Postoperative Abdominal Adhesions Research Articles

Injectable polyamide-amine dendrimer-crosslinked meloxicam-containing poly-γ-glutamic acid hydrogel for prevention of postoperative tissue adhesion through inhibiting inflammatory responses and balancing the fibrinolytic system

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 ∼ 57.31 kPa to ∼ 98.68 kPa;) and high anti-oxidant capacity (total free radical scavenging rate of ∼ 94.56 %), in conjunction with their syringeability and biocompatibility, indicate possible opportunities for the development of advanced hydrogels for postoperative tissue adhesions management.

Hybrid Bioactive Hydrogel Promotes Liver Regeneration through the Activation of Kupffer Cells and ECM Remodeling After Partial Hepatectomy.

Partial hepatectomy is an essential surgical technique used to treat advanced liver diseases such as liver tumors, as well as for performing liver transplants from living donors. However, postoperative complications such as bleeding, abdominal adhesions, wound infections, and inadequate liver regeneration pose significant challenges and increase morbidity and mortality rates. A self-repairing mixed hydrogel (O5H2/Cu2+/SCCK), containing stem cell derived cytokine (SCCK) derived from human umbilical cord mesenchymal stem cells (HUMSCs) treated with the traditional Chinese remedy Tanshinone IIA (TSA), is developed. This SCCK, in conjunction with O5H2, demonstrates remarkable effects on Kupffer cell activation and extracellular matrix (ECM) remodeling. This leads to the secretion of critical growth factors promoting enhanced proliferation of hepatocytes and endothelial cells, thereby facilitating liver regeneration and repair after partial hepatectomy. Furthermore, the hydrogel, featuring macrophage-regulating properties, effectively mitigates inflammation and oxidative stress damage in the incision area, creating an optimal environment for postoperative liver regeneration. The injectability and strong adhesion of the hydrogel enables rapid hemostasis at the incision site, while its physical barrier function prevents postoperative abdominal adhesions. Furthermore, the hydrogel's incorporation of Cu2+ provides comprehensive antibacterial effects, protecting against a wide range of bacteria types and reducing the chances of infections after surgery.

ROS-responsive sprayable hydrogel as ROS scavenger and GATA6+ macrophages trap for the prevention of postoperative abdominal adhesions

Postoperative abdominal adhesions are a common clinical problem after surgery and can cause many serious complications. Current most commonly used antiadhesion products are less effective due to their short residence time and focus primary on barrier function. Herein, we developed a sprayable hydrogel barrier (sHA-ADH/OHA-E) with self-regulated drug release based on ROS levels at the trauma site, to serve as a smart inflammatory microenvironment modulator and GATA6+ macrophages trap for non-adherent recovery from abdominal surgery. Sulfonated hyaluronic acid (HA) conjugates modified with adipic dihydrazide (sHA-ADH), and oxidized HA conjugates grafted with epigallocatechin-3-gallate (EGCG) via ROS-cleavable boronate bonds (OHA-E) were synthesized. sHA-ADH/OHA-E hydrogel was facilely fabricated within 5 s after simply mixing sHA-ADH and OHA-E through forming dynamic covalent acylhydrazones. With good biocompatibility, appropriate mechanical strength, tunable shear-thinning, self-healing, asymmetric adhesion, and reasonable in vivo retention time, sHA-ADH/OHA-E hydrogel meets the requirements of a perfect physical barrier. Intriguingly, sulfonic acid groups endowed the hydrogel with satisfactory anti-fibroblast and macrophage attachment capability, and were demonstrated for the first time to act as polyanion traps to prevent GATA6+ macrophages aggregation. Importantly, EGCG could be intelligently released by ROS triggering to alleviate oxidative stress and promote proinflammatory M1 macrophage polarize to antiinflammatory M2 phenotype. Further, the fibrinolytic system balance was restored to reduce fibrosis. Thanks to the above advantages, the sHA-ADH/OHA-E hydrogel exhibited excellent anti-adhesion effects in a rat sidewall defect–cecum abrasion model and is expected to be a promising and clinically translatable antiadhesion barrier.

Nanofibers and hydrogel composite patch with sandwich structure for prevention post-operative abdominal adhesion

Abdominal adhesions have a high incidence after surgery due to fibrosis and inflammation resulting in damaged tissues caused by trauma, bleeding, infection, foreign body stimulation. The adhesions introduced persistent chronic pain because of attachment and traction seriously affects physical health patients. Recent years, various kinds of membrances, hydrogel, nanofibers were developed to inhibit post-operative abdominal adhesion by physical isolation or drug treatment. However, the integration of physical isolation and pharmaceutical therapy in one platform still has some challenges. For example, the anti-swelling property of hydrogel is not good, membrane is easy prone to displacement. Herein, we developed a nanofiber-hydrogel composite patch (FHCP) with sandwich structure providing effectively anti swelling property and wet adhesion performance. Meanwhile, the nanofiber-hydrogel composite patch achieved combining excellent physical isolation and drug treatment, the sandwich structure of patch provided hierarchical drug release drugs release, and then made the patch realized excellent anti-inflammatory, tissue regeneration, and preventing post-operative abdominal adhesion. Our results showed that the prepared patch has better effects on anti-inflammation, effectively suppressing post-operative adhesion in the abdominal cavity. Therefore, we believe that our nanofiber-hydrogel composite patch has broad clinical application prospects.

Bioinspired Microstructured Janus Bioadhesive for the Prevention of Abdominal and Intrauterine Adhesions

AbstractAbdominal and intrauterine adhesions are common postoperative problems that can cause serious complications. Current adhesives are usually double sided and suffer from poor wet adhesion, nondegradability, and monofunctionality, which limits their application in preventing postoperative adhesions. Herein, a bioinspired microstructured Janus bioadhesive, named OD/GM@PG, with a wet adhesive inner layer and an antiadhesive outer layer is prepared by combining electrostatic spun and adhesive materials. By using both capillary suction and a catechol‐based strategy, the wet adhesive strength and interfacial toughness of the Janus bioadhesive reach 98 kPa and 325 J m−2, respectively, which are much higher than those of commercial fibrin glues and cyanoacrylate glues. The electrostatic spun outer layer acts as a physical barrier with antiadhesive and friction‐reducing effects. Additionally, the Janus bioadhesive demonstrates biodegradable, hemostatic, antioxidative, anti‐inflammatory, and prohealing properties. In vivo results show that the asymmetric adhesion effect of the Janus bioadhesive effectively preventing postoperative abdominal and intrauterine adhesions. Notably, tandem mass tags‐labeled quantitative proteomics analysis demonstrate that the expression of inflammatory response‐associated proteins (S100A8, S100A9) is associated with adhesion; the Janus bioadhesive significantly downregulates this expression. Therefore, the OD/GM@PG Janus bioadhesive is a promising candidate for preventing postoperative adhesions.

Tissue-mimicking composite barrier membranes to prevent abdominal adhesion formation after surgery

Postoperative abdominal adhesions often occur after abdominal surgery; barrier membranes which mimic peritoneal tissue can be constructed to prevent abdominal adhesions. To this end, silk fibroin (SF) sheets were coated with polyvinyl alcohol (PVA) and agarose (AGA) at PVA:AGA ratios of 100:0, 70:30, 50:50, 30:70, and 0:100 to create a composite anti-adhesive barrier and allow us to identify a suitable coating ratio. The membranes were characterized in terms of their molecular organization, structure, and morphology using Fourier transform Infrared spectrometer (FT-IR), differential scanning calorimeter (DSC), and scanning electron microscope (SEM), respectively. The physical and mechanical properties of the membranes and their biological performance (i.e., fibroblast proliferation and invasion) were tested in vitro. Each membrane showed both smooth and rough surface characteristics. Membranes coated with PVA:AGA at ratios of 100:0, 70:30, 50:50, and 30:70 exhibited more –OH and amide III moieties than those coated with 0:100 PVA:AGA, which consequently affected structural organization, degradation, and fibroblast viability. The 0:100 PVA:AGA-coated degraded the fastest. Barrier membranes coated with 100:0 and 70:30 PVA: AGA demonstrated reduced fibroblast proliferation and attachment. The membrane coated with 70:30 PVA:AGA exhibited a stable appearance, and did not curl under wet conditions. Therefore, SF sheets coated with 70:30 PVA:AGA show promise as anti-adhesive barrier membranes for further development.

Effects of linalool on postoperative peritoneal adhesions in rats.

The current study examines the effects of linalool in preventing postoperative abdominal adhesions. Twenty male Wistar rats were randomly divided into four groups. (1) Sham: in this group, the abdomen was approached, and without any manipulations, it was sutured. (2) Control: rats in this group underwent a surgical procedure to induce adhesions. This involved making three incisions on the right abdominal side and removing a 1×1-cm piece of the peritoneum on the left abdominal side. (3) Treatment groups: these groups underwent the same surgical procedure as the control group to induce adhesions. Animals in these groups received linalool orally with doses of 50 and 100 mg/kg, respectively, for a period of 14 days. Moreover, rats in the sham and control groups received normal saline via gavage for 14 days. The evaluation of TNF-α, TGF-β, VEGF, and caspase 3 was performed using western blot and IHC methods. Furthermore, oxidative stress biomarkers such as MDA, TAC, GSH, and NO were assessed in the peritoneal adhesion tissue. The findings revealed that linalool significantly reduced peritoneal adhesions by reducing TNF-α, TGF-β, VEGF, and caspase 3 levels. Moreover, MDA concentration was significantly decreased, while NO, TAC, and GSH levels were notably increased. Overall, linalool was effective in preventing adhesion formation and reduced inflammation, angiogenesis, apoptosis, and oxidative stress. Therefore, linalool as a potent antioxidant is suggested for reducing postoperative adhesions in rats.

Chitosan-crosslinked polyvinyl alcohol anti-swelling hydrogel designed to prevent abdominal wall adhesion

Abdominal adhesion is a frequent clinical issue with a high incidence rate and consequences following intra-abdominal surgery. Although many anti-adhesion materials have been used in surgical procedures, additional research is still needed to determine which ones have the most robust wet tissue adhesion, the best anti-postoperative adhesion, and the best anti-inflammatory properties. We have developed an excellent tissue adhesion and anti-swelling polyvinyl alcohol-chitosan hydrogel (AS hydrogel). According to in vitro cell testing, AS hydrogel significantly decreased inflammation around cells and exhibited good biocompatibility. Further, we assessed how well AS hydrogel prevented intraperitoneal adhesion using a rabbit model with cecum and abdominal wall injuries. According to the data, AS hydrogel has excellent anti-inflammatory and biodegradability properties compared to the control group. It can also prevent intestinal and abdominal wall injuries from occurring during surgery. Based on these results, hydrogel appears to be a perfect new material to prevent postoperative abdominal wall adhesion.

Prior abdominal surgery as a potential risk factor for colonic diverticulosis or diverticulitis.

Abnormal colonic pressure profiles have been associated with an increased risk of colonic diverticulosis. A surgical history is a known risk factor for abdominal adhesions and these may lead to increased intraluminal colonic pressure. To assess whether previous abdominal surgery is associated with colonic diverticulosis or diverticulitis. We analyzed data from a study of patients undergoing colonoscopy for different indications from 2020 through 2021. Patients completed a structured questionnaire concerning previous abdominal surgeries, dietary and lifestyle exposures including smoking, alcohol use and co-morbidities. Three hundred and fifty-nine patients were included in the study. The mean age was 67.6 and 46% were females. Diabetes mellitus, hypertension, ischemic heart disease, chronic obstructive pulmonary disease, chronic renal failure, and body mass index were similar in the diverticulosis and control groups. The overall prevalence of colonic diverticulosis was 25% (91/359) and 48% of the patients had previous abdominal surgery. As expected, the prevalence of diverticulosis increased with age. There was no difference in the rate of previous abdominal surgery between patients with or without diverticulosis (49% vs 47%, P = 0.78). In regards to specific surgeries, inguinal hernia repair was significantly associated with diverticulosis (52% vs 20%, P = 0.001), but not diverticulitis. In contrast, appendectomy was not associated with diverticulosis (6% vs 14%, P = 0.048). These findings suggest that post-operative abdominal adhesions inducing high colonic intraluminal pressures do not appear to be the mechanism for diverticula formation. Rather, inguinal hernia and diverticulosis may share similar connective tissue pathologies with no causative relationship between them.

Quercetin inhibits mesothelial-mesenchymal transition and alleviates postoperative peritoneal adhesions by blocking the TGF-β1/PI3K/AKT pathway

Ethnopharmacological relevanceCarthami flos is a dried flower of the Asteraceae plant Carthamus tinctorius (L.). Danhong injection, composed of Carthami flos and Danshen can prevent the formation of postoperative peritoneal adhesions. Quercetin (QUE), an active compound of Carthami flos, has also been proved to prevent postoperative abdominal and uterine cavity adhesions. However, whether QUE is the key component in Carthami flos and the mechanism in preventing postoperative peritoneal adhesions has not been studied. Aim of the studyTo predict whether QUE is the key molecule in Carthami flos and explore the effect and mechanism of QUE in preventing postoperative peritoneal adhesions. Materials and methodsDrug composition and target analysis was used to predict the key component in Carthami flos. The method of cecum-sidewall abrasion was used to establish adhesion models, and the antiadhesion effect of QUE was evaluated with the adhesion scoring system. Network pharmacology was used to predict the targets and potential mechanism of QUE in preventing adhesion. The mechanism was further verified by immunofluorescence, Western blot, wound healing experiment, and molecular docking. ResultsQuercetin was predicted to be the key to preventing postoperative peritoneal adhesions in Carthami flos. Animal experiments revealed that QUE effectively ameliorated adhesions and reduced the expression of mesothelial-mesenchymal transition (MMT) related markers and TGF-β1. Moreover, the TGF-β1/PI3K/AKT pathway was predicted via protein-protein interaction and Kyoto encyclopedia of Genes and Genomes enrichment analysis to play a crucial part in preventing adhesion by QUE. Furthermore, in vitro experiments and molecular docking demonstrated that QUE could block the TGF-β1/PI3K/AKT pathway through forming a stable combination with TβR-II, thereby inhibiting MMT and ameliorating peritoneal adhesion. ConclusionsQUE can not only reduce postoperative TGF-β1 but also block the TGF-β1/PI3K/AKT pathway to inhibit MMT of mesothelial cells, and finally alleviate postoperative peritoneal adhesions. These findings may provide insights towards development of a safe and effective anti-adhesive drug for prevention of postoperative peritoneal adhesions.

A Zwitterionic Hydrogel with Anti-Oxidative and Anti-Inflammatory Properties for the Prevention of Peritoneal Adhesion by Inhibiting Mesothelial-Mesenchymal Transition.

Postoperative peritoneal adhesion is a serious clinical complication. Various hydrogel barriers have been developed to prevent peritoneal adhesion. However, it remains a challenge to design a hydrogel with desirable physicochemical properties and bioactivities. In this study, a zwitterionic polysaccharide-based multifunctional hydrogel is developed using epigallocatechin-3-gallate (EGCG) to prevent postoperative abdominal adhesion. This hydrogel is simple to use and has desirable properties, such as excellent injectability, self-healing, and non-swelling properties. The hydrogel also has ultralow fouling capabilities, such as superior bactericidal performance, cell and protein adhesion, and low immunogenicity resistance. Moreover, the hydrogel exhibits good antioxidant activity, which is attributed to the integration of EGCG. Furthermore, the detailed mechanism from in vivo and in vitro experimental studies illustrates that hydrogel compositions can synergistically prevent adhesion formation through multiple pathways, including anti-inflammatory and antioxidant capabilities and inhibition effects on the mesothelial-mesenchymal transition (MMT) process induced by transforming growth factor (TGF-β). In summary, this zwitterionic multifunctional hydrogel has great potential to prevent postoperative adhesion formation in the clinical setting.

CATase-immobilized hydrogel platform molded by photo-enzyme coupling polymerization for effectively preventing postoperative abdominal adhesion

CATase-immobilized hydrogel platform molded by photo-enzyme coupling polymerization for effectively preventing postoperative abdominal adhesion

Thixotropic β-Chitin Nanofiber Hydrogel with a Living Body-Responsive Self-Hardening Property and Its Application as a Sprayable Antiadhesion Barrier.

Considering recent advances in surgical techniques, sprayable antiadhesion barriers that are compatible with minimally invasive procedures are needed. However, the relatively low mechanical stiffness of the current thixotropic reversible sol-to-gel transition hydrogels has hindered their medical application. Herein, we show a thixotropic sprayable β-chitin nanofiber hydrogel that spontaneously lost the thixotropic property in response to the environments within the living body. Furthermore, interactions between hydrogels and the biological environment result in a significant increase in mechanical stiffness. Due to these advantageous properties, β-chitin nanofiber hydrogels administered by spray prevent postoperative abdominal adhesions and are thus promising sprayable antiadhesion barriers.

Visual Observation of Abdominal Adhesion Progression Based on an Optimized Mouse Model of Postoperative Abdominal Adhesions

Background: There is no clear description of the evolution of the progression of abdominal adhesions over time. Method: The optimized model was selected using different adhesion scoring systems. Then, this model was used to observe the progression of abdominal adhesions. Visualized observation of abdominal adhesion evolution was performed by laparoscopy and computed tomography. The inflammatory cell infiltration and collagen fibers in adhesion tissues at different times were evaluated by hematoxylin-eosin and picrosirius red staining. RNA sequencing was used to predict potential key targets of abdominal adhesions at different times. Results: The abdominal adhesion model showed the highest reproducibility when it was established using a circular tool and an electric brush. Based on this model, we found that the inflammatory response was activated early in the process of adhesion formation, peaking on day 3 and then gradually decreasing until stabilization on day 7. Collagen and fibronectin formed on day 1 and gradually increased until remaining stable on day 7. In addition, the characteristic changes in the adhesion zone from initial congestion, edema and fragile tissue to later dense and stable tissue could be vividly observed in live mice by laparoscopy and artificial pneumoperitoneum CT. The RNA sequencing results revealed that Hck on day 1, Ndufs3 and Ndufs8 on day 3 and Aif1 on day 7 might play key roles in abdominal adhesion formation. Conclusion: The construction of a standard process for describing the evolution of abdominal adhesions based on an optimized mouse model will help to facilitate subsequent adhesion-related studies.

Comparison of the preventive effect of colchicine versus diphenhydramine, prednisolone, and a combination therapy on intraperitoneal adhesion bands: an experimental study in rats

BackgroundPeritoneal adhesion formation is an inevitable consequence of abnormal repair of the peritoneum following different peritoneal injuries of intra-abdominal operations with the subsequent morbidity that they represent. Vast efforts have been made to elucidate the cause and prevent the development of abdominal adhesions. The aim of our study is to compare the capability of colchicine versus diphenhydramine (DPH) and methylprednisolone (MP), and also prednisolone in adhesion prevention.MethodsSixty-one male Wistar stock rats were divided into four groups. The first group attended as the control group. Groups 2, 3, and 4 received oral combination of MP + DPH solution (20 mg/kg), colchicine (0.02 mg/kg), and prednisolone (1 mg/ kg), respectively. Adhesion bands were induced by standardized abrasion of the peritoneum through a midline laparotomy. All rats were sacrificed on the 15th-day post medication administration and the subjects underwent an exploratory laparotomy. The presence of adhesions was evaluated with the modified using Nair's classification.ResultsThe proportion of the control group with substantial adhesion bands (73.3%) was significantly higher than that of the MP + DPH (13.3%), colchicine (33.3%), and prednisolone (31.3%) groups. There were significant differences between the scores of the control and the MP + DPH, colchicine, and prednisolone groups (P = 0.001, 0.028, and 0.019, respectively). There was no statistically significant difference to favor colchicine against MP + DPH (P = 0.390) or MP + DPH against prednisolone (P = 0.394).ConclusionsBoth colchicine and combination of DPH + MP prevented postoperative abdominal adhesions separately in our study. However, the lowest adhesion formation rate was observed in the DPH + MP group, even lower than the prednisolone group.

Controlled Release of a Therapeutic Peptide in Sprayable Surgical Sealant for Prevention of Postoperative Abdominal Adhesions.

Formation of asymmetric, rigid scar tissue known as surgical adhesions is caused by traumatic disruption of mesothelial-lined surfaces in surgery. A widely adopted prophylactic barrier material (Seprafilm) for the treatment of intra-abdominal adhesions is applied operatively as a pre-dried hydrogel sheet but has reduced translational efficacy due its brittle mechanical properties. Topically administered peritoneal dialysate (Icodextrin) and anti-inflammatory drugs have failed to prevent adhesions due to an uncontrolled release profile. Hence, inclusion of a targeted therapeutic into a solid barrier host matrix with improved mechanical properties could provide dual utility in adhesion prevention and as a surgical sealant. Spray deposition of poly(lactide-co-caprolactone) (PLCL) polymer fibers through solution blow spinning has yielded a tissue-adherent barrier material with previously reported adhesion prevention efficacy due to a surface erosion mechanism that inhibits deposition of inflamed tissue. However, such an approach uniquely presents an avenue for controlled therapeutic release through mechanisms of diffusion and degradation. Such a rate is kinetically tuned via facile blending of "high" molecular weight (HMW) and "low" molecular weight (LMW) PLCL with slow and fast biodegradation rates, respectively. Here, we explore viscoelastic blends of HMW PLCL (70% w/v) and LMW PLCL (30% w/v) as a host matrix for anti-inflammatory drug delivery. In this work, COG133, an apolipoprotein E (ApoE) mimetic peptide with potent anti-inflammatory properties was selected and tested. In vitro studies with PLCL blends presented low (∼30%) and high (∼80%) percent release profiles over a 14-day period based on the nominal molecular weight of the HMW PLCL component. Two independent mouse models of cecal ligation and cecal anastomosis significantly reduced adhesion severity versus Seprafilm, COG133 liquid suspension, and no treatment control. The synergy of physical and chemical methods in a barrier material with proven preclinical studies highlights the value of COG133-loaded PLCL fiber mats in effectively dampening the formation of severe abdominal adhesions.

Peritoneal lavage with Glycyrrhiza glabra is effective in preventing peritoneal adhesion in a rat model.

Intraperitoneal adhesion formation is a significant problem following surgeries, resulting in substantial clinical and economic consequences. Glycyrrhiza glabra has several pharmacological properties consisting of anti-inflammatory, anti-microbial, anti-oxidant, anti-cancer, and immunomodulatory activities. Therefore, we aimed to investigate the impacts of G. glabra on the development of post-operative abdominal adhesion in a rat model. Male Wistar rats weighing 200-250g were divided into six groups (n = 8): Group 1: normal group (non-surgical), and the surgical groups including Group 2: control group received the vehicle, Group 3: G. glabra 0.5% w/v, Group 4: G. glabra 1% w/v, Group 5: G. glabra 2% w/v, and Group 6: dexamethasone, 0.4% w/v. The intra-abdominal adhesion was performed utilizing soft sterilized sandpaper on one side of the cecum, and the peritoneum was slightly washed with 2ml of the extract or vehicle. In addition, macroscopic examination of adhesion scoring and the levels of inflammatory mediators [interferon (IFN)-γ, prostaglandin E2 (PGE2)], fibrosis markers [interleukin (IL)-4, transforming growth factor (TGF)-ꞵ], and oxidative factors [malondialdehyde (MDA), nitric oxide metabolites (NO), and reduced glutathione (GSH)] were evaluated. In vitro toxicities were also done on mouse fibroblast L929 and NIH/3T3 cell lines. We found higher levels of adhesion (P < 0.001), IFN-γ(P < 0.001), PGE2(P < 0.001), IL-4(P < 0.001), TGF-β(P < 0.001), MDA(P < 0.001), and NO(P < 0.001), and lower levels of GSH(P < 0.001) in the control group. In contrast, G. glabra concentration dependent and dexamethasone alleviated the levels of adhesion (P < 0.05), inflammatory mediators (P < 0.001-0.05), fibrosis (P < 0.001-0.05), and oxidative (P < 0.001-0.05) factors, while propagating the anti-oxidant marker (P < 0.001-0.05) in comparison to the control group. Results also showed that the extract did not significantly reduce cell viability up to 300µg/ml (P > 0.05). G. glabra could concentration-dependently mitigate peritoneal adhesion formation through its anti-inflammatory, anti-fibrosis, and anti-oxidant properties. However, further clinical investigations are required to approve that G. glabra may be a promising candidate against post-surgical adhesive complications.

The Controlled Release and Prevention of Abdominal Adhesion of Tannic Acid and Mitomycin C-Loaded Thermosensitive Gel.

Postoperative abdominal adhesion is one of the most common complications after abdominal surgery. A single drug or physical barrier treatment does not achieve the ideal anti-adhesion effect. We developed a thermosensitive hydrogel (PPH hydrogel) consisting of poloxamer 407 (P407), poloxamer (P188), and hydroxypropyl methylcellulose (HPMC) co-blended. An injectable thermosensitive TA/MMC-PPH hydrogel was obtained by loading tannic acid (TA) with an anti-inflammatory effect and mitomycin C (MMC), which inhibits fibroblast migration or proliferation. The optimal prescriptions of PPH hydrogels with a suitable gelling time (63 s) at 37 °C was 20% (w/v) P407, 18% (w/v) P188, and 0.5% (w/v) HPMC. The scanning electron microscopy (SEM) revealed that the PPH hydrogel had a three-dimensional mesh structure, which was favorable for drug encapsulation. The PPH hydrogel had a suitable gelation temperature of 33 °C, a high gel strength, and complicated viscosity at 37 °C, according to the rheological analysis. In vitro release studies have shown that the PPH hydrogel could delay the release of TA and MMC and conform to the first-order release rate. Anti-adhesion tests performed on rats in vivo revealed that TA/MMC-PPH hydrogel significantly reduced the risk of postoperative adhesion. In conclusion, the TA/MMC-PPH hydrogel prepared in this study showed an excellent performance in both controlled drug release and anti-adhesive effects. It can be used as a protocol to prevent or reduce postoperative abdominal adhesion.

Multifunctional Microgel-Based Cream Hydrogels for Postoperative Abdominal Adhesion Prevention.

Postoperative abdominal adhesions are a common problem after surgery and can produce serious complications. Current antiadhesive strategies focus mostly on physical barriers and are unsatisfactory and inefficient. In this study, we designed and synthesized advanced injectable cream-like hydrogels with multiple functionalities, including rapid gelation, self-healing, antioxidation, anti-inflammation, and anti-cell adhesion. The multifunctional hydrogels were facilely formed by the conjugation reaction of epigallocatechin-3-gallate (EGCG) and hyaluronic acid (HA)-based microgels and poly(vinyl alcohol) (PVA) based on the dynamic boronic ester bond. The physicochemical properties of the hydrogels including antioxidative and anti-inflammatory activities were systematically characterized. A mouse cecum-abdominal wall adhesion model was implemented to investigate the efficacy of our microgel-based hydrogels in preventing postoperative abdominal adhesions. The hydrogels, with a high molecular weight HA, significantly decreased the inflammation, oxidative stress, and fibrosis and reduced the abdominal adhesion formation, compared to the commercial Seprafilm group or Injury-only group. Label-free quantitative proteomics analysis demonstrated that S100A8 and S100A9 expressions were associated with adhesion formation; the microgel-containing hydrogels inhibited these expressions. The microgel-containing hydrogels with multifunctionality decreased the formation of postoperative intra-abdominal adhesions in a murine model, demonstrating promise for clinical applications.

Zwitterionic biodegradable physical hydrogel based on ATRP technology for effective prevention of postoperative tissue adhesion

Postoperative adhesions are one of the most common complications post intraperitoneal surgery. Even after the adhesiolysis, the recurrence of adhesions is as high as 85%. Although zwitterionic-based materials have been reported for the application, unlike the conventional zwitterionic hydrogel, a series of poly (sulfobetaine methacrylate) grafted dextran derivatives (Dex-g-PSBMA) were synthesized by atom transfer radical polymerization (ATRP) reaction, making it fined controllable copolymer by its living polymerization property. Intriguingly, the Dex-g-PSBMA copolymer can self-assemble into a physical hydrogel under physiological conditions. When injected at the site of the lesions, it can immediately cover the wound area, and as the ion concentration increases, the chemical bonds dissociate and the hydrogel may degrade completely. In the abdominal wall-cecum injury adhesion model in rats, Dex-g-PSBMA hydrogel showed excellent anti-adhesion ability, effectively preventing postoperative abdominal wall-cecum adhesion. The mechanism exploration revealed that Dex-g-PSBMA hydrogel can take an effect on the TGF-β/Smad signaling pathway, which can inhibit the Smad3 and activate the Smad7 pathway, thereby reducing the probability of tissue fibrosis, reducing fibrin deposition, and resisting fibroblast adhesions. In conclusion, these findings demonstrated that this Dex-g-PSBMA physical hydrogel is a promising candidate for completely preventing post-surgical adhesions.