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Hill MA, Walkowiak OA, Head WT, Kwon JH, Kavarana MN, Rajab TK. A review of animal models for post-operative pericardial adhesions. Front Surg 2022; 9:966410. [PMID: 36171819 PMCID: PMC9510625 DOI: 10.3389/fsurg.2022.966410] [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: 06/10/2022] [Accepted: 08/22/2022] [Indexed: 11/22/2022] Open
Abstract
Post-operative pericardial adhesions remain a serious complication after cardiac surgery that can lead to increased morbidity and mortality. Fibrous adhesions can destroy tissue planes leading to injury of surrounding vasculature, lengthening of operation time, and increased healthcare costs. While animal models are necessary for studying the formation and prevention of post-operative pericardial adhesions, a standardized animal model for inducing post-operative pericardial adhesions has not yet been established. In order to address this barrier to progress, an analysis of the literature on animal models for post-operative pericardial adhesions was performed. The animal model, method used to induce adhesions, and the time to allow development of adhesions were analyzed. Our analysis found that introduction of autologous blood into the pericardial cavity in addition to physical abrasion of the epicardium caused more severe adhesion formation in comparison to abrasion alone or abrasion with desiccation (vs. abrasion alone p = 0.0002; vs. abrasion and desiccation p = 0.0184). The most common time frame allowed for adhesion formation was 2 weeks, with the shortest time being 10 days and the longest being 12 months. Finally, we found that the difference in adhesion severity in all animal species was similar, suggesting the major determinants for the choice of model are animal size, animal cost, and the availability of research tools in the particular model. This survey of the literature provides a rational guide for researchers to select the appropriate adhesion induction modality, animal model, and time allowed for the development of adhesions.
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Konovalova MV, Tsaregorodtseva DS, Venzhik AN, Poltavtseva RA, Svirshchevskya EV. Antiadhesion Effect of Materials Based on Carboxymethylchitosan and Carboxymethylcellulose. APPL BIOCHEM MICRO+ 2022. [DOI: 10.1134/s0003683822020119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
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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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Zhu L, Zhang YQ. Postoperative anti-adhesion ability of a novel carboxymethyl chitosan from silkworm pupa in a rat cecal abrasion model. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2016; 61:387-95. [DOI: 10.1016/j.msec.2015.12.080] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Revised: 12/14/2015] [Accepted: 12/28/2015] [Indexed: 01/14/2023]
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5
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Identification and analysis of an impurity inducing clinical adverse effect in anti-adhesion carboxymethyl chitosan products. J Pharm Biomed Anal 2013; 85:21-7. [DOI: 10.1016/j.jpba.2013.06.023] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2013] [Revised: 06/18/2013] [Accepted: 06/19/2013] [Indexed: 11/17/2022]
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Boyd WD, Tyberg JV, Cox JL. A review of the current status of pericardial closure following cardiac surgery. Expert Rev Cardiovasc Ther 2013; 10:1109-18. [PMID: 23098147 DOI: 10.1586/erc.12.87] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Some cardiac surgeons prefer to close the pericardium whenever possible following surgery, others specifically avoid this practice, and still others believe that neither alternative has any meaningful influence on clinical outcomes. Unfortunately, scientific evidence supporting either approach is scarce, making a consensus regarding best practice impossible. In this article, the known functions of the native intact pericardium are summarized, and the arguments for and against pericardial closure after surgery are examined. In addition, the techniques and materials that have been utilized for pericardial closure previously, as well as those that are currently being developed, are assessed.
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Affiliation(s)
- W Douglas Boyd
- University of California Davis Medical Center, Davis, CA, USA.
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Dong W, Han B, Shao K, Yang Z, Peng Y, Yang Y, Liu W. Effects of molecular weights on the absorption, distribution and urinary excretion of intraperitoneally administrated carboxymethyl chitosan in rats. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2012; 23:2945-2952. [PMID: 22890521 DOI: 10.1007/s10856-012-4747-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2012] [Accepted: 08/03/2012] [Indexed: 06/01/2023]
Abstract
Carboxymethyl chitosan (CM-chitosan) is one of water-soluble derivatives of chitosan. Numerous studies have been focused on its applications as pharmaceutical excipient, bioactive reagent and nontoxic drug carrier. Like other polysaccharides, CM-chitosan is inhomogenous in molecular weight. Originations and preparation procedures considerably influence its molecular weight and molecular weight distributions. Understanding the molecular weight related biological behaviour of this inhomogenous glycopolymer in vivo were crucial for the quality control and clinical applications of chitosan and chitosan based medical devices. In this study, we investigated the effects of molecular weights on the absorption, distribution, degradation and urinary excretion of the fluorescein isothiocyanate-labeled CM-chitosan in rats. The results indicated that molecular weight significantly influenced the uptake of CM-chitosan from the lumen of abdomen and blood vessels to peripheral tissues, the distribution of this chemical and urinary excretion after intraperitoneal administration. These findings provided an important reference for the clinical applications of this versatile derivative of chitosan as postsurgical and other biomedical materials and important clues for the exploitation of CM-chitosan based drug targeting and delivery systems.
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Affiliation(s)
- Wen Dong
- College of Marine Life Sciences, Ocean University of China, Qingdao, 266003, People's Republic of China.
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Dong W, Han B, Feng Y, Song F, Chang J, Jiang H, Tang Y, Liu W. Pharmacokinetics and Biodegradation Mechanisms of a Versatile Carboxymethyl Derivative of Chitosan in Rats: In Vivo and In Vitro Evaluation. Biomacromolecules 2010; 11:1527-33. [DOI: 10.1021/bm100158p] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Wen Dong
- College of Marine Life Sciences, Ocean University of China, Qingdao 266003, People’s Republic of China, and Qingdao Biotemed Biomaterial Co., Ltd., 268 East Hong Kong Road, Qingdao 266061, People’s Republic of China
| | - Baoqing Han
- College of Marine Life Sciences, Ocean University of China, Qingdao 266003, People’s Republic of China, and Qingdao Biotemed Biomaterial Co., Ltd., 268 East Hong Kong Road, Qingdao 266061, People’s Republic of China
| | - Yilin Feng
- College of Marine Life Sciences, Ocean University of China, Qingdao 266003, People’s Republic of China, and Qingdao Biotemed Biomaterial Co., Ltd., 268 East Hong Kong Road, Qingdao 266061, People’s Republic of China
| | - Fulai Song
- College of Marine Life Sciences, Ocean University of China, Qingdao 266003, People’s Republic of China, and Qingdao Biotemed Biomaterial Co., Ltd., 268 East Hong Kong Road, Qingdao 266061, People’s Republic of China
| | - Jing Chang
- College of Marine Life Sciences, Ocean University of China, Qingdao 266003, People’s Republic of China, and Qingdao Biotemed Biomaterial Co., Ltd., 268 East Hong Kong Road, Qingdao 266061, People’s Republic of China
| | - Huiping Jiang
- College of Marine Life Sciences, Ocean University of China, Qingdao 266003, People’s Republic of China, and Qingdao Biotemed Biomaterial Co., Ltd., 268 East Hong Kong Road, Qingdao 266061, People’s Republic of China
| | - Yingying Tang
- College of Marine Life Sciences, Ocean University of China, Qingdao 266003, People’s Republic of China, and Qingdao Biotemed Biomaterial Co., Ltd., 268 East Hong Kong Road, Qingdao 266061, People’s Republic of China
| | - Wanshun Liu
- College of Marine Life Sciences, Ocean University of China, Qingdao 266003, People’s Republic of China, and Qingdao Biotemed Biomaterial Co., Ltd., 268 East Hong Kong Road, Qingdao 266061, People’s Republic of China
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Jiang SJ, Zhou XL, Ni YD, Ru JQ, Du HY, Zheng T, Hu QL. Preventive effects of chemically-modified chitosan film with sodium hyalurate on the ischemia-induced peritoneal adhesion. Shijie Huaren Xiaohua Zazhi 2009; 17:1025-1029. [DOI: 10.11569/wcjd.v17.i10.1025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To comparatively study the preventive effects of chemically-modified chitosan film with sodium hyalurate on the ischemia-induced peritoneal adhesion in rats.
METHODS: Sixty Sprague-Dawley rats were randomly divided into saline-control group (Group A), chemically-modified chitosan film group (Group B) and sodium hyalurate group (Group C), respectively. The ischemia-induced peritoneal adhesive model was established in the caecums of vermiform processes of the rats, and the ischemia surfaces were correspondingly treated with saline, chemically-modified chitosan film and sodium hyalurate in Group A, B and C. After two and four weeks of the treatments, the abdominal cavities were reopened and the adhesive severity was graded blindly according to the Phillips' method. The caecums of vermiform processes were resected for hydroxyproline (OHP) measurement.
RESULTS: After two and four weeks of the treatments in group B and C, the adhesions were significantly lighter (2 wk: U = 3.000, 8.500, P < 0.001, P = 0.001; 4 wk: U = 2.000, 14.000, P < 0.001, P = 0.003) and the OHP levels were significantly lower (2 wk: 0.193 ± 0.029 mg/mg pr, 0.253 ± 0.028 mg/mg pr vs 0.296 ± 0.031 mg/mg pr, both P < 0.01; 4 wk: 0.179 ± 0.034 mg/mg pr, 0.237 ± 0.035 mg/mg pr vs 0.286 ± 0.036 mg/mg pr, both P < 0.01) than those of Group A, respectively. When group B was compared with group C, the former's adhesions were significantly lighter (P = 0.038, P = 0.015) and the OHP levels were significantly lower (P < 0.001, P = 0.001).
CONCLUSION: The chemically-modified chitosan film is more effective in preventing peritoneal adhesion induced by ischemia than that of sodium hyalurate.
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Biçer M, Bayram AS, Gürbüz O, Şenkaya I, Yerci Ö, Tok M, Anğ E, Moğol EB, Saba D. Assessment of the Efficacy of the Bio-Absorbable Oxidized Regenerated Cellulose for Prevention of Post-Operative Pericardial Adhesion in the Rabbit Model. J Int Med Res 2008; 36:1311-8. [DOI: 10.1177/147323000803600619] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Pericardial adhesions complicate re-operative cardiac surgery and several attempts have been made to reduce adhesion formation. The efficacy of bio-absorbable oxidized regenerated cellulose in preventing post-operative pericardial adhesions was evaluated in the present study. Forty New Zealand white rabbits were divided into four groups of 10. In all rabbits an area of pericardium (2 × 2 cm) was excised. The wound was left open in groups 1 and 2 but replaced with bio-absorbable oxidized regenerated cellulose in groups 3 and 4. Rabbits in groups 1 and 3 were killed 3 weeks after surgery and those in groups 2 and 4 were killed at 6 weeks. Groups 1 and 2 showed more severe pericardial adhesions, more fibrous reaction and increased visibility of coronary vessels than groups 3 and 4, although there was no difference in inflammation. Light microscopy showed a mesothelium-like cell layer in groups 3 and 4. It is concluded that bio-absorbable oxidized regenerated cellulose may be suitable in patients receiving staged cardiac surgery and in those with a high probability of re-operation.
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Affiliation(s)
- M Biçer
- Department of Cardiovascular Surgery, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - AS Bayram
- Department of Thoracic Surgery, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - O Gürbüz
- Department of Cardiovascular Surgery, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - I Şenkaya
- Department of Cardiovascular Surgery, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - Ö Yerci
- Department of Pathology, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - M Tok
- Department of Cardiovascular Surgery, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - E Anğ
- Department of Cardiovascular Surgery, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - EB Moğol
- Department of Anaesthesiology, Faculty of Medicine, Uludağ University, Bursa, Turkey
| | - D Saba
- Department of Cardiovascular Surgery, Faculty of Medicine, Uludağ University, Bursa, Turkey
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11
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Lodge AJ, Wells WJ, Backer CL, O'Brien JE, Austin EH, Bacha EA, Yeh T, DeCampli WM, Lavin PT, Weinstein S. A Novel Bioresorbable Film Reduces Postoperative Adhesions After Infant Cardiac Surgery. Ann Thorac Surg 2008; 86:614-21. [DOI: 10.1016/j.athoracsur.2008.04.103] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2008] [Revised: 04/23/2008] [Accepted: 04/24/2008] [Indexed: 10/21/2022]
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12
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Zhou XL, Chen SW, Liao GD, Shen ZJ, Zhang ZL, Sun L, Yu YJ, Hu QL, Jin XD. Preventive effect of gelatinizedly-modified chitosan film on peritoneal adhesion of different types. World J Gastroenterol 2007; 13:1262-7. [PMID: 17451211 PMCID: PMC4147005 DOI: 10.3748/wjg.v13.i8.1262] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To comparatively study the preventive effect of gelatinizedly-modified chitosan film on peritoneal adhesions induced by four different factors in rats.
METHODS: Chitosan was chemically modified by gelatinization, and made into films of 60 μm in thickness, and sterilized. Two hundred Sprague-Dawley rats were randomly divided into five groups, Sham-operation group (group A), wound-induced adhesion group (group B), purified talc-induced adhesion group (group C), vascular ligation-induced adhesion group (group D), and infection-induced adhesion group (group E), respectively. In each group, the rats were treated with different adhesion-inducing methods at the cecum of vermiform processes and then were divided into control and experimental subgroups. Serous membrane surface of vermiform processes were covered with the films in the experimental subgroups, and no films were used in the control subgroups. After 2 and 4 wk of treatments, the abdominal cavities were reopened and the adhesive severity was graded blindly according to Bhatia’s method. The cecum of vermiform processes were resected for hydroxyproline (OHP) measurement and pathological examination.
RESULTS: Adhesion severity and OHP level: After 2 and 4 wk of the treatments, in the experimental subgroups, the adhesions were significantly lighter and the OHP levels were significantly lower than those of the control subgroups in group B (2 wk: 0.199 ± 0.026 vs 0.285 ± 0.041 μg/mg pr, P < 0.001; 4 wk: 0.183 ± 0.034 vs 0.276 ± 0.03 μg/mg pr, P < 0.001), D (2 wk: 0.216 ± 0.036 vs 0.274 ± 0.040 μg/mg pr, P = 0.004; 4 wk: 0.211 ± 0.044 vs 0.281 ± 0.047 μg/mg pr, P = 0.003) and E (2 wk: 0.259 ± 0.039 vs 0.371 ± 0.040 μg/mg pr, P < 0.001; 4 wk: 0.242 ± 0.045 vs 0.355 ± 0.029 μg/mg pr, P < 0.001), but there were no significant differences in groups A (2wk: 0.141 ± 0.028 vs 0.137 ± 0.026 μg/mg pr, P = 0.737; 4 wk: 0.132 ± 0.031 vs 0.150 ± 0.035 μg/mg pr, P = 0.225) and C (2 wk: 0.395 ± 0.044 vs 0.378 ± 0.043 μg/mg pr, P = 0.387; 4 wk: 0.370 ± 0.032 vs 0.367 ± 0.041 μg/mg pr, P = 0.853); Pathological changes: In group B, the main pathological changes were fibroplasias in the treated serous membrane surface and in group D, the fibroplasia was shown in the whole layer of the vermiform processes. In group E, the main pathological changes were acute and chronic suppurative inflammatory reactions. These changes were lighter in the experimental subgroups than those in the control subgroups in the three groups. In group C, the main changes were foreign body giant cell and granuloma reactions and fibroplasias in different degrees, with no apparent differences between the experimental and control subgroups.
CONCLUSION: The gelatinizedly-modified chitosan film is effective on preventing peritoneal adhesions induced by wound, ischemia and infection, but the effect is not apparent in foreign body-induced adhesion.
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Affiliation(s)
- Xie-Lai Zhou
- Department of Urology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
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Chen RN, Wang GM, Chen CH, Ho HO, Sheu MT. Development ofN,O-(Carboxymethyl)chitosan/Collagen Matrixes as a Wound Dressing. Biomacromolecules 2006; 7:1058-64. [PMID: 16602721 DOI: 10.1021/bm050754b] [Citation(s) in RCA: 128] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
In an attempt to accelerate wound healing by stimulating the recruitment of fibroblasts and improve the mechanical properties of collagen matrixes, N,O-(carboxymethyl)chitosan (NOCC) was incorporated into the backbone of a collagen (COL) matrix without or with chondroitin sulfate (CS) or an acellular dermal matrix (ADM). The result of a cell migration study demonstrated that the migration of fibroblasts was significantly enhanced by NOCC in a concentration-dependent manner. In the analysis with a dynamic mechanical analyzer, NOCC/CS/COL matrixes presented higher tensile strengths than did NOCC/ADM/COL matrixes. Skin fibroblasts cultured on the matrixes containing NOCC showed increased proliferation and secretion of three kinds of cytokines compared with the control. Results of the in vivo wound healing study showed that matrixes incorporating NOCC showed markedly enhanced wound healing compared with the control. Therefore, the above results clearly suggest that NOCC/COL matrixes containing CS or ADM can be potential wound dressings for clinical applications.
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Affiliation(s)
- Ray-Neng Chen
- Graduate Institute of Pharmaceutical Sciences, College of Pharmacy, and Department of Medical Technology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan
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Chorny M, Mishaly D, Leibowitz A, Domb AJ, Golomb G. Site-specific delivery of dexamethasone from biodegradable implants reduces formation of pericardial adhesions in rabbits. J Biomed Mater Res A 2006; 78:276-82. [PMID: 16628712 DOI: 10.1002/jbm.a.30755] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Repeated sternotomy often leads to serious complications in patients due to the formation of cardiac adhesions. In this study we characterized dexamethasone-loaded biodegradable poly(lactide)-poly(ethyleneglycol) copolymer films for site-specific drug delivery and examined their efficacy in the rabbit model of postoperative cardiac adhesions. Tritiated dexamethasone-loaded films were used to determine the in vitro release and in vivo drug distribution. Dexamethasone release in serum was biphasic with 69% drug released after 72 hr. The implants produced sustained drug levels at the implantation site with low distribution into the peripheral tissues. The matrices were implanted in rabbits between the epicardium and the sternum following sternotomy, pericardiectomy and epicardium abrasion, with the drug-releasing surface facing the epicardium. The tenacity and density of the adhesions was examined 21 days post procedure in comparison to both groups of untreated and rabbits implanted with blank matrices. Similarly tenacious and dense adhesions were observed in both control groups. In contrast, epicardial adhesions' formation was significantly reduced and the anatomy was preserved in the treated animals. It is concluded that local delivery of dexamethasone from biodegradable implants provides a promising approach for the prevention of pericardial adhesions while potentially minimizing the systemic adverse effects inherent to systemic therapy or high blood levels of the drug.
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Affiliation(s)
- Michael Chorny
- Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
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A novel adhesion barrier facilitates reoperations in complex congenital cardiac surgery. J Thorac Cardiovasc Surg 2005; 129:359-63. [DOI: 10.1016/j.jtcvs.2004.07.011] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Iliopoulos J, Cornwall GB, Evans RON, Manganas C, Thomas KA, Newman DC, Walsh WR. Evaluation of a bioabsorable polylactide film in a large animal model for the reduction of retrosternal adhesions. J Surg Res 2004; 118:144-53. [PMID: 15100003 DOI: 10.1016/j.jss.2003.10.023] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2003] [Indexed: 11/19/2022]
Abstract
OBJECTIVES An adult pig model of retrosternal adhesion formation via an inferior hemisternotomy was used to evaluate the formation and development of pericardial and retrosternal adhesions, as well as adhesion reduction using two thicknesses of a bioabsorbable polylactide film. MATERIALS AND METHODS Twenty-five adult female pigs (70 kg) were allocated to either a control group or four different treatments using two thicknesses (0.02 or 0.05 mm) of a polylactide film. In each animal, the film was placed either inside the pericardium or inside and outside the pericardium. RESULTS All animals demonstrated adhesions between the posterior and lateral surfaces of the heart and pericardium. Thick fibrous retrosternal adhesions and pericardial adhesions were noted in the control animals with complete obliteration of the anatomical plane. The polylactide films preserved the anatomical planes and reduced the adhesion response. CONCLUSIONS A reproducible animal model was used to examine the formation and reduction of retrosternal and pericardial adhesions. A polylactide film placed inside the pericardium or between the heart and sternum was able to limit adhesion formation and maintain the anatomical planes, which would facilitate reentry.
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Affiliation(s)
- J Iliopoulos
- Orthopaedic Research Laboratories, Division of Surgery, University of New South Wales, Prince of Wales Hospital, Sydney, Australia
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Diamond MP, Luciano A, Johns DA, Dunn R, Young P, Bieber E. Reduction of postoperative adhesions by N,O-carboxymethylchitosan: a pilot study. Fertil Steril 2003; 80:631-6. [PMID: 12969711 DOI: 10.1016/s0015-0282(03)00759-3] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To examine the logistics, safety, and efficacy of N,O-carboxymethylchitosan (NOCC) in reducing adhesions in women. DESIGN Multicenter, prospective, randomized, reviewer-blinded clinical trial. SETTING Gynecologic practices. PATIENT(S) Thirty-four patients were enrolled; 17 in each group were available for the safety analysis and 16 for the efficacy analysis. INTERVENTION(S) Adhesion reduction by administration of NOCC vs. Ringer's lactate at the conclusion of the initial surgical procedure, as assessed at second-look laparoscopy. The NOCC was applied as 200 mL of a 1% NOCC gel that was tamped in place, followed by 100 mL of 2% NOCC solution. Efficacy was assessed by covariate analysis. MAIN OUTCOME MEASURE(S) Safety and postoperative adhesion formation. RESULT(S) Groups did not differ in age, ethnicity distribution, height, weight, or body mass index. No deaths or serious adverse events were attributable to NOCC, and no adverse events were definitively or probably related to NOCC administration. Adhesions recurred at 61% of sites in controls and 38% of sites in NOCC recipients. De novo grade 1a and 1b adhesions tended to occur more commonly in controls than NOCC recipients. Adhesion extent and severity at second look were also less in NOCC recipients. CONCLUSION(S) Intraperitoneal use of NOCC gel and solution appears to be safe. Despite the small sample, strong trends were identified for reduction of occurrence, extent, and severity of adhesion recurrence and de novo adhesion formation.
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Affiliation(s)
- Michael P Diamond
- Wayne State University/Detroit Medical Center, Detroit, Michigan, USA.
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Duran B, Ak D, Cetin A, Guvenal T, Cetin M, Imir AG. Reduction of Postoperative Adhesions by N,O-Carboxymethylchitosan and Spermine NONOate in Rats. Exp Anim 2003; 52:267-72. [PMID: 14562602 DOI: 10.1538/expanim.52.267] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
Abstract
BACKGROUND Postsurgical adhesions can occur following virtually all types of surgery, resulting in serious clinical complications. Therefore, prevention of adhesions is an important goal of surgical practice. A rat uterine horn model was used to investigate the efficacy of N,O-carboxymethylchitosan (NOCC) and spermine NONOate (SPER/NO) alone and in combination in preventing adhesion formation. METHODS Sixty Wistar albino rats underwent bilateral uterine horn injury with a unipolar cautery. Study groups were as follows: (i) control group, no adjuvant therapy; and those with adjuvant applied, (ii) normal saline group, 2 ml of normal saline was given; (iii) NOCC group, 2 ml of 2% NOCC gel was given; (iv) SPER/NO group, 2 ml of SPER/NO (0.5 mg/ml) was given, and (v) NOCC plus SPER/NO group, 2 ml of 2% NOCC gel including SPER/NO (0.5 mg/ml) was given. After 14 days, all animals were euthanatized, and a standard adhesion scoring system including extent and severity scores was applied by a blinded examiner. RESULTS The extent score in NOCC plus SPER/NO group was significantly lower than those of control and normal saline groups (p < 0.05). The extent score in NOCC group was significantly lower than that of normal saline group (p < 0.05). The extent score in NOCC plus SPER/NO group was significantly lower than that of SPER/NO group (p < 0.05). The severity score was significantly lower in NOCC plus SPER/NO and NOCC groups than that of control group (p < 0.05). The severity score was significantly lower in NOCC plus SPER/NO group than that of SPER/NO group (p < 0.05). CONCLUSIONS Postoperative administration of NOCC gel and SPER/NO alone and especially in combination to the site of peritoneal injury reduces the formation of adhesions in the rat uterine horn model.
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Affiliation(s)
- Bulent Duran
- Department of Obstetrics and Gynecology, Cumhuriyet University School of Medicine, 58140 Sivas, Turkey
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