CoChat
Sign Up
Cited by 12Hydrogels: synthesis, properties, applicationsIntestinal and Peritoneal AdhesionsPolysaccharides Composition and Applications

Chemically Modified Hyaluronic Acid for Prevention of Post-Surgical Adhesions: New Aspects of Gel Barriers Physical Profiles

Open access
Torres-de la Roche, Luz Angela, Bérard, Véronique, de Wilde, Maya Sophie, Devassy, Rajesh, Wallwiener, Markus, De Wilde, Rudy Leon·2022·Journal of Clinical Medicine
DOI 10.3390/jcm11040931PMC PMC8874822
Open this paper in CoChat — free accountOpen PDF

Abstract

This study was conducted to provide information regarding the chemistry—including structure, synthesis, formulation, and mechanical properties—of two types of chemically modified anti-adhesion gels made of hyaluronic acid. Gel A (Hyalobarrier®) and gels B and C (HyaRegen® and MetaRegen®) that are used in postsurgical adhesion prevention. To date, little information is available on their physicochemical attributes. This information is necessary in order to understand the differences in their in vivo behavior. Methods: Comparative analyses were conducted under laboratory-controlled conditions, including measuring the shear viscosity, storage modulus G’, peel strength, and extrusion forces. Results: All polymers exhibited viscoelastic behavior. Polymer A showed a shear viscosity approximately three times larger than both polymers B and C (114 Pa.s−1 vs. 36–38 Pa.s−1) over the shear-rate range measured, indicating a possible better ability to resist flows and potentially remain in place at the site of application in vivo. The results of storage modulus (G’) measurements showed 100 Pa for polymer A and 16 Pa and 20 Pa for polymers B and C, respectively. This translated into a weaker elastic behavior for gels B and C, and a lower ability to resist sudden deformation. The peel test results showed a rupture strength of 72 mN (0.016 lbf) for polymer A, 39.6 mN (0.0089 lbf) for polymer B, and 38.3 mN (0.0086 lbf) for polymers C, indicating possible higher adhesive properties for polymer A. Tests measuring the extrudability of the hyaluronic acid gels in their commercial syringes showed an average extrusion force of 20 N (4.5 lbf) for polymer A, 28 N (6.33 lbf) for polymer B, and 17 N (3.79 lbf) for polymer C. Conclusions: Modified anti-adhesion gels made of hyaluronic acid differed in mechanical properties and concentration. Further clinical studies are needed to confirm whether these differences make one polymer easier to apply during surgery and more likely to stay in place longer after in vivo application, and to determine which is potentially superior in terms of preventing 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 · 10.3390/jcm11040931

Cites

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?

  • A comparative study evaluating Hyalobarrier®, HyaRegen®, and MetaRegen® found that Hyalobarrier® demonstrated significantly higher viscosity (114 Pa·s), elasticity (G' = 100 Pa), and peel strength (72 mN) compared to the other gels.

    “A comparative study evaluating three commercial formulations—Hyalobarrier®, HyaRegen®, and MetaRegen®—found that Hyalobarrier® demonstrated significantly higher viscosity (114 Pa·s), elasticity (G’ = 100 Pa), and peel strength (72 mN) compared to the other gels.”

    From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [121]

    The Abstract reports 114 for Hyalobarrier®’s viscosity, G′ = 100 Pa, and peel strength of 72 mN, all higher than the values for the other two gels; Results §3.2 also confirms the higher viscosity and peel strength. The paper does not report statistical significance for these comparisons, so the claim’s use of “significantly” is not supported if meant statistically. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Hyalobarrier® had a moderate increase in extrusion force (20 N), indicating a trade-off between mechanical stability and ease of application.

    “However, this came with a moderate increase in extrusion force (20 N), indicating a trade-off between mechanical stability and ease of application.”

    From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [121]

    The Results (§3.2) identify Hyalobarrier® as polymer A and report its extrusion force as 20 N, compared with 17 N for polymer C and 28 N for polymer B. The Discussion (§4) suggests polymer A may be more likely to remain in place, but the paper does not establish a trade-off with ease of application; its Abstract says further clinical studies are needed to determine whether the measured differences affect application during surgery. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The higher viscosity, elasticity, and peel strength of Hyalobarrier® suggest a stronger capacity to remain in place and resist deformation post-application, potentially enhancing its anti-adhesion efficacy.

    “These properties suggest a stronger capacity to remain in place and resist deformation post-application, potentially enhancing the gel′s anti-adhesion efficacy.”

    From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [121]

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

No references could be resolved yet.

Research works printed but not linked: 39

  1. [1]Ahmad G. Thompson M. Kim K. Agarwal P. Mackie F.L. Dias S. Metwally M. Watson A. Fluid and pharmacological agents for adhesion prevention after gynaecological surgery Cochrane Database Syst. Rev. 2014 7 CD001298 10.1002/14651858.CD001298.pub4 32683695 PMC7388178 · DOI
  2. [2]Menzies D. Ellis H. Intestinal obstruction from adhesions—How big is the problem? Ann. R. Coll. Surg. Engl. 1990 72 60 63 2301905 PMC2499092
  3. [3]Stommel M.W. Ten Broek R.P. Strik C. Slooter G.D. Verhoef C. Grünhagen D.J. van Duijvendijk P. Bemelmans M.H. den Dulk M. Sietses C. Multicenter observational study of adhesion formation after open- and laparoscopic surgery for colorectal cancer Ann. Surg. 2018 267 743 748 10.1097/SLA.0000000000002175 28207436 · DOI
  4. [4]Diamond M.P. Freeman M.L. Clinical implications of postsurgical adhesions Hum. Reprod Update 2001 7 567 576 10.1093/humupd/7.6.567 11727865 · DOI
  5. [5]Ten Broek R.P.G. Strik C. Issa Y. Bleichrodt R.P. van Goor H. Adhesiolysis-related morbidity in abdominal surgery Ann. Surg. 2013 258 98 106 10.1097/SLA.0b013e31826f4969 23013804 · DOI
  6. [6]Ording Olsen K. Juul S. Berndtsson I. Oresland T. Laurberg S. Ulcerative colitis: Female fecundity before diagnosis, during disease, and after surgery compared with a population sample Gastroenterology 2002 122 15 19 10.1053/gast.2002.30345 11781275 · DOI
  7. [7]Parikh J.A. Ko C.Y. Maggard M.A. Zingmond D.S. What is the rate of small bowel obstruction after colectomy? Am. Surg. 2008 74 1001 1005 10.1177/000313480807401026 18942632 · DOI
  8. [8]Leung T.T. Dixon E. Gill M. Mador B.D. Moulton K.M. Kaplan G.G. MacLean A.R. Bowel obstruction following appendectomy: What is the true incidence? Ann. Surg. 2009 250 51 53 10.1097/SLA.0b013e3181ad64a7 19561482 · DOI
  9. [9]De Wilde R.L. Trew G. Angioni S. Audebert A. Barri P. Chapron C. Cocci M.E. Degueldre M. DiZerega G. García E. Postoperative abdominal adhesions and their prevention in gynaecological surgery. Expert consensus position Gynecol. Surg. 2007 4 161 168 10.1007/s10397-007-0338-x · DOI
  10. [10]Ait Menguellet S. Collinet P. Cosson M. Mariette C. Triboulet J.P. Vinatier D. Interest in agents for adhesion prevention after gynecologic surgery Gynecol. Obstet. Fertil. 2007 35 290 296 10.1016/j.gyobfe.2007.02.011 17337231 · DOI
  11. [11]Imai A. Suzuki N. Topical non-barrier agents for postoperative adhesion prevention in animal models Eur. J. Obstet. Gynecol. Reprod. Biol. 2010 149 131 135 10.1016/j.ejogrb.2009.12.026 20074848 · DOI
  12. [12]Koninckx P.R. Corona R. Timmerman D. Verguts J. Adamyan L. Peritoneal full-conditioning reduces postoperative adhesions and pain: A randomised controlled trial in deep endometriosis surgery J. Ovarian Res. 2013 6 90 10.1186/1757-2215-6-90 24326155 PMC4029570 · DOI
  13. [13]Krielen P. Stommel M.W. Pargmae P. Bouvy N.D. Bakkum E.A. Ellis H. Parker M.C. Griffiths E.A. van Goor H. Broek R.P.G.T. Adhesion-related Readmissions After Open and Laparoscopic Surgery: A Retrospective Cohort Study (SCAR Update) Lancet 2020 395 33 41 Erratum in Lancet 2020, 395, 272 10.1016/S0140-6736(19)32636-4 31908284 · DOI
  14. [14]Ten Broek R.P.G. Stommel M.W. Strik C. van Laarhoven C.J.M. Keus F. van Goor H. Benefits and harms of adhesion barriers for abdominal surgery: A systematic review and meta-analysis Lancet 2014 383 48 59 10.1016/S0140-6736(13)61687-6 24075279 · DOI
  15. [15]van Steensel S. van den Hil L.C.L. Schreinemacher M.H.F. Ten Broek R.P.G. van Goor H. Bouvy N.D. Adhesion awareness in 2016: An update of the national survey of surgeons PLoS ONE 2018 13 e0202418 10.1371/journal.pone.0202418 30118503 PMC6097683 · DOI
  16. [16]Park H. Baek S. Kang H. Lee D. Biomaterials to Prevent Post-Operative Adhesion Materials 2020 13 3056 10.3390/ma13143056 32650529 PMC7412384 · DOI · Paper page
  17. [17]Chandel A.K.S. Shimizu A. Hasegawa K. Ito T. Advancement of Biomaterial-Based Postoperative Adhesion Barriers Macromol. Biosci. 2021 21 e2000395 10.1002/mabi.202000395 33463888 · DOI · Paper page
  18. [18]Laurent T.C. Fraser J.R.E. Hyaluronan FASEB J. 1992 6 2397 10.1096/fasebj.6.7.1563592 1563592 · DOI
  19. [19]Meaume S. Hyaluronic acid Ann. Dermatol. Venereol. 2001 47 (Suppl. S3–S4) 536 566 11526823
  20. [20]Bonnetblanc J.M. Propriétés pharmacologiques de l’acide hyaluronique [Pharmacological properties of hyaluronic acid] Ann. Dermatol. Venereol. 2001 S9 S12 (In French) 11526825
  21. [21]Navsaria H. L’acide hyaluronique, matériel biotechnologique [Pharmacological properties of hyaluronic acid] Ann. Dermatol. Venereol. 2002 129 1227 1230 (In French) 12442148
  22. [22]Nappi C. Di Spiezio Sardo A. Greco E. Guida M. Bettocchi S. Bifulco G. Prevention of adhesions in gynaecological endoscopy Hum. Reprod. Update 2007 13 379 394 10.1093/humupd/dml061 17452399 · DOI
  23. [23]Mensitieri M. Ambrosio L. Nicolais L. Bellini D. O’Regan M. Viscoelastic properties modulation of a novel autocrosslinked hyaluronic acid polymer J. Mater. Sci. Mater. Med. 1996 7 695 698 10.1007/BF00123409 · DOI
  24. [24]De Laco P.A. Stefanetti M. Pressato D. Piana S. Donà M. Pavesio A. Bovicelli L. A novel hyaluronan-based gel in laparoscopic adhesion prevention: Preclinical evaluation in an animal model Fertil. Steril. 1998 69 318 323 10.1016/S0015-0282(98)00496-8 9496348 · DOI
  25. [25]Johns B.D. Keyport G.M. Hoehler F. DiZerega G. Reduction of postsurgical adhesions with Intergel adhesion prevention solution: A multicenter study of safety and efficacy after conservative gynecologic surgery Fertil. Steril. 2001 76 595 604 10.1016/S0015-0282(01)01954-9 11532487 · DOI
  26. [26]Revaux A. Ducarme G. Luton D. Prevention of intrauterine adhesions after hysteroscopic surgery Gynecol. Obstet. Fertil. 2008 36 311 317 10.1016/j.gyobfe.2007.11.014 18308609 · DOI
  27. [27]Farag S. Padilla P.F. Smith K.A. Sprague M.L. Zimberg S.E. Management, Prevention, and Sequelae of Adhesions in Women Undergoing Laparoscopic Gynecologic Surgery: A Systematic Review Minim. Invasive Gynecol. 2018 25 1194 1216 10.1016/j.jmig.2017.12.010 29289627 · DOI
  28. [28]Shu X.Z. Liu Y. Luo Y. Roberts M.C. Prestwich G.D. Disulfide cross-linked hyaluronan hydrogels Biomacromelecules 2002 3 1304 1311 10.1021/bm025603c 12425669 · DOI
  29. [29]Liu Y. Shu X.Z. Gray S.D. Prestwich G.D. Disulfide-crosslinked hyaluronan–gelatin sponge: Growth of fibrous tissue in vivo J. Biomed. Mater. Res. 2004 68 142 149 10.1002/jbm.a.10142 14661259 · DOI
  30. [30]Shu X.Z. Liu Y. Palumbo F.S. Luo Y. Prestwich G.D. In situ crosslinkable hyaluronan hydrogels for tissue engineering Biomaterials 2004 25 1339 1348 14643608
  31. [31]Shu X.Z. Liu Y. Palumbo F. Prestwich G.D. Disulfide-crosslinked hyaluronan-gelatin hydrogel films: A covalent mimic of the extracellular matrix for in vitro cell growth Biomaterials 2003 24 3825 3834 10.1016/S0142-9612(03)00267-9 12818555 · DOI
  32. [32]Wallwiener M. Koninckx P.R. Hackethal A. Brölmann H. Lundorff P. Mara M. Wattiez A. De Wilde R.L. A European survey on awareness of post-surgical adhesions among gynecological surgeons Gynecol. Surg. 2014 11 105 112 10.1007/s10397-013-0824-2 24795546 PMC4003340 · DOI
  33. [34]Frenkel J.S. The role of hyaluronan in wound healing Int Wound J. 2014 11 159 163 10.1111/j.1742-481X.2012.01057.x 22891615 PMC7950635 · DOI
  34. [35]Neuman M.G. Nanau R.M. Oruña-Sanchez L. Coto G. Hyaluronic Acid and Wound Healing J. Pharm. Pharm. Sci 2015 18 53 60 10.18433/J3K89D 25877441 · DOI
  35. [36]Guida M. Acunzo G. Di Spiezio Sardo A. Bifulco G. Piccoli R. Pellicano M. Cerrota G. Cirillo D. Nappi C. Effectiveness of auto-crosslinked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic surgery: A prospective, randomized, controlled study Hum. Reprod. 2004 19 1461 1464 10.1093/humrep/deh238 15105384 · DOI
  36. [37]Hooker A.B. de Leeuw R. van de Ven P.M. Bakkum E.A. Thurkow A.L. Vogel N.E.A. van Vliet H.A.A.A.M. Bongers M.Y. Emanuel M.H. Verdonkschot A.E.M. Prevalence of intrauterine adhesions after the application of hyaluronic acid gel after dilatation and curettage in women with at least one previous curettage: Short-term outcomes of a multicenter, prospective randomized controlled trial Fertil. Steril. 2017 107 1223 1231 10.1016/j.fertnstert.2017.02.113 28390688 · DOI
  37. [38]Liu C. Lu Q. Zhang Z. Xue M. Zhang Y. Zhang Y. Wang H. Li H. Zhou Y. Zhang Z. A Randomized Controlled Trial on the Efficacy and Safety of a New Crosslinked Hyaluronan Gel in Reducing Adhesions after Gynecologic Laparoscopic Surgeries J. Minim. Invasive Gynecol. 2015 22 853 863 10.1016/j.jmig.2015.04.011 25906706 · DOI
  38. [39]Li X. Wu L. Zhou Y. Fan X. Huang J. Wu J. Yu R. Lou J. Yang M. Yao Z. New Crosslinked Hyaluronan Gel for the Prevention of Intrauterine Adhesions after Dilation and Curettage in Patients with Delayed Miscarriage: A Prospective, Multicenter, Randomized, Controlled Trial J. Minim. Invasive Gynecol. 2019 26 94 99 10.1016/j.jmig.2018.03.032 29678756 · DOI
  39. [40]Zhou Q. Shi X. Saravelos S. Huang X. Zhao Y. Huang R. Xia E. Li T.C. Auto-cross-linked hyaluronic acid gel for prevention of intrauterine adhesions after hysteroscopic adhesiolysis: A randomized controlled trial J. Minim. Invasive Gynecol. 2021 28 307 313 10.1016/j.jmig.2020.06.030 32681996 · DOI

Cited by

Sorted by citations

Authors
Torres-de la Roche, L. A., Bérard, V., de Wilde, M. S., Devassy, R., Wallwiener, M., & De Wilde, R. L.
Affiliations
  • University Hospital for Gynecology, Pius Hospital, University Medicine Oldenburg, 26121 Oldenburg, Germany
  • Laboratoire Interdisciplinaire Carnot de Bourgogne (FR)
  • Carl von Ossietzky Universität Oldenburg (DE)
  • Heidelberg University (DE)
ORCID
Venue
Journal of Clinical Medicine
Publisher
MDPI AG
Published
2022-02-11
Volume
11
Issue
4
Pages
931
ISSN
2077-0383 (ISSN-L)
DOI
10.3390/jcm11040931
PMC
PMC8874822
OpenAlex
W4211019705
Cited by
12
References
0
Citations by year
2026: 3 · 2025: 5 · 2024: 2 · 2023: 2
FWCI
0.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Nordic Pharma, Paris, France (CB_RLDW_06112020)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Health Sciences › Medicine › Surgery › Intestinal and Peritoneal Adhesions
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Polysaccharides Composition and Applications
Keywords
postoperative adhesions, viscoelasticity, shear viscosity, storage modulus, peel strength, extrusion force, gel formulation, adhesion prevention

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