scholarly journals Nanoengineered Shear-Thinning Hydrogel Barrier for Preventing Postoperative Abdominal Adhesions

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Guillermo U. Ruiz-Esparza ◽  
Xichi Wang ◽  
Xingcai Zhang ◽  
Sofia Jimenez-Vazquez ◽  
Liliana Diaz-Gomez ◽  
...  
Keyword(s):  
Adhesion Formation ◽  
Shear Thinning ◽  
Ease Of Use ◽  
Postoperative Adhesions ◽  
Scoring Method ◽  
Adhesion Barrier ◽  
Surgical Interventions ◽  
Wide Range ◽  
Poly Ethylene

AbstractMore than 90% of surgical patients develop postoperative adhesions, and the incidence of hospital re-admissions can be as high as 20%. Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive interventions. To solve this clinical limitation, we developed an injectable and sprayable shear-thinning hydrogel barrier (STHB) composed of silicate nanoplatelets and poly(ethylene oxide). We optimized this technology to recover mechanical integrity after stress, enabling its delivery though injectable and sprayable methods. We also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in vitro. The STHB was then tested in a rodent model of peritoneal injury to determine its efficacy preventing the formation of postoperative adhesions. After two weeks, the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions, and STHB formulations presented superior efficacy compared to a commercially available adhesion barrier. Histological and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB formulations. Our technology demonstrated increased efficacy, ease of use in complex anatomies, and compatibility with different delivery methods, providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions.

scholarly journals Local Toxicity of Topically Administrated Thermoresponsive Systems: In Vitro Studies with In Vivo Correlation

2018 ◽  
Vol 47 (3) ◽  
pp. 426-432 ◽  
Author(s):  
Sivan Yogev ◽  
Ayelet Shabtay-Orbach ◽  
Abraham Nyska ◽  
Boaz Mizrahi
Keyword(s):  
Block Copolymer ◽  
Ethylene Glycol ◽  
Medical Devices ◽  
Poly Lactic Acid ◽  
Poly Ethylene Glycol ◽  
Thermoresponsive Polymers ◽  
Wide Range ◽  
Poly Ethylene

Thermoresponsive materials have the ability to respond to a small change in temperature—a property that makes them useful in a wide range of applications and medical devices. Although very promising, there is only little conclusive data about the cytotoxicity and tissue toxicity of these materials. This work studied the biocompatibility of three Food and Drug Administration approved thermoresponsive polymers: poly( N-isopropyl acrylamide), poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) tri-block copolymer, and poly(lactic acid-co-glycolic acid) and poly(ethylene glycol) tri-block copolymer. Fibroblast NIH 3T3 and HaCaT keratinocyte cells were used for the cytotoxicity testing and a mouse model for the in vivo evaluation. In vivo results generally showed similar trends as the results seen in vitro, with all tested materials presenting a satisfactory biocompatibility in vivo. pNIPAM, however, showed the highest toxicity both in vitro and in vivo, which was explained by the release of harmful monomers and impurities. More data focusing on the biocompatibility of novel thermoresponsive biomaterials will facilitate the use of existing and future medical devices.

Abstract 17133: A Novel, Shear-Thinning and Rapidly Self-Healing Polymer Nanoparticle Hydrogel Diminishes Post-Operative Adhesions in Rodent and Ovine Models of Cardiac Adhesion Formation

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Lyndsay M Stapleton ◽  
Amanda N Steele ◽  
Hanjay N Wang ◽  
Michael J Paulsen ◽  
Hector L Hernandez ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Heart Function ◽  
Adhesion Formation ◽  
Shear Thinning ◽  
Adhesion Prevention ◽  
Large Animal ◽  
Self Healing ◽  
Adhesion Barrier ◽  
Polymer Nanoparticle ◽  
Large Animal Models

Objective: Adhesions develop after 95% of operations, represent a major clinical challenge, and cost the U.S healthcare system $2.5B annually. In cardiac surgery, adhesions are problematic during re-operations, increasing operative times and posing risks of hemorrhage and injury to the heart and lungs during sternal reentry and cardiac dissection. We hypothesized that shear-thinning, self-healing polymer nanoparticle hydrogels (PNP) would provide a viscoelastic barrier, effectively preventing adhesion formation (Fig 1A). Methods: Multiple PNP formulations underwent rheologic characterization. Male Sprague Dawley rats (n=52) underwent permanent ligation of the LAD to induce robust postinfarct adhesions, followed by epicardial application of PNP (200L), Seprafilm®(1cm 2 ), or no treatment. Male Dorset sheep (n=8) underwent an anterolateral epicardial abrasion followed by application of PNP (25mL), Seprafilm® (12 cm 2 ), or no treatment. Degree of adhesion formation, standardized dissection time, heart function, and immune response were assessed 4-weeks following surgery. Results: PNP exhibited formulation-dependent mechanical properties indicating the effect of hydrogel stiffness on adhesion barrier efficacy (Fig 1B). Infarct size and heart function were controlled to ensure similar inflammatory responses contributing to adhesion formation across treatment groups. Treatment with certain PNP formulations significantly reduced the development of adhesions compared to controls (Fig 1C). Ovine hearts treated with the PNP 1:10 revealed a pristine epicardial surface (Fig 1D, 1E, and 1F) and resulted in a shorter dissection time relative to the controls (Fig 1G). Conclusion: Administration of a shear-thinning, self-healing hydrogel reduces the extent of adhesion formation in the thoracic cavity following surgery in small and large animal models. PNP provides an easily delivered, scalable solution for post-operative adhesion prevention.

OPTIMIZATION OF TREATMENT OF TUBAL-PERITONEAL INFERTILITY CAUSED BY CHRONIC SALPINGITIS

2021 ◽  
pp. 52-58
Author(s):  
Kalinkina O.B.
Keyword(s):  
Inflammatory Diseases ◽  
Reproductive Function ◽  
Clinical Effectiveness ◽  
Vitro Fertilization ◽  
Surgical Interventions ◽  
Normal Microflora ◽  
Wide Range ◽  
Inflammatory Processes ◽  
Favorable Conditions

The outpatient stage of therapy is the primary and very responsible link in the introduction of patients with chronic forms of VZOMT, since this pathology has a significant impact on such indicators as perinatal, maternal morbidity and mortality. In addition, VZOMT directly affects the development of infertility, ectopic pregnancy, habitual miscarriage, as well as a decrease in the ovarian reserve after unsuccessful attempts of in vitro fertilization, surgical interventions on the appendages of the uterus. To preserve the reproductive function in patients with VZOMT, an important stage is the implementation of a number of therapeutic and rehabilitation measures. The problems of treatment and rehabilitation of patients with VZOMT undoubtedly remain relevant, since cases of relapses and chronization of inflammatory processes significantly worsen the prognosis for a woman's reproductive function. These problems are both social and economic. Taking into account the wide range of infectious agents of VZOMT, it is recommended to use a complex of antibacterial drugs that cover as many varieties of pathogenic and conditionally pathogenic flora as possible. Moreover, an important aspect of the treatment of inflammatory diseases of the female reproductive system is the use of different forms of drugs and ways of their administration. It is rational to combine oral or parenteral with intravaginal. This combination makes it possible to increase the effectiveness of treatment and contributes to the prevention of relapse of the disease. The inclusion of prednisolone – 21 phosphate in the therapy complex also contributes to increasing the effectiveness of therapy, since it creates favorable conditions for the vital activity of normal microflora and unfavorable conditions for conditionally pathogenic microflora. The results obtained in the study indicate a good clinical effectiveness of complex therapy with the inclusion of Elzhina in the treatment regimen for the treatment of fibrotic processes in the fallopian tubes. The use of a combined drug for intravaginal use containing ornidazole-500 mg, prednisolone-3 mg, econazole-150 mg, neomycin 65000ME (Elzhina drug) allows optimizing the management tactics of patients with tubal – peritoneal infertility caused by chronic salpingitis and increasing the fertility rates in this group of patients.

Peritoneal Adhesions and their Prevention - Current Trends

2021 ◽  
Author(s):  
Bernhard Krämer ◽  
Felix Neis ◽  
Sara Brucker ◽  
Stefan Kommoss ◽  
Jürgen Andress ◽  
...  
Keyword(s):  
Financial Burden ◽  
Adhesion Formation ◽  
Surgical Techniques ◽  
Gynecologic Surgery ◽  
Adhesion Prevention ◽  
Regenerated Cellulose ◽  
Adhesion Barrier ◽  
Peritoneal Adhesions ◽  
Severe Problem ◽  
Wide Range

The development of adhesions after gynecologic surgery is a severe problem with ramifications that go beyond the medical complications patients suffer (which most often include pain, obstruction and infertility), since they also impose a huge financial burden on the health care system and increase the workload of surgeons and all personnel involved in surgical follow-up care. Surgical techniques to avoid adhesion formation have not proven to be sufficient and pharmaceutical approaches for their prevention are even less effective, which means that the use of adhesion prevention devices is essential for achieving decent prophylaxis. This review explores the wide range of adhesion prevention products currently available on the market. Particular emphasis is put on prospective randomized controlled clinical trials that include second-look interventions, as these offer the most solid evidence of efficacy. We focused on adhesion scores, which are the most common way to quantify adhesion formation. This enables a direct comparison of the efficacies of different devices. While the greatest amount of data are available for oxidized regenerated cellulose, the outcomes with this adhesion barrier are mediocre and several studies have shown little efficacy. The best results have been achieved using adhesion barriers based on either modified starch, i.e., 4DryField® PH (PlantTec Medical GmbH, Lüneburg, Germany), or expanded polytetrafluoroethylene, i.e., GoreTex (W.L. Gore & Associates, Inc., Medical Products Division, Flagstaff, AZ), albeit the latter, as a non-resorbable barrier, has a huge disadvantage of having to be surgically removed again. Therefore, 4DryField® PH currently appears to be a promising approach and further studies are recommended.

scholarly journals BIOMATERIALS BASED ON CHITOSAN AND ITS DERIVATIVES TO PREVENT ADHESION FORMATION

2021 ◽  
Vol 26 ◽  
pp. 11-22
Author(s):  
Mariya Konovalova ◽  
◽  
Daria Tsaregorodtseva ◽  
Elena Svirshchevskaya ◽  
Keyword(s):  
Quality Of Life ◽  
Intestinal Obstruction ◽  
Abdominal Cavity ◽  
Adhesion Formation ◽  
Reproductive Function ◽  
Postoperative Adhesions ◽  
Surgical Interventions ◽  
Adhesion Process ◽  
Mechanisms Of Adhesion

An increase in the number and volume of surgical interventions leads to an increase in the frequency of postoperative adhesions. The development of the adhesion process in the abdominal cavity causes pain, a decrease in the quality of life of patients, a violation of the reproductive function of women as well as acute adhesion intestinal obstruction. Recently, polymer biomaterials, including those based on chitosan, have been widely used for the prevention of adhesions. Due to their biocompatibility and biodegradation ability, they do not require repeated operations to extract the material. It is believed that these materials act as barriers, physically separating the damaged surfaces. The molecular mechanism of their action is still poorly understood. In this review, the main mechanisms of adhesion formation, as well as ways to prevent them with the help of materials based on chitosan and its derivatives, are discussed.

scholarly journals Use of Icodextrin 4% Solution in the Prevention of Adhesion Formation Following General Surgery: From the Multicentre ARIEL Registry

2006 ◽  
Vol 88 (4) ◽  
pp. 375-382 ◽  
Author(s):  
D Menzies ◽  
M Hidalgo Pascual ◽  
MK Walz ◽  
JJ Duron ◽  
F Tonelli ◽  
...  
Keyword(s):  
Adverse Events ◽  
Surgical Procedures ◽  
General Surgery ◽  
Adhesion Formation ◽  
Healthcare Providers ◽  
Abdominal Distension ◽  
Ease Of Use ◽  
Patient Acceptability ◽  
Wide Range ◽  
Adhesion Reduction

INTRODUCTION Intra-abdominal adhesions occur in many patients following major abdominal surgery and represent a serious burden to patients and healthcare providers. The multicentre ARIEL (Adept® Registry for Clinical Evaluation) Registry was established to gather clinical experiences in the use of icodextrin 4% solution, an approved adhesion-reduction agent, during routine general surgery. PATIENTS AND METHODS General surgeons from five European countries completed anonymised data collection forms for patients undergoing laparotomy or laparoscopy. Surgeons recorded patient demographics, use of icodextrin 4% solution and adverse events, and made subjective assessments of ease of use and patient acceptability with the agent. RESULTS The general surgery registry included 1738 patients (1469 laparotomies, 269 laparoscopies). Leakage of fluid from the surgical site did not appear to be affected by icodextrin 4% solution and was classified as ‘normal’ or ‘less than normal’ in most patients (laparotomies 86%, laparoscopies 88%). Overall, satisfaction with ease of use was rated as ‘good’ or ‘excellent’ by the majority of surgeons (laparotomies 77%, laparoscopies 86%). Patient acceptability was also good, with ratings of ‘as expected’ or ‘less than expected’ in most cases for both abdominal distension (laparotomies 90%, laparoscopies 91%) and abdominal discomfort (laparotomies 91%, laparoscopies 93%). Adverse events occurred in 30.6% of laparotomy patients and 16.7% of laparoscopy patients; the most common events were septic/infective events (4.2% and 3.4% in the laparotomy and laparoscopy groups, respectively). Anastomotic wound-healing problems were reported in 7.6% of patients in the subset of laparoscopy patients undergoing anastomotic procedures (n = 66). DISCUSSION Volumes of icodextrin 4% solution used as an irrigant and instillate were in line with recommendations. Surgeons considered the agent to be easy to use and acceptable to patients. The reported frequencies of adverse events were in line with those published in the literature for surgical procedures, supporting the good safety profile of this agent. CONCLUSIONS Icodextrin 4% solution can be used in a wide range of surgical procedures. In combination with good surgical technique, it may play an important role in adhesion reduction.

Photobiomodulation Therapy for Dementia: A Systematic Review of Pre-Clinical and Clinical Studies

2021 ◽  
pp. 1-22
Author(s):  
Farzad Salehpour ◽  
Mahsa Khademi ◽  
Michael R. Hamblin
Keyword(s):  
Systematic Review ◽  
Clinical Studies ◽  
Near Infrared ◽  
Irradiation Time ◽  
Ease Of Use ◽  
Infrared Light ◽  
Medical Disorders ◽  
Number Of Patients ◽  
Wide Range

Background: Photobiomodulation (PBM) involves the use of red and/or near-infrared light from lasers or LEDs to improve a wide range of medical disorders. Transcranial PBM, sometimes accompanied by intranasal PBM, has been tested to improve many brain disorders, including dementia. Objective: To conduct a systematic review according to PRISMA guidelines of pre-clinical and clinical studies reporting the use of PBM, which were considered relevant to dementia. Methods: Literature was searched between 1967 and 2020 using a range of keywords relevant to PBM and dementia. The light source and wavelength(s), output power, irradiance, irradiation time, fluence or total energy (dose), operation mode (continuous or pulsed) irradiation, approach and site, number of treatment sessions, as well as study outcome(s) were extracted. Results: Out of 10,473 initial articles, 36 studies met the inclusion criteria. Nine articles reported in vitro studies, 17 articles reported studies in animal models of dementia, and 10 studies were conducted in dementia patients. All of the included studies reported positive results. The clinical studies were limited by the small number of patients, lack of placebo controls in some instances, and only a few used objective neuroimaging methods. Conclusion: The preliminary evidence of clinical benefit, the lack of any adverse effects, and the remarkable ease of use, suggest larger clinical trials should be conducted as soon as possible.

scholarly journals Well-Defined Diblock Poly(ethylene glycol)-b-Poly(ε-caprolactone)-Based Polymer-Drug Conjugate Micelles for pH-Responsive Delivery of Doxorubicin

Materials ◽  
2020 ◽  
Vol 13 (7) ◽  
pp. 1510 ◽  
Author(s):  
Amin Jafari ◽  
Lingyue Yan ◽  
Mohamed Alaa Mohamed ◽  
Yun Wu ◽  
Chong Cheng
Keyword(s):  
Ethylene Glycol ◽  
Diblock Copolymer ◽  
Click Reaction ◽  
Ph Responsive ◽  
Poly Ethylene Glycol ◽  
Polymer Backbone ◽  
Drug Conjugate ◽  
Wide Range ◽  
Poly Ethylene

Nanoparticles have emerged as versatile carriers for various therapeutics and can potentially treat a wide range of diseases in an accurate and disease-specific manner. Polymeric biomaterials have gained tremendous attention over the past decades, owing to their tunable structure and properties. Aliphatic polyesters have appealing attributes, including biodegradability, non-toxicity, and the ability to incorporate functional groups within the polymer backbone. Such distinctive properties have rendered them as a class of highly promising biomaterials for various biomedical applications. In this article, well-defined alkyne-functionalized poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) diblock copolymer was synthesized and studied for pH-responsive delivery of doxorubicin (DOX). The alkyne-functionalized PEG-b-PCL diblock copolymer was prepared by the synthesis of an alkyne-functionalized ε-caprolactone (CL), followed by ring-opening polymerization (ROP) using PEG as the macroinitiator. The alkyne functionalities of PEG-b-PCL were modified through copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction to graft aldehyde (ALD) groups and obtain PEG-b-PCL-g-ALD. Subsequently, DOX was conjugated on PEG-b-PCL-g-ALD through the Schiff base reaction. The resulting PEG-b-PCL-g-DOX polymer-drug conjugate (PDC) self-assembled into a nano-sized micellar structure with facilitated DOX release in acidic pH due to the pH-responsive linkage. The nanostructures of PDC micelles were characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). In vitro studies of the PDC micelles, revealed their improved anticancer efficiency towards MCF-7 cells as compared to free DOX.

Evaluation of 99mTc-Label led Vitamin K4 as an Agent for Testicular Imaging

1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan
Keyword(s):  
Soft Tissue ◽  
Room Temperature ◽  
Normal Subjects ◽  
Left Testis ◽  
Wide Range ◽  
Activity Ratios ◽  
The Right ◽  
Radioactivity Levels

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.

In Vitro Clot Lysis as a Potential Indicator of Thrombus Resistance to Fibrinolysis – Study in Healthy Subjects and Correlation with Blood Fibrinolytic Parameters

1997 ◽  
Vol 77 (04) ◽  
pp. 725-729 ◽  
Author(s):  
Mario Colucci ◽  
Silvia Scopece ◽  
Antonio V Gelato ◽  
Donato Dimonte ◽  
Nicola Semeraro
Keyword(s):  
Plasminogen Activator ◽  
Clot Lysis ◽  
Individual Response ◽  
Plasminogen Activator Inhibitor 1 ◽  
Autologous Plasma ◽  
Wide Range ◽  
Blood Clots ◽  
Physiological Variations ◽  
Pai 1

SummaryUsing an in vitro model of clot lysis, the individual response to a pharmacological concentration of recombinant tissue plasminogen activator (rt-PA) and the influence on this response of the physiological variations of blood parameters known to interfere with the fibrinolytic/thrombolytic process were investigated in 103 healthy donors. 125I-fibrin labelled blood clots were submersed in autologous plasma, supplemented with 500 ng/ml of rt-PA or solvent, and the degree of lysis was determined after 3 h of incubation at 37° C. Baseline plasma levels of t-PA, plasminogen activator inhibitor 1 (PAI-1), plasminogen, α2-anti-plasmin, fibrinogen, lipoprotein (a), thrombomodulin and von Willebrand factor as well as platelet and leukocyte count and clot retraction were also determined in each donor. rt-PA-induced clot lysis varied over a wide range (28-75%) and was significantly related to endogenous t-PA, PAI-1, plasminogen (p <0.001) and age (p <0.01). Multivariate analysis indicated that both PAI-1 antigen and plasminogen independently predicted low response to rt-PA. Surprisingly, however, not only PAI-1 but also plasminogen was negatively correlated with rt-PA-ginduced clot lysis. The observation that neutralization of PAI-1 by specific antibodies, both in plasma and within the clot, did not potentiate clot lysis indicates that the inhibitor, including the platelet-derived form, is insufficient to attenuate the thrombolytic activity of a pharmacological concentration of rt-PA and that its elevation, similarly to the elevation of plasminogen, is not the cause of clot resistance but rather a coincident finding. It is concluded that the in vitro response of blood clots to rt-PA is poorly influenced by the physiological variations of the examined parameters and that factors other than those evaluated in this study interfere with clot dissolution by rt-PA. In vitro clot lysis test might help to identify patients who may be resistant to thrombolytic therapy.

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