Prevention Of Postoperative Adhesions Research Articles

Study on Prevention of Postoperative Abdominal Adhesions with PLGA Nanofiber Membrane

Objective: To evaluate the effectiveness of poly (lactic-co-glycolic acid) (PLGA) nanofiber membrane on prevention of postoperative abdominal adhesion. Methods: PLGA nanofiber membrane was prepared by high-voltage electrospinning technique. The effectiveness of the membrane in prevention of postoperative abdominal adhesions was characterized with rat abdominal adhesion models. Results: PLGA nanofiber membrane was prepared successfully by electrospinning technique. Scanning electron microscopy (SEM) observation showed that the average diameter of PLGA fibers was approximately 800 nm, and the membrane had microporous structures. Mechanical tests showed that the tensile strength of PLGA nanofiber membrane was 6.36 ± 0.39 MPa, which was significantly higher than the tensile strength of DIKANG absorbable medical film. The results of in vivo experiments showed that PLGA nanofiber membrane and DIKANG absorbable medical film could both reduce the degree of abdominal adhesions. The histological results showed that there was only a small extent of inflammatory cell infiltration in the PLGA group and the control group. The proliferation of connective tissue was reduced, and so was the degree of adhesion. Conclusion: PLGA nanofiber membrane can significantly reduce the incidence and severity of postoperative adhesions, and bodes well for future clinical applications.

An injectable and antifouling self-fused supramolecular hydrogel for preventing postoperative and recurrent adhesions

Abdominal adhesions is a type of serious complication of abdominal surgery. Existing barrier hydrogels are severely limited in the prevention of adhesions due to their poor controllability and long retention time in vivo. Here, we fabricate a supramolecular hydrogel (PNAGA-PHPMA) by copolymerization of N-acryloyl glycinamide (NAGA), a hydrogen bonding monomer, and highly hydrophilic N-(2-hydroxypropyl) methacrylamide (HPMA). The injectable PNAGA-PHPMA hydrogel cross-linked by reversible hydrogen bonds exhibits tunable rheological properties, preferable self-fused ability governed by H-bonds, excellent antifouling capability, and on-demand retention time in vivo. Squeezed out of a syringe to the abdominal cavity, the fragmented gel piece self-fused into an intact hydrogel, thus demonstrating an efficient inhibitory effect on postoperative abdominal adhesions and recurrent adhesions after adhesiolysis. The molecular mechanism studies reveal that the hydrogel significantly downregulates fibrosis-related cytokines (TGF-β1 and Fibrinogen) and pro-inflammatory cytokines (TNF-α and IL-6), regulates the fibrinolytic system balance (t-PA and PAI-1), and inhibits the activity of Erk1/2 and p38 kinase in the mitogen-activated protein kinase (MAPK) signaling pathway, thereby showing an excellent anti-fibrotic and anti-inflammatory effect. This injectable and antifouling self-fused supramolecular hydrogel has a profound clinical significance for the prevention of postoperative adhesions and recurrent adhesions.

Research progress on mechanisms of traditional Chinese medicine in prevention and treatment of postoperative peritoneal adhesion

Peritoneal adhesion is one of the common complications after abdominal operation, which could seriously affect the quality of life in patients. Although the development of modern surgical technology and the improvement of doctors' operation level have reduced the incidence of peritoneal adhesion to a certain extent, due to the lack of special treatment drugs, the therapeutic effect still cannot meet the expectations and requirements of clinicians and patients. Traditional Chinese medicines(TCM) have unique advantages and remarkable curative effect in the treatment of peritoneal adhesion, and they can play an important role in regulating multiple pathological links. However, the relevant researches and product development of TCM against peritoneal adhesion have not attracted enough attention from industry scholars. As for the related work that has been carried out, most of the studies on the efficacy and mechanism are not thorough and systematic enough, seriously restricting the industrial development in this field. In this paper, the efficacy and mechanism were systematically described and summarized based on the review of papers in the recent years, so as to provide a reference for the thorough study of TCM in the prevention and treatment of peritoneal adhesions, and promote the deep development and industrialization process of related products.

Acetabular Labral Reconstruction with Iliotibial Band Autograft: Outcome and Survivorship at a Minimum 10-Year Follow-up.

Labral reconstruction has been shown to result in improved patient-reported outcomes (PROs) at mid-term follow-up in patients with a deficient labrum. The purpose of this study was to determine survivorship and PROs at a minimum 10-year follow-up. A retrospective evaluation of a prospectively collected single-surgeon database included 91 hips (89 patients) that underwent arthroscopic labral reconstruction with iliotibial band autograft between 2006 and 2008. The primary PRO was the Hip Outcome Score (HOS)-activities of daily living (ADL). The modified Harris hip score (mHHS), HOS-sports, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and patient satisfaction (on a scale of 1 to 10) were also collected at a 10-year minimum follow-up. Survivorship analysis curves were evaluated. Eighty-two hips were evaluated at a 10-year minimum follow-up. Overall survivorship, with revision hip arthroscopy or total hip arthroplasty (THA) as the end point, was 70% at 5 years and 61% at 10 years, and the mean survival time was 9 years (95% confidence interval = 7.6 to 10 years). For the patients who did not undergo subsequent surgery, on average the mHHS increased from 60 preoperatively to 82 at the 10-year follow-up (p = 0.001), the HOS-ADL improved from 69 to 90 (p = 0.004), the HOS-sports improved from 43 to 76 (p = 0.001), and the median patient satisfaction was 10 of 10. Eighty percent of the patients achieved the minimal clinically important difference (MCID) in the HOS-ADL, and 87% obtained a patient acceptable symptom state (PASS). Following arthroscopic labral reconstruction with iliotibial band autograft, 9% of the hips underwent revision arthroscopy and 27% underwent THA. At 10 years, the survival rate, with revision hip arthroscopy or THA as the end point, was 61%; however, for those with >2 mm of joint space, the current indication for labral reconstruction, the 10-year survival rate was 90%. Excellent PROs and patient satisfaction were reported by those who did not require revision or THA. With appropriate patient selection and prevention of postoperative adhesions, labral reconstruction results in excellent outcomes and high patient satisfaction that is sustained at a minimum 10-year follow-up. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

H-Bonding Supramolecular Hydrogels with Promising Mechanical Strength and Shape Memory Properties for Postoperative Antiadhesion Application.

Development of a physical barrier with mechanical properties similar to human smooth muscle and an on-demand degradation profile is crucial for the clinical prevention of postoperative adhesion. Herein, a series of supramolecular hydrogels (PMI hydrogels) composed of poly(ethylene glycol) (PEG), methylenediphenyl 4, 4-diisocyanate (MDI), and imidazolidinyl urea (IU, hydrogen bonding reinforced factor) with biodegradability and high toughness are reported to serve as physical barriers for abdominal adhesion prevention. The tensile fracture strength and strain of the PMI hydrogels could be adjusted in the ranges of 0.6-2.3 MPa and 100-440%, respectively, and their Young's moduli (0.2-1.6 MPa) are close to that of human soft tissues like smooth muscle and skin tissue as well as they have outstanding shape memory properties. The PMI hydrogels show good cell and tissue biocompatibility, and the in vivo retention time is in accord with the needs for the postoperative antiadhesion physical barriers. Through an abdominal defect model on mice, this study shows that the PMI hydrogel can completely prevent tissue adhesion compared to the commercialized Seprafilm with high safety. Owing to the promising mechanical properties and good biocompatibility, the PMI hydrogels may be extended for various biomedical applications and the development of advanced flexible electronic devices.

A novel coenzyme-Q approach for the prevention of postsurgical adhesion.

Postoperative intraperitoneal adhesions are an unsolved and important problem in abdominal surgery. In the present study, the probable preventive role of coenzyme-Q in the development of peritoneal adhesions was investigated. Sixteen Wistar Hannover male rats weighing 300-350 g were randomly separated into two groups of 8 rats each. The cecum was abraded with a sterile gauze until sub-serosal hemorrhage developed. A patch of peritoneum located opposite to the cecal abrasion was completely dissected. No treatment was given to Group 1. Group 2 received 30 mg/kg coenzyme-Q, which was injected 2 mL intraperitoneally. All the rats were sacrificed on the postoperative 21st day, and after adhesions were scored macroscopically, tissue specimens of the peritoneum and bowel were subjected to histopathological investigation. Tissue and blood specimens were also taken for biochemical analysis to investigate antioxidant efficiency. Adhesion scores were significantly different between the control group and the coenzyme-Q group (p= 0.001). According to the tissue levels of GSH-Px, MDA, and SOD levels, there was no significant difference between the study groups (p= 0.074, p= 0.208, p= 0.526). According to the plasma GSH-Px and SOD levels, there was significant difference between the groups (p= 0.002, p= 0.001), but the difference was not significant at MDA levels (p= 0.793). The differences between the pathological scores of the control and coenzyme-Q (p= 0.028 for fibrosis; p= 0.025 for inflammation) groups were statistically significant. This study confirms that coenzyme-Q is the potential application in the prevention of early postoperative adhesions.

Dual dynamically crosslinked thermosensitive hydrogel with self-fixing as a postoperative anti-adhesion barrier

Tissue adhesion is a severe postoperative complication. Various strategies have been developed to minimize postoperative adhesion, but the clinical efficacy is still far from satisfactory. Herein, we present a dual dynamically crosslinked hydrogel to serve as a physical postoperative anti-adhesion barrier. The hydrogel was generated by dynamic chemical oxime bonding from alkoxyamine-terminated Pluronic F127 (AOP127) and oxidized hyaluronic acid (OHA), as well as hydrophobic association of AOP127. Rheological analysis demonstrated that the hydrogel exhibits temperature sensitivity. At 37 °C, it shows much higher modulus and higher stability than the Pluronic F127 hydrogel. Hemolytic assays suggested that the hydrogel undergoes low hemolysis. In addition, it exhibited anti-adhesion to blood cells in blood cell adhesion tests. It also showed an anti-attachment effect to fibroblasts and biocompatibility in vitro cell studies. Macroscopic evaluation and lap-shear tests revealed that the hydrogel has a moderate adhesive capacity to tissue, which is important for self-fixation. A rat model of sidewall defect-bowel abrasion was established to evaluate the anti-adhesion effect in vivo. The gross observation and pathological analysis revealed a significant reduction in postoperative peritoneal adhesion in the AOP127/OHA hydrogel-treated group than those treated with normal saline or Pluronic F127 hydrogel. Hence, the dual dynamically crosslinked hydrogel with self-fixable capacity may be suitable as a physical barrier for postoperative adhesion prevention. Statement of SignificanceDespite the development of numerous postoperative anti-adhesion barriers, their anti-adhesion efficacy is still limited in clinical trials due to poor tissue adhesion and rapid clearance from injured areas. Herein, we have developed a dual dynamic crosslinked hydrogel, generated by dynamic oxime bonds and hydrophobic interactions. The hydrogel is temperature-sensitive and demonstrates moderate tissue adhesion capacity, which allows for self-fixation when applied to defects. The introduction of dynamic covalent bonds improves the stability of the hydrogel. Moreover, the hydrogel not only displays appropriate hemocompatibility, cytocompatibility and anti-adhesion of blood cells and fibroblasts, but it also effectively contributes to preventing postoperative peritoneal adhesions in vivo. Hence, this dual dynamic crosslinked hydrogel may have potential applications as a physical barrier in clinical practice.

The Effect of Extractum Cepae, Heparin Sodium, and Allantoin in Experimental Peritoneal Adhesion

The purpose of the study is to investigate the effects of extractum cepae (EC), heparin sodium (HS), and allantoin (AA) on postoperative peritoneal adhesion (PPA) prevention. Forty-eight rats were allocated into six groups (n = 8). PPA was performed by Harris method. In group 1, no additional procedure was done. Abdominal cavity was washed with normal saline in group 2, EC in group 3, HS in group 4, AA in group 5, and EC-HS-AA mixture (EHA-m) in group 6. On the 21st postoperative day, PPA was scored with Nair adhesion score and examined for fibrosis histopathologically and hydroxy-proline levels (OHP) biochemically. Macroscopically, PPA was decreased in groups 2, 4, and 6 compared to groups 1, 3, and 5 (p < 0.05) and decreased in group 2 compared to other groups (p < 0.05). Histopathologically, fibrosis was decreased in groups 2, 4, and 6 compared to other groups and decreased in group 2 compared to other groups (p < 0.05). Tissue OHP level was decreased in groups 2, 3, 4, and 5 compared to groups 1 and 6 (p < 0.05). Tissue OHP level was decreased in group 6 compared to group 1, but the difference was not statistically significant. PPA formation decreases with normal saline, HS and EHA-m, whereas increases with EC and AA both macroscopically and microscopically. Although HS and EHA-m seem to have adhesion prevention effect, washing the intestines with saline seems to be more effective.

Polysaccharide-based films for the prevention of unwanted postoperative adhesions at biological interfaces

Postoperative adhesions protect, repair, and supply nutrients to injured tissues; however, such adhesions often remain permanent and complicate otherwise successful surgeries by tethering tissues together that are normally separated. An ideal adhesion barrier should not only effectively prevent unwanted adhesions but should be easy to use, however, those that are currently available have inconsistent efficacy and are difficult to handle or to apply. A robust hydrogel film composed of alginate and a photo-crosslinkable hyaluronic acid (HA) derivative (glycidyl methacrylate functionalized hyaluronic acid (GMHA)) represents a solution to this problem. A sacrificial porogen (urea) was used in the film manufacture process to impart macropores that yield films that are more malleable and tougher than equivalent films produced without the sacrificial porogen. The robust mechanical behavior of these templated alginate/GMHA films directly facilitated handling characteristics of the barrier film. In a rat peritoneal abrasion model for adhesion formation, the polysaccharide films successfully prevented adhesions with statistical equivalence to the leading anti-adhesion technology on the market, Seprafilm®. Statement of SignificancePostoperative adhesions often remain permanent and complicate otherwise successful surgeries by tethering tissues together that are normally separated and pose potentially significant challenges to patients. Therefore, the generation of adhesion barriers that are easy to deploy during surgery and effectively prevent unwanted adhesions is a big challenge. In this study robust hydrogel films composed of alginate and a photo-crosslinkable hyaluronic acid (HA) derivative (glycidyl methacrylate functionalized HA, GMHA) were fabricated and investigated for their potential to act as a solution to this problem using a rat peritoneal abrasion model for adhesion formation. We observed the polysaccharide films successfully prevented adhesions with statistical equivalence to the leading anti-adhesion technology on the market, Seprafilm®, suggesting that such films represent a promising strategy for the prevention of postoperative adhesions.

Reliability of combination of hyaluronic acid application and early rehabilitation in prevention of postoperative adhesions after primary tendon repair

Background: The aim of the study was to evaluate the efficacy of hyaluronic acid application after tendon repair in prevention of postoperative adhesions, and to clarify the best circumstances that must be fulfilled to obtain this goal. Tissue adhesion usually happens due to injury, foreign-body reaction, bleeding, or infection but is considered an important factor for wound healing. As a result, tendons repair after injury is usually complicated due to limited postoperative movement. Several methods were used to try to prevent postoperative adhesions but most of them did not give satisfactory results as the mechanism of adhesion formation is still unclear.Methods: Fifty patients were included in this prospective study performed at department of plastic, reconstruction and burn surgery, faculty of medicine, Menoufia University over the period of approximately two years (January 2016 to November 2017).Results: Close follow up of the function of the repaired tendons was evaluated repeatedly over the period of 6 months. 40 patients showed excellent progress in regaining function with less possibility of performing adhesions, these patients also expressed satisfaction and comfort toward the regained function. 10 patients showed reasonable progress and were mildly satisfied.Conclusions: Application of hyaluronic acid in addition to a well-planned rehabilitation plan is a good and reliable method against adhesions when performing primary tendon repair.

Practical considerations in the use of a porcine model (Sus scrofa domesticus) to assess prevention of postoperative peritubal adhesions.

Infertility has been a common postoperative problem caused by peritoneal adhesions. Since several prophylactic agents have recently shown promising preliminary results, more complete studies comparing their real efficacy and safety are needed urgently. The aim of this study was to investigate and describe practical considerations of a porcine model that can be used to assess such prophylactic agents. First, 10 healthy 5½ months old female pigs (24.3–31.3 Kg) underwent a standardized laparoscopy to provoke peritubal adhesion formation without prophylactic agents. After 30 days, a second-look laparoscopy was performed to evaluate adhesions and perform adnexectomy for histopathological evaluation. Adhesions at different sites were classified by grade, for which the scores range from 0 (no adhesion) to 3 (very strong vascularized adhesions), and also by area, with scores ranging from 0 (no adhesion) to 4 (>75% of the injured area). The histopathological evaluation of the distal uterine horns, oviducts and ovaries were compared withthose from a control group of six healthy pigs with no previous surgery. Biological samples were collected to assess vitality, inflammation and renal, hepatic and hematopoietic systems. There were small (but significant) changes in serum albumin (P = 0.07), globulin (P = 0.07), C-reactive protein (P = 0.011), fibrinogen (P = 0.023) and bilirubin (P<0.01) after 30 days, but all values were within the normal range. No inflammation or abscess formation was observed, but different degrees of adhesion were identified. The estimated occurrence of adhesion (scores >0) and of strong / very strong adhesion (scores >1) was 75% (95% CI: 55–94.9) and 65% (95% CI: 45–85), respectively. The porcine model represents a useful animal platform that can be used to test the efficacy and safety of candidate prophylactic agents intended to prevent postoperative peritubal adhesions formation. We present several practical considerations and measures that can help to minimize animal suffering and avoid problems during such experiments.

Injectable and Sprayable Albumin/Serum Hydrogels that Demonstrate the Complete Coverage of a Wound and Possess Dynamically and Spatially Controllable Material Properties for the Prevention of Post-Operative Adhesion

Since the degree of severity and geometry of wounds vary, it is necessary to prepare an anti-adhesive hydrogel that possesses dynamically controllable material properties, exhibits biodegradability, and possesses drug-releasing properties. Injectable, sprayable, oxygen peroxide (H2O2)-sensitive and photo-cross-linkable hydrogels that permit in situ dynamic and spatial control of their physicochemical properties were synthesized for the prevention of postoperative adhesion. Albumin is the most abundant protein in blood serum and serves as a carrier for a number of molecules that exhibit poor water solubility. It is therefore a suitable biomaterial for the fabrication of hydrogels since it presents a low risk of life-threatening complications and does not require immunosuppressive therapy for preventing graft rejection. As micromolar concentrations of endogenous H2O2 are produced after tissue damage, aqueous pre-polymer solutions that exhibit solution-to-gel transition behaviors in response to H2O2 were developed. These solutions form a thin layer of hydrogel that fully covers the wound site and acts as a barrier. The physicochemical properties of this hydrogel can then be spatially post-adjusted via transdermal exposure to light to release drugs, depending on what is required for the particular injury. A significant reduction in postoperative peritoneal adhesion was observed in an animal model involving severe sidewall and bowel abrasions. This study demonstrated that the fabricated dually cross-linked, albumin-based hydrogels have great potential in such applications because they showed a low immune response, easy handling, full wound coverage, and tunable biodegradability. Precise spatial and controllable drug-release profiles may also be achieved via in situ transdermal post-tuning of the biomaterials, depending on the injury.

Anti-interleukin-6 receptor antibody treatment ameliorates postoperative adhesion formation

Postoperative adhesion formation often ruins the quality of life or is an obstacle to illnesses with curative operation such as cancer. Previously we demonstrated that interferon-γ-promoted fibrin deposition drove postoperative adhesion formation. However, its underlying cellular and molecular mechanisms remain poorly understood. We found that myofibroblasts of the adhesion predominantly expressed signature molecules of mesothelial cells that line the serosa. Microarray analysis revealed IL-6 as a key underlying player, supported by elevated IL-6 levels in the peritoneal fluid of post-laparotomy human subjects. Injured serosa of cecum-cauterized mice also exhibited induction of Il6, which was followed by Tnf, concomitant with rapid accumulation of neutrophils, substantial population of which expressed TGF-β1, a master regulator of fibrosis. Besides, neutrophil-ablated mice showed reduction in induction of the adhesion, suggesting that TGF-β1+neutrophils triggered the adhesion. Human neutrophils expressed TGFB1 in response to TNF-α and TNF in response to IL-6. Moreover, anti-IL-6 receptor monoclonal antibody abrogated neutrophil recruitment and adhesion formation. Thus, IL-6 signaling represents a potential target for the prevention of postoperative adhesions.

Thermosensitive hydrogels based on methylcellulose derivatives for prevention of postoperative adhesion

Postoperative adhesions commonly cause severe complications, and also increase the risk of adhesiolysis. To improve postoperative adhesion, a series of 2-methacryloyloxy ethyl phosphorylcholine conjugated methylcellulose (MC-g-MPC) derivatives were synthesized to utilize the anti-protein adsorption of 2-methacryloyloxy ethyl phosphorylcholine and the thermosensitivity of methylcellulose. The structures of MC-g-MPC derivatives were characterized by Fourier transform infrared spectroscopy (FTIR) and 1H nuclear magnetic resonance (1H NMR) analyses, and their thermosensitivities were studied by rheological analysis. The gelling temperature of the MC-g-MPC hydrogel was 33 °C and gelling time of the hydrogel under body temperature was 2.5 min. The morphology of the MC-g-MPC hydrogel was observed by scanning electron microscopy (SEM). The results of in vitro cytotoxicity and immunotoxicity, and hemolysis assays demonstrated the good biocompatibility of MC-g-MPC hydrogels. Following the injection of the MC-g-MPC hydrogel, the postoperative adhesion of damaged ceca in Sprague–Dawley rats was improved when compared with a control group (no treatment). In addition, MC-g-MPC-0.25 hydrogel could downregulate the expression of Col-I and Col-IV collagen proteins, thus exert its anti-protein absorption capacity. Therefore, the MC-g-MPC hydrogel is a promising biomaterial for preventing postoperative adhesion.

Ibuprofen-Loaded Hyaluronic Acid Nanofibrous Membranes for Prevention of Postoperative Tendon Adhesion through Reduction of Inflammation.

A desirable multi-functional nanofibrous membrane (NFM) for prevention of postoperative tendon adhesion should be endowed with abilities to prevent fibroblast attachment and penetration and exert anti-inflammation effects. To meet this need, hyaluronic acid (HA)/ibuprofen (IBU) (HAI) NFMs were prepared by electrospinning, followed by dual ionic crosslinking with FeCl3 (HAIF NFMs) and covalent crosslinking with 1,4-butanediol diglycidyl ether (BDDE) to produce HAIFB NFMs. It is expected that the multi-functional NFMs will act as a physical barrier to prevent fibroblast penetration, HA will reduce fibroblast attachment and impart a lubrication effect for tendon gliding, while IBU will function as an anti-inflammation drug. For this purpose, we successfully fabricated HAIFB NFMs containing 20% (HAI20FB), 30% (HAI30FB), and 40% (HAI40FB) IBU and characterized their physico-chemical properties by scanning electron microscopy, Fourier transformed infrared spectroscopy, thermal gravimetric analysis, and mechanical testing. In vitro cell culture studies revealed that all NFMs except HAI40FB possessed excellent effects in preventing fibroblast attachment and penetration while preserving high biocompatibility without influencing cell proliferation. Although showing significant improvement in mechanical properties over other NFMs, the HAI40FB NFM exhibited cytotoxicity towards fibroblasts due to the higher percentage and concentration of IBU released form the membrane. In vivo studies in a rabbit flexor tendon rupture model demonstrated the efficacy of IBU-loaded NFMs (HAI30FB) over Seprafilm® and NFMs without IBU (HAFB) in reducing local inflammation and preventing tendon adhesion based on gross observation, histological analyses, and biomechanical functional assays. We concluded that an HAI30FB NFM will act as a multi-functional barrier membrane to prevent peritendinous adhesion after tendon surgery.

Use of a supramolecular polymeric hydrogel as an effective post-operative pericardial adhesion barrier.

Post-operative adhesions form as a result of normal wound healing processes following any type of surgery. In cardiac surgery, pericardial adhesions are particularly problematic during reoperations, as surgeons must release the adhesions from the surface of the heart before the intended procedure can begin, thereby substantially lengthening operation times and introducing risks of haemorrhage and injury to the heart and lungs during sternal re-entry and cardiac dissection. Here we show that a dynamically crosslinked supramolecular polymer-nanoparticle hydrogel, with viscoelastic and flow properties that enable spraying onto tissue as well as robust tissue adherence and local retention in vivo for two weeks, reduces the formation of pericardial adhesions. In a rat model of severe pericardial adhesions, the hydrogel markedly reduced the severity of the adhesions, whereas commercial adhesion barriers (including Seprafilm and Interceed) did not. The hydrogels also reduced the severity of cardiac adhesions (relative to untreated animals) in a clinically relevant cardiopulmonary-bypass model in sheep. This viscoelastic supramolecular polymeric hydrogel represents a promising clinical solution for the prevention of post-operative pericardial adhesions.

Comparison of the effects of atorvastatin, hyaluronic acid and oxidized cellulose (Interceed) on reducing intestinal adhesions postoperative after open abdominal surgery in animal models

Background: Abdominal adhesions are considered as an important problem in abdominal surgery. In this study we compared the effectiveness of atorvastatin, hyaluronic acid and interceed (oxidized cellulose) in prevention of postoperative intestinal adhesions. Material and Methods: A total of 40 Wistar-albino rats were randomly divided into 5 groups: Group 1 (Sham); Group 2 (Control or Adhesion induction); Group 3 (Adhesion induction + hyaluronic acid); Group 4 (Adhesion induction + oxidized cellulose); and Group 5 (Adhesion induction + atorvastatin). A same experimental method of cecal abrasion and ligature was used to produce adhesions in all rats. Fourteen days after adhesions formation, animals were killed and adhesions were scored according to macromorphological characteristics and adhesion-carrying tissues under standard histologic examination. Inflammation, vascularization and fibrosis in granulation sites were graded in all samples. Results: Adhesion scores in all experimental groups were slightly lower than control group. Group 3 had the lowest mean adhesions score (1.18 ± 1.24) based on surgeon observation. The mean of adhesion score in Group 3 (1.18 ± 1.24) was significantly lower than that in Group 4 (3.43 ± 0.53) (p=0.004). Group 5 showed the lowest mean adhesions score on pathological examination (5.62 ± 3.73). The mean of adhesion total score in Group 3 was slightly lower than that in other groups; however, this difference was not significant. Conclusion: Hyaluronic acid, oxidized cellulose, and atorvastatin are effective in treatment and prevention of intestinal adhesions during open abdominal surgery. Although hyaluronic acid was slightly more effective, further studies are needed to evaluate the effect of combination therapy with these agents.

Controlled release Ibu-cryobarriers for the prevention of post-operative adhesions: In-vitro/in-vivo comparative study.

Post-operative adhesion is a common cause of several complications including intestinal obstruction, chronic pelvic pain and/or infertility. Adhesions are fibrous bands that result from the inflammatory reactions due to peritoneum damage. The current study focused on designing an effective anti-inflammatory loaded barrier for the prevention of post-operative adhesions. The proposed method is based on the use of polyvinyl alcohol (PVA), cryobarrier loaded with Ibuprofen (Ibu). Anti-adhesive Ibu-cryobarriers were prepared in different forms, and subjected to in-vitro evaluation comprising; drug release rate, maximum swelling index, morphological examination using scanning electron microscope (SEM), fourier-transform infrared spectroscopy (FTIR) and mechanical properties. Optimized cryobarriers were further investigated for their in-vivo effectiveness in preventing post-operative adhesions in female Sprague-Dawley rats. All formulations showed appropriate physical and morphological characteristics, in-vitro controlled sustained drug release profiles during a period of seven days with acceptable maximum swelling index. Invivo, all cryobarriers were equivalent to each other concerning serum or tissue parameter. However, morphological and histopathological evaluations revealed that both xerocryogel and lyophilized cryofilms are more effective than the cryogel in prevention of post-operative peritoneal adhesions. The current study showed the possibility of preparing drug loaded cryobarriers using simple technique with an effective in vivo post-operative adhesion prevention.

Oxaliplatin-loaded chemically cross-linked hydrogels for prevention of postoperative abdominal adhesion and colorectal cancer therapy

Colorectal cancer (CRC) is the third most commonly diagnosed cancer among both men and women worldwide. New therapeutic strategies involving cytoreductive surgery and intra-peritoneal chemotherapy could lead to a definitive cure in some cases. However, postoperative intra-abdominal adhesion can cause further complications. In this study, hyaluronic acid (HA)- and carboxymethyl cellulose sodium (CMCNa)-based novel cross-linked hydrogels (HC hydrogels) were synthesized and fully characterized. We demonstrated that varied compositions of HA and CMCNa altered the microstructure, rheology, and degradation behavior of hydrogels. Pre-constructed hydrogels were further loaded with oxaliplatin to prevent intra-abdominal adhesion following chemotherapy. Sustained release of oxaliplatin was observed from hydrogels compared that from solutions, which release drugs through diffusion, following the Higuchi and Korsmeyer-Peppas models. Moreover, low adhesion scores in an in vivo SD rat model demonstrated inhibition of intra-peritoneal adhesion in response to HC hydrogels. Therefore, HC hydrogels offer a novel formulation strategy for providing an intra-abdominal anti-adhesion barrier after cytoreductive surgery and intra-peritoneal chemotherapy for CRC treatment.

Does Preservation of Ligamentum Flavum in Percutaneous Endoscopic Lumbar Interlaminar Discectomy Improve Clinical Outcomes?

ObjectiveLigamentum flavum (LF) is an important anatomical structure for prevention of postoperative adhesions, but the opening of LF is necessary for percutaneous endoscopic lumbar interlaminar discectomy (PEID). Although the defect in LF is small with conventional PEID, the defect could be minimized with LF splitting technique. The objective of this study was to compare clinical outcomes of PEID with opening of LF versus splitting of LF. MethodsA retrospective study was performed for patients underwent PEID for L5–S1. PEID with the opening of LF (open-group) was performed for 55 patients and with splitting of LF (split-group) was performed for 34 patients. The defect of LF in Open-group was 3–5 mm, but the defect was negligible in split-group because the split LF was reapproximated by its elasticity. Clinical outcomes were evaluated with Korean version of the Oswestry Disability Index (K-ODI) and visual analogue pain scores for back (VASB) and leg (VASL). The changes of clinical outcomes during postoperative 24 months between groups were evaluated with linear mixed-effects model. ResultsThe clinical outcomes were similar between groups for K-ODI (p=0.98), VASB (p=0.52), and VASL (p=0.59). Each outcome demonstrated significant improvement from preoperative baseline throughout the postoperative 24 months (p<0.05). Complications included recurrence in 4 patients and dural tear in 1 in open-group (9.1%), and residual disc herniation in 2 patients and transient weakness in 1 in split-group (8.8%). ConclusionSplitting versus opening LF in PEID may be left to the surgeon’s discretion. The potential risks and benefits of LF handling should be considered when performing this surgical technique in PEID.