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1.
J Orthop Surg Res ; 19(1): 457, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095889

RESUMEN

BACKGROUND: There are many adhesion barrier materials, cross-linked or non-cross-linked hyaluronic acid (HA), used during surgeries. PURPOSE: This study investigates the efficacy of cross-linked and non-cross-linked HA in preventing Achilles tendon adhesions. We hypothesized that non-cross-linked HA may be more effective than cross-linked HA in preventing Achilles tendon adhesions following injury and repair. METHODS: Twenty male Sprague Dawley rats, totaling 40 legs, underwent Achilles tendon transection and repair. Following the surgery, they were treated simultaneously with cross-linked and non-cross-linked HA formulations. The rats were divided into four groups: a positive control group, a group treated with BMC non-cross-linked HA gel, a group treated with DEFEHERE cross-linked HA gel, and a group treated with ANIKA cross-linked HA gel. Four weeks after surgery, macroscopic evaluation of peritendinous adhesion and histological analysis were conducted to assess the effectiveness of the treatments. RESULTS: Non-cross-linked BMC HA demonstrated superior efficacy in preventing tendon adhesions compared to cross-linked HA and control groups. Histological analysis confirmed reduced adhesion severity in the non-cross-linked HA group (P < 0.05). The findings support the potential of non-cross-linked HA as a treatment to inhibit tendon adhesions. Further research, including clinical trials, is warranted to validate these results in human subjects. CONCLUSIONS: Non-cross-linked BMC HA had significantly lower tendon adhesions parameters and better healing scores in histological analysis than cross-linked HA and control group did. Non-cross-linked HA holds promise as a potential treatment to inhibit the formation of such adhesions.


Asunto(s)
Tendón Calcáneo , Ácido Hialurónico , Complicaciones Posoperatorias , Ratas Sprague-Dawley , Animales , Tendón Calcáneo/lesiones , Tendón Calcáneo/cirugía , Adherencias Tisulares/prevención & control , Adherencias Tisulares/etiología , Masculino , Ratas , Complicaciones Posoperatorias/prevención & control , Modelos Animales de Enfermedad , Reactivos de Enlaces Cruzados , Traumatismos de los Tendones/prevención & control , Traumatismos de los Tendones/cirugía , Resultado del Tratamiento
2.
ACS Appl Bio Mater ; 7(7): 4679-4689, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38963794

RESUMEN

Postoperative peritoneal adhesion (PPA) is a prevalent complication of abdominal surgery, posing a significant hindrance to postsurgical recovery. Although several strategies have been developed to alleviate and prevent adhesions, their efficacy remains unsatisfactory. For the first time, we studied the therapeutic effect and mechanism of our recently developed thermally stable oligonucleotide-based mimetics of hepatocyte growth factor (HGF DNA aptamer) to prevent PPA. The HGF DNA aptamer effectively inhibited canonical TGF-ß1 signaling transduction, partially suppressing mesothelial mesenchymal transition. Additionally, the aptamer, respectively, upregulated and downregulated the expression of tissue plasminogen activator and plasminogen activator inhibitor 1, thereby enhancing fibrinolytic activity. As a pleiotropic factor, the HGF DNA aptamer also enhanced the migratory and proliferative capacities of mesothelial cells. Finally, the aptamer demonstrated a higher level of effectiveness in preventing PPAs than the commercially available antiperitoneal adhesion barrier, Seprafilm. Due to its therapeutic benefits, excellent stability, biosafety, cost-effectiveness, and versatility, the HGF DNA aptamer demonstrates promise for preventing PPA in future clinical settings.


Asunto(s)
Aptámeros de Nucleótidos , Transición Epitelial-Mesenquimal , Fibrinólisis , Factor de Crecimiento de Hepatocito , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/farmacología , Factor de Crecimiento de Hepatocito/metabolismo , Adherencias Tisulares/prevención & control , Humanos , Fibrinólisis/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ensayo de Materiales , Tamaño de la Partícula , Complicaciones Posoperatorias/prevención & control
3.
Anticancer Res ; 44(8): 3349-3353, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39060053

RESUMEN

BACKGROUND/AIM: Neskeep®, an absorbable polyglycolic acid spacer, has been developed as the optimal material for spacer placement surgery. However, preventing its severe adhesion is a crucial concern. Therefore, we aimed to identify an effective anti-adhesion agent for Neskeep® using rat models. MATERIALS AND METHODS: Animal experiments were performed using 60 rats, which underwent Neskeep® placement on the abdominal wall. Three types of anti-adhesion agents were employed, establishing four subgroups: Seprafilm®, INTERCEED®, AdSpray®, and only Neskeep® (control) groups. Rats were sacrificed on postoperative days 7, 14, and 28 to assess adhesion levels around the Neskeep® Macroscopic visual assessment with the Lauder score and histopathological evaluation were performed to assess the degree of adhesion. RESULTS: There were no significant differences in the proportion of Lauder scores on days 7 and 14 between the four groups. Histological evaluation revealed no significant differences between groups at any observation time. However, the mean Lauder scores at day 28 were 5.0, 1.6, 4.0, and 4.8 in the Neskeep®, Seprafilm®, INTERCEED®, and AdSpray® groups, respectively. The proportion of milder Lauder score was significantly higher in the Seprafilm® group on day 28. CONCLUSION: Seprafilm® may exhibit an anti-adhesive effect when used with Neskeep®.


Asunto(s)
Ácido Poliglicólico , Animales , Adherencias Tisulares/prevención & control , Adherencias Tisulares/patología , Ratas , Ácido Poliglicólico/química , Masculino , Ácido Hialurónico/farmacología , Implantes Absorbibles , Modelos Animales de Enfermedad , Pared Abdominal/cirugía , Pared Abdominal/patología , Ratas Sprague-Dawley , Celulosa Oxidada
5.
BMC Womens Health ; 24(1): 400, 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39003483

RESUMEN

BACKGROUND: Intrauterine adhesions (IUA) are a challenging clinical problem in reproductive infertility. The most common causes are intrauterine surgery and abortions. We aimed to investigate whether early second-look office hysteroscopy can prevent IUA. METHODS: A single-center, prospective, two-armed, randomized controlled trial was designed to explore the efficacy of early office hysteroscopy after first-trimester induced abortion (suction dilatation and curettage [D&C]) and to further analyze fertility outcomes. Women aged 20-45 years undergoing suction D&C and desiring to conceive were recruited. Between October 2019 and September 2022, 66 women were enrolled, of whom 33 were allocated to group A (early hysteroscopy intervention). The women in intervention group A were planned to receive 2 times of hysteroscopies (early and late). In group B, women only underwent late (6 months post suction D&C) hysteroscopy. RESULTS: The primary outcome was the IUA rate assessed using office hysteroscopy 6 months after artificial abortion. Secondary outcomes included menstrual amount/durations and fertility outcomes. In intervention group A, 31 women underwent the first hysteroscopy examination, and 15 completed the second. In group B (late hysteroscopy intervention, 33 patients), 16 completed the hysteroscopic exam 6 months after an artificial abortion. Twenty-one women did not receive late hysteroscopy due to pregnancy. The IUA rate was 16.1% (5/31) at the first hysteroscopy in group A, and no IUA was detected during late hysteroscopy. Neither group showed statistically significant differences in the follow-up pregnancy and live birth rates. CONCLUSIONS: Early hysteroscopy following suction D&C can detect intrauterine lesions. IUA detected early by hysteroscopy can disappear on late examination and become insignificant for future pregnancies. Notably, the pregnancy outcomes showed a favorable trend in the early hysteroscopy group, but there were no statistically significant differences. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT04166500. Registered on 2019-11-10. https://clinicaltrials.gov/ct2/show/NCT04166500 .


Asunto(s)
Aborto Inducido , Histeroscopía , Enfermedades Uterinas , Humanos , Femenino , Histeroscopía/métodos , Histeroscopía/efectos adversos , Adherencias Tisulares/prevención & control , Adulto , Enfermedades Uterinas/diagnóstico , Enfermedades Uterinas/cirugía , Enfermedades Uterinas/prevención & control , Embarazo , Aborto Inducido/efectos adversos , Aborto Inducido/métodos , Estudios Prospectivos , Persona de Mediana Edad , Adulto Joven , Dilatación y Legrado Uterino/métodos , Dilatación y Legrado Uterino/efectos adversos
6.
Int J Mol Sci ; 25(11)2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38892384

RESUMEN

The purpose of this study was to explore the effect of Semaglutide on intrauterine adhesions and discover new drugs for such adhesions. In this study, the cell model was simulated by TGF-ß1-induced human endometrial epithelial cells, and the animal model was established through mechanical curettage and inflammatory stimulation. After co-culturing with TGF-ß1 with or without different concentrations of Semaglutide for 48 h, cells were collected for RT-qPCR and Western blotting analyses. Three doses were subcutaneously injected into experimental mice once a day for two weeks, while the control group received sterile ddH2O. The serum and uterine tissues of the mice were collected. HE and Masson staining were used for the uterine histomorphological and pathological analyses. RT-qPCR and Western blotting were used for mRNA and protein expression analyses. Serum indicators were detected using ELISA kits. The results showed that Semaglutide significantly reduced the mRNA levels of fibrosis indicators ACTA2, COL1A1, and FN and inflammatory indicators TNF-α, IL-6, and NF-κB in the two models. Semaglutide improved endometrium morphology, increased the number of endometrial glands, and reduced collagen deposition in IUA mice. The results also showed that Semaglutide could inhibit vimentin, E-Cadherin, and N-Cadherin in the two models. In summary, Semaglutide can ameliorate fibrosis and inflammation of intrauterine adhesions as well as inhibit epithelial-mesenchymal transition in IUA models.


Asunto(s)
Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal , Fibrosis , Péptidos Similares al Glucagón , Animales , Femenino , Transición Epitelial-Mesenquimal/efectos de los fármacos , Adherencias Tisulares/tratamiento farmacológico , Adherencias Tisulares/metabolismo , Adherencias Tisulares/patología , Adherencias Tisulares/prevención & control , Ratones , Péptidos Similares al Glucagón/farmacología , Humanos , Endometrio/efectos de los fármacos , Endometrio/patología , Endometrio/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Útero/efectos de los fármacos , Útero/patología , Útero/metabolismo
7.
ACS Nano ; 18(27): 17651-17671, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38932673

RESUMEN

Postoperative adhesion is a common complication after abdominal surgery, but current clinical products have unsatisfactory therapeutic effects. Here, we present a hydrogel patch formed in a single step through dialysis. The exchange of DMSO into water facilitates hydrophobic aggregate in situ formation and the formation of hydrogen bonds within the hydrogel. Thanks to the optimized component ratio and precise structural design. The hydrogel patch has soft-tissue-like mechanical characteristics, including high strength, high toughness, low modulus similar to the abdominal wall, good fatigue resistance, and fast self-recovery properties. The nonswellable hydrogel patch retains over 80% of its original mechanical properties after 7 days of immersion in physiological saline, with a maximum swelling ratio of 5.6%. Moreover, the hydrophobic biomultifunctionality of benzyl isothiocyanate can self-assemble onto the hydrogel patch during the sol-gel transition process, enabling it to remodel the inflammatory microenvironment through synergistic antibacterial, antioxidant, and anti-inflammatory effects. The hydrogel patch prevents postsurgical adhesion in a rat sidewall defect-cecum abrasion model and outperforms the leading commercial Interceed. It holds promising potential for clinical translation, considering that FDA-approved raw materials (PVA and gelatin) form the backbone of this effective hydrogel patch.


Asunto(s)
Hidrogeles , Hidrogeles/química , Hidrogeles/farmacología , Animales , Ratas , Adherencias Tisulares/prevención & control , Ratas Sprague-Dawley , Antibacterianos/farmacología , Antibacterianos/química , Masculino , Antiinflamatorios/química , Antiinflamatorios/farmacología
8.
Arch Gynecol Obstet ; 310(2): 655-672, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38878233

RESUMEN

IMPORTANCE: The formation of adhesions after gynecological surgery not only has detrimental impacts on those affected, including pain, obstruction, and infertility, but also imposes a high economic burden on healthcare systems worldwide. OBJECTIVE: The aim of this review was to evaluate the adhesion prevention potential of all currently available adhesion barriers for gynecological surgery. EVIDENCE ACQUISITION: We systematically searched MEDLINE and CENTRAL databases for randomized controlled trials (RCTs) on the use of adhesion barriers as compared with peritoneal irrigation or no treatment in gynecological surgery. Only RCTs with second-look surgery to evaluate adhesions in the pelvic/abdominal (but not intrauterine) cavity were included. RESULTS: We included 45 RCTs with a total of 4,120 patients examining a total of 10 unique types of barriers in second-look gynecological surgery. While RCTs on oxidized regenerated cellulose (significant improvement in 6 of 14 trials), polyethylene glycol with/without other agents (4/10), hyaluronic acid and hyaluronate + carboxymethylcellulose (7/10), icodextrin (1/3), dextran (0/3), fibrin-containing agents (1/2), expanded polytetrafluoroethylene (1/1), N,O-carboxymethylchitosan (0/1), and modified starch (1/1) overall showed inconsistent findings, results for expanded polytetrafluoroethylene, hyaluronic acid, and modified starch yielded the greatest improvements regarding adhesion reduction at 75%, 0-67%, and 85%, respectively. CONCLUSIONS AND RELEVANCE: Best results for adhesion prevention were reported after applying Gore-Tex Surgical Membrane, hyaluronic acid, and 4DryField®. As Gore-Tex Surgical Membrane is nonabsorbable, it is associated with a greater risk of new adhesion formation due to second-look surgery to remove the product. 4DryField® yielded the greatest improvement in adhesion score compared to all other barrier agents (85%). For better comparability, future studies should use standardized scores and put more emphasis on patient-reported outcome measures, such as pain and infertility.


Asunto(s)
Procedimientos Quirúrgicos Ginecológicos , Complicaciones Posoperatorias , Humanos , Adherencias Tisulares/prevención & control , Adherencias Tisulares/etiología , Femenino , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Segunda Cirugía , Enfermedades Peritoneales/prevención & control , Enfermedades Peritoneales/etiología
9.
Int J Biol Macromol ; 273(Pt 2): 133191, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38880455

RESUMEN

Abdominal hernia mesh is a common product which is used for prevention of abdominal adhesion and repairing abdominal wall defect. Currently, designing and preparing a novel bio-mesh material with prevention of adhesion, promoting repair and good biocompatibility simultaneously remain a great bottleneck. In this study, a novel siloxane-modified bacterial cellulose (BC) was designed and fabricated by chemical vapor deposition silylation, then the effects of different alkyl chains length of siloxane on surface properties and cell behaviors were explored. The effect of preventing of abdominal adhesion and repairing abdominal wall defect in rats with the siloxane-modified BC was evaluated. As the grafted alkyl chains become longer, the surface of the siloxane-modified BC can be transformed from super hydrophilic to hydrophobic. In vivo results showed that BC-C16 had good long-term anti-adhesion effect, good tissue adaptability and histocompatibility, which is expected to be used as a new anti-adhesion hernia repair material in clinic.


Asunto(s)
Celulosa , Animales , Celulosa/química , Celulosa/farmacología , Ratas , Adherencias Tisulares/prevención & control , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Masculino , Pared Abdominal/cirugía , Pared Abdominal/patología , Interacciones Hidrofóbicas e Hidrofílicas , Ratones , Propiedades de Superficie , Hernia Abdominal/prevención & control , Mallas Quirúrgicas , Ratas Sprague-Dawley
10.
Int J Biol Macromol ; 273(Pt 2): 133193, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38885859

RESUMEN

A major problem after tendon injury is adhesion formation to the surrounding tissue leading to a limited range of motion. A viable strategy to reduce adhesion extent is the use of physical barriers that limit the contact between the tendon and the adjacent tissue. The purpose of this study was to fabricate an electrospun bilayered tube of hyaluronic acid/polyethylene oxide (HA/PEO) and biodegradable DegraPol® (DP) to improve the anti-adhesive effect of the implant in a rabbit Achilles tendon full laceration model compared to a pure DP tube. Additionally, the attachment of rabbit tenocytes on pure DP and HA/PEO containing scaffolds was tested and Scanning Electron Microscopy, Fourier-transform Infrared Spectroscopy, Differential Scanning Calorimetry, Water Contact Angle measurements, and testing of mechanical properties were used to characterize the scaffolds. In vivo assessment after three weeks showed that the implant containing a second HA/PEO layer significantly reduced adhesion extent reaching levels comparable to native tendons, compared with a pure DP implant that reduced adhesion formation only by 20 %. Tenocytes were able to attach to and migrate into every scaffold, but cell number was reduced over two weeks. Implants containing HA/PEO showed better mechanical properties than pure DP tubes and with the ability to entirely reduce adhesion extent makes this implant a promising candidate for clinical application in tendon repair.


Asunto(s)
Ácido Hialurónico , Polietilenglicoles , Andamios del Tejido , Animales , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Conejos , Polietilenglicoles/química , Andamios del Tejido/química , Tenocitos/efectos de los fármacos , Tenocitos/metabolismo , Tendón Calcáneo/efectos de los fármacos , Traumatismos de los Tendones/terapia , Adhesión Celular/efectos de los fármacos , Adherencias Tisulares/prevención & control , Tendones/efectos de los fármacos , Ingeniería de Tejidos/métodos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Poliésteres/química , Poliuretanos
11.
Ulus Travma Acil Cerrahi Derg ; 30(6): 406-414, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38863295

RESUMEN

BACKGROUND: This study evaluated the use of metformin or pioglitazone in preventing or reducing the development of post-operative intra-abdominal adhesion (PIAA) by employing histopathological, immunohistochemical, and biochemical analyses in an experimental adhesion model. METHODS: Fifty Wistar-Albino rats were divided into five groups: Group I (Control), Group II (Sham Treatment), Group III (Hy-aluronic Acid), Group IV (Metformin), and Group V (Pioglitazone). Adhesions were induced in the experimental groups, except for the sham group, using the scraping method. After 10 days, rats were euthanized for evaluation. Macroscopic adhesion degrees were assessed using Nair's scoring system. Immunohistochemical and enzyme-linked immunosorbent assay (ELISA) methods were utilized to assess serum, peritoneal lavage, and intestinal tissue samples. Fructosamine, interleukin-6 (IL-6), transforming growth factor-beta (TGF-ß), and fibronectin levels were measured in serum and peritoneal lavage samples. RESULTS: The groups exhibited similar Nair scores and Type I or Type III Collagen staining scores (all, p>0.05). Pioglitazone significantly reduced serum IL-6 and TGF-ß levels compared to controls (p=0.002 and p=0.008, respectively). Both metformin and pioglitazone groups showed elevated IL-6 in peritoneal lavage relative to controls, while fibronectin levels in the lavage were lower in pioglitazone-treated rats compared to the sham group (all, p<0.005). CONCLUSION: Pioglitazone, but not metformin, demonstrated a positive biochemical impact on preventing PIAA formation in an experimental rat model, although histological impacts were not observed. Further experimental studies employing different dose/duration regimens of pioglitazone are needed to enhance our understanding of its effect on PIAA formation.


Asunto(s)
Modelos Animales de Enfermedad , Metformina , Pioglitazona , Ratas Wistar , Animales , Pioglitazona/farmacología , Metformina/farmacología , Adherencias Tisulares/prevención & control , Adherencias Tisulares/tratamiento farmacológico , Ratas , Hipoglucemiantes/farmacología , Masculino , Tiazolidinedionas/farmacología , Complicaciones Posoperatorias/prevención & control
12.
Biomed Mater ; 19(5)2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38917812

RESUMEN

Stopping postoperative soft tissue adhesions is one of the most challenging clinical problems that needs to be addressed urgently to avoid secondary injury and pain to patients. Currently, membrane materials with anti-protein adsorption and antibacterial activity are recognized as an effective and promising anti-adhesion barrier to prevent postoperative adhesion and the recurrent adhesion after adhesiolysis. Herein, poly(amino acid) (PAA), which is structurally similar to collagen, is selected as the membrane base material to successfully synthesize PAA-5 membranes with excellent mechanical and degradation properties by in-situ melt polymerization and hot-melt film-forming technology. Subsequently, the co-deposition of polydopamine/polysulfobetaine methacrylate (PDA/PSBMA) coatings induced by CuSO4/H2O2on PAA-5 membranes results in the formation of PDC-5S and PDC-10S, which exhibit excellent hemocompatibility, protein antifouling properties, and cytocompatibility. Additionally, PDC-5S and PDC-10S demonstrated significant antibacterial activity againstEscherichia coliandStaphylococcus aureus, with an inhibition rate of more than 90%. As a result, this study sheds light on newly discovered PAA membranes with anti-protein adsorption and antibacterial activity can sever as one of the promising candidates for the prevention of postoperative peritoneum adhesions.


Asunto(s)
Antibacterianos , Escherichia coli , Peróxido de Hidrógeno , Indoles , Membranas Artificiales , Metacrilatos , Polímeros , Staphylococcus aureus , Antibacterianos/química , Antibacterianos/farmacología , Polímeros/química , Adsorción , Indoles/química , Indoles/farmacología , Metacrilatos/química , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Humanos , Peróxido de Hidrógeno/química , Animales , Ensayo de Materiales , Aminoácidos/química , Incrustaciones Biológicas/prevención & control , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Betaína/química , Betaína/análogos & derivados , Adherencias Tisulares/prevención & control
13.
J Control Release ; 372: 251-264, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38908755

RESUMEN

Drug-loaded porous membranes have been deemed to be effective physicochemical barriers to separate postoperative adhesion-prone tissues in tendon healing. However, cell viability and subsequent tissue regeneration might be severely interfered with the unrestricted release and the locally excessive concentration of anti-inflammatory drugs. Herein, we report a double-layered membrane with sustained and uni-directional drug delivery features to prevent peritendinous adhesion without hampering the healing outcome. A vortex-assisted electrospinning system in combination with ibuprofen (IBU)-in-water emulsion was utilized to fabricate IBU-loaded poly-ʟ-lactic-acid (PLLA) fiber bundle membrane (PFB-IBU) as the anti-adhesion layer. The resultant highly porous structure, oleophilic and hydrophobic nature of PLLA fibers enabled in situ loading of IBU with a concentration gradient across the membrane thickness. Aligned collagen nanofibers were further deposited at the low IBU concentration side of the membrane for regulating cell growth and achieving uni-directional release of IBU. Drug release kinetics showed that the release amount of IBU from the high concentration side reached 79.32% at 14 d, while it was only 0.35% at the collagen side. Therefore, fibroblast proliferation at the high concentration side was successfully inhibited without affecting the oriented growth of tendon-derived stem cells at the other side. In vivo evaluation of the rat Achilles adhesion model confirmed the successful peritendinous anti-adhesion of our double-layered membrane, in that the macrophage recruitment, the inflammatory factor secretion and the deposition of pathological adhesion markers such as α-SMA and COL-III were all inhibited, which greatly improved the peritendinous fibrosis and restored the motor function of tendon.


Asunto(s)
Antiinflamatorios no Esteroideos , Liberación de Fármacos , Ibuprofeno , Poliésteres , Ratas Sprague-Dawley , Animales , Ibuprofeno/administración & dosificación , Ibuprofeno/farmacología , Ibuprofeno/química , Poliésteres/química , Adherencias Tisulares/prevención & control , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Masculino , Membranas Artificiales , Fibroblastos/efectos de los fármacos , Nanofibras/química , Ratas , Tendones/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Preparaciones de Acción Retardada , Tendón Calcáneo/efectos de los fármacos , Porosidad
14.
Acta Biomater ; 184: 98-113, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38914412

RESUMEN

Postoperative abdominal adhesion (PAA) widely occurs after abdominal surgery, which often produces severe complications. However, there were still no satisfactory anti-adhesive products including barriers and anti-adhesive agents. Herein, we developed a ROS-responsive and scavenging hydrogel barrier, termed AHBC/PSC, wherein the monomer AHBC was synthesized by phenylboronic acid (PBA)-modified hyaluronic acid (HA-PBA) further grafted with adipic dihydrazide (ADH) and PBA-based chlorogenic acid (CGA) via ROS-sensitive borate ester bond, and the other monomer PSC was constructed by polyvinyl alcohol (PVA) grafted with sulfated betaine (SB) and p-hydroxybenzaldehyde (CHO). Further, the double crosslinked AHBC/PSC hydrogel was successfully fabricated between AHBC and PSC via forming dynamic covalent acylhydrazone bonds and borate ester bonds. Results showed that AHBC/PSC hydrogel had in situ gelation behavior, satisfactory mechanical properties (storage modulus of about 1 kPa and loss factor Tan δ of about 0.5), suitable wet tissue adhesion strength of about 2.3 kPa on rat abdominal wall, and good biocompatibility, achieving an ideal physical barrier. Particularly, CGA could be responsively released from the hydrogel by breakage of borate ester bonds between CGA and PBA based on high reactive oxygen species (ROS) levels of damaged tissue and exhibited great ROS scavenging capability to regulate inflammation and promote the polarization of macrophages from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. Moreover, the grafted SB as a zwitterionic group could reduce protein adsorption and fibroblast adhesion. Finally, the in vivo experiments revealed that AHBC/PSC hydrogel with good safety and in vivo retention behavior of about 2 weeks, effectively prevented PAA by regulating the inflammatory microenvironment and alleviating the fibrosis process. In brief, the versatile AHBC/PSC hydrogel would provide a more convenient and efficient approach for PAA prevention. STATEMENT OF SIGNIFICANCE: Postoperative abdominal adhesion (PAA) widely occurs after surgery and is often accompanied by severe complications. Excessive inflammation and oxidative stress are very crucial for PAA formation. This study provides a ROS-responsive and scavenging hydrogel with suitable mechanical properties, good biocompatibility and biodegradability, and resistance to protein and fibroblast. The antioxidant and anti-inflammatory active ingredient could be responsively released from the hydrogel via triggering by the high ROS levels in the postoperative microenvironment thereby regulating the inflammatory balance. Finally, the hydrogel would effectively regulate the development process of PAA thereby achieving non-adhesion wound healing.


Asunto(s)
Hidrogeles , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno , Animales , Adherencias Tisulares/prevención & control , Adherencias Tisulares/patología , Hidrogeles/química , Hidrogeles/farmacología , Especies Reactivas de Oxígeno/metabolismo , Ratas , Ácidos Borónicos/química , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Complicaciones Posoperatorias/prevención & control , Ratones , Masculino , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/química , Células RAW 264.7 , Adipatos/química
15.
Int J Pharm ; 661: 124386, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38942182

RESUMEN

Postoperative tissue adhesion is a well-recognized and common complication. Despite ongoing developments in anti-adhesion agents, complete prevention remains a challenge in clinical practice. Colorectal cancer necessitates both adhesion prevention and postoperative chemotherapy. Accordingly, drug-loading into an anti-adhesion agent could be employed as a treatment strategy to maximize the drug effects through local application and minimize side effects. Herein, we introduce an anti-adhesion agent that functions as a drug delivery system by loading drugs within an emulsion that forms a gel matrix in the presence of polysaccharides, xanthan gum, and pectin. Based on the rheological analysis, the xanthan gum-containing emulsion gel formed a gel matrix with suitable strength and mucosal adhesiveness. In vitro dissolution tests demonstrated sustained drug release over 12 h, while in vivo pharmacokinetic studies revealed a significant increase in the Tmax (up to 4.03 times) and area under the curve (up to 2.62 times). However, most of the drug was released within one day, distributing systemically and raising toxicity concerns, thus limiting its efficacy as a controlled drug delivery system. According to in vivo anti-adhesion efficacy evaluations, the xanthan gum/pectin emulsion gels, particularly F2 and F3, exhibited remarkable anti-adhesion capacity (P < 0.01). The emulsion gel formulation exhibited no cytotoxicity against fibroblasts or epithelial cell lines. Thus, the xanthan gum/pectin emulsion gel exhibits excellent anti-adhesion properties and could be developed as a drug delivery system.


Asunto(s)
Sistemas de Liberación de Medicamentos , Emulsiones , Fluorouracilo , Geles , Pectinas , Polisacáridos Bacterianos , Animales , Fluorouracilo/administración & dosificación , Fluorouracilo/química , Polisacáridos Bacterianos/química , Adherencias Tisulares/prevención & control , Masculino , Pectinas/química , Pectinas/administración & dosificación , Liberación de Fármacos , Complicaciones Posoperatorias/prevención & control , Ratones , Humanos , Ratas Sprague-Dawley , Ratas , Preparaciones de Acción Retardada , Polisacáridos/química , Polisacáridos/administración & dosificación
16.
J Mater Chem B ; 12(28): 6968-6980, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38915270

RESUMEN

Postoperative adhesions, a prevalent complication following abdominal surgery, affect 90% of patients undergoing abdominal surgical procedures. Currently, the primary approach to prevent postoperative adhesions involves physical isolation of the surgical site and surrounding tissues using a hydrogel; however, this method represents a rudimentary strategy. Herein, considering the impact of oxidative stress and free radicals on postoperative adhesion during wound healing, an injectable antioxidant hydrogel, named PU-OHA-D, was successfully synthesized, which is formed by the crosslinking of dopamine-modified oxidized hyaluronic acid (OHA-D) and dihydrazide-terminated polyurethane (PU-ADH) through hydrazone bonding. PU-OHA-D hydrogel possesses versatile characteristics such as rapid gel formation, injectability, self-repair capability and biodegradability. Additionally, they exhibit an excellent ability to clear free radicals and superior tissue adhesion. PU-OHA-D can be injected in situ to form a hydrogel to prevent abdominal wall-cecum adhesion. Importantly, it can effectively eliminate free radicals and inhibit oxidative stress at the wound site. Thereby, it leads to collagen physiological degradation and prevents the occurrence of postoperative adhesions. The bioinspired hydrogel demonstrates its great potential in preventing postoperative adhesion and promoting wound healing.


Asunto(s)
Antioxidantes , Hidrogeles , Adherencias Tisulares/prevención & control , Antioxidantes/química , Antioxidantes/farmacología , Hidrogeles/química , Animales , Ratones , Complicaciones Posoperatorias/prevención & control , Ácido Hialurónico/química , Estrés Oxidativo/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Humanos , Poliuretanos/química , Ratas
17.
Langenbecks Arch Surg ; 409(1): 191, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38900305

RESUMEN

PURPOSE: The recovery of gastrointestinal function and postoperative ileus are the leading goals for clinicians following surgery for adhesive small bowel obstruction. While enhanced recovery programs may improve recovery, their feasibility in emergency surgery has not yet been proven. We sought to assess the incidence of postoperative ileus in patients following surgery for ASBO and the feasibility of enhanced recovery programs, including their benefits in the recovery of gastrointestinal functions and reducing the length of hospitalization. METHODS: This prospective study includes the first 50 patients surgically treated for ASBO between June 2021 and November 2022. Their surgery was performed either as an emergency procedure or after a short course of medical treatment. The main aim was to compare the observed rate of postoperative ileus with a theoretical rate, set at 40%. The study protocol was registered in clinicaltrials.gov under the number NCT04929275. RESULTS: Among the 50 patients included in this study, it reported postoperative ileus in 16%, which is significantly lower than the hypothetical rate of 40% (p = 0.0004). The median compliance with enhanced recovery programs was 75% (95%CI: 70.1-79.9). The lowest item observed was the TAP block (26%) and the highest observed items were preoperative counselling and compliance with analgesic protocols (100%). The overall morbidity was 26.5%, but severe morbidity (Dindo-Clavien > 3) was observed in only 3 patients (6%). Severe morbidity was not related with the ERP. CONCLUSION: Enhanced recovery programs are feasible and safe in adhesive small bowel obstruction surgery patients and could improve the recovery of gastrointestinal functions. CLINICAL TRIAL REGISTRY: NCT04929275. WHAT DOES THE STUDY CONTRIBUTE TO THE FIELD?: Perioperative management of adhesive small bowel obstruction (ASBO) surgery needs to be improved in order to reduce morbidity. Enhanced recovery programs (ERP) are both feasible and safe following urgent surgery for ASBO. ERPs may improve the recovery of gastrointestinal (GI) functions.


Asunto(s)
Estudios de Factibilidad , Ileus , Obstrucción Intestinal , Intestino Delgado , Complicaciones Posoperatorias , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuperación Mejorada Después de la Cirugía , Ileus/prevención & control , Ileus/etiología , Ileus/epidemiología , Obstrucción Intestinal/cirugía , Intestino Delgado/cirugía , Tiempo de Internación , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Recuperación de la Función , Adherencias Tisulares/prevención & control
18.
Int J Colorectal Dis ; 39(1): 79, 2024 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-38797803

RESUMEN

BACKGROUND: Empty Pelvis Syndrome, subsequent to the removal of pelvic organs, results in the descent of the small bowel into an inflamed pelvic cavity, leading to the formation of adhesions and subsequent small bowel obstruction. However, no effective measures have been previously described. OBJECTIVE: Describe a simple and autologous solution to prevent "Empty Pelvis Syndrome," small bowel obstruction, and adhesions by utilizing the cecum to occlude the pelvis. DESIGN: Mobilization of the right colon to lower the cecum into the pelvic cavity to occlude the superior pelvic ring to some degree and changing the direction of the terminal ileum. SETTINGS: Hospital Universitario Fundación Jiménez Díaz, Department of General Surgery, Colorectal Service. PATIENTS: Eight anonymized patients were included in this study, each with varying colorectal pathologies. Patients were above 18 years old. MAIN OUTCOME MEASURES: Percent of blockage of the superior pelvic ring produced by the descended cecum recorded in percentage; the amount of small intestine descended past the superior pelvic ring recorded in cm. RESULTS: The mobilization of the cecum achieved partial occlusion of the superior pelvic ring. The descent of the small bowel beyond this landmark ranged from 0 to 4.9 cm. LIMITATIONS: Given the small number of patients included in this study, these results cannot be generalized to the whole of the population. A bladder emptying protocol prior to CT scans was not implemented, resulting in variations in measurements among patients. CONCLUSION: The cecum-to-pelvis technique is a simple method that can serve as an autologous solution to EPS (enteropelvic fistula) and help reduce postoperative complications such as SBO (small bowel obstruction) and adhesions. It is not essential to completely occlude the superior pelvic ring to achieve successful outcomes.


Asunto(s)
Ciego , Pelvis , Complicaciones Posoperatorias , Humanos , Ciego/cirugía , Pelvis/cirugía , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Femenino , Masculino , Persona de Mediana Edad , Adherencias Tisulares/prevención & control , Adherencias Tisulares/etiología , Adulto , Obstrucción Intestinal/prevención & control , Obstrucción Intestinal/etiología , Obstrucción Intestinal/cirugía , Anciano
19.
J Colloid Interface Sci ; 670: 486-498, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38772264

RESUMEN

Establishing a physical barrier between the peritoneum and the cecum is an effective method to reduce the risk of postoperative abdominal adhesions. Meloxicam (MX), a nonsteroidal anti-inflammatory drug has also been applied to prevent postoperative adhesions. However, its poor water solubility has led to low bioavailability. Herein, we developed an injectable hydrogel as a barrier and drug carrier for simultaneous postoperative adhesion prevention and treatment. A third-generation polyamide-amine dendrimer (G3) was exploited to dynamically combine with MX to increase the solubility and the bioavailability. The formed G3@MX was further used to crosslink with poly-γ-glutamic acid (γ-PGA) to prepare a hydrogel (GP@MX hydrogel) through the amide bonding. In vitro and in vivo experiments evidenced that the hydrogel had good biosafety and biodegradability. More importantly, the prepared hydrogel could control the release of MX, and the released MX is able to inhibit inflammatory responses and balance the fibrinolytic system in the injury tissues in vivo. The tunable rheological and mechanical properties (compressive moduli: from âˆ¼ 57.31 kPa to âˆ¼ 98.68 kPa;) and high anti-oxidant capacity (total free radical scavenging rate of âˆ¼ 94.56 %), in conjunction with their syringeability and biocompatibility, indicate possible opportunities for the development of advanced hydrogels for postoperative tissue adhesions management.


Asunto(s)
Dendrímeros , Hidrogeles , Meloxicam , Nylons , Ácido Poliglutámico , Hidrogeles/química , Hidrogeles/farmacología , Animales , Ácido Poliglutámico/química , Ácido Poliglutámico/farmacología , Ácido Poliglutámico/análogos & derivados , Nylons/química , Adherencias Tisulares/prevención & control , Dendrímeros/química , Dendrímeros/farmacología , Meloxicam/química , Meloxicam/farmacología , Meloxicam/administración & dosificación , Ratones , Inflamación/prevención & control , Inflamación/tratamiento farmacológico , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/administración & dosificación , Ratas , Ratas Sprague-Dawley , Fibrinólisis/efectos de los fármacos , Complicaciones Posoperatorias/prevención & control , Tamaño de la Partícula , Inyecciones , Portadores de Fármacos/química
20.
J Ethnopharmacol ; 331: 118290, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38703872

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: HuoXueTongFu Formula (HXTF) is a traditional Chinese herbal formula that has been used as a supplement and alternative therapy for intraperitoneal adhesion (IA). However, its specific mechanism of action has not been fully understood. AIM OF THE STUDY: In surgery, IA presents an inevitable challenge, significantly impacting patients' physical and mental well-being and increasing the financial burden. Our previous research has confirmed the preventive effects of HXTF on IA formation. However, the precise mechanism of its action still needs to be understood. METHODS: In this study, the IA model was successfully established by using the Ischemic buttons and treated with HXTF for one week with or without Mer Tyrosine Kinase (MerTK) inhibitor. We evaluated the pharmacodynamic effect of HXTF on IA mice. The MerTK/phosphoinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway-associated proteins were detected by Western blotting. Neutrophil extracellular traps (NETs) were detected by immunofluorescence. Macrophage phenotype was assessed by immunohistochemistry and flow cytometry. Inflammatory cytokines were detected by Real Time Quantitative PCR and Western blotting. RESULTS: HXTF reduced inflammatory response and alleviated IA. HXTF significantly enhanced MerTK expression, increased the number of M2c macrophages, and decreased the formation of NETs. In addition, the MerTK/PI3K/AKT pathway was significantly activated by HXTF. However, after using MerTK inhibitors, the role of HXTF in inducing M2c macrophage through activation of the PI3K/AKT pathway was suppressed and there was no inhibitory effect on NETs formation and inflammatory responses, resulting in diminished inhibition of adhesion. CONCLUSION: HXTF may improve IA by activating the MerTK/PI3K/AKT pathway to induce M2c polarization, which removes excess NETs and attenuates the inflammatory response.


Asunto(s)
Medicamentos Herbarios Chinos , Macrófagos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Tirosina Quinasa c-Mer , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Medicamentos Herbarios Chinos/farmacología , Ratones , Tirosina Quinasa c-Mer/metabolismo , Transducción de Señal/efectos de los fármacos , Masculino , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Adherencias Tisulares/prevención & control , Adherencias Tisulares/metabolismo , Trampas Extracelulares/efectos de los fármacos , Trampas Extracelulares/metabolismo , Modelos Animales de Enfermedad
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