CoChat
Sign Up
Cited by 64Intestinal and Peritoneal AdhesionsHydrogels: synthesis, properties, applicationsSurgical Sutures and Adhesives

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

Open access
Mayes, Sarah M., Davis, Jessica, Scott, Jessica, Aguilar, Vanessa, Zawko, Scott A., Swinnea, Steve, Peterson, Daniel L., Hardy, John G. +1 more·2020·Acta Biomaterialia
DOI 10.1016/j.actbio.2020.02.027PMC PMC8552357
Open this paper in CoChat — free accountOpen PDF

Abstract

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

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.actbio.2020.02.027

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • CMC combined with HA, as in Seprafilm®, improves mechanical stability and prolongs retention time at the surgical site.

    “Often combined with HA, as in Seprafilm®, CMC improves mechanical stability and prolongs retention time at the surgical site [136].”

    From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [136]

    The Introduction identifies Seprafilm® as a CMC–HA membrane, but says its dry form is brittle and its wet form has poor mechanical integrity. The Results and Discussion (In vivo validation studies) describe the authors’ alginate/GMHA film—not Seprafilm—as mechanically robust and potentially longer-lasting. The paper does not attribute improved stability or prolonged surgical-site retention to adding CMC to HA. (LLM, conf=0.88)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 55

  1. [1]Weibel MA, Majno G, Peritoneal adhesions and their relation to abdominal surgery. A postmortem study, Am J Surg 126 (1973) 345– 353. 4580750
  2. [2]Lee CH, Kim H, Han IW, Kim SM, Kwak BS, Baik YH, Park YJ, Oh MG, Effect of polylactic film (Surgi-Wrap) on preventing postoperative ileus after major hepato-pancreato-biliary surgery, Ann Hepatobiliary Pancreat Surg 20(4) (2016) 191– 196. 28261699 PMC5325149
  3. [3]Mattei P, Rombeau JL, Review of the pathophysiology and management of postoperative ileus, World J Surg 30 (2006) 1382– 1391. 16850151
  4. [4]Hirschelmann A, Tchartchian G, Wallwiener M, Hackethal A, De Wilde RL, A review of the problematic adhesion prophylaxis in gynaecological surgery, Arch Gynecol Obstet 285(4) (2012) 1089– 97. 22037682 PMC3303068
  5. [5]Menzies D, Ellis H, Intestinal obstruction from adhesions--how big is the problem?, Ann R Coll Surg Engl 72 (1990) 60– 63. 2301905 PMC2499092
  6. [7]Ellis H, Cause and prevention of postoperative intraperitoneal adhesions, Surgery Gynecology and Obstetrics with International Abstracts of Surgery 133(3) (1971) 497– 511. 4398338
  7. [8]Ellis H, Moran BJ, Thompson JN, Parker MC, Wilson MS, Menzies D, McGuire A, Lower AM, Hawthorn RJ, O’Brien F, Buchan S, Crowe AM, Adhesion-related hospital readmissions after abdominal and pelvic surgery: a retrospective cohort study, Lancet 353(9163) (1999) 1476– 80. 10232313
  8. [9]Brochhausen C, Schmitt VH, Rajab TK, Planck CNE, Krämer B, Wallwiener M, Hierlemann H, Kirkpatrick CJ, Intraperitoneal adhesions—An ongoing challenge between biomedical engineering and the life sciences, J. of Biomed. Mater. Res 98A(1) (2011) 143– 156. 21548063
  9. [10]Li J, Feng X, Liu B, Yu Y, Sun L, Liu T, Wang Y, Ding J, Chen X, Polymer materials for prevention of postoperative adhesion, Acta Biomater 61 (2017) 21– 40. 28780432
  10. [11]Van der Wal JB, Jeekel J, Biology of the peritoneum in normal homeostasis and after surgical trauma, Colorectal Dis. 9 (2007) 9– 13. 17824965
  11. [12]Sulaiman H, Gabella G, Davis MSc C, Mutsaers SE, Boulos P, Laurent GJ, Herrick SE, Presence and distribution of sensory nerve fibers in human peritoneal adhesions, Ann. Surg 234(2) (2001) 256– 261. 11505072 PMC1422013
  12. [14]Ouaïssi M, Gaujoux S, Veyrie N, Denève E, Brigand C, Castel B, Duron JJ, Rault A, Slim K, Nocca D, Post-operative adhesions after digestive surgery: their incidence and prevention: review of the literature, J. Visc. Surg 149(2) (2012) 104– 114. 22261580
  13. [15]Van Goor H, Consequences and complications of peritoneal adhesions, Colorectal Dis. 9 (2007) 25– 34. 17824967
  14. [16]diZerega GS, Contemporary adhesion prevention, Fertil. Steril 61(2) (1994) 219– 235. 8299773
  15. [18]Yeo Y, Highley CB, Bellas E, Ito T, Marini R, Langer R, Kohane DS, In situ cross-linkable hyaluronic acid hydrogels prevent post-operative abdominal adhesions in a rabbit model, Biomaterials 27(27) (2006) 4698– 4705. 16750564
  16. [19]Wiseman DM, Meidler R, Lyahovetsky Y, Kurman E, Horn S, Nur I, Evaluation of a fibrin preparation containing tranexamic acid (Adhexil) in a rabbit uterine horn model of adhesions with and without bleeding and in a model with two surgical loci, Fertil. Steril 93(4) (2010) 1045– 1051. 19147133
  17. [20]Beck CZ E D, Fleshman JW, Kaufman HS, van Goor H, Wolff BG, A prospective, randomized, multicenter, controlled study of the safety of Seprafilm adhesion barrier in abdominopelvic surgery of the intestine Dis Colon Rectum 46 (2003) 1310– 1319. 14530667
  18. [21]Zeng Q, Yu Z, You J, Zhang Q, Efficacy and safety of Seprafilm for preventing postoperative abdominal adhesion: systematic review and meta-analysis, World J Surg 31 (2007) 2125– 2131. 17899250
  19. [22]Brochhausen C, Schmitt VH, Planck CN, Rajab TK, Hollemann D, Tapprich C, Krämer B, Wallwiener C, Hierlemann H, Zehbe R, Planck H, Kirkpatrick CJ, Current strategies and future perspectives for intraperitoneal adhesion prevention, J. Gastrointest. Surg 16(6) (2012) 1256– 1274. 22297658
  20. [23]Holmdahl L, Risberg B, Beck DE, Burns JW, Chegini N, diZerega GS, Ellis H, Adhesions: pathogenesis and prevention-panel discussion and summary, Eur. J. Surg. Suppl 577 (1997) 56– 62. 9076453
  21. [24]Liu Y, Li H, Shu XZ, Gray SD, Prestwich GD, Crosslinked hyaluronan hydrogels containing mitomycin C reduce postoperative abdominal adhesions, Fertil. Steril 83 Suppl 1 (2005) 1275– 83. 15831302
  22. [25]Gago LA, Saed GM, Chauhan S, Elhammady EF, Diamond MP, Seprafilm (modified hyaluronic acid and carboxymethylcellulose) acts as a physical barrier, Fertil. Steril 80(3) (2003) 612– 616. 12969707
  23. [27]Kusuki I, Suganuma I, Ito F, Akiyama M, Sasaki A, Yamanaka K, Tatsumi H, Kitawaki J, Usefulness of Moistening Seprafilm Before Use in Laparoscopic Surgery, Surg Laparosc Endosc Percutan Tech. 24(1) (2014) e13– e15. 24487168
  24. [28]Hong MK, Ding D-C, Seprafilm® Application Method in Laparoscopic Surgery, JSLS, 2017, p. e2016.00097. PMC5370214 28400696
  25. [29]Allegre L, Le Teuff I, Leprince S, Warembourg S, Taillades H, Garric X, Letouzey V, Huberlant S, A new bioabsorbable polymer film to prevent peritoneal adhesions validated in a post-surgical animal model, PLoS One 13(11) (2018) e0202285. 30395571 PMC6218020
  26. [30]Kayaoglu HA, Ozkan N, Hazinedaroglu SM, Ersoy OF, Koseoglu RD, An Assessment of the Effects of Two Types of Bioresorbable Barriers to Prevent Postoperative Intra-Abdominal Adhesions in Rats, Surg. Today 35(11) (2005) 946– 950. 16249849
  27. [31]Chen CH, Chen SH, Mao SH, Tsai MJ, Chou PY, Liao CH, Chen JP, Injectable thermosensitive hydrogel containing hyaluronic acid and chitosan as a barrier for prevention of postoperative peritoneal adhesion, Carbohydr Polym 173 (2017) 721– 731. 28732919
  28. [32]Yeo Y, Highley CB, Bellas E, Ito T, Marini R, Langer R, Kohane DS, In situ cross-linkable hyaluronic acid hydrogels prevent post-operative abdominal adhesions in a rabbit model, Biomaterials 27(27) (2006) 4698– 705. 16750564
  29. [33]Yeo Y, Adil M, Bellas E, Astashkina A, Chaudhary N, Kohane DS, Prevention of peritoneal adhesions with an in situ cross-linkable hyaluronan hydrogel delivering budesonide, J. Control. Release 120(3) (2007) 178– 85. 17582645
  30. [34]Burdick JA, Prestwich GD, Hyaluronic acid hydrogels for biomedical applications, Advanced materials (Deerfield Beach, Fla.) 23(12) (2011) H41– H56. PMC3730855 21394792
  31. [35]Lee M-W, Tsai H-F, Wen S-M, Huang C-H, Photocrosslinkable gellan gum film as an anti-adhesion barrier, Carbohydrate Polymers 90(2) (2012) 1132– 1138. 22840050
  32. [36]Yurdakul Sikar E, Sikar HE, Top H, Aygit AC, Effects of Hyalobarrier gel and Seprafilm in preventing peritendinous adhesions following crush-type injury in a rat model, Ulus. Travma Acil Cerrahi Derg 25(2) (2019) 93– 98. 30892673
  33. [37]Na SY, Oh SH, Song KS, Lee JH, Hyaluronic acid/mildly crosslinked alginate hydrogel as an injectable tissue adhesion barrier, J. Mater. Sci. Mater. Med 23 (2012) 2303– 2313. 22661246
  34. [38]Wu NWQ, He T, Shang J, Li L, Song L, Yang X, Li X, Luo N, Zhang W, Gong C,, p. 13553, Thermosensitive hydrogel containing dexamethasone micelles for preventing postsurgical adhesion in a repeated-injury model, Sci. Rep 5 (2015) 13553. 26324090 PMC4555101
  35. [39]Shi YLWK, Qu Y, Liao JF, Chu BY, Zhang HP, Luo F, Qian ZY, Synthesis, characterization, and application of reversible PDLLA-PEG-PDLLA copolymer thermogels in vitro and in vivo, Sci. Rep 6 (2016) 19077. 26752008 PMC4707506
  36. [40]Blaine G, Experimental Observations on Absorbable Alginate Products in Surgery * Gel, Film, Gauze and Foam, Ann Surg 125(1) (1947) 102– 114. 17858907 PMC1803201
  37. [41]Kuo SM, Chang SJ, Wang HY, Tang SC & Yang SW, Evaluation of the ability of xanthan hum/gellan gum/hyaluronan hydrogel membranes to prevent the adhesion of postrepaired tendons., Carbohydrate Polymers 114 (2014) 230– 237. 25263886
  38. [42]Chen CHCSH, Shalumon KT, Chen JP, Preparation and characterization of antiadhesion barrier film from hyaluronic acid-grafted electrospun poly(caprolactone) nanofibrous membranes for prevention of flexor tendon postoperative peritendinous adhesion, Int. J. Nanomed 9 (2014) 4079– 4092. PMC4149458 25187711
  39. [43]Li L, Wang N, Jin X, Deng R, Nie S, Sun L, Wu Q, Wei Y, Gong C, Biodegradable and injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for postoperative adhesion prevention, Biomaterials 35 (2014) 3903– 3917. 24507411
  40. [44]Davidovich-Pinhas M, Bianco-Peled H, Alginate-PEGAc: a new mucoadhesive polymer, Acta Biomater 7(2) (2011) 625– 33. 20858555
  41. [46]Cho WJ, Oh SH, Lee JH, Alginate Film as a Novel Post-Surgical Tissue Adhesion Barrier, J. Biomater. Sci. Polym. Ed 21(6–7) (2010) 701– 713. 20482979
  42. [47]Zawko SA, Schmidt CE, Crystal templating dendritic pore networks and fibrillar microstructure into hydrogels, Acta Biomater 6(7) (2010) 2415– 21. 20167293
  43. [49]Bencherif SA, Srinivasan A, Horkay F, Hollinger JO, Matyjaszewski K, Washburn NR, Influence of the degree of methacrylation on hyaluronic acid hydrogels properties, Biomaterials 29(12) (2008) 1739– 49. 18234331
  44. [52]Multilayer Thin Films, Wiley-VCH Verlag GmbH & Co. KGaA2002.
  45. [53]Peh K, Khan T, Ch’ng H, Mechanical, bioadhesive strength and biological evaluations of chitosan films for wound dressing, J. Pharm. Pharm. Sci 3(3) (2000) 303– 311. 11177648
  46. [55]Nagarsenker MS, Hegde DD, Optimization of the mechanical properties and water-vapor transmission properties of free films of hydroxypropylmethylcellulose, Drug Dev. Ind. Pharm 25(1) (1999) 95– 8. 10028424
  47. [56]Sezer AD, Hatipoglu F, Cevher E, Ogurtan Z, Bas AL, Akbuga J, Chitosan film containing fucoidan as a wound dressing for dermal burn healing: preparation and in vitro/in vivo evaluation, AAPS PharmSciTech 8(2) (2007) E94– E101. 17622117 PMC2750378
  48. [60]Febriyenti F, Noor A, Bin Bai S, Mechanical properties and water vapour permeability of film from Haruan (Channa striatus) and Fusidic acid spray for wound dressing and wound healing, Pak. J. Pharm. Sci 23 (2010) 155– 9. 20363692
  49. [61]Preis M, Woertz C, Schneider K, Kukawka J, Broscheit J, Roewer N, Breitkreutz J, Design and evaluation of bilayered buccal film preparations for local administration of lidocaine hydrochloride, Eur. J. Pharm. Biopharm 86(3) (2014) 552– 61. 24388912
  50. [63]Nishimura K, Blume P, Ohgi S, Sumpio BE, Effect of different frequencies of tensile strain on human dermal fibroblast proliferation and survival, Wound Repair Regen. 15(5) (2007) 646– 656. 17971010
  51. [64]Sufiyarov IF, Experimental validation for the use of a film on the basis of modified hyaluronic acid for prevention of postoperative peritoneal adhesions, Bull. Exp. Biol. Med 144(2) (2007) 269– 71. 18399298
  52. [65]Ersoy E, Ozturk V, Yazgan A, Ozdogan M, Gundogdu H, Comparison of the two types of bioresorbable barriers to prevent intra-abdominal adhesions in rats, J. Gastrointest. Surg 13(2) (2009) 282– 6. 18777122
  53. [66]Lo HY, Kuo HT, Huang YY, Application of polycaprolactone as an anti-adhesion biomaterial film, Artif. Organs 34(8) (2010) 648– 53. 20698842
  54. [67]Rajab TK, Wallwiener M, Planck C, Brochhausen C, Kraemer B, Wallwiener CW, A direct comparison of seprafilm, adept, intercoat, and spraygel for adhesion prophylaxis, J. Surg. Res 161(2) (2010) 246– 9. 19375716
  55. [69]Ozel H, Avsar FM, Topaloglu S, Sahin M, Induction and assessment methods used in experimental adhesion studies, Wound Repair Regen. 13(4) (2005) 358– 364. 16008724

Cited by

Sorted by citations

Authors
Mayes, S. M., Davis, J., Scott, J., Aguilar, V., Zawko, S. A., Swinnea, S., Peterson, D. L., Hardy, J. G., & Schmidt, C. E.
Affiliations
  • The University of Texas at Austin (US)
  • University of Florida (US)
Corresponding author
  • Mayes, Sarah M.
  • Hardy, John G.
  • Schmidt, Christine E.
ORCID
Venue
Acta Biomaterialia
Publisher
Elsevier BV
Published
2020-04
Volume
106
Pages
92-101
ISSN
1742-7061 (ISSN-L)
DOI
10.1016/j.actbio.2020.02.027
PMC
PMC8552357
OpenAlex
W3008982256
Cited by
64
References
1
Citations by year
2026: 5 · 2025: 15 · 2024: 9 · 2023: 17 · 2022: 9 · 2021: 7 · 2020: 2
FWCI
7.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Biomaterialia (publishedVersion)
  • PubMed (publishedVersion)
  • Lancaster EPrints (Lancaster University) (acceptedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation (0805298)
  • Division of Materials Research
  • NIH (4R42GM103158-02)
Topics
  • Health Sciences › Medicine › Surgery › Intestinal and Peritoneal Adhesions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Health Sciences › Medicine › Surgery › Surgical Sutures and Adhesives
Keywords
postoperative adhesions, anti-adhesion barrier, macroporous films, biointerfaces
MeSH terms
Tissue Adhesions, Alginates, Animals, Epoxy Compounds, Female, Fibroblasts, Humans, Hyaluronic Acid, Membranes, Artificial, Methacrylates, Postoperative Complications, Tensile Strength, Urea, Porosity, Anisotropy, Rats, Sprague-Dawley, Hydrogels

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review