Elsevier

Acta Biomaterialia

Volume 61, 1 October 2017, Pages 21-40
Acta Biomaterialia

Review article
Polymer materials for prevention of postoperative adhesion

https://doi.org/10.1016/j.actbio.2017.08.002Get rights and content

Abstract

Postoperative adhesion (POA) is a common complication that often occurs after a variety of surgeries, such as plastic surgery, repair operations of abdominal, pelvic, and tendon, and so forth. Moreover, POA leads to chronic abdominal pain, secondary infertility in women, intestinal obstruction, and other severe complications, which significantly reduce the life quality of patients. In order to prevent the formation of POA, a number of strategies have been developed, among which an emerging method is physical barriers consisting of polymer materials. This review highlights the most commonly used natural and synthetic polymer materials in anti-adhesion physical barriers. The specific features of polymer materials are analyzed and compared, and the possible prospect is also predicted.

Statement of Significance

Postoperative adhesion (POA) is a serious complication accompanied with various surgeries. Polymer material-based physical barriers have attracted a large amount of attention in POA prevention. The polymer barriers can effectively avoid the formation of fibrous tissues among normal organs by reducing the interconnection of injured tissues. In this review, specific features of the natural and synthetic polymer materials for application in POA prevention were presented, and the possible prospects were predicted. All in all, our work can provide inspiration for researchers to choose proper polymer materials for preclinical and even clinical anti-adhesion studies.

Introduction

Postoperative adhesion (POA) is a comprehensive inflection of various abnormal tissue hyperplasias, characterized by proliferated fibrous tissues sticking to the nearby normal organs. The adhesion bands can take diversified phenotypes ranging from a thin layer of fibrous films between the adjacent tissues to a mixture of fibrous tissues, blood vessels, and nerves [1]. Depending on distinct positions and levels of the adhesion, POA may be accompanied with acute complications or be “silent” for several years. These complications, such as chronic pain, dysfunction of adjacent organs, and intestinal obstruction, can reduce the life quality of patients or even become life-threatening [2], [3], [4].

Despite extensive efforts to prevent POA, its pathophysiology is not entirely understood. The factors involved in the formation of adhesion are complex, such as mechanical injury, ischemia, infection, local inflammation, endometriosis, and physical and chemical nature of the anti-adhesion materials [3], [5]. At present, the local inflammatory reaction is reckoned as the main cause of POA [6]. To be more specific, after receiving a surgery, our body would mistakenly assume that we are in a serious trauma, which will trigger the release of histamine, vasoactive peptides, and various cytokines from stromal mast cells. Moreover, vasodilators will be excreted from macrophages, increasing the permeability of blood vessels and leading to effusion of a large number of fibrous tissues, which will ultimately interrupt the balance between thrombin activity and plasmin activity. Consequently, plenty of fibrous bridges will be formed at inflamed sites and result in POA [7].

A large variety of methods have been conducted aiming at the alleviation of surgery associated complications. These strategies can be roughly divided into four categories: general principles, surgical techniques, physical barriers, and chemical agents [8]. For the past 30 years, biocompatible and biodegradable polymers have attracted wide attention in treating POA as promising physical barriers among tissues. For easy operation during surgery and overall coverage of wounded area, qualified anti-adhesion biomaterials are supposed to meet several basic requirements, such as excellent biocompatibility and biodegradability, appropriate retention time, good water solubility, and outstanding mechanical properties. Overall, natural and synthetic materials can significantly prevent the formation of POA with minimal side effects to wound healing.

In this review, the natural and synthetic polymer materials applied to postoperative anti-adhesion were introduced, as shown in Scheme 1. As to natural polymer materials, there are hyaluronic acid (HA), cellulose (CEL), dextran (DEX), chitosan (CS), icodextrin (ICO), and so forth. Synthetic polymer materials include polylactide (PLA), poly(ethylene glycol) (PEG), polyglycolide (PGA), poly(ε-caprolactone) (PCL), and poly(vinyl alcohol) (PVA), etc. The applications of these polymer-based materials in POA prevention are summarized in Table 1. Moreover, the specific features of polymer physical barriers are presented, and the possible prospects in POA prevention will be predicted.

Section snippets

Hyaluronic acid (HA)

The anti-adhesion effect of HA has been confirmed in many studies, including acting as a physical barrier, promoting the dissolution of fibrin and proliferation of mesothelial cells, inhibiting the inflammatory response, and promoting wound healing. Besides, it was shown that the inhibitory effect of HA toward granulocytes is positively correlated with its concentration and molecular weight. Therefore, HA with high concentration and large molecular weight exhibited better efficacy in

Discussion

POA has become a challenging clinical problem on account of the health issues it brings about as well as the heavy financial burdens exerted on patients. Therefore, researchers make it a priority to seek efficient methods to prevent or alleviate POA. In recent years, physical barriers composed of biocompatible and biodegradable polymers have attracted wide attention in treating POA. These barriers can prevent the contact among damaged tissues for the first few days after surgery, so as to

Conclusion

In this review, we focused on natural and synthetic polymer materials in prevention of POA, which showed notable capability in adhesion prevention profile. The specific features of each kind of anti-adhesion polymer materials were also presented and analyzed. Our review provides researchers with important insights to choose specific polymers for anti-adhesion studies or product manufacturing.

In general, natural polymer materials enjoy high bioadhesive ability and good hemostasis feature.

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (Grant Nos. 51673190, 51673187, 51603204, and 51520105004) and the Science and Technology Development Program of Jilin Province (Grant No. 20160204015SF).

References (171)

  • C.H. Jang et al.

    The effect of Interceed® for reducing adhesion as a middle ear packing agent: An experimental study

    Int. J. Pediatr. Otorhinolaryngol.

    (2008)
  • R.L. Reid et al.

    A randomized clinical trial of oxidized regenerated cellulose adhesion barrier (Interceed®, TC7) alone or in combination with heparin

    Fertil. Steril.

    (1997)
  • K.E. Rodgers et al.

    Effect of Oxiplex® films (PEO/CMC) on adhesion formation and reformation in rabbit models and on peritoneal infection in a rat model

    Fertil. Steril.

    (2000)
  • R. Schonman et al.

    Intercoat gel (Oxiplex®): Efficacy, safety, and tissue response in a laparoscopic mouse model

    J. Minim. Invas. Gynecol.

    (2009)
  • P. Young et al.

    G. diZerega, Reduction of postoperative adhesions after laparoscopic gynecological surgery with Oxiplex/AP® Gel: A pilot study

    Fertil. Steril.

    (2005)
  • G.S. diZerega et al.

    Clinical evaluation of endometriosis and differential response to surgical therapy with and without application of Oxiplex/AP® adhesion barrier gel

    Fertil. Steril.

    (2007)
  • K.E. Rodgers et al.

    G.S. diZerega, R.A. Berg, Reduction of epidural fibrosis in lumbar surgery with Oxiplex® adhesion barriers of carboxymethylcellulose and polyethylene oxide

    Spine J.

    (2003)
  • E. Somigliana et al.

    Adhesion prevention in endometriosis: A neglected critical challenge

    J. Minim. Invas. Gynecol.

    (2012)
  • S. Isik et al.

    Prevention of restrictive adhesions in primary tendon repair by HA-membrane: Experimental research in chickens

    Br. J. Plast. Surg.

    (1999)
  • R.E. Bristow et al.

    Prevention of adhesion formation after radical oophorectomy using a sodium hyaluronate-carboxymethylcellulose (HA-CMC) barrier

    Gynecol. Oncol.

    (2005)
  • S. Tsuji et al.

    Effectiveness of antiadhesion barriers in preventing adhesion after myomectomy in patients with uterine leiomyoma

    Eur. J. Obstet. Gynecol. Reprod. Biol.

    (2005)
  • H.K. Sheldon et al.

    A sprayable hyaluronate/carboxymethylcellulose adhesion barrier exhibits regional adhesion reduction efficacy and does not impair intestinal healing

    J. Gastrointest. Surg.

    (2012)
  • M. Inoue et al.

    Efficacy of Seprafilm for preventing adhesive bowel obstruction and cost-benefit analysis in pediatric patients undergoing laparotomy

    J. Pediatr. Surg.

    (2013)
  • J.P. Cheung et al.

    Adjuvant therapy for the reduction of postoperative intra-abdominal adhesion formation

    Asian J. Surg.

    (2009)
  • T. Ito et al.

    Dextran-based in situ cross-linked injectable hydrogels to prevent peritoneal adhesions

    Biomaterials

    (2007)
  • C.I. Jones et al.

    The antithrombotic effect of dextran-40 in man is due to enhanced fibrinolysis in vivo

    J. Vasc. Surg.

    (2008)
  • M. Nagelschmidt et al.

    Influence of poly(ethylene glycol) 4000 and dextran 70 on adhesion formation in rats

    J. Surg. Res.

    (1997)
  • M.J. Weinans et al.

    Transient liver function disturbances after the intraperitoneal use of 32% dextran 70 as adhesion prophylaxis in infertility surgery

    Fertil. Steril.

    (1990)
  • C.I. Lauder et al.

    Use of a modified chitosan-dextran gel to prevent peritoneal adhesions in a rat model

    J. Surg. Res.

    (2011)
  • C.I. Lauder et al.

    Use of a modified chitosan-dextran gel to prevent peritoneal adhesions in a porcine hemicolectomy model

    J. Surg. Res.

    (2012)
  • W. Lou et al.

    In vivo evaluation of in situ polysaccharide based hydrogel for prevention of postoperative adhesion

    Carbohyd. Polym.

    (2012)
  • R. Kennedy et al.

    Prevention of experimental postoperative peritoneal adhesions by N O-carboxymethyl chitosan

    Surgery

    (1996)
  • M. Cetin et al.

    Use of methylene blue and N, O-carboxymethylchitosan to prevent postoperative adhesions in a rat uterine horn model

    Fertil. Steril.

    (2003)
  • M.P. Diamond et al.

    Reduction of postoperative adhesions by N, O-carboxymethylchitosan: A pilot study

    Fertil. Steril.

    (2003)
  • E. Shahram et al.

    Evaluation of chitosan-gelatin films for use as postoperative adhesion barrier in rat cecum model

    Int. J. Surg.

    (2013)
  • S.H. Chen et al.

    Prevention of peritendinous adhesions with electrospun chitosan-grafted polycaprolactone nanofibrous membranes

    Acta Biomater.

    (2014)
  • L. Li et al.

    Biodegradable and injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for postoperative adhesion prevention

    Biomaterials

    (2014)
  • J.B. Lopes et al.

    Synergism between keratinocyte growth factor and carboxymethyl chitosan reduces pericardial adhesions

    Ann. Thorac. Surg.

    (2010)
  • J. Zhou et al.

    Reduction in postoperative adhesion formation and re-formation after an abdominal operation with the use of N O-carboxymethyl chitosan

    Surgery

    (2004)
  • C.B. Brown et al.

    G.S. diZerega, Adept (icodextrin 4% solution) reduces adhesions after laparoscopic surgery for adhesiolysis: A double-blind, randomized, controlled study

    Fertil. Steril.

    (2007)
  • C. Yigitler et al.

    Adhesion-preventing properties of 4% icodextrin and canola oil: A comparative experimental study

    Clinics

    (2012)
  • F. Catena et al.

    P.O.P.A. study: Prevention of postoperative abdominal adhesions by icodextrin 4% solution after laparotomy for adhesive small bowel obstruction. A prospective randomized controlled trial

    J. Gastrointest. Surg.

    (2012)
  • R.A. Lang et al.

    Polyvinyl alcohol gel prevents abdominal adhesion formation in a rabbit model

    Fertil. Steril.

    (2007)
  • W. Arung et al.

    Pathophysiology and prevention of postoperative peritoneal adhesions

    World J. Gastroenterol.

    (2011)
  • B.W. Hellebrekers et al.

    Pathogenesis of postoperative adhesion formation

    Br. J. Surg.

    (2011)
  • B. Shi et al.

    Drug-incorporated electrospun fibers efficiently prevent postoperative adhesion

    Curr. Pharm. Des.

    (2015)
  • J.B. van der Wal et al.

    Biology of the peritoneum in normal homeostasis and after surgical trauma

    Colorectal Dis.

    (2007)
  • G.Y. Ozgenel

    The effects of a combination of hyaluronic and amniotic membrane on the formation of peritendinous adhesions after flexor tendon surgery in chickens

    J. Bone Joint Surg. Br.

    (2004)
  • J.Y. Kim et al.

    Efficacy and safety of hyaluronate membrane in the rabbit cecum-abdominal wall adhesion model

    J. Korean Surg. Soc.

    (2013)
  • J.H. Back et al.

    Application of hyaluronic acid/sodium alginate-based microparticles to prevent tissue adhesion in a rabbit model

    Surg. Today

    (2016)
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