitis that the abalone-inspired MPs are firmly adhesive and can controlled-release drugs on the tooth, and thus have outstanding antibacterial efficacy against Porphyromonas gingivalis. These results indicate the particular values of the abalone-inspired MPs for oral-related disease treatment.

A Universal and Reversible Wet Adhesive via Straightforward Aqueous Self-Assembly of Polyethylenimine and Polyoxometalate.

The excellent adhesion of mussels under wet conditions has inspired the development of numerous catechol-based wet adhesives. Nevertheless, the performance of catechol-based wet adhesive suffers from the sensitivity toward temperature, pH, or oxidation stimuli. Therefore, it is of great significance to develop non-catechol-based wet adhesives to fully recapitulate nature's dynamic function. Herein, a novel type of non-catechol-based wet adhesive is reported, which is readily formed by self-assembly of commercially available branched polyethylenimine and phosphotungstic acid in aqueous solution through the combination of electrostatic interaction and hydrogen bonding. This wet adhesive shows reversible, tunable, and strong adhesion on diverse substrates and further exhibits high efficacy in promoting biological wound healing. During the healing of the wound, the as-prepared wet adhesive also possesses inherent antimicrobial properties, thus avoiding inflammations and infections due to microorganism accumulation.

Middle Meningeal Artery Embolization Using Combined Particle Embolization and n-BCA with the Dextrose 5% in Water Push Technique for Chronic Subdural Hematomas: A Prospective Safety and Feasibility Study.

BACKGROUND AND PURPOSE: Embolization of the middle meningeal artery for treatment of refractory or recurrent chronic subdural hematomas has gained momentum during the past few years. Little has been reported on the use of the n-BCA liquid embolic system for middle meningeal artery embolization. We present the technical feasibility of using diluted n-BCA for middle meningeal artery embolization. MATERIALS AND METHODS: We sought to examine the safety and technical feasibility of the diluted n-BCA liquid embolic system for middle meningeal artery embolization. Patients with chronic refractory or recurrent subdural hematomas were prospectively enrolled from September 2019 to June 2020. The primary outcome was the safety and technical feasibility of the use of diluted n-BCA for embolization of the middle meningeal artery. The secondary end point was the efficacy in reducing hematoma volume. RESULTS: A total of 16 patients were prospectively enrolled. Concomitant burr-hole craniotomies were performed in 12 of the 16 patients. Two patients required an operation following middle meningeal artery embolization for persistent symptoms. The primary end point was met in 100% of cases in which there were no intra- or postprocedural complications. Distal penetration of the middle meningeal artery branches was achieved in all the enrolled cases. A 7-day post-middle meningeal artery embolization follow-up head CT demonstrated improvement (>50% reduction in subdural hematoma volume) in 9/15 (60%) patients, with 6/15 (40%) showing an unchanged or stable subdural hematoma. At day 21, available CT scans demonstrated substantial further improvement (>75% reduction in subdural hematoma volume). CONCLUSIONS: Embolization of the middle meningeal artery using diluted n-BCA and ethiodized oil (1:6) is safe and feasible from a technical standpoint. The use of a dextrose 5% bolus improves distal penetration of the glue.

Gelatin-Poly (γ-Glutamic Acid) Hydrogel as a Potential Adhesive for Repair of Intervertebral Disc Annulus Fibrosus: Evaluation of Cytocompatibility and Degradability.

STUDY DESIGN: An in vitro experimental study testing a Gelatin-poly (γ-glutamic acid) hydrogel for disc repair. OBJECTIVE: To evaluate the cytocompatibility and degradability of the above mentioned hydrogel for intervertebral disc annular fibrosis (AF) repair. SUMMARY OF BACKGROUND DATA: No repair strategies for correcting annular defects in lumbar discectomy have been clinically well recognized. Exogenous supplementation of regenerative materials to fill defects is a minimally invasive way to restore compromised mechanical properties. The injected materials, most commonly gelatin-based materials with cross-linking agents, serve as sealants and as a scaffold for incorporating biomaterials for augmentation. However, cytotoxicity of hydrogel crosslinking agents is of concern in developing viable materials. METHODS: This in vitro experimental study evaluated a newly developed gelatin-based hydrogel for intervertebral disc AF repair. Mechanical strength was augmented by γ-PGA, and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDC) was used for material crosslinking. Isolated bovine tail intervertebral discs (IVDs) were used to test the hydrogel, and hydrogel surface monolayer AF cell culture was used to investigate efficacy in hydrogel constructs of different EDC concentrations. Cell metabolic activity was evaluated with Alamar blue assay, cell viability assay with live/dead stain, and sulfated glycosaminoglycan (GAG) and double strain DNA were quantified to evaluate proliferation of implanted cells and synthesis of extracellular matrix (ECM) proteins. RESULTS: EDC concentrations from 10 to 40 mM resulted in significant decreases in AF cell proliferation without obvious influence on cell viability. Higher EDC concentrations resulted in decreased percentage of Alamar blue reduction and GAG and DNA concentration, but did not affect GAG/DNA and live-dead ratios. Degradation tests revealed that higher EDC concentrations decreased the hydrogel degradation rate. CONCLUSION: The developed gelatin-poly (γ-PGA) hydrogel with 20 mM EDC concentration provides an effective gap-filling biomaterial with good cytocompatibility, suggesting substantial promise for use as a sealant for small AF defects.Level of Evidence: N/A.

Embolization using warmed glue via the triaxial microballoon occlusion system for various vascular disorders.

PURPOSE: We aimed to illustrate the benefits of using warmed glue for viscosity reduction via the triaxial microballoon system for the treatment of various vascular disorders. METHODS: Seven patients who underwent 10 treatment sessions for hemoptysis, type II endoleak, post-pancreatic surgical bleeding, spontaneous retroperitoneal bleeding, or ovarian tumor bleeding were evaluated based on technical and clinical outcomes. In the procedure, the triaxial system, consisting of a 4.5-Fr guiding catheter, a 2.8-Fr microballoon catheter, and a 1.9-Fr no-taper microcatheter, was advanced into the target lesion. Glue (33% n-butyl cyanoacrylate mixed with Lipiodol) warmed to 40°C was injected under balloon occlusion. RESULTS: The common hepatic, right bronchial, intercostals, internal mammary, costocervical, lateral thoracic, superior thoracic, thoracoacromial, inferior thyroid, iliolumbar, lumbar, internal pudendal arteries, and branch of the inferior mesenteric artery were successfully embolized; 100% technical success and 100% clinical success were obtained after each session. CONCLUSION: Our modified balloon-occluded glue embolization may lead to better handling with more distal glue penetration capability.

Adhesive pyramidal thorn patches provide pain relief to athletes.

Pain in athletes is ideally treated without systemic medicine. Therefore, complementary and alternative medicine, including patch treatments, is often used. The physiologic mechanisms of pain relief produced by patch treatment, however, are not well elucidated. In the present study, we introduce a pyramidal thorn (PT) patch that we developed, demonstrate the effects of this PT patch for the treatment of various types of pain in 300 subjects, and suggest a physiologic mechanism for the pain relief effects. One treatment with the PT patch effectively relieved pain in almost half the subjects evaluated. Except for pain generated deeply under the skin, such as low-back pain, pain was eliminated within four treatments with the PT patch in almost all of the subjects. Interestingly, the pain-sensing region moved along the nerve fibers after each trial. Further, patches without PT also provided some pain relief. We considered that this effect was due to hair deflection on the skin; that is, adhesion of the PT patch activates Merkel cells directly as well as Merkel cell-neurite complexes around the hair follicles by deflecting the hair follicles, whereas adhesion of a patch without PT only activates the Merkel cell-neurite complexes. In any case, patch adhesion stimulates Aß fibers to alleviate pain. Finally, we found that the pain threshold is increased by electric stimulation, suggesting that the gentle adhesion of a PT patch would be more effective. To our knowledge, this is the first study to demonstrate physiologically the validity of an adherent patch for pain relief.

Randomized clinical trial of a mucoadhesive formulation containing curcuminoids (Zingiberaceae) and Bidens pilosa Linn (Asteraceae) extract (FITOPROT) for prevention and treatment of oral mucositis - phase I study.

Preclinical repeated-dose toxicity and efficiency studies developed by our group suggest the potential of FITOPROT in treating mucositis. This serious limiting side effect is observed at a rate of 40-100% in patients under antineoplastic therapy and despite different palliative measures and therapeutic agents have been investigated, still no therapy was completely successful. Therefore, this study aimed to establish the safety and recommended phase II dose of FITOPROT for the prevention and treatment of chemoradiotherapy-induced oral mucositis (OM) in patients with head and neck cancer. Twenty healthy adult participants were randomized into two groups that received pre-established concentrations of the collutory: group 1 (FITOPROT A - mucoadhesive formulation containing 10 mg/mL of curcuminoids extract plus 20% v/v of Bidens pilosa L. extract) and group 2 (FITOPROT B - mucoadhesive formulation containing 20 mg/mL of curcuminoids extract, plus 40% v/v of Bidens pilosa L. extract). Participants rinsed their mouths with FITOPROT, three times daily, for ten consecutive days. No participant experienced toxicity or unacceptable discomfort and/or adverse reactions (CTCAE v5.0), with laboratory and clinical parameters under normal conditions. Side effects observed were low intensity and temporary mucosa/dental surface pigmentation (n = 7) and tooth sensitivity (n = 4), which disappeared after formulation use ceased. No significant cellular genotoxic effects were observed (p > 0.05), and micronuclei frequencies were not changed (p > 0.05). Biochemical assays reveled no altered levels of myeloperoxidase (p = 0.2268), malondialdehyde (p = 0.1188) nor nitric oxide (p = 0.5709) concentration, and no significant difference were found in the levels of pro-inflammatory cytokines (p > 0.05). Thus, FITOPROT demonstrated to be safe and tolerable in both tested doses and is suitable for evaluation in a phase II trial as treatment against OM.

Promise of Combining Antifungal Agents in Denture Adhesives to Fight Candida Species Infections.

PURPOSE: Several complications may arise in patients wearing complete prosthetic appliances, including denture-associated infections and mucosal stomatitis due to Candida species. This study evaluated the activity of anti-Candida agents in denture adhesive and the cytotoxicities of these preparations for primary human gingival epithelial (GE) keratinocytes. MATERIALS AND METHODS: The anti-Candida activities of antimicrobial peptides, antimicrobial lipids, and antifungal agents against C. albicans ATCC 64124 or HMV4C were assessed in microdilution assays containing water or 1% denture adhesive. The minimal inhibitory concentrations (MIC) and the minimal bactericidal concentrations (MBC) were determined. The cytotoxicities of denture adhesive compounded with these agents were assessed in 1.0 × 105 primary GE keratinocytes in LGM-3 media with resazurin. RESULTS: Lactoferricin B, SMAP28, sphingosine, dihydrosphingosine, and phytosphingosine in 1% denture adhesive lost antimicrobial activity for C. albicans (p < 0.05). Amphotericin B, chlorhexidine dihydrochloride, chlorhexidine gluconate, fluconazole, and nystatin in 1% denture adhesive or compounded directly into denture adhesive and then diluted to 1% adhesive, did not lose antimicrobial activity. Compounded formulations were not cytotoxic (LD50 > 100.0 µg/ml) against primary human GE keratinocytes. CONCLUSIONS: Antimicrobial peptides and antimicrobial lipids had diminished activities in 1% adhesive, suggesting that components in adhesives may inactivate local innate immune factors in the oral cavity, possibly predisposing denture wearers to Candida species infections. More importantly, antifungal agents retained their anti-C. albicans activities in denture adhesive, strongly suggesting that antifungal agents could be candidates for inclusion in adhesive formulations and used as prescribed topical treatments for individuals with denture stomatitis.

Double Coaxial Microcatheter Technique for Glue Embolization of Renal Arteriovenous Malformations.

PURPOSE: To demonstrate the technical benefit of the double coaxial microcatheter technique for embolization of renal arteriovenous malformations (AVMs) with n-butyl cyanoacrylate and iodized oil (glue). MATERIALS AND METHODS: Six consecutive patients (1 man and 5 women; mean age 61 years; range 44-77 years) with renal AVMs were included. Five patients had hematuria, and one had a risk of heart failure due to a large intrarenal arteriovenous shunt. All patients underwent transarterial embolization using glue and the double coaxial microcatheter technique with outer 2.6F and inner 1.9F microcatheters. After glue injection, the inner microcatheter was retracted, while the outer microcatheter was retained. We assessed the complications and clinical outcomes of this technique. RESULTS: Technical success was achieved in all patients. In 9 sessions, 34 feeding arteries were embolized with glue using the double coaxial microcatheter technique, 1 was embolized with glue using a single microcatheter, and 2 were embolized with coils. The double coaxial microcatheter technique was useful for selecting small tortuous feeding arteries, preventing glue reflux to the proximal arteries, and approaching multiple feeding arteries without complete retraction of the microcatheters. As a minor complication, glue migrated into the venous system in four patients without any sequelae. In all patients, favorable clinical outcomes, including hematuria cessation in five patients and improvement of the large intrarenal arteriovenous shunt in one patient, were obtained without deterioration of renal function. CONCLUSION: Glue embolization with the double coaxial microcatheter technique was useful for treating renal AVMs with multiple tortuous feeding arteries.

CT-guided injection of N-butyl cyanoacrylate glue for treatment of chylous leak after aorto-mesenteric bypass.

Lymphangiography and thoracic duct embolization are well-described techniques for the diagnosis and treatment of thoracic lymphatic leaks refractory to conservative treatment. However, thoracic duct embolization is not an option in patients with abdominal chylous leaks. The present report describes a 68-year-old man who underwent an aortomesenteric bypass complicated by a high-output postoperative chylothorax (>2,000 ml/day) and chylous ascites (>7,000 ml/paracentesis). Ultrasound-guided intranodal lymphangiography demonstrated a retroperitoneal lymphatic leak tracking along the vascular graft into the peritoneal cavity. Computed tomography-guided lymphatic duct occlusion with N-butyl cyanoacrylate glue was performed, resulting in successful treatment of both chylothorax and chylous ascites.

A preliminary investigation into the use of denture adhesives combined with dietary advice to improve diets in complete denture wearers.

OBJECTIVES: To investigate how nutritional advice and denture adhesives may be associated with eating healthier foods. METHODS: 35 edentulous subjects (13 males and 22 females, mean age 73.9 years (55-84 years)), wearing complete dentures more than one year old, completed validated questionnaires analysing saturated fat, protein, Vitamin C, the number of servings of fruit/vegetables. In addition subjects completed the NDNS and OHIP Edent questionnaires. At baseline, nutritional information and the use of denture adhesive was provided. Subjects returned after 30 consecutive days and the questionnaires were repeated. A Wilcoxon signed rank test was used to test the effect of the denture adhesive on diet and on quality of life measures. RESULTS: The subjects increased mean intake from 2.2 portions of fruit/vegetables a day to 3.6. Fat and saturated fats were reduced from 23.2g to 11.3g and Vitamin C intake increased by 34.4mg. All were statistically significant (p<0.0001). There was a statistically significant improvement over the 30-day treatment period in subjects' ability as measured by using OHIP Edent scores to bite (p=0.017) and chew a range of foods (p=0.007). CONCLUSION: Within the confines of the study, use of simple dietary advice and denture adhesives improved diet. CLINICAL SIGNIFICANCE: The results of this pilot study suggest that denture fixatives may improve dietary behaviour of complete denture wearers.

Mepitel: a non-adherent wound dressing with Safetac technology.

OBJECTIVE: Wound pain and tissue trauma are two main considerations of wound management, and appropriate dressing selection plays an important role in both. Traditional dressings may adhere to wounds resulting in significant pain and trauma to new tissue upon removal. The development of primary wound contact materials has provided a unique approach to solving this problem. This article aims to aid clinicians in identifying wound types on which Mepitel, a primary wound contact dressing with Safetac soft silicone adhesive technology, can be used by summarizing the published clinical literature relating to its use. METHOD: Searches of bibliographic databases and internet sites were supplemented with manual searches of journals of relevance to wound management for clinical data relating to the use of Mepitel. RESULTS: The literature search identified a number of articles, presenting data generated from randomized controlled trials, non-randomized controlled trials and case study evaluations of Mepitel on a wide range of wound types and skin injuries. CONCLUSION: The results of the clinical evaluations demonstrate that Mepitel is associated with atraumatic and virtually pain-free dressing changes. The dressing with Safetac can be used cost-effectively in the treatment of a wide range of wound types and skin injuries.

The efficacy of the bioadhesive patches containing licorice extract in the management of recurrent aphthous stomatitis.

This study evaluated the efficacy of licorice bioadhesive hydrogel patches to control the pain and reduce the healing time of recurrent aphthous ulcer.This study was carried out in three episodes of ulcers: in the first episode of ulcer, all 15 patients were asked to record their baseline individual pain level by a visual analog scale. In the second and third episodes, comparative and consecutive subjective and objective evaluations of the bioadhesive were done. The effects of the following variables were investigated: (1) VAS pain score for 5 consecutive days, (2) profile of aphthous ulcers on days 3 and 5, (3) time to complete relief of pain and healing of the ulcers, (4) diameter of the lesions and necrotic zone.A significant reduction in VAS was recorded following application of the licorice patches on days 2, 3, 4 and 5 compared with the no-treatment group (p < 0.001). Licorice patches caused a significant reduction in the diameter of the inflammatory halo and necrotic center compared with the placebo group (p = 0.03).According to the results of this study, licorice bioadhesive can be effective in the reduction of pain and of the inflammatory halo and necrotic center of aphthous ulcers.

Re-attachment of anterior tooth fragment using a self-etching adhesive: a case report.

AIM: The purpose of this case report is to describe the re-attachment of an anterior tooth fragment using a self-etching adhesive. BACKGROUND: Fracture of anterior teeth by trauma is a common problem in children and teenagers due to their active lifestyle. Restoration of these teeth often presents a challenge because of the large pulp in young teeth and open apical foramen depending on the age of the child. New dental adhesive materials offer an alternative solution for the treatment of some anterior tooth fractures. REPORT: A 17-year-old female patient presented for treatment of a fractured maxillary left central incisor. The clinical examination revealed the exposure of dentin, but there was no exposure of the pulp. The patient saved the tooth fragment making it available for re-attachment to the remaining tooth structure. Under local anesthesia and rubber dam isolation the tooth fragment was re-attached using a self-etching adhesive and a microhybrid composite. SUMMARY: The re-attached tooth fragment was assessed clinically, radiographically, and using photographs at one, six, 12, 24, and 36 month intervals. The tooth remained vital, and there was no change in the color of the tooth at the three-year recall.

Effect of different mucosal and acrylic resin surface treatments in a denture retention model for patients with radiotherapy-induced xerostomia.

The purpose of this study was to determine the effect of oral moisturizing agents, denture adhesives, and surface treatments on the retention of an acrylic resin test base dislodged from the maxillary alveolar ridges of xerostomic radiotherapy patients. Acrylic resin test bases prepared for 10 edentulous xerostomia patients were subjected to 8 surface treatment methods: method 1 = untreated dry surface; method 2 = use of Biotène oral moisturizer; method 3 = use of Protefix denture adhesive; method 4 = combination of Biotène and Protefix; method 5 = sandblasting of test bases; method 6 = use of Biotène on sandblasted surface; method 7 = use of Protefix on sandblasted surface; method 8 = combination of Protefix and Biotène on sandblasted surface. After each treatment, a tensile testing apparatus was used to dislodge the inserted test bases, and force values (N) were recorded. A significant difference in retentive force was observed between the 4 Protefix groups and those that did not use denture adhesive (P < .001). There were no differences among the 4 combinations of denture adhesive treatments (P > .05). Sandblasting the denture surfaces did not increase retentive forces alone or in combination with any other treatments. Biotène oral moisturizing agent was used in 4 treatment methods, but only had a significant effect on increasing retentive force when used with a nonsandblasted surface (P < .05). Biotène had no effect on retentive force compared to a nonsandblasted surface without moisturizer or when it was used in combination with any other methods. Protefix denture adhesive offered the greatest improvement in retentive force. Sandblasting the intaglio surface did not improve retentive force. Biotène was reported to improve patient comfort but had minimal effect on retentive force; however, Biotène can be assumed to be a more advantageous method of increasing retention compared to sandblasting (P < .05).

Formulation and evaluation of lactoferrin bioadhesive tablets.

For the treatment of chronic inflammation in the oral cavity, we attempted to develop bioadhesive tablets of bovine lactoferrin (B-LF) which has antibacterial properties and immune regulatory functions. B-LF tablets containing pectin, tamarind gum or carboxymethylcellulose (CMC) were prepared by direct compression. Tablets consisting of B-LF, pectin and xylitol passed through 60- or 100-mesh sieves were also prepared. The tablets containing CMC had insufficient bioadhesive force. Although the tablets containing tamarind gum showed the longest residence time in the oral cavity, an unpleasant taste gradually developed. The tablets containing pectin showed the highest value of bioadhesive force and the taste was acceptable. The characteristics of the B-LF tablets were improved by adding an appropriate amount of xylitol and using the ingredients sieved by a 100-mesh sieve. The therapeutic effect was evaluated by using rats with an ulcer on the oral mucosa. In the present study, swelling on the periphery of the ulcer was observed after administration of the B-LF tablets, and then the ulcer has reduced overall.

Semisolid systems containing propolis for the treatment of periodontal disease: in vitro release kinetics, syringeability, rheological, textural, and mucoadhesive properties.

Formulations containing poloxamer 407 (P407), carbopol 934P (C934P), and propolis extract (PE) were designed for the treatment of periodontal disease. Gelation temperature, in vitro drug release, rheology, hardness, compressibility, adhesiveness, mucoadhesion, and syringeability of formulations were determined. Propolis release from formulations was controlled by the phenomenon of relaxation of polymer chains. Formulations exhibited pseudoplastic flow and low degrees of thixotropy or rheopexy. In most samples, increasing the concentration of C934P content significantly increased storage modulus (G'), loss modulus (G''), and dynamic viscosity (eta'), at 5 degrees C, G'' exceeded G'. At 25 and 37 degrees C, eta' of each formulation depended on the oscillatory frequency. Formulations showed thermoresponsive behavior, existing as a liquid at room temperature and gel at 34-37 degrees C. Increasing the C934P content or temperature significantly increased formulation hardness, compressibility, and adhesiveness. The greatest mucoadhesion was noted in the formulation containing 15% P407 (w/w) and 0.25% C934P (w/w). The work of syringeability values of all formulations were similar and very desirable with regard to ease of administration. The data obtained in these formulations indicate a potentially useful role in the treatment of periodontitis and suggest they are worthy of clinical evaluation.

Opuntia ficus indica (L.) Mill. mucilages show cytoprotective effect on gastric mucosa in rat.

Opuntia ficus indica cladodes possess a protective action against ethanol-induced ulcer in the rat. The major components of cladodes are carbohydrate polymers, mainly mucilages and pectin. To clarify the cytoprotective effects of cladodes on experimental ethanol-induced ulcer in rat, mucilages and pectin were extracted and were administered instead of cladodes. The above mentioned effects induced by cladodes may be attributed to mucilages, and not significantly to pectin.

Assessment and management of surgical wounds in clinical practice.

Successful nursing care of surgical wounds is dependent on the nurse's knowledge and understanding of normal wound healing physiology, the type of surgery performed, the method of closure and the optimal treatment of the resultant wound. Using this knowledge, nurses can provide a systematic and holistic patient assessment, and consider any potential wound-related complications.