The efficiency of two different synthetic bone graft materials on alveolar ridge preservation after tooth extraction: a split-mouth study.

BACKGROUND: Alveolar Bone loss occurs frequently during the first six months after tooth extraction. Various studies have proposed different methods to reduce as much as possible the atrophy of the alveolar ridge after tooth extraction. Filling the socket with biomaterials after extraction can reduce the resorption of the alveolar ridge. We compared the height of the alveolar process at the mesial and distal aspects of the extraction site and the resorption rate was calculated after the application of HA/ß-TCP or synthetic co-polymer polyglycolic - polylactic acid PLGA mixed with blood to prevent socket resorption immediately and after tooth extraction. METHODS: The study was conducted on 24 extraction sockets of impacted mandibular third molars bilaterally, vertically, and completely covered, with a thin bony layer. HA/ß-TCP was inserted into 12 of the dental sockets immediately after extraction, and the synthetic polymer PLGA was inserted into 12 of the dental sockets. All sockets were covered completely with a full-thickness envelope flap. Follow-up was performed for one year after extraction, using radiographs and stents for the vertical alveolar ridge measurements. RESULTS: The mean resorption rate in the HA/ß-TCP and PLGA groups was ± 1.23 mm and ± 0.1 mm, respectively. A minimal alveolar bone height reduction of HA/ß-TCP was observed after 9 months, the reduction showed a slight decrease to 0.93 mm, while this rate was 0.04 mm after 9 months in the PLGA group. Moreover, the bone height was maintained after three months, indicating a good HA/ß-TCP graft performance in preserving alveolar bone (1.04 mm) while this rate was (0.04 mm) for PLGA. CONCLUSION: The PLGA graft demonstrated adequate safety and efficacy in dental socket preservation following tooth extraction. However, HA/ß-TCP causes greater resorption at augmented sites than PLGA, which clinicians should consider during treatment planning.

Surgical sealant using free pericardial fat pad with fibrin glue and polyglycolic acid sheets for secondary spontaneous pneumothorax: a novel technique.

We report on the "Triple-FP technique," a novel surgical approach for secondary spontaneous pneumothoraces, which combines a free pericardial fat pad, fibrin glue, and polyglycolic acid sheets. In our experience with 13 patients suffering from secondary spontaneous pneumothoraces, this method effectively prevented postoperative air leaks and re-operations. The technique includes the following steps: (1) harvesting free pericardial fat; (2) suturing around the lung parenchymal defect with the needles and thread left outside the thoracic cavity; (3) ensuring contact between the mediastinal pleural side of the fat and the lung; (4) applying fibrin glue to both the lung and fat before suturing; (5) securing the fat to the lung via the suture thread, reinforced with fibrin glue; and (6) stabilization with polyglycolic acid sheets and additional fibrin glue. This innovative technique is a reliable and effective treatment strategy for secondary spontaneous pneumothoraces, especially for patients with fragile lung tissue.

Endoscopic sealing hemostasis with polyglycolic acid sheet and fibrin glue as a novel endoscopic hemostatic technique: a report of three cases.

Polyglycolic acid sheets and fibrin glue are routinely used in surgical procedures. Their usefulness in gastrointestinal endoscopy is mainly to prevent complications (bleeding, delayed perforation, stenosis, etc.) associated with procedures such as endoscopic submucosal dissection and endoscopic mucosal resection, with most reports on iatrogenic and secondary conditions. However, there are few reports on primary gastrointestinal diseases. Herein, we report three cases of gastrointestinal bleeding that were successfully treated with endoscopic hemostasis by sealing the lesions with polyglycolic acid sheets and fibrin glue. Case 1 was of an 83-year-old woman with a rare duodenal perforation that was treated with omental plugging who experienced subsequent bleeding from the greater omentum. Case 2 was of a 73-year-old woman with an acute hemorrhagic rectal ulcer that was difficult to treat even after performing standard endoscopic hemostasis techniques; however, surgery was avoided by sealing. Case 3 was that of an 89-year-old woman with a stercoral ulcer, treated curatively using a combination of sealing and argon plasma coagulation right from presentation based on the lessons learned from Cases 1 and 2. Endoscopic hemostasis using a polyglycolic acid sheet and fibrin glue may be a new treatment option for gastrointestinal bleeding particularly in refractory or rare causes.

Innovative Combination Treatment to Expand the Indications of Particle Therapy: Spacer Placement Surgery Using Bio-Absorbable Polyglycolic Acid Spacer.

BACKGROUND: Particle therapy has favorable dose distribution and high curability. However, radiotherapy for malignant tumors adjacent to the gastrointestinal tract is contraindicated owing to its low tolerance. To overcome this, combination treatment with surgery to make a space between the tumor and adjacent gastrointestinal tract followed by particle therapy has been developed. Several materials have been used for the spacer and recently, we developed the absorbable polyglycolic acid (PGA) spacer, which has been used since 2019. This study is the first report of consecutive case series of spacer placement surgery using the PGA spacer. STUDY DESIGN: Fifty consecutive patients undergoing spacer placement surgery with the PGA spacer were evaluated. Postoperative laboratory data, morbidity related to the treatment, and spacer volume after treatment were evaluated. RESULTS: There were no treatment-related deaths, and all but 2 patients completed combination treatment. The median ratios of postoperative PGA spacer volume to the pretreatment volume were 96.9%, 87.7%, and 74.6% at weeks 2, 4, and 8, respectively. The spacer volume was maintained at 80% at 7 weeks and was predicted to be 50% at 15 weeks and 20% in 24 weeks. CONCLUSIONS: Spacer placement surgery using the PGA spacer was feasible and tolerable. The PGA spacers maintained sufficient thickness during the duration of subsequent particle therapy. Combination treatment using the PGA spacer is innovative and has the potential to become a new standard curative local treatment.

Useful combination of Gehanno method, polyglycolic acid sheet and fibrin glue for prevention of postoperative dysfunction after soft palate resection with TORS.

Oropharyngeal cancer requiring combined resection of the soft palate is relatively out of indication for transoral robotic surgery (TORS) due to postoperative functional problems. We report the case of a patient with oropharyngeal cancer in which half of the soft palate was resected, and good function was maintained using the Gehanno method, polyglycolic acid (PGA) sheet and fibrin glue. The patient was a woman in her 50 s with oropharyngeal squamous cell carcinoma (p16-positive, T2N1M0 stage I). TORS and right neck dissection were performed the same day. About half of the soft palate was resected cranially. After closing the right nasopharynx with the Gehanno method, the sutured part was reinforced by covering with a PGA sheet of about 10 mm on a side and fibrin glue. Oral feeding was started on postoperative day 4, but no nasal reflux was observed. Three weeks postoperatively, no nasal reflux was evident, normal food intake was possible, and nasal breathing was maintained. This technique may be effective after TORS surgery that requires soft palate resection.

Hepatic artery protection using a polyglycolic acid sheet during pancreaticoduodenectomy: A multicenter study.

BACKGROUND: Postpancreatectomy hemorrhage (PPH) is the most feared complication after pancreaticoduodenectomy (PD). The most common cause is erosion of the gastroduodenal artery stump. Preventive measures have been previously reported, but a consensus is lacking. The aim of this study was to analyze the preventive effect of reinforcing the hepatic artery using a polyglycolic acid (PGA) sheet during PD. METHODS: A multicenter retrospective study was performed, collecting data from three tertiary hospitals in Korea. Patients receiving PD from January 2016 to December 2021 were included. The primary endpoint was rate of PPH from the hepatic artery. Arterial reinforcement (AR) was performed by wrapping the artery with Neoveil (Gunze Ltd) and applying fibrin glue. The perioperative data of patients who did not receive AR were compared with data of those who received AR. RESULTS: A total of 904 patients were analyzed. The rate of PPH from the hepatic artery was significantly lower in the AR group. (3.5% vs 0.7%, p = .002) In patients with CR-POPF, the 90 day mortality rate of the AR group was less than half that of the non-AR group (7.2% vs 3.5%, p = .455) Risk factor analysis showed CR-POPF to be an independent risk factor for PPH. Arterial reinforcement was shown to be a strong protective factor for PPH (OR 0.20, 95% CI: 0.05-0.72, p = .014). CONCLUSIONS: AR of the hepatic artery using Neoveil and fibrin glue is a simple method that greatly reduces the rate of PPH after PD.

Evaluating the Efficacy of Polyglycolic Acid-Loading Tetrandrine Nanoparticles in the Treatment of Dry Eye.

INTRODUCTION: Dry eye disease (DED) is a multifactor-induced disease accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. Traditional anti-inflammation agent corticosteroids applied in DED treatment could result in high intraocular pressure, especially in long-term treatment. Therefore, we explored a nano drug that aimed to block the formation pathway of DED which had anti-inflammatory, sustained release, and good biocompatibility characteristics in this study. METHODS: We prepared a novel nanomedicine (Tet-ATS@PLGA) by the thin film dispersion-hydration ultrasonic method and detected its nanostructure, particle size, and zeta potential. Flow cytometry was used to detect the cell survival rate of each group after 24 h of drug treatment on inflammed Statens Seruminstitut Rabbit Corneal (SIRC) cells. Observed and recorded corneal epithelial staining, tear film rupture time, and Schirmer test to detect tear secretion on the ocular surface of rabbits. The corneal epithelial thickness, morphology, and number of bulbar conjunctival goblet cells were recorded by H&E staining. Finally, we detected the expression of VEGF, IL-1ß, PGE2, and TNF-α by cellular immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA). RESULTS: The encapsulation efficiency and drug loading of Tet-ATS@PLGA were 79.85% and 32.47%, respectively. At eye surface temperature, Tet can easily release from Tet-ATS@PLGA while that it was difficult to release at storage temperature and room temperature. After 2 weeks medication, Tet-ATS@PLGA can effectively improve the tear film rupture time and tear secretion time in a DED model (p <0.05). Compared with the normal group (62.34 ± 4.86 mm), the thickness of corneal epithelium in ATS (29.47 ± 3.21 mm), Tet-ATS (46.23 ± 2.87 mm), and Tet-ATS@PLGA (55.76 ± 3.95 mm) gradually increased. Furthermore, the flow cytometry indicated that Tet-ATS@PLGA can effectively promote the apoptosis of inflammatory SIRC cells, and the cellular immunofluorescence and ELISA experiments showed that the expression intensity of inflammatory factors such as VEGF, IL-1ß, PGE2, and TNF-α decreased in this process. Interestingly, Tet also had the effect of reducing intraocular pressure. CONCLUSION: Tet-ATS@PLGA can effectively promote the apoptosis of inflammatory corneal epithelial cells, thus inhibiting the expression of inflammatory factors to block the formation of DED and improve the secretion of tear on the ocular surface.

Molecular Complex of HSIM-loaded Polymeric Nanoparticles: Potential Carriers in Osteoporosis.

BACKGROUND: Statins, especially simvastatin promote bone formation by stimulating the activity of osteoblasts and suppressing osteoclast activity via the BMP-Smad signaling pathway. Statins present the liver first-pass metabolism. This study attempts to fabricate and evaluate simvastatin functionalized hydroxyapatite encapsulated in poly(lactic-co-glycolic) acid (PLGA) nanoparticles (HSIM-PLGA NPs) administered subcutaneously with sustained release properties for effective management of osteoporosis. METHODS: Simvastatin functionalized hydroxyapatite (HSIM) was prepared by stirring and validated by docking studies, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). Further, HSIM-loaded PLGA nanoparticles (HSIM-PLGA NPs) were developed via the solvent emulsification method. The nanoparticles were evaluated for zeta potential, particle size, entrapment efficiency, stability studies, and in vitro drug release studies. in vitro binding affinity of nanoparticles for hydroxyapatite was also measured. Bone morphology and its effect on bone mineral density were examined by using a glucocorticoid-induced osteoporosis rat model. RESULTS: The optimized nanoparticles were found to be amorphous and showed no drug-polymer interaction. The particle size of formulated nanoparticles varied from 196.8 ± 2.27nm to 524.8 ± 5.49 nm and the entrapment efficiency of nanoparticles varied from 41.9 ± 3.44% to 70.8 ± 4.46%, respectively. The nanoparticles showed sustained release behaviour (75% in 24 hr) of the drug followed by non-fickian drug release. The nanoparticles exhibited high binding affinity to bone cell receptors, increasing bone mineral density. A significant difference in calcium and phosphorous levels was observed in disease and treatment rats. Porous bone and significant improvement in porosity were observed in osteoporotic rats and treated rats, respectively (P < 0.05). CONCLUSION: Bone-targeting nanoparticles incorporating functionalized simvastatin can target bone. Thus, in order to distribute simvastatin subcutaneously for the treatment of osteoporosis, the developed nanoparticles may act as a promising approach.

Repeated steroid injection and polyglycolic acid shielding for prevention of refractory esophageal stricture.

BACKGROUND: Postoperative stricture and refractory stricture are severe adverse events which occur after expansive esophageal endoscopic submucosal dissection (ESD). The aim of this study was to assess the efficacy of steroid injection, polyglycolic acid (PGA) shielding, and of additional steroid injection thereafter for the prevention of refractory esophageal stricture. METHODS: This is a retrospective cohort study of 816 consecutive cases of esophageal ESD performed between 2002 and 2021 at the University of Tokyo Hospital. After 2013, all patients with a diagnosis of superficial esophageal carcinoma covering over 1/2 the esophageal circumference underwent preventive treatment immediately after ESD with either "PGA shielding", "steroid injection", or "steroid injection + PGA shielding". Additional steroid injection was performed for high-risk patients after 2019. RESULTS: The risk of refractory stricture was especially high in the cervical esophagus (OR 24.77, p = 0.002) and after total circumferential resection (OR 894.04, p < 0.001). "Steroid injection + PGA shielding" was the only method significantly effective in preventing stricture occurrence (OR 0.36; 95% CI 0.15-0.83, p = 0.012). This method also decreased the risk of refractory stricture (OR 0.38; 95% CI 0.10-1.28, p = 0.096), but additional steroid injection was the only significantly effective method for prevention of refractory stricture (OR 0.42; 95% CI 0.14-0.98, p = 0.029). CONCLUSION: Combining steroid injection and PGA shielding is effective for preventing post-ESD stricture and refractory stricture. Additional steroid injection is a viable option for patients at high-risk for refractory stricture.

Efficacy of the polyglycolic acid sheet for preventing anastomotic leakage in double-stapling technique anastomosis for left-sided colon or rectal cancer surgery: a propensity score-matched study.

BACKGROUND: To prevent anastomotic leakage in patients with left-sided colorectal cancer who underwent double-stapling technique (DST) anastomosis, we investigated a new method: DST anastomosis with a polyglycolic acid (PGA) sheet. This procedure has been shown to have the potential to decrease the rate of anastomotic leakage. However, due to the small number of cases enrolled in our previous study, it was not possible to compare the outcomes of the new and conventional procedures. The aim of this study was to evaluate the effect of the PGA sheet on preventing anastomotic leakage in patients with left-sided colorectal cancer who underwent DST anastomosis by retrospectively comparing the anastomotic leakage rate between the PGA sheet and conventional groups. METHODS: A total of 356 patients with left-sided colorectal cancer who underwent DST anastomosis during surgery at Osaka City University Hospital between January 2016 and April 2022 were enrolled in this study. Propensity score matching was performed to reduce the confounding effects secondary to imbalances in the use of PGA sheets. RESULTS: The PGA sheet was used in 43 cases (PGA sheet group) and it was not used in 313 cases (conventional group). After propensity score matching, the incidence of anastomotic leakage in the PGA sheet group was significantly lower than that in the conventional group. CONCLUSION: DST anastomosis with PGA sheet, which is easy to perform, contributes to the reduction of anastomotic leakage rate by increasing the strength of the anastomotic site.

Development of novel layered polyglycolic acid sheet for regeneration of critical-size defect in rat trachea.

OBJECTIVES: Polyglycolic acid (PGA) sheets are difficult to adapt to the central airway because of poor durability against high air pressure. Therefore, we developed a novel layered PGA material to cover the central airway and examined its morphologic traits and functional performance as a potential tracheal replacement. METHODS: A critical-size defect in rat cervical tracheas was covered with the material. Morphologic changes were bronchoscopically and pathologically evaluated. Functional performance was evaluated by regenerated ciliary area, ciliary beat frequency and ciliary transport function determined by measuring the moving distance of microspheres dropped onto the trachea (µm/s). The evaluation time points were 2 weeks, 1 month, 2 months and 6 months after surgery (n = 5, respectively). RESULTS: Forty rats underwent implantation, and all survived. Histological examination confirmed ciliated epithelization on the luminal surface after 2 weeks. Neovascularization was observed after 1 month, tracheal glands after 2 months and chondrocyte regeneration after 6 months. Although the material was gradually replaced by self-organization, tracheomalacia was not bronchoscopically observed at any time point. The area of regenerated cilia significantly increased between 2 weeks and 1 month (12.0% vs 30.0%; P = 0.0216). The median ciliary beat frequency significantly improved between 2 weeks and 6 months (7.12 vs 10.04 Hz; P = 0.0122). The median ciliary transport function was significantly improved between 2 weeks and 2 months (5.16 vs 13.49 µm/s; P = 0.0216). CONCLUSIONS: The novel PGA material showed excellent biocompatibility and tracheal regeneration both morphologically and functionally 6 months after tracheal implantation.

Factors affecting polyglycolic acid sheet engraftment success for covering mucosal defects from head and neck surgery.

BACKGROUND: Polyglycolic acid (PGA) sheets have been used with fibrin glue to cover extensive mucosal defects in oral and pharyngeal surgery; however, the sheets can fall off before wound healing is completed. Hence, prolonged fasting is often recommended in such patients. However, there are few studies on the factors that shape PGA sheet engraftment. We studied sheet engraftment rates considering these factors. METHODS: All consecutive cases of oral surgery in 2013-21 in which the defect was covered with fibrin glue and Neoveil® or Neoveil Nano® PGA sheets were identified. The loss of all sheets was defined as an engraftment failure. Multiple logistic regression analysis was conducted to identify whether the PGA-sheet type, application site, defect size and postoperative fasting duration predicted engraftment. RESULTS: Overall, 137 patients were identified (mean age, 73 years; 57% male). The surgeries were conducted with Neoveil® in 66% of the patients; the most common site was the buccal mucosa (25%), and the mean defect size and fasting duration were 709 mm2 and 4 days, respectively. The engraftment rate was 76%. Neoveil Nano® PGA sheets were associated with a 2.8-fold better engraftment rate than Neoveil® (univariate: 87 vs. 70%, P = 0.032; multivariate: 95% confidence intervals = 1.067-7.410, P = 0.036). Other variables, including fasting duration, were not predictive of engraftment. CONCLUSIONS: This is the largest case series of patients with head and neck cancer who underwent fibrin glue-PGA sheet defect coverage. The fasting duration did not influence engraftment. Therefore, early oral intake is not contraindicated in such patients.

Neutrophil hitchhiking for drug delivery to the bone marrow.

Pharmaceuticals have been developed for the treatment of a wide range of bone diseases and disorders, but suffer from problematic delivery to the bone marrow. Neutrophils are naturally trafficked to the bone marrow and can cross the bone marrow-blood barrier. Here we report the use of neutrophils for the targeted delivery of free drugs and drug nanoparticles to the bone marrow. We demonstrate how drug-loaded poly(lactic-co-glycolic acid) nanoparticles are taken up by neutrophils and are then transported across the bone marrow-blood barrier to boost drug concentrations in the bone marrow. We demonstrate application of this principle to two models. In a bone metastasis cancer model, neutrophil delivery is shown to deliver cabazitaxel and significantly inhibit tumour growth. In an induced osteoporosis model, neutrophil delivery of teriparatide is shown to significantly increase bone mineral density and alleviate osteoporosis indicators.

The effect of polyglycolic acid sheet in preventing postoperative recurrent pneumothorax: a prospective cohort study.

BACKGROUND: Primary spontaneous pneumothorax occasionally relapses, even after bullectomy; therefore, coverage of the bullectomy staple line for pleural reinforcement is common in Japan. However, the appropriate covering materials have not yet been determined. METHODS: This was a longitudinal prospective cohort study. Data were available for patients aged < 40 years with primary spontaneous pneumothorax who underwent their first thoracoscopic bullectomy between July 2015 and June 2021. We used oxidized regenerated cellulose (ORC) sheets from July 2015 to June 2018, and polyglycolic acid (PGA) sheets from July 2018 to June 2021. The postoperative recurrence-free survival rate was evaluated. The characteristics of the recurrent cases (radiographic, intraoperative, and pathological findings) were also evaluated. The extent of pleural adhesions was classified into the following three groups: none, medium, or extensive. RESULTS: A total of 187 patients were included in the study. There were 92 and 95 participants in the ORC and PGA sheet groups, respectively. The postoperative recurrence-free survival rates were significantly higher in the PGA sheet group than in the ORC sheet group (ORC group vs. PGA group, 82.9% vs. 95.4%, p = 0.031). In recurrent cases, there was a significant difference in terms of pleural adhesion (0.0% [12 of 12, none] vs. 100.0% [four of four, extensive], p < 0.001). CONCLUSIONS: Compared with ORC sheets, PGA sheets are an effective material for preventing early recurrence of primary spontaneous pneumothorax. Strong local pleural adhesions potentially contribute to decreasing recurrence.

Interaction of gentamicin and gentamicin-AOT with poly-(lactide-co-glycolate) in a drug delivery system - density functional theory calculations and molecular dynamics simulation.

Gentamicin is used to treat brucellosis, an infectious disease caused by the Brucella species but the drug faces several issues such as low efficacy, instability, low solubility, and toxicity. It also has a very short half-life, therefore, requiring frequent dosing. Consequently, several other antibiotics are also being used for the treatment of brucellosis as a single dose as well as in combination with other antibiotics but none of these therapies are satisfactory. Nanoparticles in particular polymer-based ones utilizing polymers that are biodegradable and biocompatible for instance PLGA are a method of choice to overcome such drug delivery issues and enable potential targeted delivery. The current study focuses on the evaluation of the structural and dynamical properties of a drug-polymer system consisting of gentamicin drug and PLGA polymer nanoparticles in the water representing a targeted drug delivery system for the treatment of brucellosis. For this purpose, all-atom molecular dynamics simulations were carried out on the drug-polymer systems in the absence and presence of the surfactant bis(2-Ethylhexyl) sulfosuccinate (AOT) to determine the structural and dynamical properties as well as the effect of the surfactant on these properties. We also investigated systems in which the polymer constituents were in the form of monomeric units toward decoupling the primary interactions of the monomer units and polymer effects. The simulation results explain the nature of the interactions between the drug and the polymer as well as transport properties in terms of drug diffusion coefficients, which characterize the molecular behavior of gentamicin-polymer nanoparticles for use in brucellosis.

Progress in oral insulin delivery by PLGA nanoparticles for the management of diabetes.

Currently, the only practical way to treat type 1 and advanced insulin-dependent type 2 diabetes mellitus (T1/2DM) is the frequent subcutaneous injection of insulin, which is significantly different physiologically from endogenous insulin secretion from pancreatic islets and can lead to hyperinsulinemia, pain, and infection in patients with poor compliance. Hence, oral insulin delivery has been actively pursued to revolutionize the treatment of insulin-dependent diabetes. In this review, we provide an overview of recent progress in developing poly(lactic co-glycolic acid) (PLGA) nanoparticles (NPs) for oral insulin delivery. Different strategies for insulin-loaded PLGA NPs to achieve normoglycemic effects are discussed. Finally, challenges and future perspectives of PLGA NPs for oral insulin delivery are put forward.