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Li Z, Yang L, Jin Q, Li W, Li Y, Zheng Y, Dong M, Bian Y. An anti-inflammatory and anti-fibrotic Janus hydrogel for preventing postoperative peritoneal adhesion. Mater Today Bio 2025; 31:101637. [PMID: 40151614 PMCID: PMC11946495 DOI: 10.1016/j.mtbio.2025.101637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Revised: 02/23/2025] [Accepted: 03/03/2025] [Indexed: 03/29/2025] Open
Abstract
Postoperative peritoneal adhesion (PPA) is pathological tissue hyperplasia between surgical wounds and nearby organs. Currently, traditional double-sided bioadhesives are limited in preventing PPA due to the indiscriminate adhesive properties and the poor interaction with wet tissues. Herein, we developed a Janus hydrogel, named PAA-Cos, by using the polycationic carbohydrate polymer of chitooligosaccharide (Cos) and the polyanionic polymer of polyacrylic acid (PAA). The adhesive layer of Janus hydrogels could adhere to wet tissue tightly due to surfaces composed of carboxyls, and the positively charged biomaterial (Cos) neutralized carboxyls on one side of PAA hydrogel to form Janus hydrogels. Moreover, PAA-Cos can further load with ligustrazine hydrochloride (Ligu), a pharmaceutical compound with anti-inflammatory and anti-fibrotic effects, finally obtaining PAA-Cos@Ligu. After the application of PAA-Cos@Ligu on the surgical trauma, the bottom surface can adhere to wet tissues robustly to restore the wound, while the top surface acts as a physical barrier with antiadhesive effects to avoid PPA. PAA-Cos@Ligu also exhibited anti-inflammatory effects by promoting M2 macrophage polarization, inhibiting the myofibroblast-like differentiation of peritoneal mesothelial cells, and blocking the TGF-β/Smad2/3 signaling pathway to hinder collagen deposition. Our findings suggest that PAA-Cos@Ligu has great potential as an anti-adhesion candidate with biocompatibility and ease of preparation.
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Affiliation(s)
- Zhengjun Li
- Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Lili Yang
- Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- Jingwen Library, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Qi Jin
- Department of Polymer Science and Engineering, State Key Laboratory of Coordination Chemistry, Key Laboratory of High-Performance Polymer Material and Technology, MOE, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu, 210023, China
| | - Wen Li
- Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- School of Health Preservation and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yue Li
- Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yan Zheng
- Department of Polymer Science and Engineering, College of Materials Science and Engineering, Nanjing Tech University, Nanjing, Jiangsu, 211816, China
| | - Mei Dong
- Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yaoyao Bian
- Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- School of Health Preservation and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- TCM Rehabilitation Center, Jiangsu Second Chinese Medicine Hospital, Nanjing, 210023, China
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Maekawa T, Miyake T, Kojima M, Tani S, Matsunaga T, Nishina Y, Kaida S, Maehira H, Shimizu T, Tani M. Impact of leptin on postoperative peritoneal adhesion formations in colorectal resection. Int J Colorectal Dis 2025; 40:67. [PMID: 40088288 PMCID: PMC11910413 DOI: 10.1007/s00384-025-04851-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/03/2025] [Indexed: 03/17/2025]
Abstract
PURPOSE Postoperative peritoneal adhesion formation (PAF) is a distressing complication. Leptin, secreted by fat tissues, may be associated with PAF. However, the relationships between PAF and leptin are unclear. This study investigated the impact of leptin on PAF after colorectal tumor resection. METHODS A cecum cauterization mouse model was used to investigate PAF and its association with leptin. Mice adhesion score (AS) was evaluated on day 7 after treatment. The clinical study included patients who underwent elective colorectal resection with temporary ileostomy between April 2021 and December 2024. The AS was evaluated at the time of ileostomy closure. Patients with the highest AS quartile were classified into the high-AS group; clinical factors associated with PAF were examined. An enzyme-linked immunosorbent assay was used to measure human and murine serum leptin concentrations. RESULTS The animal experiment revealed that serum leptin levels on postoperative day 7 were negatively correlated with mice ASs (P = 0.0043, r = -0.6241). In a clinical study, eight patients had a high AS (27.6%). Visceral fat mass and preoperative serum leptin levels were higher in the high-AS group than in the low-AS group. The serum leptin ratio (postoperative value to preoperative value) on postoperative day 7 was lower in the high-AS group. In multivariate analysis, the serum leptin ratio was an independent factor for classifying into the high-AS group. CONCLUSIONS A decrease in postoperative serum leptin levels was associated with severe PAF. Leptin may be a novel key molecule in PAF.
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Affiliation(s)
- Takeru Maekawa
- Department of Surgery, Shiga University of Medical Science, Seta tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
| | - Toru Miyake
- Department of Surgery, Shiga University of Medical Science, Seta tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.
| | - Masatsugu Kojima
- Department of Surgery, Shiga University of Medical Science, Seta tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
| | - Soichiro Tani
- Department of Surgery, Shiga University of Medical Science, Seta tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
| | - Takashi Matsunaga
- Department of Surgery, Shiga University of Medical Science, Seta tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
| | - Yusuke Nishina
- Department of Surgery, Shiga University of Medical Science, Seta tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
| | - Sachiko Kaida
- Department of Surgery, Shiga University of Medical Science, Seta tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
| | - Hiromitsu Maehira
- Department of Surgery, Shiga University of Medical Science, Seta tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
| | - Tomoharu Shimizu
- Medical Safety Section, Shiga University of Medical Science Hospital, Shiga, Japan
| | - Masaji Tani
- Department of Surgery, Shiga University of Medical Science, Seta tsukinowa-cho, Otsu, Shiga, 520-2192, Japan
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Pu Z, Nian H, Li Z, Zhong P, Ma S, Li J. Research progress on animal models of peritoneal adhesion. Surgery 2025; 178:108929. [PMID: 39613659 DOI: 10.1016/j.surg.2024.10.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 10/01/2024] [Accepted: 10/16/2024] [Indexed: 12/01/2024]
Abstract
Peritoneal adhesion is a common complication of abdominal and pelvic surgery that can cause various clinical symptoms, including abdominal pain, intestinal obstruction, and female infertility, significantly impacting patient quality of life. Animal models of peritoneal adhesion are important tools for studying the mechanisms of adhesion formation and evaluating the effectiveness of prevention and treatment. Various methods for constructing animal models of peritoneal adhesion include physical injury, chemical injury, ischemia, infection, foreign body stimulation, and simulated surgery; however, none can fully simulate peritoneal adhesion in patients clinically. Therefore, this review aimed to explore previous methods used to construct peritoneal adhesion animal models and summarize their principles, characteristics, and applications. Similarly, it summarizes macroscopic and microscopic evaluation indicators, such as peritoneal adhesion gross assessment, histological scoring, and molecular markers. On the basis of this, we proposed a new animal model of peritoneal adhesion that simulates the factors contributing to peritoneal adhesion formation in clinical surgery. peritoneal adhesion formation was stable and standardized using our proposed model, providing a foundation for the establishment and application of peritoneal adhesion animal models.
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Affiliation(s)
- Zhenjun Pu
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, China
| | - Hongyu Nian
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, China
| | - Zhiyuan Li
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, China
| | - Pengfei Zhong
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, China
| | - Shengxu Ma
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, China
| | - Junliang Li
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, China; NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, Gansu, China; Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China; Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, China; Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.
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Tanigaki S, Batra A, Chan T, Kang JH, Lam S, Lim TY, Mayya R, Nur Azurah AG, Walker G. Adhesion barriers in gynecologic surgeries and cesarean section: An Asia-Pacific expert panel consensus recommendation. Int J Gynaecol Obstet 2025; 168:436-448. [PMID: 39277817 PMCID: PMC11726167 DOI: 10.1002/ijgo.15903] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 08/13/2024] [Accepted: 08/27/2024] [Indexed: 09/17/2024]
Abstract
Adhesions arising from gynecologic surgeries and cesarean sections pose substantial clinical, social, and economic challenges, leading to issues like pelvic pain, infertility, bowel obstruction, and recurring surgeries. Preventing adhesions is a pressing unmet need, hindered by difficulties in assessing postoperative adhesions and understanding barriers. To bridge adhesion prevention gaps, statements on clinical practices were synthesized to present Asia-Pacific expert perspectives on gynecologic surgery and cesarean section adhesion prevention. An expert panel of eight physicians from various healthcare settings in the Asia-Pacific region was convened and a comprehensive literature search on topics related to adhesion prevention in gynecologic surgeries and cesarean sections was performed. Information from full-text publications was used to develop draft consensus statements, with each statement assigned the highest available evidence level based on a systematic literature review and graded using the Oxford Center for Evidence-based Medicine criteria. A modified Delphi process, involving two rounds of online voting and discussions with an extended group of 109 experts, was employed to reach a consensus on six topics related to adhesion barriers. A set of 15 consensus statements were synthesized. Key topics include adhesion incidence in Asia, cesarean section complications, barrier application status, adhesion formation and prevention, absorbable barriers' effectiveness, recommendations, and future considerations. The statements provide guidance for healthcare professionals, especially in the Asia-Pacific region, to tackle the challenges posed by postoperative adhesions and improve patient outcomes. Further research is needed to enhance understanding and prevention of adhesions in this region.
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Affiliation(s)
- Shinji Tanigaki
- Department of Obstetrics and GynecologyKyorin University School of MedicineTokyoJapan
| | - Achla Batra
- Department of Obstetrics and GynecologySafdarjung HospitalNew DelhiIndia
| | - Te‐Fu Chan
- Department of Obstetrics and GynecologyKaohsiung Medical University Chung‐Ho Memorial HospitalKaohsiungTaiwan
| | - Julian Hean‐Leng Kang
- Department of Obstetrics and GynecologyKK Women's and Children's HospitalSingaporeSingapore
| | | | - Timothy Yong‐Kuei Lim
- Timothy Lim Clinic for Women & Cancer SurgeryMount Alvernia HospitalSingaporeSingapore
| | - Raghavendra Mayya
- Advanced Surgery DivisionBaxter Worldwide Medical AffairsSingaporeSingapore
| | - Abdul Ghani Nur Azurah
- Department of Obstetrics and GynecologyUniversiti Kebangsaan Malaysia Medical CentreKuala LumpurMalaysia
| | - Graeme Walker
- Department of Obstetrics and GynecologyGold Coast Private HospitalGold CoastAustralia
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Obana A, Akabane M, Hamilton M, Shah K, Punjala RS, Limkemann A, Schenk A, Singh N, Rajab A, Bumgardner G, Washburn K, Alebrahim M. Kidney Allograft Torsion After Simultaneous Pancreas Kidney Transplantation: Case Report and Review of Literature. Case Rep Transplant 2025; 2025:2902758. [PMID: 39871918 PMCID: PMC11769581 DOI: 10.1155/crit/2902758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 12/17/2024] [Indexed: 01/29/2025] Open
Abstract
Kidney allograft torsion (KAT) is a rare but critical complication of kidney transplantation that can lead to graft loss due to acute ischemia. This report presents a case of KAT resulting in graft loss 9 months following intraperitoneal simultaneous pancreas and kidney (SPK) transplant and reviews previous reports to identify potential high-risk features. A 38-year-old female with end-stage renal disease secondary to Type 1 diabetes mellitus underwent an intraperitoneal enteric drained SPK transplant. Nine months post-transplantation, she presented with nausea, vomiting, severe abdominal pain, decreased urine output, and diarrhea. An ultrasound showed moderate hydronephrosis and no blood flow to the renal hilum. Exploratory laparotomy revealed a necrotic renal allograft twisted 360° counterclockwise on its vascular pedicles. Despite detorsion, the graft showed no signs of viability, necessitating transplant nephrectomy. This case highlights the rarity and severity of KAT, particularly in intraperitoneal kidney transplants. The patient's low body mass index (BMI) (23.4 kg/m2), female sex (wider pelvis), and minimal intra-abdominal adhesions may have contributed to increased graft mobility, predisposing to KAT. Other potential risk factors include elongated vascular pedicle and immunosuppression-related reduced adhesion formation. The nonspecific presentation of KAT emphasizes the need for high clinical suspicion and prompt ultrasonographic evaluation in cases of graft abnormalities. This report underscores the importance of considering patient- and graft-specific factors in assessing KAT risk and the critical nature of early detection and intervention to prevent graft loss.
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Affiliation(s)
- Ayato Obana
- Comprehensive Transplant Center, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Miho Akabane
- Comprehensive Transplant Center, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Matthew Hamilton
- Comprehensive Transplant Center, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Kejal Shah
- Comprehensive Transplant Center, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Rithin Sai Punjala
- Comprehensive Transplant Center, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Ashley Limkemann
- Comprehensive Transplant Center, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Austin Schenk
- Comprehensive Transplant Center, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Navdeep Singh
- Comprehensive Transplant Center, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Amer Rajab
- Comprehensive Transplant Center, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Ginny Bumgardner
- Comprehensive Transplant Center, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Kenneth Washburn
- Comprehensive Transplant Center, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Musab Alebrahim
- Comprehensive Transplant Center, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA
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Sim B, Chang JJ, Lin Q, Wong JHM, Ow V, Leow Y, Wong YJ, Boo YJ, Goh R, Loh XJ. Hydrogels Based on Polyelectrolyte Complexes: Underlying Principles and Biomedical Applications. Biomacromolecules 2024; 25:7563-7580. [PMID: 39557662 DOI: 10.1021/acs.biomac.4c01240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2024]
Abstract
Ionic complexes of electrostatically charged biomacromolecules are key players in various biological processes like nucleotide transportation, organelle formation, and protein folding. These complexes, abundant in biological systems, contribute to the function, responsiveness, and mechanical properties of organisms. Coherent with these natural phenomena, hydrogels formed through the complexation of oppositely charged polymers exhibit unique attributes, such as rapid self-assembly, hierarchical microstructures, tunable properties, and protective encapsulation. Consequently, polyelectrolyte complex (PEC) hydrogels have garnered considerable interest, emerging as an up-and-coming platform for various biomedical applications. This review outlines the underlying principles governing PEC hydrogels. The classification of polyelectrolytes and the self-assembly of PEC hydrogels are discussed, including the factors influencing their self-assembly process. Recent developments of PEC hydrogels for biomedical applications, including drug delivery, tissue engineering, wound healing and management, and wearable sensors, are summarized. This review concludes with the prospective directions for the next generation of PEC hydrogel research.
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Affiliation(s)
- Belynn Sim
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634, Republic of Singapore
- School of Materials Science and Engineering, Nanyang Technological University (NTU), Singapore 639798, Republic of Singapore
| | - Jun Jie Chang
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634, Republic of Singapore
| | - Qianyu Lin
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634, Republic of Singapore
| | - Joey Hui Min Wong
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634, Republic of Singapore
| | - Valerie Ow
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634, Republic of Singapore
- Department of Biomedical Engineering, National University of Singapore (NUS), 4 Engineering Drive 3, Singapore 117583, Singapore
| | - Yihao Leow
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634, Republic of Singapore
- School of Materials Science and Engineering, Nanyang Technological University (NTU), Singapore 639798, Republic of Singapore
| | - Yi Jing Wong
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634, Republic of Singapore
- School of Materials Science and Engineering, Nanyang Technological University (NTU), Singapore 639798, Republic of Singapore
| | - Yi Jian Boo
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634, Republic of Singapore
| | - Rubayn Goh
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634, Republic of Singapore
| | - Xian Jun Loh
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634, Republic of Singapore
- School of Materials Science and Engineering, Nanyang Technological University (NTU), Singapore 639798, Republic of Singapore
- Department of Materials Science and Engineering, National University of Singapore (NUS), 9 Engineering Drive, Singapore 117576, Singapore
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Liu D, Wang Y, Sun L, Pan L, Wang J, Lu Y, Cui Z, Li J, Geng H. Establishment and validation of a nomogram for predicting postoperative intestinal adhesion in children with acute appendicitis. BMC Pediatr 2024; 24:730. [PMID: 39533226 PMCID: PMC11558897 DOI: 10.1186/s12887-024-05213-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Accepted: 11/04/2024] [Indexed: 11/16/2024] Open
Abstract
PURPOSE This study aims to explore the value of multiple indicators in the evaluation of risk factors for intestinal adhesion (IA) after appendectomy in children with acute appendicitis (AA). METHODS A retrospective study was conducted on 608 patients who underwent appendectomy in the Department of Pediatric Surgery, Children's Medical Center of Jilin Province from January 2017 to April 2023, with a one-year follow-up period to record the occurrence of IA after appendectomy. Univariate and multivariate analysis were used to screen the risk factors of postoperative IA, and a prediction model was established to predict postoperative IA. RESULTS There were 527 patients in the non-IA group and 81 patients in the IA group. Binary Logistic regression was used to determine the strength of correlation with postoperative intestinal adhesion. The risk factors identified were as follows: DS ≥ 43 h (OR = 3.903, 5points), CRP ≥ 65 mg/L (OR = 3.424, 4.5points), PCT ≥ 0.9 µg/L (OR = 8.683, 8points), Surgical duration ≥ 100 min (OR = 6.457, 7points), Appendiceal perforation (OR = 6.073, 6.5points), Postoperative exhaust time ≥ 55 h (OR = 14.483, 10points). After test, the nomogram drawn based on binary logistic regression can obtain good prediction efficiency. In the training set, the area under the curve was 0.960, the sensitivity was 0.898, and the specificity was 0.905. In the test set, the area under the curve was 0.957, the sensitivity was 0.864, and the specificity was 0.906. CONCLUSION Postoperative exhaust time ≥ 55 h has a high risk of IA after appendicitis surgery in children. Early recovery of intestinal peristalsis function is essential. This scoring model is a novel and promising method for predicting postoperative IA.
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Affiliation(s)
- Dezhao Liu
- Graduate School, Changchun University of Chinese Medicine, Changchun, Jilin, 130000, China
- Department of Pediatric Surgery, Children's Medical Center of Jilin Province, Changchun, Jilin, 130000, China
| | - Yuchi Wang
- Department of Pediatric Surgery, Children's Medical Center of Jilin Province, Changchun, Jilin, 130000, China
| | - Liyun Sun
- Graduate School, Changchun University of Chinese Medicine, Changchun, Jilin, 130000, China
- Department of Pediatric Surgery, Children's Medical Center of Jilin Province, Changchun, Jilin, 130000, China
| | - Lijia Pan
- Graduate School, Changchun University of Chinese Medicine, Changchun, Jilin, 130000, China
- Department of Pediatric Surgery, Children's Medical Center of Jilin Province, Changchun, Jilin, 130000, China
| | - Junkui Wang
- Graduate School, Changchun University of Chinese Medicine, Changchun, Jilin, 130000, China
- Department of Pediatric Surgery, Children's Medical Center of Jilin Province, Changchun, Jilin, 130000, China
| | - Ying Lu
- Department of Pediatric Surgery, Children's Medical Center of Jilin Province, Changchun, Jilin, 130000, China
| | - Zhao Cui
- Department of Pediatric Surgery, Children's Medical Center of Jilin Province, Changchun, Jilin, 130000, China
| | - Jingying Li
- Department of Pediatric Surgery, Children's Medical Center of Jilin Province, Changchun, Jilin, 130000, China
| | - Hui Geng
- Graduate School, Changchun University of Chinese Medicine, Changchun, Jilin, 130000, China.
- Department of Pediatric Surgery, Children's Medical Center of Jilin Province, Changchun, Jilin, 130000, China.
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Nian H, Pu Z, Li Z, Zhong P, Ma S, Li J. Establishment and evaluation of a stable and reliable rat model of peritoneal adhesions. Surgery 2024; 176:1256-1262. [PMID: 39034213 DOI: 10.1016/j.surg.2024.06.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 06/04/2024] [Accepted: 06/19/2024] [Indexed: 07/23/2024]
Abstract
BACKGROUND In this study, we aimed to establish a stable and standardized animal model of peritoneal adhesions. METHODS Forty-eight male Sprague-Dawley rats were randomly divided (n = 12 each) into blank control, classic cecum sidewall, ischemic button, and cecum-sidewall suture groups. The modified American Fertility Society adhesion score was used on postoperative day 7 to evaluate adhesions. Sixty male Sprague-Dawley rats were used to dynamically observe the adhesion characteristics of cecum-sidewall ischemic injury suture model at different time points (n = 60, randomly divided into groups a-e with 12 rats each). The modified American Fertility Society and Zühlke histologic scoring systems, hematoxylin-eosin staining, Masson staining, and computed tomography of the abdomen were used to evaluate adhesions on postoperative days 1, 3, 5, 7, and 14. RESULTS No peritoneal adhesions were observed in the blank control group on postoperative day 7. In the classic cecum sidewall group, 8 rats had inconsistent adhesions, which had a modified American Fertility Society adhesion score of 2.25 ± 1.96. All rats in the ischemic button and cecum-sidewall suture groups developed significant adhesions with modified American Fertility Society scores of 3.08 ± 1.31 and 4.67 ± 0.78, respectively. When the modified American Fertility Society score was used, statistically significant differences were observed between the classic cecum sidewall groups and cecum-sidewall suture groups and between the ischemic button groups and cecum-sidewall suture groups. All animals in groups a-e developed adhesions; adhesion scores increased gradually with time. CONCLUSIONS The cecum-sidewall ischemic injury suture model is a stable and standardized animal model of peritoneal adhesions.
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Affiliation(s)
- Hongyu Nian
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, China; Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
| | - Zhenjun Pu
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, China; Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
| | - Zhiyuan Li
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, China
| | - Pengfei Zhong
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, China
| | - Shengxu Ma
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, China
| | - Junliang Li
- The First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, China; Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China; Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou, China; Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.
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Zhang T, Huang Y, Gong Y, Shi X, Xiao D, Ren L, Dai X, Zeng Z, Zhao C. A ROS-responsive and scavenging hydrogel for postoperative abdominal adhesion prevention. Acta Biomater 2024; 184:98-113. [PMID: 38914412 DOI: 10.1016/j.actbio.2024.06.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 06/14/2024] [Accepted: 06/18/2024] [Indexed: 06/26/2024]
Abstract
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.
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Affiliation(s)
- Tao Zhang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China
| | - Yanjuan Huang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China
| | - Yujun Gong
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China
| | - Xianmin Shi
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China
| | - Danni Xiao
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China
| | - Lingling Ren
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China
| | - Xiuling Dai
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China
| | - Zishan Zeng
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China
| | - Chunshun Zhao
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.
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10
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Chen X, Yan D, Deng H, Yang H, Peng S, Zhang W, Cai S, Zhang Q, Ren H, Yan Y. CuSO 4/H 2O 2induced polydopamine/polysulfobetaine methacrylate co-deposition on poly(amino acid) membranes for improved anti-protein adsorption and antibacterial activity. Biomed Mater 2024; 19:055008. [PMID: 38917812 DOI: 10.1088/1748-605x/ad5ba6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 06/25/2024] [Indexed: 06/27/2024]
Abstract
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.
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Affiliation(s)
- Xiaolu Chen
- College of Physics, Sichuan University, Chengdu, Sichuan 610065, People's Republic of China
| | - Dawei Yan
- College of Physics, Sichuan University, Chengdu, Sichuan 610065, People's Republic of China
| | - Hao Deng
- College of Physics, Sichuan University, Chengdu, Sichuan 610065, People's Republic of China
| | - Hulin Yang
- College of Physics, Sichuan University, Chengdu, Sichuan 610065, People's Republic of China
| | - Suping Peng
- School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, People's Republic of China
| | - Wei Zhang
- College of Physics, Sichuan University, Chengdu, Sichuan 610065, People's Republic of China
| | - Shijie Cai
- College of Physics, Sichuan University, Chengdu, Sichuan 610065, People's Republic of China
| | - Qiyi Zhang
- School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, People's Republic of China
| | - Haohao Ren
- College of Physics, Sichuan University, Chengdu, Sichuan 610065, People's Republic of China
| | - Yonggang Yan
- College of Physics, Sichuan University, Chengdu, Sichuan 610065, People's Republic of China
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11
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Lutfi H, Kirsch-Mangu TK, Fletcher-King NM, Ruden DM, Diamond MP, Saed GM. Epigenetics: new insights into postoperative adhesion development. Minerva Obstet Gynecol 2024; 76:231-237. [PMID: 36222785 DOI: 10.23736/s2724-606x.22.05158-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
BACKGROUND The link between post-operative adhesion development and epigenetic modifications is important in understanding the mechanism behind their formation. The aim of this study was to determine whether epigenetic differences exist between primary fibroblasts of normal peritoneum and adhesion tissues isolated from the same patient(s). METHODS DNA from fibroblasts isolated from normal peritoneum and adhesion tissues was isolated using Qiagen's EZ1 Advanced Kit. Methylation patterns of genes were quantified and compared in both cell lines using the Infinium Human Methylation 27 BeadChip® system (Illumina, San Diego, CA, USA). RESULTS A total of 7364 genes had been found to manifest significantly different DNA methylation levels in adhesion fibroblasts as compared to normal peritoneal fibroblasts (P<0.01). A total of 1685 genes were found to have increased DNA methylation by 50% in adhesion compared to peritoneal fibroblasts, and were enriched in gene ontology categories, glycoprotein, and defense response. Furthermore, 1287 genes were found to have decreased DNA methylation patterns with enriched gene ontology categories, "homeobox," and transcription factor activity in adhesion fibroblasts. CONCLUSIONS Epigenetic differences in fibroblasts isolated from normal peritoneum and adhesion tissues were observed. Future studies focusing on the precise role of these genes in the development of postoperative adhesions will allow us to more fully appreciate regulatory mechanisms leading to adhesion development, thereby establishing targets for therapeutic interventions to prevent or limit adhesion development.
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Affiliation(s)
- Hala Lutfi
- School of Medicine, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University, Detroit, MI, USA
| | - Thea K Kirsch-Mangu
- School of Medicine, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University, Detroit, MI, USA
| | - Nicole M Fletcher-King
- School of Medicine, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University, Detroit, MI, USA
| | - Douglas M Ruden
- School of Medicine, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University, Detroit, MI, USA
| | - Michael P Diamond
- Department of Obstetrics and Gynecology, Medical College of Georgia Augusta University, Augusta, GA, USA
| | - Ghassan M Saed
- School of Medicine, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, The C.S. Mott Center for Human Growth and Development, Wayne State University, Detroit, MI, USA -
- Karmanos Cancer Center, Detroit, MI, USA
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12
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Deng K, Li E, Li G, Ren Y, Shen T, Jiang Z, Li X, Zhou C. Research landscape of abdominal adhesions from 2004 to 2023: A bibliometric analysis. Heliyon 2024; 10:e30343. [PMID: 38707325 PMCID: PMC11068820 DOI: 10.1016/j.heliyon.2024.e30343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 03/22/2024] [Accepted: 04/24/2024] [Indexed: 05/07/2024] Open
Abstract
Adhesions are the most common complication of abdominal or pelvic surgery and remain a challenging problem. To better understand the development tendency of abdominal adhesions, we performed a comprehensive bibliometric analysis of the field of abdominal adhesions. In total, 2219 articles regarding abdominal adhesions were screened and analyzed from 3410 manuscripts indexed in the Web of Science-indexed manuscripts regarding abdominal adhesion from 2004 to 2023. A bibliometric analysis was performed, and CiteSpace [version 6.2. R3 (64-bit)] and VOSviewer (version 1.6.19) were used to visualize the results. The number of annual publications showed slight growth before 2019, and the USA contributed the most publications. The most prolific author in this domain was Diamond, while the publications from Ten Broek had the strongest influence. The most popular journal in this field was the Journal of Surgical Research, and the most frequently co-cited journal was Fertility and Sterility. After analyzing the keywords, "prevention", "surgery" and "peritoneal adhesion" were the 3 most co-cited keywords, while "adhesive small bowel obstruction" was the strongest keyword in the citation burst. Here, for the first time, we used bibliometric methods to study abdominal adhesions over the past ten years. By summarizing the characteristics of publications and predicting future research prospects, we established a framework for researchers and provided a basis for subsequent research.
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Affiliation(s)
- Kai Deng
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Enmeng Li
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Gan Li
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Yiwei Ren
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Tianli Shen
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Zhengdong Jiang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Xuqi Li
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
- Department of Talent Highland, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Cancan Zhou
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
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13
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Ren Y, Li G, Li E, Deng K, Lian J, Gao Q, Wang H, Wang X, Wang Z, Shen T, Jiang Z, Li X, Qiu G. Luteolin blocks the ROS/PI3K/AKT pathway to inhibit mesothelial-mesenchymal transition and reduce abdominal adhesions. Eur J Pharmacol 2024; 964:176272. [PMID: 38110140 DOI: 10.1016/j.ejphar.2023.176272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 11/21/2023] [Accepted: 12/08/2023] [Indexed: 12/20/2023]
Abstract
BACKGROUND Postoperative abdominal adhesion (PAA) is a common postoperative complication. Clinically, various methods have been used to prevent the occurrence of PAA, such as drugs and physiotherapy; however, no satisfactory results have been obtained. Luteolin (LUT) is a natural flavonoid that reduces inflammation and acts as an antioxidant. This research aimed to examine the impact and mechanism of LUT in reducing PAA. METHODS C57/BL6 mice were used in vivo experiments. PAA model was established using a brush friction method. Visual scoring and hematoxylin and eosin staining were used to score the severity of adhesions. Network pharmacology was used to infer potential targets and core pathways of LUT. Hydrogen peroxide (H2O2) was used to induce oxidative stress in vitro, while the reactive oxygen species (ROS) assay kit was used to evaluate oxidative stress levels. Western blotting, cell immunofluorescence, and multiple immunofluorescence assays were used to detect α-SMA, vimentin, E-cadherin, collagen I, or AKT phosphorylation level. Scratch assay was used to detect cell migration. RESULTS LUT reduced the degree of PAA in mice. It attenuated H2O2-induced ROS production and reversed mesothelial-mesenchymal transition (MMT) in HMrSV5 cells. Network pharmacology analysis showed that LUT likely exerted anti-adhesion activity by regulating the PI3K-Akt signaling pathway. Phosphorylated Akt levels were significantly reduced in LUT-treated HMrSV5 cells. LUT also significantly reduced the expression of vimentin and collagen I in adherent tissues and upregulated E-cadherin expression. CONCLUSION LUT blocks the ROS/PI3K/AKT pathway, thereby inhibiting MMT and reducing PAA. To this end, LUT has potential in PAA therapy.
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Affiliation(s)
- Yiwei Ren
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Gan Li
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Enmeng Li
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Kai Deng
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Jie Lian
- Department of Pathology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Qi Gao
- Department of General Surgery, Shaanxi Provincial People's Hospital, Xi'an Medical University, 710061 Xi'an, Shaanxi, China
| | - Huijun Wang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Xingjie Wang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Zijun Wang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Tianli Shen
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Zhengdong Jiang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China
| | - Xuqi Li
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China; Department of Talent Highland, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
| | - Guanglin Qiu
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
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14
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Serrano AB, Díaz-Cambronero Ó, Montiel M, Molina J, Núñez M, Mendía E, Mané MN, Lisa E, Martínez-Botas J, Gómez-Coronado D, Gaetano A, Casarejos MJ, Gómez A, Sanjuanbenito A. Impact of Standard Versus Low Pneumoperitoneum Pressure on Peritoneal Environment in Laparoscopic Cholecystectomy. Randomized Clinical Trial. Surg Laparosc Endosc Percutan Tech 2024; 34:1-8. [PMID: 37963307 DOI: 10.1097/sle.0000000000001244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Accepted: 10/05/2023] [Indexed: 11/16/2023]
Abstract
BACKGROUND High CO 2 pneumoperitoneum pressure during laparoscopy adversely affects the peritoneal environment. This study hypothesized that low pneumoperitoneum pressure may be linked to less peritoneal damage and possibly to better clinical outcomes. MATERIALS AND METHODS One hundred patients undergoing scheduled laparoscopic cholecystectomy were randomized 1:1 to low or to standard pneumoperitoneum pressure. Peritoneal biopsies were performed at baseline time and 1 hour after peritoneum insufflation in all patients. The primary outcome was peritoneal remodeling biomarkers and apoptotic index. Secondary outcomes included biomarker differences at the studied times and some clinical variables such as length of hospital stay, and quality and safety issues related to the procedure. RESULTS Peritoneal IL6 after 1 hour of surgery was significantly higher in the standard than in the low-pressure group (4.26±1.34 vs. 3.24±1.21; P =0.001). On the contrary, levels of connective tissue growth factor and plasminogen activator inhibitor-I were higher in the low-pressure group (0.89±0.61 vs. 0.61±0.84; P =0.025, and 0.74±0.89 vs. 0.24±1.15; P =0.028, respectively). Regarding apoptotic index, similar levels were found in both groups and were 44.0±10.9 and 42.5±17.8 in low and standard pressure groups, respectively. None of the secondary outcomes showed differences between the 2 groups. CONCLUSIONS Peritoneal inflammation after laparoscopic cholecystectomy is higher when surgery is performed under standard pressure. Adhesion formation seems to be less in this group. The majority of patients undergoing surgery under low pressure were operated under optimal workspace conditions, regardless of the surgeon's expertise.
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Affiliation(s)
| | - Óscar Díaz-Cambronero
- Department of Anesthesiology, Perioperative Medicine Research Group, Hospital Universitari i Politécnic La Fe, Valencia, Spain
- EuroPeriscope: The ESA-IC Onco-Anaesthesiology Research Group
| | | | | | | | | | | | | | | | | | - Andrea Gaetano
- Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid
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Chen J, Tang X, Wang Z, Perez A, Yao B, Huang K, Zhang Y, King MW. Techniques for navigating postsurgical adhesions: Insights into mechanisms and future directions. Bioeng Transl Med 2023; 8:e10565. [PMID: 38023705 PMCID: PMC10658569 DOI: 10.1002/btm2.10565] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 05/27/2023] [Accepted: 06/01/2023] [Indexed: 12/01/2023] Open
Abstract
Postsurgical adhesions are a common complication of surgical procedures that can lead to postoperative pain, bowel obstruction, infertility, as well as complications with future procedures. Several agents have been developed to prevent adhesion formation, such as barriers, anti-inflammatory and fibrinolytic agents. The Food and Drug Administration (FDA) has approved the use of physical barrier agents, but they have been associated with conflicting clinical studies and controversy in the clinical utilization of anti-adhesion barriers. In this review, we summarize the human anatomy of the peritoneum, the pathophysiology of adhesion formation, the current prevention agents, as well as the current research progress on adhesion prevention. The early cellular events starting with injured mesothelial cells and incorporating macrophage response have recently been found to be associated with adhesion formation. This may provide the key component for developing future adhesion prevention methods. The current use of physical barriers to separate tissues, such as Seprafilm®, composed of hyaluronic acid and carboxymethylcellulose, can only reduce the risk of adhesion formation at the end stage. Other anti-inflammatory or fibrinolytic agents for preventing adhesions have only been studied within the context of current research models, which is limited by the lack of in-vitro model systems as well as in-depth study of in-vivo models to evaluate the efficiency of anti-adhesion agents. In addition, we explore emerging therapies, such as gene therapy and stem cell-based approaches, that may offer new strategies for preventing adhesion formation. In conclusion, anti-adhesion agents represent a promising approach for reducing the burden of adhesion-related complications in surgical patients. Further research is needed to optimize their use and develop new therapies for this challenging clinical problem.
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Affiliation(s)
- Jiahui Chen
- Department of Textile Engineering, Chemistry and ScienceNorth Carolina State UniversityRaleighNorth CarolinaUSA
| | - Xiaoqi Tang
- Department of Textile Engineering, Chemistry and ScienceNorth Carolina State UniversityRaleighNorth CarolinaUSA
| | - Ziyu Wang
- Department of Textile Engineering, Chemistry and ScienceNorth Carolina State UniversityRaleighNorth CarolinaUSA
| | - Arielle Perez
- UNC School of Medicine Department of SurgeryUniversity of North CarolinaChapel HillNorth CarolinaUSA
| | - Benjamin Yao
- Montefiore Medical Center Department of Obstetrics & Gynecology & Women's Health ServicesMontefiore Medical CenterBronxNew YorkUSA
| | - Ke Huang
- Joint Department of Biomedical EngineeringNorth Carolina State University & University of North Carolina at Chapel HillRaleighNorth CarolinaUSA
- Department of Molecular Biomedical SciencesNorth Carolina State UniversityRaleighNorth CarolinaUnited States
| | - Yang Zhang
- Department of Textile Engineering, Chemistry and ScienceNorth Carolina State UniversityRaleighNorth CarolinaUSA
| | - Martin W. King
- Department of Textile Engineering, Chemistry and ScienceNorth Carolina State UniversityRaleighNorth CarolinaUSA
- College of Textiles, Donghua UniversityShanghaiSongjiangChina
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16
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Liu X, Song X, Zhang Z, Yang S, Li L, Lin C, Chen M, Liu C, Li X, Zhang Y, Hu G. Multifunctional Oxidized Dextran-Metformin as a Tissue-Adhesive Hydrogel to Prevent Postoperative Peritoneal Adhesions in Patients with Metabolic Syndrome. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2303767. [PMID: 37845002 PMCID: PMC10667813 DOI: 10.1002/advs.202303767] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 09/26/2023] [Indexed: 10/18/2023]
Abstract
Patients with metabolic syndrome (MetS) undergoing surgery are at high risk of developing peritoneal adhesions and other severe postoperative complications. However, the single shielding function and absence of physiological activity render conventional methods less useful in preventing adhesions in patients with MetS. To address this challenge, a convenient method is introduced for developing a novel tissue-adhesive hydrogel called oxidized dextran-metformin (ODE-ME) via Schiff base linkages. This injectable ODE-ME hydrogel exhibits excellent tissue-adhesive properties and various physiological functions, particularly enhanced antibacterial effects. Furthermore, in vivo experiments demonstrate that the hydrogel can effectively alleviate hyperglycemia, reduce excessive inflammation, and improve fibrinolytic activity in MetS mice, thereby preventing adhesions and promoting incisional healing. The hydrogel concurrently isolates injured tissues and lowers the blood glucose levels immediately after surgery in mice. Therefore, the ODE-ME hydrogel functions as a multifunctional barrier material and has potential for preventing postoperative peritoneal adhesions in patients with MetS in clinical settings.
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Affiliation(s)
- Xi Liu
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Tongzipo Road, Changsha, Hunan, 410013, P. R. China
| | - Xianwen Song
- Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, P. R. China
| | - Zequn Zhang
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Tongzipo Road, Changsha, Hunan, 410013, P. R. China
| | - Shutong Yang
- Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, P. R. China
| | - Liang Li
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Tongzipo Road, Changsha, Hunan, 410013, P. R. China
| | - Changwei Lin
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Tongzipo Road, Changsha, Hunan, 410013, P. R. China
| | - Miao Chen
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Tongzipo Road, Changsha, Hunan, 410013, P. R. China
| | - Chuntai Liu
- National Engineering Research Center for Advanced Polymer Processing Technology, Zhengzhou University, Zhengzhou, 450002, P. R. China
| | - Xiaorong Li
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Tongzipo Road, Changsha, Hunan, 410013, P. R. China
| | - Yi Zhang
- Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, P. R. China
| | - Gui Hu
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Tongzipo Road, Changsha, Hunan, 410013, P. R. China
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17
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Dawodu O, Baxter B, Kim JH. Update on antiadhesion barriers and therapeutics in gynecological surgery. Curr Opin Obstet Gynecol 2023; 35:352-360. [PMID: 37387697 DOI: 10.1097/gco.0000000000000892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/01/2023]
Abstract
PURPOSE OF REVIEW Postoperative adhesions remain a clinical challenge to both patients and providers, as they are associated with significant complications and a high economic burden. This article provides a clinical review of currently available antiadhesive agents and promising new therapies that have advanced past animal studies. RECENT FINDINGS Several agents have been investigated on their ability to reduce adhesion formation; however, there is no widely acceptable option. The few available interventions are barrier agents and while low-quality evidence suggests that they may be more effective than no treatment, there is no general agreement on their overall efficacy. There is an abundance of research on new solutions; however, their clinical efficacy is yet to be determined. SUMMARY Although a wide range of therapeutics have been investigated, majority are halted in animal models with only a select few being studied in humans and ultimately available in the market. Many agents have shown effectiveness in reducing adhesion formation, however, that has not been translated to improvement in clinically relevant outcomes; hence the need for high-quality large randomized trials.
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Affiliation(s)
- Olanrewaju Dawodu
- Division of Gynecologic Specialty Surgery, Department of Obstetrics & Gynecology, Columbia University Irving Medical Center, New York, New York, USA
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Liu H, Xu H, Sun H, Xu H, Han J, Zhao L, Li X, Sun X, Dong X, Xu R, Chen Z, Du M, Tang P, Chen Y, Lin Y, Zhang Y, Han W, Liu X. Tetrahydroberberrubine prevents peritoneal adhesion by suppressing inflammation and extracellular matrix accumulation. Eur J Pharmacol 2023:175803. [PMID: 37295764 DOI: 10.1016/j.ejphar.2023.175803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 05/09/2023] [Accepted: 05/22/2023] [Indexed: 06/12/2023]
Abstract
Peritoneal adhesion is a common abdominal surgical complication that induces abdominal haemorrhage, intestinal obstruction, infertility, and so forth. The high morbidity and recurrence rate of this disease indicate the need for novel therapeutic approaches. Here, we revealed the protective roles of tetrahydroberberrubine (THBru), a novel derivative of berberine (BBR), in preventing peritoneal adhesion and identified its underlying mechanism in vivo and in vitro. Abrasive surgery was used to create a peritoneal adhesion rat model. We found that THBru administration markedly ameliorated peritoneal adhesion, as indicated by a lowered adhesion score and ameliorated caecal tissue damage. By comparison, THBru exhibited more potent anti-adhesion effects than BBR at the same dose. Mechanistically, THBru inhibited inflammation and extracellular matrix (ECM) accumulation in the microenvironment of adhesion tissue. THBru suppressed the expression of inflammatory cytokines including interleukin-1β (IL-1β), IL-6, transforming growth factor β (TGF-β), tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1), by regulating the transforming growth factor beta-activated kinase 1 (TAK1)/c-Jun N-terminal kinase (JNK) and TAK1/nuclear factor κB (NF-κB) signaling pathways. However, THBru promoted the activation of MMP-3 by directly blocking the TIMP-1 activation core and subsequently decreased collagen deposition. Taken together, this study identifies THBru as an effective anti-adhesion agent that regulates diverse mechanisms, thereby outlining its potential therapeutic implications for the treatment of peritoneal adhesion.
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Affiliation(s)
- Heng Liu
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China
| | - Henghui Xu
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China
| | - Heyang Sun
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China
| | - Honglin Xu
- Department of Michael Smith Building, Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - Jingjing Han
- Department of Pharmaceutics, Caoxian People's Hospital, Shandong, People's Republic of China
| | - Limin Zhao
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China
| | - Xiaohan Li
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China
| | - XiuXiu Sun
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China
| | - Xinxin Dong
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China
| | - Run Xu
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China
| | - Zhouxiu Chen
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China
| | - Menghan Du
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China
| | - Pingping Tang
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China
| | - Yongchao Chen
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China
| | - Yuan Lin
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China
| | - Yong Zhang
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China
| | - Weina Han
- Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Harbin, 150081, People's Republic of China.
| | - Xin Liu
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, People's Republic of China.
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Wang YL, Zhang HX, Chen YQ, Yang LL, Li ZJ, Zhao M, Li WL, Bian YY, Zeng L. Research on Mechanisms of Chinese Medicines in Prevention and Treatment of Postoperative Adhesion. Chin J Integr Med 2023; 29:556-565. [PMID: 37052766 DOI: 10.1007/s11655-023-3735-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/13/2022] [Indexed: 04/14/2023]
Abstract
Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.
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Affiliation(s)
- Ya-Li Wang
- School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- Jiangsu Provincial Engineering Center of Traditional Chinese Medicine External Medication Researching and Industrializing, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Hui-Xiang Zhang
- School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yan-Qi Chen
- School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- Jiangsu Provincial Engineering Center of Traditional Chinese Medicine External Medication Researching and Industrializing, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Li-Li Yang
- School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- Jiangsu Provincial Engineering Center of Traditional Chinese Medicine External Medication Researching and Industrializing, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- Jingwen Library, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Zheng-Jun Li
- College of Health Economics Management, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Min Zhao
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Wen-Lin Li
- Jingwen Library, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yao-Yao Bian
- Jiangsu Provincial Engineering Center of Traditional Chinese Medicine External Medication Researching and Industrializing, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- School of Second Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Li Zeng
- School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
- Jiangsu Provincial Engineering Center of Traditional Chinese Medicine External Medication Researching and Industrializing, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
- Jingwen Library, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
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Ghimire P, Maharjan S. Adhesive Small Bowel Obstruction: A Review. JNMA J Nepal Med Assoc 2023; 61:390-396. [PMID: 37208871 PMCID: PMC10089019 DOI: 10.31729/jnma.8134] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Indexed: 08/10/2023] Open
Abstract
UNLABELLED Adhesion is a leading cause of small bowel obstruction. Adhesive small bowel obstruction has significant challenges in diagnosis, treatment and prevention with considerable impact on morbidity and socioeconomic burden. Small bowel obstruction caused by adhesion or any other aetiology is clinically indistinguishable due to similar clinical presentation. Computed Tomography scans and water-soluble contrast studies are more specific in diagnosis and possess value in predicting the need for surgery. Surgical management is indicated only in complicated cases or failed conservative treatments with the majority resolving with non-operative management. However, there is no clear-cut consensus about the timing of operative intervention. Meticulous surgical practice is the keystone in preventing adhesion formation despite the availability of numerous pharmacological and surgical strategies. This review aims to update the current knowledge of the pathophysiology of adhesion formation, treatment options and various prevention modalities of adhesive small bowel obstruction. KEYWORDS diagnosis; laparotomy; prevention; surgery.
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Affiliation(s)
- Pradeep Ghimire
- Department of Surgery, Manipal College of Medical Sciences, Fulbari, Pokhara, Nepal
| | - Shailesh Maharjan
- Department of Surgery, Manipal College of Medical Sciences, Fulbari, Pokhara, Nepal
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Zou Y, Yue P, Cao H, Wu L, Xu L, Liu Z, Wu S, Ye Q. Biocompatible and biodegradable chitin-based hydrogels crosslinked by BDDE with excellent mechanical properties for effective prevention of postoperative peritoneal adhesion. Carbohydr Polym 2023; 305:120543. [PMID: 36737194 DOI: 10.1016/j.carbpol.2023.120543] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 12/23/2022] [Accepted: 01/02/2023] [Indexed: 01/07/2023]
Abstract
Postoperative peritoneal adhesions are common complications caused by abdominal and pelvic surgery, which seriously impact the quality of life of patients and impose additional financial burdens. Using of biomedical materials as physical barriers to completely isolate the traumatic organ and injured tissue is an optimal strategy for preventing postoperative adhesions. However, the limited efficacy and difficulties in the complete degradation or integration of biomedical materials with living tissues restrict the application of these materials. In this study, novel chitin-based crosslinked hydrogels with appropriate mechanical properties and flexibilities were developed using a facile and green strategy. The developed hydrogels simultaneously exhibited excellent biocompatibilities and resistance to nonspecific protein adsorption and NIH/3T3 fibroblast adhesion. Furthermore, these hydrogels were biodegradable and could be completely integrated into the native extracellular matrix. The chitin-based crosslinked hydrogels also effectively inhibited postoperative peritoneal adhesions in rat models of adhesion and recurrence. Therefore, these novel chitin-based crosslinked hydrogels are excellent candidate physical barriers for the efficient prevention of postoperative peritoneal adhesions and provide a new anti-adhesion strategy for biomedical applications.
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Affiliation(s)
- Yongkang Zou
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan 430071, China
| | - Pengpeng Yue
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan 430071, China
| | - Hankun Cao
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan 430071, China
| | - Liqin Wu
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan 430071, China
| | - Li Xu
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan 430071, China
| | - Zhongzhong Liu
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan 430071, China
| | - Shuangquan Wu
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan 430071, China.
| | - Qifa Ye
- Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-based Medical Materials, Wuhan 430071, China; The Third Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha 410013, China.
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22
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Zhou J, Wang H, Chen H, Ling Y, Xi Z, Lv M, Chen J. pH-responsive nanocomposite hydrogel for simultaneous prevention of postoperative adhesion and tumor recurrence. Acta Biomater 2023; 158:228-238. [PMID: 36563777 DOI: 10.1016/j.actbio.2022.12.025] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 12/09/2022] [Accepted: 12/14/2022] [Indexed: 12/24/2022]
Abstract
Abdominal adhesion and tumor recurrence are two thorny problems in the postoperative treatment of abdominal tumors. Although important progress has been made in the application of hydrogels in adjuvant therapy after tumor surgery, most of the products can not effectively combine the prevention of abdominal adhesion and the removal of residual cancer cells. In this study, a nanocomposite hydrogel (Col-APG-Cys@HHD) was prepared by crosslinking collagen and recombinant albumin nanoparticles (HHD NPs) with aldehydeylated polyethylene glycol (APG6K) followed by immobilizing zwitterionic cysteine (Cys) to one surface. One surface of the hydrogel adhered to the postoperative wound due to the adhesive properties of collagen, while the other surface coated with cysteine formed a hydration layer to hinder the stick of proteins and cells, thereby reducing the adhesion between tissues. Additionally, Col-APG-Cys@HHD hydrogel disintegrated under acidic condition and released HHD NPs that targeted into cancer cells and released drugs in response to low pH environment. The in vivo experiments' results demonstrated that Col-APG-Cys@HHD hydrogel could prevent intraperitoneal adhesions and inhibit tumor growth with minimal side effects, providing a potential strategy for the hydrogel-based drug delivery system in postoperative adjuvant therapy of tumors. STATEMENT OF SIGNIFICANCE: Tissue adhesion and tumor recurrence usually occur after abdominal tumor surgery. Hydrogels have been widely studied in adjuvant treatment of abdominal tumors, but their synergy in terms of controllable drug release and anti-peritoneal adhesion still needs to be improved. Herein, a nanocomposite hydrogel (Col-APG-Cys@HHD) was designed and constructed with one side that was tissue adhesive and the other side as antifouling. Additionally, the Col-APG-Cys@HHD hydrogel showed controlled drug release behavior in response to a pH gradient (6.5 to 5.5). This was conducive to its dissociation in an acidic tumor environment followed by the release of nanoparticles that entered into tumor cells and delivered docetaxel . To sum up, the Col-APG-Cys@HHD hydrogel demonstrated synergistic therapy for prevention of abdominal adhesion and tumor recurrence after abdominal tumor surgery.
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Affiliation(s)
- Juan Zhou
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China
| | - Hong Wang
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China
| | - Hao Chen
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China
| | - Yan Ling
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China
| | - Ziqi Xi
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China
| | - Mingting Lv
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China
| | - Jinghua Chen
- School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China.
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23
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Chizen DR, Rislund DC, Robertson LM, Lim HJ, Tulandi T, Gargiulo AR, De Wilde RL, Velygodskiy A, Pierson RA. A Randomized Double-Blind Controlled Proof-of-Concept Study of Alanyl-Glutamine for Reduction of Post-Myomectomy Adhesions. Eur J Obstet Gynecol Reprod Biol 2023; 284:180-188. [PMID: 37023559 DOI: 10.1016/j.ejogrb.2023.03.032] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 03/16/2023] [Accepted: 03/27/2023] [Indexed: 03/31/2023]
Abstract
STUDY OBJECTIVE To test the hypothesis that intraperitoneal instillation of a single bolus dose of l-alanyl-l-glutamine (AG) will reduce the incidence, extent and/or severity of adhesions following myomectomy and establish preliminary safety and tolerability of AG in humans. DESIGN Phase 1,2 Randomized, double-blind, placebo-controlled study (DBRCT). SETTING Tertiary care gynecology surgical centre. PATIENTS Thirty-eight women who underwent myomectomies by laparoscopy (N = 38; AG-19 vs Placebo-19) or laparotomy (N = 10; AG-5 vs Placebo-5) with a scheduled second-look laparoscopy (SLL) 6-8 weeks later. Thirty-two patients in the laparoscopy arm completed SLL. INTERVENTIONS Bolus dose of AG or normal saline solution control (0.9% NaCl) administered intraperitoneally immediately prior to suture closure of the laparoscopic ports. The average dose was 170 mL of AG or control based on a dosing scheme of 1 g/kg bodyweight. MEASUREMENTS Digital recordings obtained for all procedures. The primary endpoint was reduction in the incidence, severity and extent of post-operative adhesions analyzed by intention-to-treat (ITT) approach. Three independent, blinded reviewers evaluated all operative video recordings to assess presence of adhesions. Post-hoc analysis assessed presence or absence of adhesions in the peritoneal cavity. Secondary endpoints assessed safety and tolerability of AG. MAIN RESULTS Administration of AG reduced the incidence, severity and/or extent of post-operative adhesions (p = 0.046). The presence of adhesions in the AG group was lower than in the Control group (p = 0.041). Adhesion improvement was achieved in 15 of 15 (100%) in the AG group versus 5 of 17 (29.6%) in the placebo group. No serious adverse events were reported. No differences in safety parameters were observed. CONCLUSIONS Intraperitoneal l-alanyl-l-glutamine reduced adhesion formation in all patients following laparoscopic myomectomy. Complete absence of adhesions was achieved at all abdominal sites in 93% of patients. Results confirm AG's known effects on cellular mechanisms of adhesiogenesis and lay the foundation for new adhesion prophylaxis research and treatment.
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Liu B, Kong Y, Alimi OA, Kuss MA, Tu H, Hu W, Rafay A, Vikas K, Shi W, Lerner M, Berry WL, Li Y, Carlson MA, Duan B. Multifunctional Microgel-Based Cream Hydrogels for Postoperative Abdominal Adhesion Prevention. ACS NANO 2023; 17:3847-3864. [PMID: 36779870 PMCID: PMC10820954 DOI: 10.1021/acsnano.2c12104] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
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.
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Affiliation(s)
- Bo Liu
- Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, 68198, USA
- Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Yunfan Kong
- Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, 68198, USA
- Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Olawale A. Alimi
- Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, 68198, USA
- Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Mitchell A. Kuss
- Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, 68198, USA
- Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Huiyin Tu
- Department of Emergency Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Wenfeng Hu
- Department of Emergency Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Abu Rafay
- Mass Spectrometry & Proteomics Core, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Kumar Vikas
- Mass Spectrometry & Proteomics Core, University of Nebraska Medical Center, Omaha, NE, 68198, USA
- Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Wen Shi
- Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, 68198, USA
- Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Megan Lerner
- Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA
| | - William L. Berry
- Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA
| | - Yulong Li
- Department of Emergency Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Mark A. Carlson
- Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA
- Department of Surgery-General Surgery, University of Nebraska Medical Center, Omaha, NE, 68198, USA
| | - Bin Duan
- Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, 68198, USA
- Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA
- Department of Surgery-General Surgery, University of Nebraska Medical Center, Omaha, NE, 68198, USA
- Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588, USA
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25
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De Lazari MGT, Viana CTR, Pereira LX, Orellano LAA, Ulrich H, Andrade SP, Campos PP. Sodium butyrate attenuates peritoneal fibroproliferative process in mice. Exp Physiol 2023; 108:146-157. [PMID: 36459573 PMCID: PMC10103766 DOI: 10.1113/ep090559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 11/07/2022] [Indexed: 12/03/2022]
Abstract
NEW FINDINGS What is the central question of this study? Peritoneal injury can result in a persistent fibroproliferative process in the abdominal cavity, causing pain and loss of function of internal organs. This study aimed to demonstrate the use of sodium butyrate (NaBu) as a potential agent to attenuate peritoneal fibrosis induced by a synthetic matrix. What is the main finding and its importance? Our findings provide the first evidence that NaBu attenuates the inflammatory, angiogenesis and fibrogenesis axes involved in the formation of peritoneal fibrovascular tissue, indicating the potential of this compound to ameliorate peritoneal fibrosis. ABSTRACT The aim of this study was to identify the bio-efficacy of sodium butyrate (NaBu) on preventing the development of peritoneal fibrovascular tissue induced by implantation of a synthetic matrix in the abdominal cavity. Polyether-polyurethane sponge discs were implanted in the peritoneal cavity of mice, which were treated daily with oral administration of NaBu (100 mg/kg). Control animals received water (100 μl). After 7 days, the implants were removed for assessment of inflammatory, angiogenic and fibrogenic markers. Compared with control values, NaBu treatment decreased mast cell recruitment/activation, inflammatory enzyme activities, levels of pro-inflammatory cytokines, and the proteins p65 and p50 of the nuclear factor-κB pathway. Angiogenesis, as determined by haemoglobin content, vascular endothelial growth factor levels and the number of blood vessels in the implant, was reduced by the treatment. In NaBu-treated animals, the predominant collagen present in the abdominal fibrovascular tissue was thin collagen, whereas in control implants it was thick collagen. Transforming growth factor-β1 levels were also lower in implants of treated animals. Sodium butyrate downregulated the inflammatory, angiogenesis and fibrogenesis axes of the fibroproliferative tissue induced by the intraperitoneal synthetic matrix. This compound has potential to control/regulate chronic inflammation and adverse healing processes in the abdominal cavity.
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Affiliation(s)
| | | | - Luciana Xavier Pereira
- Department of Experimental PathologyUniversidade Federal de São João del‐ReiDivinópolisMinas GeraisBrazil
| | | | - Henning Ulrich
- Department of BiochemistryInstitute of ChemistryUniversity of São PauloSão PauloSão PauloBrazil
| | - Silvia Passos Andrade
- Department of Physiology and BiophysicsInstitute of Biological SciencesUniversidade Federal de Minas GeraisBelo HorizonteMinas GeraisBrazil
| | - Paula Peixoto Campos
- Department of General PathologyInstitute of Biological SciencesUniversidade Federal de Minas GeraisBelo HorizonteMinas GeraisBrazil
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Erdi M, Rozyyev S, Balabhadrapatruni M, Saruwatari MS, Daristotle JL, Ayyub OB, Sandler AD, Kofinas P. Sprayable tissue adhesive with biodegradation tuned for prevention of postoperative abdominal adhesions. Bioeng Transl Med 2023; 8:e10335. [PMID: 36684071 PMCID: PMC9842025 DOI: 10.1002/btm2.10335] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 04/20/2022] [Accepted: 04/23/2022] [Indexed: 01/25/2023] Open
Abstract
Adhesions are dense, fibrous bridges that adjoin tissue surfaces due to uncontrolled inflammation following postoperative mesothelial injury. A widely used adhesion barrier material in Seprafilm often fails to prevent transverse scar tissue deposition because of its poor mechanical properties, rapid degradation profile, and difficulty in precise application. Solution blow spinning (SBS), a polymer fiber deposition technique, allows for the placement of in situ tissue-conforming and tissue-adherent scaffolds with exceptional mechanical properties. While biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) have desirable strength, they exhibit bulk biodegradation rates and inflammatory profiles that limit their use as adhesion barriers and result in poor tissue adhesion. Here, viscoelastic poly(lactide-co-caprolactone) (PLCL) is used for its pertinent biodegradation mechanism. Because it degrades via surface erosion, spray deposited PLCL fibers can dissolve new connections formed by inflamed tissue, allowing them to function as an effective, durable, and easy-to-apply adhesion barrier. Degradation kinetics are tuned to match adhesion formation through the design of PLCL blends comprised of highly adhesive "low"-molecular weight (LMW) constituents in a mechanically robust "high"-molecular weight (HMW) matrix. In vitro studies demonstrate that blending LMW PLCL (30% w/v) with HMW PLCL (70% w/v) yields an anti-fibrotic yet tissue-adhesive polymer sealant with a 14-day erosion rate countering adhesion formation. PLCL blends additionally exhibit improved wet tissue adhesion strength (~10 kPa) over a 14-day period versus previously explored biodegradable polymer compositions, such as PLGA. In a mouse cecal ligation model, select PLCL blends significantly reduce abdominal adhesions severity versus no treatment and Seprafilm-treated controls.
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Affiliation(s)
- Metecan Erdi
- Department of Chemical and Biomolecular EngineeringUniversity of MarylandCollege ParkMarylandUSA
| | - Selim Rozyyev
- Sheikh Zayed Institute for Pediatric Surgical Innovation, Joseph E. Robert Jr. Center for Surgical CareChildren's National Medical CenterWashingtonDistrict of ColumbiaUSA
| | | | - Michele S. Saruwatari
- Sheikh Zayed Institute for Pediatric Surgical Innovation, Joseph E. Robert Jr. Center for Surgical CareChildren's National Medical CenterWashingtonDistrict of ColumbiaUSA
| | - John L. Daristotle
- David H. Koch Institute for Integrative Cancer ResearchMassachusetts Institute of TechnologyCambridgeMassachusettsUSA
| | - Omar B. Ayyub
- Department of Chemical and Biomolecular EngineeringUniversity of MarylandCollege ParkMarylandUSA
| | - Anthony D. Sandler
- Sheikh Zayed Institute for Pediatric Surgical Innovation, Joseph E. Robert Jr. Center for Surgical CareChildren's National Medical CenterWashingtonDistrict of ColumbiaUSA
| | - Peter Kofinas
- Department of Chemical and Biomolecular EngineeringUniversity of MarylandCollege ParkMarylandUSA
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Moradi E, Rakhshandeh H, Rahimi Baradaran V, Ghadiri M, Hasanpour M, Iranshahi M, Askari V. HPLC/MS characterization of Syzygium aromaticum L. and evaluation of its effects on peritoneal adhesion: Investigating the role of inflammatory cytokines, oxidative factors, and fibrosis and angiogenesis biomarkers. Physiol Rep 2023; 11:e15584. [PMID: 36695659 PMCID: PMC9875745 DOI: 10.14814/phy2.15584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 01/04/2023] [Accepted: 01/05/2023] [Indexed: 01/26/2023] Open
Abstract
The dried flower bud of Syzygium aromaticum L. (S. aromaticum) (Myrtaceae), cloves, have been used for their analgesic and anti-inflammatory activities. Peritoneal adhesion (PA) is the most common complication of abdominal and pelvic surgeries, which causes significant adverse effects and severe economic burden. The present study aimed to evaluate the preventive effect of S. extract (SAE) on PA formation in a rat model. Male Wistar 8-week-old rats were randomly divided into sham, control (received vehicle), and treatment (0.25%, 0.5%, and 1% w/v of SAE) groups. The adhesion and related factors were examined using the Nair scoring system and immunological and biochemical kits for the levels of inflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)-α], growth factors [transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF)], oxidative [nitric oxide (NO) and malondialdehyde (MDA)], and anti-oxidative [glutathione (GSH)] factors. Our results figured out that the adhesion score and IL-6, TNF-α, TGF-β1, VEGF, NO, and MDA levels were significantly increased, but the GSH level was decreased in the control group compared to the sham group (p < 0.001-0.05). On the other hand, the 0.25% SAE group had a lower adhesion score, and IL-6, TNF-α, TGF-β1, VEGF, NO, and MDA levels were significantly decreased compared with the vehicle group, and the level of GSH was increased (p < 0.001-0.05). SAE could efficiently reduce adhesion score and regulate inflammatory cytokines, oxidative and anti-oxidative factors, and biomarkers of fibrosis and angiogenesis. Therefore, clove extract can be considered a potential candidate for PA management.
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Affiliation(s)
- Elham Moradi
- Pharmacological Research Center of Medicinal PlantsMashhad University of Medical SciencesMashhadIran
| | - Hassan Rakhshandeh
- Pharmacological Research Center of Medicinal PlantsMashhad University of Medical SciencesMashhadIran
| | - Vafa Rahimi Baradaran
- Department of Cardiovascular Diseases, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
| | - Mobarakeh Ghadiri
- Pharmacological Research Center of Medicinal PlantsMashhad University of Medical SciencesMashhadIran
| | - Maedeh Hasanpour
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical SciencesMashhadIran
| | - Mehrdad Iranshahi
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical SciencesMashhadIran
| | - Vahid Reza Askari
- International UNESCO Center for Health‐Related Basic Sciences and Human NutritionMashhad University of Medical SciencesMashhadIran
- Applied Biomedical Research CenterMashhad University of Medical SciencesMashhadIran
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EROĞLU E, UYANIKGİL Y. İntrabdominal Adezyon Oluşum Mekanizmalarına ve Tedavi Stratejilerine Histopatolojik Bakış. ARŞIV KAYNAK TARAMA DERGISI 2022. [DOI: 10.17827/aktd.1116761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Hayat standartlarını olumsuz etkileyen abdominal adezyonlar, postoperatif dönemde görülen önemli bir sağlık sorunudur. Peritoneal kavite ve serozal yüzeylerde oluşan, abdominal travmalara sebep olan kimyasal ve termal faktörler ya da enfeksiyon ve yabancı cisim reaksiyonları adezyon oluşumuna sebep olabilir. Abdominal adezyonların sınıflandırması genellikle adezyon yoğunluğuna ve prognoz ciddiyetine göre yapılsa da henüz dünya çapında kabul görmüş standart bir sınıflandırma sistemi mevcut değildir. Abdominal adezyonlar ağrı, infertilite, cerrahi sonrası hastanede yatış süresinin uzaması ve ekonomik yük gibi olumsuz sonuçlarla klinik yansımalar gösterir. Sonuç olarak, postoperatif süreçte karşılaşılan adezyonlar ciddi bir sorundur ve adezyon oluşumunu engellemek için ileri çalışmaların laboratuvar ortamından klinik araştırma modellerine uyarlanması gerekmektedir. Bu derleme çalışması intraabdominal adezyon oluşumu, histopatolojisi, derecelendirilmesi, önlenmesi ve klinik önemi ile ilgili literatürü gözden geçirmek için hazırlanmıştır.
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Nadri S, Rahmani A, Hosseini SH, Habibizadeh M, Araghi M, Mostafavi H. Prevention of peritoneal adhesions formation by core-shell electrospun ibuprofen-loaded PEG/silk fibrous membrane. ARTIFICIAL CELLS, NANOMEDICINE, AND BIOTECHNOLOGY 2022; 50:40-48. [PMID: 35296208 DOI: 10.1080/21691401.2021.1883043] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Revised: 01/15/2021] [Accepted: 01/24/2021] [Indexed: 06/14/2023]
Abstract
Adhesion bands are pathological fibrous tissues that create in the middle of tissues and organs, often reasons of intestinal obstruction, and female infertility. Here, we explored the anti-adhesive and inflammatory capacities of PEG/silk and Ibuprofen-loaded PEG/Silk core-shell nanofibrous membranes, respectively. The ibuprofen-loaded Silk Fibroin-Poly ethylene Glycol (SF-PEG) core-shell membrane was fabricated by electrospinning and considered in terms of morphology, surface wettability, drug release, and degradation. To reveal the membrane capability for adhesion bands inhibition, the membrane was stitched among the abdominal partition and peritoneum and then evaluated using two scoring adhesion systems. According to results, the fibrous membrane hindered cell proliferation, and the scoring systems and pathology showed that in a rat model, Ibuprofen-loaded PEG/Silk core-shell membrane caused a lightening in post-operative adhesion bands and the low-grade inflammatory reaction in animal models. Collectively, we fabricated new ibuprofen-loaded PEG/SF membranes with anti-adhesion and anti-inflammation properties. Moreover, this core-shell electrospun fibrous membrane has not even now been used to prevent peritendinous adhesion generation.
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Affiliation(s)
- Samad Nadri
- Department of Medical Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
- Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
- Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Ali Rahmani
- Department of Medical Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Seyed Hojjat Hosseini
- Department of Pharmacology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mina Habibizadeh
- Department of Pharmacy Biomaterial, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Mahmood Araghi
- Department of Pathology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Hossein Mostafavi
- Department of Physiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
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Gao J, Wen J, Hu D, Liu K, Zhang Y, Zhao X, Wang K. Bottlebrush inspired injectable hydrogel for rapid prevention of postoperative and recurrent adhesion. Bioact Mater 2022; 16:27-46. [PMID: 35386330 PMCID: PMC8958549 DOI: 10.1016/j.bioactmat.2022.02.015] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/28/2022] [Accepted: 02/10/2022] [Indexed: 12/28/2022] Open
Abstract
Postsurgical adhesion is a common clinic disease induced by surgical trauma, accompanying serious subsequent complications. Current non-surgical approaches of drugs treatment and biomaterial barrier administration only show limited prevention effects and couldn't effectively promote peritoneum repair. Herein, inspired by bottlebrush, a novel self-fused, antifouling, and injectable hydrogel is fabricated by the free-radical polymerization in aqueous solution between the methacrylate hyaluronic acid (HA-GMA) and N-(2-hydroxypropyl) methacrylamide (HPMA) monomer without any chemical crosslinkers, termed as H-HPMA hydrogel. The H-HPMA hydrogel can be tuned to perform excellent self-fused properties and suitable abdominal metabolism time. Intriguingly, the introduction of the ultra-hydrophilic HPMA chains to the H-HPMA hydrogel affords an unprecedented antifouling capability. The HPMA chains establish a dense hydrated layer that rapidly prevents the postsurgical adhesions and recurrent adhesions after adhesiolysis in vivo. The H-HPMA hydrogel can repair the peritoneal wound of the rat model within 5 days. Furthermore, an underlying mechanism study reveals that the H-HPMA hydrogel significantly regulated the mesothelial-to-mesenchymal transition (MMT) process dominated by the TGF-β-Smad2/3 signal pathway. Thus, we developed a simple, effective, and available approach to rapidly promote peritoneum regeneration and prevent peritoneal adhesion and adhesion recurrence after adhesiolysis, offering novel design ideas for developing biomaterials to prevent peritoneal adhesion.
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Affiliation(s)
- Jushan Gao
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Jinpeng Wen
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Datao Hu
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Kailai Liu
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Yuchen Zhang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Xinxin Zhao
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China
| | - Ke Wang
- School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, China
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Lai CW, Bagadia P, Barisas DAG, Jarjour NN, Wong R, Ohara T, Muegge BD, Lu Q, Xiong S, Edelson BT, Murphy KM, Stappenbeck TS. Mesothelium-Derived Factors Shape GATA6-Positive Large Cavity Macrophages. THE JOURNAL OF IMMUNOLOGY 2022; 209:742-750. [DOI: 10.4049/jimmunol.2200278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 06/15/2022] [Indexed: 01/04/2023]
Abstract
Abstract
The local microenvironment shapes macrophage differentiation in each tissue. We hypothesized that in the peritoneum, local factors in addition to retinoic acid can support GATA6-driven differentiation and function of peritoneal large cavity macrophages (LCMs). We found that soluble proteins produced by mesothelial cells lining the peritoneal cavity maintained GATA6 expression in cultured LCMs. Analysis of global gene expression of isolated mesothelial cells highlighted mesothelin (Msln) and its binding partner mucin 16 (Muc16) as candidate secreted ligands that potentially regulate GATA6 expression in peritoneal LCMs. Mice deficient for either of these molecules showed diminished GATA6 expression in peritoneal and pleural LCMs that was most prominent in aged mice. The more robust phenotype in older mice suggested that monocyte-derived macrophages were the target of Msln and Muc16. Cell transfer and bone marrow chimera experiments supported this hypothesis. We found that lethally irradiated Msln−/− and Muc16−/− mice reconstituted with wild-type bone marrow had lower levels of GATA6 expression in peritoneal and pleural LCMs. Similarly, during the resolution of zymosan-induced inflammation, repopulated peritoneal LCMs lacking expression of Msln or Muc16 expressed diminished GATA6. These data support a role for mesothelial cell–produced Msln and Muc16 in local macrophage differentiation within large cavity spaces such as the peritoneum. The effect appears to be most prominent on monocyte-derived macrophages that enter into this location as the host ages and also in response to infection.
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Affiliation(s)
- Chin-Wen Lai
- Department of Pathology and Immunology, Washington University Medical School, St. Louis, MO
| | - Prachi Bagadia
- Department of Pathology and Immunology, Washington University Medical School, St. Louis, MO
| | - Derek A. G. Barisas
- Department of Pathology and Immunology, Washington University Medical School, St. Louis, MO
| | - Nicholas N. Jarjour
- Department of Pathology and Immunology, Washington University Medical School, St. Louis, MO
| | - Rachel Wong
- Department of Pathology and Immunology, Washington University Medical School, St. Louis, MO
| | - Takahiro Ohara
- Department of Pathology and Immunology, Washington University Medical School, St. Louis, MO
| | - Brian D. Muegge
- Department of Pathology and Immunology, Washington University Medical School, St. Louis, MO
| | - Qiuhe Lu
- Department of Pathology and Immunology, Washington University Medical School, St. Louis, MO
| | - Shanshan Xiong
- Department of Pathology and Immunology, Washington University Medical School, St. Louis, MO
| | - Brian T. Edelson
- Department of Pathology and Immunology, Washington University Medical School, St. Louis, MO
| | - Kenneth M. Murphy
- Department of Pathology and Immunology, Washington University Medical School, St. Louis, MO
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Combined treatment of xyloglucan derivative hydrogel and anti-C5a receptor antibody in preventing peritoneal adhesion. Acta Biomater 2022; 151:163-173. [DOI: 10.1016/j.actbio.2022.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 07/15/2022] [Accepted: 08/01/2022] [Indexed: 11/19/2022]
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Rosendorf J, Klicova M, Herrmann I, Anthis A, Cervenkova L, Palek R, Treska V, Liska V. Intestinal Anastomotic Healing: What do We Know About Processes Behind Anastomotic Complications. Front Surg 2022; 9:904810. [PMID: 35747439 PMCID: PMC9209641 DOI: 10.3389/fsurg.2022.904810] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 05/11/2022] [Indexed: 11/13/2022] Open
Abstract
Colorectal surgery has developed rapidly in the recent decades. Nevertheless, colorectal anastomotic leakage continues to appear postoperatively in unpleasant rates and leads to life-threatening conditions. The development of valid complication-preventing methods is inefficient in many aspects as we are still lacking knowledge about the basics of the process of anastomotic wound healing in the gastrointestinal tract. Without the proper understanding of the crucial mechanisms, research for prevention of anastomotic leakage is predestined to be unsuccessful. This review article discusses known pathophysiological mechanisms together with the most lately found processes to be further studied. The aim of the article is to facilitate the orientation in the topic, support the better understanding of known mechanisms and suggest promising possibilities and directions for further research.
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Affiliation(s)
- J. Rosendorf
- Department of Surgery, University Hospital in Pilsen, Pilsen, Czech Republic
- Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
- Correspondence: Jachym Rosendorf
| | - M. Klicova
- Department of Nonwovens and Nanofibrous Materials, Faculty of Textile Engineering, Technical University of Liberec, Liberec, Czech Republic
| | - I. Herrmann
- Department of Mechanical and Process Engineering, Nanoparticle Systems Engineering Laboratory, ETH Zurich, Switzerland
| | - A. Anthis
- Department of Mechanical and Process Engineering, Nanoparticle Systems Engineering Laboratory, ETH Zurich, Switzerland
| | - L. Cervenkova
- Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - R. Palek
- Department of Surgery, University Hospital in Pilsen, Pilsen, Czech Republic
- Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - V. Treska
- Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - V. Liska
- Department of Surgery, University Hospital in Pilsen, Pilsen, Czech Republic
- Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
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Abstract
BACKGROUND Peritoneal adhesion formation is common after abdominal surgery and results in severe complications. Tissue hypoxia is one of the main drivers of peritoneal adhesions. Thus, we determined the clinical role of hypoxia-inducible factor (HIF)-1 signaling in peritoneal adhesions and investigated whether the biguanide antidiabetic drug metformin shows HIF-inhibitory effects and could be repurposed to prevent adhesion formation. STUDY DESIGN As part of the ReLap study (DRKS00013001), adhesive tissue from patients undergoing relaparotomy was harvested and graded using the adhesion grade score. HIF-1 signaling activity within tissue biopsies was determined and correlated with adhesion severity. The effect of metformin on HIF-1 activity was analyzed by quantification of HIF target gene expression and HIF-1 protein stabilization in human mesothelial cells and murine fibroblast under normoxia and hypoxia. Mice were treated with vehicle or metformin 3 days before and until 7 days after induction of peritoneal adhesions; alternatively, metformin treatment was discontinued 48 hours before induction of peritoneal adhesions. RESULTS HIF-1 signaling activity correlated with adhesion severity in patient biopsies. Metformin significantly mitigated HIF-1 activity in vitro and in vivo. Oral treatment with metformin markedly prevented adhesion formation in mice even when the treatment was discontinued 48 hours before surgery. Although metformin treatment did not alter macrophage polarization, metformin reduced proinflammatory leucocyte infiltration and attenuated hypoxia-induced profibrogenic expression patterns and myofibroblast activation. CONCLUSIONS Metformin mitigates adhesion formation by inhibiting HIF-1-dependent (myo)fibroblast activation, conferring an antiadhesive microenvironment after abdominal surgery. Repurposing the clinically approved drug metformin might be useful to prevent or treat postoperative adhesions.
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Marchegiani G, Perri G, Giovinazzo F, Zanini S, Turri G, Innamorati G, Salvia R, Bassi C. High Values of Drain Fluid Epidermal Growth Factor and Transforming Growth Factor-Beta Are Associated with the Development of Pancreatic Fistula after Pancreatoduodenectomy. Dig Surg 2022; 39:125-132. [PMID: 35468606 DOI: 10.1159/000524678] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Accepted: 04/04/2022] [Indexed: 12/10/2022]
Abstract
INTRODUCTION Postoperative inflammatory response may act as a major determinant of anastomotic failure after pancreaticoduodenectomy. In this pilot study, we investigated the potential role of drain fluid cytokines in predicting postoperative pancreatic fistula (POPF). METHODS Drain fluid TGF-β, IGF-1, EGF, and IL-6, together with serum amylase and drain fluid amylase, were measured on POD1 and correlated with the development of POPF. RESULTS The study population consisted of 66 patients. POPF and Clavien-Dindo ≥3 morbidity rates were 12.1% and 9.1%, respectively. Patients developing POPF presented significantly higher values of POD1 serum amylase level (477 vs. 54 UI/L, p < 0.001), drain fluid amylase (7,500 vs. 127 UI/L, p < 0.001), TGFβ (94 vs. 40 pg/g, p = 0.045), and EGF (17 vs. 13, p = 0.015). There were no differences in terms of IGF-1 and IL-6 values. CONCLUSION Assessing the local inflammatory response after pancreatoduodenectomy could represent a promising field of research since both TGFβ and EGF seem to be associated with the occurrence of POPF.
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Affiliation(s)
- Giovanni Marchegiani
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Giampaolo Perri
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Francesco Giovinazzo
- Liver Transplant and General Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Sara Zanini
- Translational Surgery Lab, LURM, University of Verona Hospital Trust, Verona, Italy
| | - Giulia Turri
- Department of General and Hepatobiliary Surgery, University of Verona Hospital Trust, Verona, Italy
| | - Giulio Innamorati
- Translational Surgery Lab, LURM, University of Verona Hospital Trust, Verona, Italy
| | - Roberto Salvia
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Claudio Bassi
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
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Elucidating the Novel Mechanism of Ligustrazine in Preventing Postoperative Peritoneal Adhesion Formation. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:9226022. [PMID: 35308169 PMCID: PMC8930249 DOI: 10.1155/2022/9226022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 12/12/2021] [Accepted: 01/13/2022] [Indexed: 11/18/2022]
Abstract
Postoperative peritoneal adhesion (PPA) is a major clinical complication after open surgery or laparoscopic procedure. Ligustrazine is the active ingredient extracted from the natural herb Ligusticum chuanxiong Hort, which has promising antiadhesion properties. This study is aimed at revealing the underlying mechanisms of ligustrazine in preventing PPA at molecular and cellular levels. Both rat primary peritoneal mesothelial cells (PMCs) and human PMCs were used for analysis in vitro. Several molecular biological techniques were applied to uncover the potential mechanisms of ligustrazine in preventing PPA. And molecular docking and site-directed mutagenesis assay were used to predict the binding sites of ligustrazine with PPARγ. The bioinformatics analysis was further applied to identify the key pathway in the pathogenesis of PPA. Besides, PPA rodent models were prepared and developed to evaluate the novel ligustrazine nanoparticles in vivo. Ligustrazine could significantly suppress hypoxia-induced PMC functions, such as restricting the production of profibrotic cytokines, inhibiting the expression of migration and adhesion-associated molecules, repressing the expression of cytoskeleton proteins, restricting hypoxia-induced PMCs to obtain myofibroblast-like phenotypes, and reversing ECM remodeling and EMT phenotype transitions by activating PPARγ. The antagonist GW9662 of PPARγ could restore the inhibitory effects of ligustrazine on hypoxia-induced PMC functions. The inhibitor KC7F2 of HIF-1α could repress hypoxia-induced PMC functions, and ligustrazine could downregulate the expression of HIF-1α, which could be reversed by GW9662. And the expression of HIF-1α inhibited by ligustrazine was dramatically reversed after transfection with si-SMRT. The results showed that the benefit of ligustrazine on PMC functions is contributed to the activation of PPARγ on the transrepression of HIF-1α in an SMRT-dependent manner. Molecular docking and site-directed mutagenesis tests uncovered that ligustrazine bound directly to PPARγ, and Val 339/Ile 341 residue was critical for the binding of PPARγ to ligustrazine. Besides, we discovered a novel nanoparticle agent with sustained release behavior, drug delivery efficiency, and good tissue penetration in PPA rodent models. Our study unravels a novel mechanism of ligustrazine in preventing PPA. The findings indicated that ligustrazine is a potential strategy for PPA formation and ligustrazine nanoparticles are promising agents for preclinical application.
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Syanda AM, Kringstad VI, Blackford SJI, Kjesbu JS, Ng SS, Ma L, Xiao F, Coron AE, Rokstad AMA, Modi S, Rashid ST, Strand BL. Sulfated Alginate Reduces Pericapsular Fibrotic Overgrowth on Encapsulated cGMP-Compliant hPSC-Hepatocytes in Mice. Front Bioeng Biotechnol 2022; 9:816542. [PMID: 35308825 PMCID: PMC8928731 DOI: 10.3389/fbioe.2021.816542] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 12/24/2021] [Indexed: 12/12/2022] Open
Abstract
Intra-peritoneal placement of alginate encapsulated human induced pluripotent stem cell-derived hepatocytes (hPSC-Heps) represents a potential new bridging therapy for acute liver failure. One of the rate-limiting steps that needs to be overcome to make such a procedure more efficacious and safer is to reduce the accumulation of fibrotic tissue around the encapsulated cells to allow the free passage of relevant molecules in and out for metabolism. Novel chemical compositions of alginate afford the possibility of achieving this aim. We accordingly used sulfated alginate and demonstrated that this material reduced fibrotic overgrowth whilst not impeding the process of encapsulation nor cell function. Cumulatively, this suggests sulfated alginate could be a more suitable material to encapsulate hPSC-hepatocyte prior to human use.
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Affiliation(s)
- Adam M. Syanda
- Department of Metabolism, Digestion and Reproduction, Imperial College London (ICL), London, United Kingdom
| | - Vera I. Kringstad
- Department of Biotechnology and Food Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Samuel J. I. Blackford
- Department of Metabolism, Digestion and Reproduction, Imperial College London (ICL), London, United Kingdom
| | - Joachim S. Kjesbu
- Department of Biotechnology and Food Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Soon Seng Ng
- Department of Metabolism, Digestion and Reproduction, Imperial College London (ICL), London, United Kingdom
| | - Liang Ma
- Department of Metabolism, Digestion and Reproduction, Imperial College London (ICL), London, United Kingdom
| | - Fang Xiao
- Department of Metabolism, Digestion and Reproduction, Imperial College London (ICL), London, United Kingdom
| | - Abba E. Coron
- Department of Biotechnology and Food Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Anne Mari A. Rokstad
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Sunil Modi
- Department of Metabolism, Digestion and Reproduction, Imperial College London (ICL), London, United Kingdom
| | - S. Tamir Rashid
- Department of Metabolism, Digestion and Reproduction, Imperial College London (ICL), London, United Kingdom
| | - Berit Løkensgard Strand
- Department of Biotechnology and Food Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- *Correspondence: Berit Løkensgard Strand,
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Wei G, Wang Z, Liu R, Zhou C, Li E, Shen T, Wang X, Wu Y, Li X. A combination of hybrid polydopamine-human keratinocyte growth factor nanoparticles and sodium hyaluronate for the efficient prevention of postoperative abdominal adhesion formation. Acta Biomater 2022; 138:155-167. [PMID: 34653692 DOI: 10.1016/j.actbio.2021.10.015] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 10/06/2021] [Accepted: 10/07/2021] [Indexed: 12/12/2022]
Abstract
Postoperative abdominal adhesion (PAA) is one of the more universal complications of abdominal surgery with a frequent incidence. Currently available keratinocyte growth factor (KGF)-based glues for the prevention of adhesions remain a great bottleneck since their long-term biological activity in vivo is insufficient. In this study, we fabricated hybrid polydopamine (PDA)-KGF nanoparticles (PDA-KGF NPs) by using an in situ self-assembly and polymerization method. The physicochemical properties of the PDA-KGF nanoparticles were systematically characterized. The effect of preventing PAA in rats was evaluated by using hybrid PDA-KGF NPs combined with hyaluronate (Ha). The expression levels of inflammatory factors and the degree of inflammatory cell infiltration in the injured peritoneum were evaluated by enzyme-linked immunosorbent assays and hematoxylin-eosin staining, respectively. The levels of phospho-Src expression were revealed by Western blotting. The degree of fibrosis and the density of deposited collagen fibers were measured with real-time reverse-transcription polymerase chain reaction and picrosirius red staining. The results indicated that the PDA-KGF NPs combined with Ha greatly prevented the incidence of abdominal adhesion s and promoted the repair of mesothelial cells in injured peritoneum. More importantly, the PDA-KGF NPs combined with Ha obviously reduced collagen deposition and fibrosis and inhibited the inflammatory response. Our results suggest that PDA-KGF NPs combined with Ha are promising barrier-like biomaterials for the effective prevention of postoperative tissue adhesion. STATEMENT OF SIGNIFICANCE: Postoperative abdominal adhesion (PAA) as an inevitable postoperative complication affected the quality of life of patients. Currently available methods for preventing adhesions mainly employ degradable biomaterials. Previous research demonstrated that a hybrid keratinocyte growth factor (KGF)-sodium hyaluronate (Ha) gel could prevent the formation of PAAs. However, its clinical outcomes are not satisfactory since their bioactivity in vivo is too short. In this article, we fabricated hybrid polydopamine (PDA)-KGF nanoparticles (PDA-KGF NPs), which extend KGF bioactivity, effectively prevent PAA. Moreover, PDA-KGF NPs could remarkably reduce both collagen deposition and fibrosis, inhibit the inflammatory response, and promote mesothelial regeneration. Overall, the PDA-KGF NPs combined with Ha exhibit efficient antiadhesion properties, may provide a promising clinical protocol for the prevention of PAA.
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Affiliation(s)
- Guangbing Wei
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China
| | - Zijun Wang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China
| | - Ruilin Liu
- College of Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China; College of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
| | - Cancan Zhou
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China
| | - Enmeng Li
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China
| | - Tianli Shen
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China
| | - Xingjie Wang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China
| | - Yunhua Wu
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China; Department of General Surgery, Shaanxi Provincial People's Hospital, Xi' an 710068, PR China
| | - Xuqi Li
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China; Department of Talent Highland, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
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Jamshidi-adegani F, Vakilian S, Al-kindi J, Rehman NU, Alkalbani L, Al-Broumi M, Al-Wahaibi N, Shalaby A, Al-Sabahi J, Al-Harrasi A, Al-Hashmi S. Prevention of post-surgical adhesion bands by local administration of frankincense n-hexane extract. J Tradit Complement Med 2021; 12:367-374. [PMID: 35747348 PMCID: PMC9209871 DOI: 10.1016/j.jtcme.2021.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 10/10/2021] [Accepted: 10/13/2021] [Indexed: 12/04/2022] Open
Abstract
Background and purpose: The formation of postoperative intra-abdominal adhesion band formation may lead to severe complications. This study aimed to evaluate the preventive effect of local administration of frankincense n-hexane extract (FHE) on the formation of postsurgical adhesion bands. Materials and methods FHE was extracted from the resin of a Boswellia sacra tree and its components were identified by gas chromatography-mass spectrometry (GC-MS). In an animal model, the expression levels of TNF-α and TGF-β1 cytokines after application of FHE were assessed to check the inflammatory and fibrotic cues, respectively. Results Following FHE compound analysis, in vivo experiments demonstrated that intraoperative local administration of FHE resulted in the prevention of adhesion band formation. The adhesion grades in the FHE-treated group were significantly lower than those in the negative control (NC) and the positive control (Interceed). The infiltration of inflammatory cells observed by histopathology revealed a significant anti-inflammatory potential of FHE. Furthermore, the gene expression results proved that significant suppression of TNF-α and TGF-β1 was responsible for its antiadhesion properties. Conclusions The study reported the potential of FHE as an ointment for the prevention of adhesion bands.
Recognition of compounds with anti-inflammatory, antifibrotic activities in FHE using gas chromatography-mass spectrometry. The avoidance of adhesion bands formation, in vivo following intraoperative local administration of FHE. A notable anti-inflammatory potential of FHE detected by histopathology results. Approving the regulation of TNF-α and TGF-β1 involved in the intra-abdomen adhesion preventive properties of FHE.
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The Study of Efficiency of the Approach to Prevent the Adhesions in the Abdominal Cavity of Rats. Bull Exp Biol Med 2021; 171:416-420. [PMID: 34542744 DOI: 10.1007/s10517-021-05240-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Indexed: 10/20/2022]
Abstract
Adhesions in rat abdominal cavity were studied after laparotomy and subsequent single intraperitoneal injection of 2 ml of 5% aqueous solution of oxidized dextran (OD) with a molecular weight of 40 kDa (oxidation degree 10%). On days 7 and 21 after laparotomy, the number of adhesions in OD-treated rats was lower by 7.5 and 4 times than in animals not receiving OD. The number of neutrophils in adhesions on day 21 was manyfold lower in OD-treated rats. In 7 and 21 days after laparotomy, the number of fibroblasts in the adhesions of rats receiving and not receiving OD was similar, but 2-fold higher than in the peritoneum of non-operated rats. The content of collagen in adhesions on day 21 after laparotomy in OD-treated rats was 10-fold lower than in animals no receiving OD.
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Awonuga AO, Chatzicharalampous C, Thakur M, Rambhatla A, Qadri F, Awonuga M, Saed G, Diamond MP. Genetic and Epidemiological Similarities, and Differences Between Postoperative Intraperitoneal Adhesion Development and Other Benign Fibro-proliferative Disorders. Reprod Sci 2021; 29:3055-3077. [PMID: 34515982 DOI: 10.1007/s43032-021-00726-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 08/22/2021] [Indexed: 12/11/2022]
Abstract
Intraperitoneal adhesions complicate over half of abdominal-pelvic surgeries with immediate, short, and long-term sequelae of major healthcare concern. The pathogenesis of adhesion development is similar to the pathogenesis of wound healing in all tissues, which if unchecked result in production of fibrotic conditions. Given the similarities, we explore the published literature to highlight the similarities in the pathogenesis of intra-abdominal adhesion development (IPAD) and other fibrotic diseases such as keloids, endometriosis, uterine fibroids, bronchopulmonary dysplasia, and pulmonary, intraperitoneal, and retroperitoneal fibrosis. Following a literature search using PubMed database for all relevant English language articles up to November 2020, we reviewed relevant articles addressing the genetic and epidemiological similarities and differences in the pathogenesis and pathobiology of fibrotic diseases. We found genetic and epidemiological similarities and differences between the pathobiology of postoperative IPAD and other diseases that involve altered fibroblast-derived cells. We also found several genes and single nucleotide polymorphisms that are up- or downregulated and whose products directly or indirectly increase the propensity for postoperative adhesion development and other fibrotic diseases. An understanding of the similarities in pathophysiology of adhesion development and other fibrotic diseases contributes to a greater understanding of IPAD and these disease processes. At a very fundamental level, blocking changes in the expression or function of genes necessary for the transformation of normal to altered fibroblasts may curtail adhesion formation and other fibrotic disease since this is a prerequisite for their development. Similarly, applying measures to induce apoptosis of altered fibroblast may do the same; however, apoptosis should be at a desired level to simultaneously ameliorate development of fibrotic diseases while allowing for normal healing. Scientists may use such information to develop pharmacologic interventions for those most at risk for developing these fibrotic conditions.
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Affiliation(s)
- Awoniyi O Awonuga
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
| | - Charalampos Chatzicharalampous
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, 48201, USA
| | - Mili Thakur
- Reproductive Genomics Program, The Fertility Center, Grand Rapids, MI, USA.,Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA
| | - Anupama Rambhatla
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, 48201, USA
| | - Farnoosh Qadri
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, 48201, USA
| | - Modupe Awonuga
- Division of Neonatology, Department of Pediatrics and Human Development, Michigan State University, 1355 Bogue Street, East Lansing, MI, USA
| | - Ghassan Saed
- Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, 48201, USA
| | - Michael P Diamond
- Department of Obstetrics and Gynecology, Augusta University, 1120 15th Street, CJ-1036, Augusta, GA, 30912, USA
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Effect of intraperitoneal and systemic sirolimus administration on postoperative peritoneal adhesions in rats. JOURNAL OF BASIC AND CLINICAL HEALTH SCIENCES 2021. [DOI: 10.30621/jbachs.977476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Fatehi Hassanabad A, Zarzycki AN, Jeon K, Deniset JF, Fedak PWM. Post-Operative Adhesions: A Comprehensive Review of Mechanisms. Biomedicines 2021; 9:biomedicines9080867. [PMID: 34440071 PMCID: PMC8389678 DOI: 10.3390/biomedicines9080867] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 06/27/2021] [Accepted: 07/15/2021] [Indexed: 11/16/2022] Open
Abstract
Post-surgical adhesions are common in almost all surgical areas and are associated with significant rates of morbidity, mortality, and increased healthcare costs, especially when a patient requires repeat operative interventions. Many groups have studied the mechanisms driving post-surgical adhesion formation. Despite continued advancements, we are yet to identify a prevailing mechanism. It is highly likely that post-operative adhesions have a multifactorial etiology. This complex pathophysiology, coupled with our incomplete understanding of the underlying pathways, has resulted in therapeutic options that have failed to demonstrate safety and efficacy on a consistent basis. The translation of findings from basic and preclinical research into robust clinical trials has also remained elusive. Herein, we present and contextualize the latest findings surrounding mechanisms that have been implicated in post-surgical adhesion formation.
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Affiliation(s)
- Ali Fatehi Hassanabad
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.F.D.)
| | - Anna N. Zarzycki
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.F.D.)
| | - Kristina Jeon
- Department of Anesthesiology and Pain Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R7, Canada;
| | - Justin F. Deniset
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.F.D.)
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N 1N4, Canada
| | - Paul W. M. Fedak
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.F.D.)
- Correspondence:
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Fatehi Hassanabad A, Zarzycki AN, Jeon K, Dundas JA, Vasanthan V, Deniset JF, Fedak PWM. Prevention of Post-Operative Adhesions: A Comprehensive Review of Present and Emerging Strategies. Biomolecules 2021; 11:biom11071027. [PMID: 34356652 PMCID: PMC8301806 DOI: 10.3390/biom11071027] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 07/06/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
Post-operative adhesions affect patients undergoing all types of surgeries. They are associated with serious complications, including higher risk of morbidity and mortality. Given increased hospitalization, longer operative times, and longer length of hospital stay, post-surgical adhesions also pose a great financial burden. Although our knowledge of some of the underlying mechanisms driving adhesion formation has significantly improved over the past two decades, literature has yet to fully explain the pathogenesis and etiology of post-surgical adhesions. As a result, finding an ideal preventative strategy and leveraging appropriate tissue engineering strategies has proven to be difficult. Different products have been developed and enjoyed various levels of success along the translational tissue engineering research spectrum, but their clinical translation has been limited. Herein, we comprehensively review the agents and products that have been developed to mitigate post-operative adhesion formation. We also assess emerging strategies that aid in facilitating precision and personalized medicine to improve outcomes for patients and our healthcare system.
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Affiliation(s)
- Ali Fatehi Hassanabad
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.A.D.); (V.V.); (J.F.D.)
| | - Anna N. Zarzycki
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.A.D.); (V.V.); (J.F.D.)
| | - Kristina Jeon
- Department of Anesthesiology and Pain Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R7, Canada;
| | - Jameson A. Dundas
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.A.D.); (V.V.); (J.F.D.)
| | - Vishnu Vasanthan
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.A.D.); (V.V.); (J.F.D.)
| | - Justin F. Deniset
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.A.D.); (V.V.); (J.F.D.)
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB T2N 1N4, Canada
| | - Paul W. M. Fedak
- Section of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 2N9, Canada; (A.F.H.); (A.N.Z.); (J.A.D.); (V.V.); (J.F.D.)
- Correspondence:
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Sarabadani M, Tavana S, Mirzaeian L, Fathi R. Co-culture with peritoneum mesothelial stem cells supports the in vitro growth of mouse ovarian follicles. J Biomed Mater Res A 2021; 109:2685-2694. [PMID: 34228401 DOI: 10.1002/jbm.a.37260] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 06/21/2021] [Accepted: 06/22/2021] [Indexed: 12/23/2022]
Abstract
The important roles played by the ovarian microenvironment and cell interactions in folliculogenesis suggest promising approaches for in vivo growth of ovarian follicles using appropriate scaffolds containing suitable cell sources. In this study, we have investigated the growth of early preantral follicles in the presence of decellularized mesenteric peritoneal membrane (MPM), peritoneum mesothelial stem cells (PMSCs), and conditioned medium (CM) of PMSCs. MPM of mouse was first decellularized; PMSCs were isolated from MPM and cultured and their conditioned medium (CM) was collected. Mouse follicles were separated into four groups: (1) culture in base medium (control), (2) culture in decellularized MPM (DMPM), (3) co-culture with PMSCs (Co-PMSCs), and (4) culture in CM of PMSCs (CM-PMSCs). Qualitative and quantitative assessments were performed to evaluate intact mesenteric peritoneal membrane (IMPM) as well as decellularized ones. After culturing the ovarian follicles, follicular and oocyte diameter, viability, eccentric oocyte percentage, and estradiol hormone amounts were evaluated. Quantitative and qualitative evaluations confirmed removal of cells and retention of the essential fibers in MPM after the decellularization process. Follicular parameters showed that Co-PMSCs better support in vitro growth and development of ovarian follicles than the other groups. The eccentric rate and estradiol production were statistically higher for the Co-PMSCs group than for the CM-PMSCs and control groups. Although the culture of early preantral follicles on DMPM and CM-PMSCs could improve in vitro follicular growth, co-culture of follicles with PMSCs showed even greater improvements in terms of follicular growth and diameter.
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Affiliation(s)
- Mahdieh Sarabadani
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.,Department of Developmental Biology, University of Science and Culture, Tehran, Iran
| | - Somayeh Tavana
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Leila Mirzaeian
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
| | - Rouhollah Fathi
- Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
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Simple fabrication of gelatin–polyvinyl alcohol bilayer hydrogel with wound dressing and nonadhesive duality. POLYM ADVAN TECHNOL 2021. [DOI: 10.1002/pat.5442] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Adhesion prevention after endometriosis surgery - results of a randomized, controlled clinical trial with second-look laparoscopy. Langenbecks Arch Surg 2021; 406:2133-2143. [PMID: 34036409 PMCID: PMC8481146 DOI: 10.1007/s00423-021-02193-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 05/10/2021] [Indexed: 12/02/2022]
Abstract
Purpose Adhesion formation after endometriosis surgery is a severe problem affecting up to 90% of patients. Possible complications include chronic pain, ileus, and secondary infertility. Therefore, effective adhesion prophylaxis is desirable, for which the adhesion barrier 4DryField® PH is evaluated in the present clinical study. It is a starch-based powder that forms a gel after irrigation with saline solution and thus separates surgical sites as physical barrier for adhesion prevention. Methods Fifty patients with extensive and deep infiltrating endometriosis were included in this prospective, randomized, controlled clinical trial with two-staged laparoscopic approach. The patients were randomized into two groups, one receiving 4DryField® PH and the other irrigation with saline solution for adhesion prevention. Adhesion formation was directly scored during second-look interventions considering incidence, extent, and severity. Adhesion prevention treatment in the second surgery was performed corresponding to the first intervention to evaluate the long-term outcome in the later course. Results Both groups were comparable with respect to relevant patient parameters. Severity and extent of adhesions were significantly reduced by 85% in the 4DryField® PH group compared to the control group (mean total adhesion score 2.2 vs. 14.2; p = 0.004). Incidence of adhesion formation based on the number of affected sites was significantly reduced by 53% in the intervention vs. control group (mean 1.1 vs. 2.3 sites; p = 0.004). Follow-up of secondary endpoints is not yet completed; results will become available at a later stage. Conclusion Adhesion formation could be reduced significantly by 85% by application of the adhesion barrier 4DryField® PH. Trial registration Trial registration main ID: DRKS00014720, secondary ID: U1111-1213-4142; date of registration 09th May 2018.
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Raisi A, Dezfoulian O, Davoodi F, Taheri S, Ghahremani SA. Salvia miltiorrhiza hydroalcoholic extract inhibits postoperative peritoneal adhesions in rats. BMC Complement Med Ther 2021; 21:126. [PMID: 33879143 PMCID: PMC8056503 DOI: 10.1186/s12906-021-03300-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Accepted: 04/08/2021] [Indexed: 01/22/2023] Open
Abstract
Background One of the most prevalent postoperative complications is believed to be intra-abdominal peritoneal adhesions, which is followed by several complications. Several adhesion prevention products have been examined, yet none of them were found to be completely effective. The current research is conducted to evaluate the beneficial effects of Salvia miltiorrhiza hydroalcoholic extract in inhibiting postoperative peritoneal adhesions in rats. Methods Forty rats were randomly classified into five equal groups (n = 8): 1) the normal group did not undergo surgical operations, 2) the control group in which the adhesion was induced, and which did not receive any treatment, 3) distilled water group that received distilled water, and 4,5) treatment groups treated with 1 and 5% of Salvia miltiorrhiza hydroalcoholic extract. The rats were euthanized 14 days following the surgery and the macroscopic score, the microscopic score of granulomatous inflammation and granulation tissue formation, IHC markers (vimentin, CD31, IL-1β, COX-2, and iNOS), and oxidative stress biomarkers (MDA, GPx, CAT, and TAC) were assessed in the experimental groups of the study. Results The difference between the control group and other groups for the adhesions macroscopic score, microscopic score, IHC markers, and oxidative stress biomarkers was significant (p < 0.05). Distilled water had no protective effect on the formation of peritoneal adhesions. Salvia miltiorrhiza treatment in two different doses significantly reduced macroscopic and microscopic scores, MDA concentration, Vimentin, IL-1β, COX-2, and iNOS compared to the control group (p < 0.05). The levels of GPx, CAT, and TAC in the treatment groups increased significantly compared with the control group (p < 0.05). Our findings revealed that a higher dose of Salvia miltiorrhiza was more effective in reducing peritoneal adhesions, proinflammatory and mesenchymal cell markers, and oxidative stress. Conclusions Salvia miltiorrhiza extract, owing to its strong antioxidant and anti-inflammatory properties, could effectively reduce peritoneal adhesions. Therefore, Salvia miltiorrhiza is recommended to be used as an effective anti-peritoneal post-operative adhesive agent.
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Affiliation(s)
- Abbas Raisi
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, Iran.
| | - Omid Dezfoulian
- Department of Pathobiology, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, Iran.
| | - Farshid Davoodi
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, Iran
| | - Shayan Taheri
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, Iran
| | - Soroush Afshar Ghahremani
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Lorestan University, Khorramabad, Iran
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Yoshizaki Y, Nagata T, Fujiwara S, Takai S, Jin D, Kuzuya A, Ohya Y. Postoperative Adhesion Prevention Using a Biodegradable Temperature-Responsive Injectable Polymer System and Concomitant Effects of the Chymase Inhibitor. ACS APPLIED BIO MATERIALS 2021; 4:3079-3088. [PMID: 35014396 DOI: 10.1021/acsabm.0c01467] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Postoperative adhesion remains a problem in surgery and causes postoperative complications. Laparoscopic surgery is now common, making it increasingly important to develop injectable formulations of adhesion barriers that can be applied during such surgeries. Temperature-responsive injectable polymer (IP) systems exhibiting a sol-to-gel transition in response to temperature are promising candidates as effective adhesion barriers that can be applied conveniently during laparoscopic surgery. We previously developed IP systems exhibiting temperature-responsive irreversible gelation based on a triblock copolymer of poly(ε-caprolactone-co-glycolic acid) (PCGA) and poly(ethylene glycol) (PEG) (PCGA-b-PEG-b-PCGA: tri-PCG) and a tri-PCG derivative with acrylate groups at the termini (tri-PCG-acryl). A mixture of tri-PCG-acryl micelle solution and tri-PCG micelle solution containing polythiol exhibited an irreversible sol-to-gel transition in response to a temperature increase. The gel contains partial covalent cross-linking, and the degradation and physical properties of these IP hydrogels can easily be controlled by changing the mixing ratio of tri-PCG-acryl in the formulation. In this study, we investigated the effect of physical properties of the IP hydrogel on the efficacy of adhesion prevention using our IP system containing various amounts of tri-PCG-acryl. Our results show that an IP system with lower physical strength and rapid degradation reduces adhesion more effectively. Chymase plays a crucial role in exacerbating adhesion formation, and a peptide derivative-type chymase inhibitor (CI), Suc-Val-Pro-PheP(OPh)2, was previously reported to prevent adhesion. We thus investigated the concomitant use of this CI with our IP system using two methods: separate administration of the CI and IP and entrapping the CI in the IP hydrogel. IP systems with separately administrated CI provided better results than the administration of an IP system entrapping the CI or sole IP systems. These findings suggest that the pharmacological effect of the CI and a physical barrier generated by our IP system effectively prevents adhesion.
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Affiliation(s)
- Yuta Yoshizaki
- Organization for Research and Development of Innovative Science and Technology (ORDIST), Kansai University, 3-3-35 Yamate, Suita 564-8680, Osaka, Japan
| | - Takuya Nagata
- Faculty of Chemistry, Materials, Bioengineering, Kansai University, 3-3-35 Yamate, Suita 564-8680, Osaka, Japan
| | - Soichiro Fujiwara
- Faculty of Chemistry, Materials, Bioengineering, Kansai University, 3-3-35 Yamate, Suita 564-8680, Osaka, Japan
| | - Shinji Takai
- Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki 569-8686, Osaka, Japan
| | - Denan Jin
- Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki 569-8686, Osaka, Japan
| | - Akinori Kuzuya
- Faculty of Chemistry, Materials, Bioengineering, Kansai University, 3-3-35 Yamate, Suita 564-8680, Osaka, Japan.,Collaborate Research Center of Engineering, Medicine and Pharmacology (CEMP), Kansai University, 3-3-35 Yamate, Suita 564-8680, Osaka, Japan
| | - Yuichi Ohya
- Faculty of Chemistry, Materials, Bioengineering, Kansai University, 3-3-35 Yamate, Suita 564-8680, Osaka, Japan.,Collaborate Research Center of Engineering, Medicine and Pharmacology (CEMP), Kansai University, 3-3-35 Yamate, Suita 564-8680, Osaka, Japan
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Gitonga EN, Shen H. Small bowel obstruction and strangulation secondary to an adhesive internal hernia post ESWL for right ureteral calculi: a case report and review of literature. BMC Gastroenterol 2021; 21:176. [PMID: 33865311 PMCID: PMC8052854 DOI: 10.1186/s12876-021-01760-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 04/09/2021] [Indexed: 11/20/2022] Open
Abstract
Background Extracorporeal shock wave lithotripsy (ESWL) is a relatively safe and convenient mode of treatment for ureteral and renal stones, despite its relative safety; ESWL is not without its complications. We present a case of a patient we managed for small bowel obstruction and strangulation due to an adhesive internal hernia after ESWL was done because of right ureteral calculi. Case presentation We report a case of a 59-year-old patient who presented with severe abdominal pain a few hours after ESWL because of a right upper ureteric calculus. The abdominal pain increased in severity in time and became more generalized. The patient had one episode of gross hematochezia as she was being prepped for emergency laparotomy. Intra-op, she had a strangulated internal hernia because of an omental-mesenteric adhesion. Conclusion This case report hopes to highlight the potential of complications like acquired IH due to adhesions in patients with a history of ureteral calculi, and also the complications that may come about post-ESWL. Patients who present with signs of persistent abdominal pain post-ESWL should be vigilantly observed. If symptoms persist, increase in intensity or there is a general deterioration of the patients’ hemodynamic status, even in light of negative MDCT findings, prompt surgical intervention is crucial for definitive diagnosis as well as management.
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Affiliation(s)
- Elaine N Gitonga
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China
| | - Haitao Shen
- Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.
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