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Use of a supramolecular polymeric hydrogel as an effective post-operative pericardial adhesion barrier

Nature Biomedical Engineering volume 3, pages 611–620 (2019)Cite this article

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Abstract

Post-operative adhesions form as a result of normal wound healing processes following any type of surgery. In cardiac surgery, pericardial adhesions are particularly problematic during reoperations, as surgeons must release the adhesions from the surface of the heart before the intended procedure can begin, thereby substantially lengthening operation times and introducing risks of haemorrhage and injury to the heart and lungs during sternal re-entry and cardiac dissection. Here we show that a dynamically crosslinked supramolecular polymer–nanoparticle hydrogel, with viscoelastic and flow properties that enable spraying onto tissue as well as robust tissue adherence and local retention in vivo for two weeks, reduces the formation of pericardial adhesions. In a rat model of severe pericardial adhesions, the hydrogel markedly reduced the severity of the adhesions, whereas commercial adhesion barriers (including Seprafilm and Interceed) did not. The hydrogels also reduced the severity of cardiac adhesions (relative to untreated animals) in a clinically relevant cardiopulmonary-bypass model in sheep. This viscoelastic supramolecular polymeric hydrogel represents a promising clinical solution for the prevention of post-operative pericardial adhesions.

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Fig. 1: Overview of PNP hydrogel adhesion barrier.
Fig. 2: Mechanical characterization of PNP hydrogel adhesion barrier.
Fig. 3: Prevention of pericardial adhesion in a rat model.
Fig. 4: In vivo retention of PNP hydrogel adhesion barrier.
Fig. 5: Prevention of adhesion in an epicardial abrasion model in sheep.
Fig. 6: Sheep cardiopulmonary bypass and aortotomy model.

Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. The raw and analysed datasets generated during the study are available for research purposes from the corresponding authors on reasonable request.

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Acknowledgements

This work was made possible by the financial support from the Stanford BIOX Interdisciplinary Initiatives Program Seed Grant (E.A.A. and Y.J.W.), the Stanford-Coulter Translational Research Grant (E.A.A. and Y.J.W.), the National Institutes of Health (R01HL089315-01, Y.J.W.), the American Heart Association postdoctoral fellowship (H.W. and M.J.P.) and predoctoral fellowship (L.M.S.), the National Science Foundation AGEP California Alliance Postdoctoral Fellowship (H.L.H.) and Graduate Research Fellowship Program (DGE-1147470, L.M.S., A.N.S. and G.A.), the Stanford Interdisciplinary Graduate Fellowship (L.M.S.), and the American Association for Thoracic Surgery Summer Intern Scholarship (K.M.W.). The authors thank the Bogyo laboratory for the use of the Pearl instrument, the Stanford Veterinary Services Center for assistance with ovine surgeries and the Stanford Animal Histology Services for assistance with histology.

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Authors and Affiliations

  1. Department of Bioengineering, Stanford University, Stanford, CA, USA

    Lyndsay M. Stapleton, Amanda N. Steele, Gillie A. Roth, Kailey P. Totherow, Eric A. Appel & Y. Joseph Woo

  2. Department of Cardiothoracic Surgery, Stanford University, Stanford, CA, USA

    Lyndsay M. Stapleton, Amanda N. Steele, Hanjay Wang, Michael J. Paulsen, Akshara D. Thakore, Haley J. Lucian, Justin M. Farry, Anahita Eskandari, Camille E. Hironaka, Kevin J. Jaatinen, Kiah M. Williams, Hunter Bergamasco, Clifton Marschel, Blaine Chadwick, Frederick Grady, Michael Ma & Y. Joseph Woo

  3. Department of Materials Science & Engineering, Stanford University, Stanford, CA, USA

    Hector Lopez Hernandez, Anthony C. Yu, Anton A. A. Smith & Eric A. Appel

  4. Department of Comparative Medicine, Stanford University, Stanford, CA, USA

    Sam W. Baker

  5. Department of Cardiovascular Medicine, Stanford University, Stanford, CA, USA

    Yuko Tada

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Contributions

L.M.S., A.N.S., A.C.Y., H.W., M.J.P., A.A.A.S., Y.J.W. and E.A.A. designed experiments; L.M.S., H.W., H.J.L., A.D.T., H.L.H., G.A., K.P.T. and E.A.A. conducted experiments; J.M.F., H.J.L., A.D.T., A.E., K.M.W., C.E.H., K.J.J., M.J.P., S.W.B., B.C., C.M., F.G., H.B. and M.M. assisted with ovine surgeries; L.M.S., A.N.S., Y.T., Y.J.W. and E.A.A. analysed data; and L.M.S., Y.J.W. and E.A.A. wrote the paper.

Corresponding authors

Correspondence to Eric A. Appel or Y. Joseph Woo.

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The authors declare no competing interests.

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Supplementary information

Supplementary Information

Supplementary figures and video captions.

Reporting Summary

Supplementary Video 1

An untreated heart in a rodent pericardial-adhesion model

Supplementary Video 2

Seprafilm-treated heart in a rodent pericardial-adhesion model

Supplementary Video 3

Interceed-treated heart in a rodent pericardial-adhesion model

Supplementary Video 4

PNP-2:10-hydrogel-treated heart in a rodent pericardial-adhesion model

Supplementary Video 5

PNP-1:10-hydrogel-treated heart in a rodent pericardial-adhesion model

Supplementary Video 6

PNP-1:5-hydrogel-treated heart in a rodent pericardial-adhesion model

Supplementary Video 7

PNP-1:1-hydrogel-treated heart in a rodent pericardial-adhesion model

Supplementary Video 8

PNP-0.2:10-hydrogel-treated heart in a rodent pericardial-adhesion model

Supplementary Video 9

Spraying the PNP-1:10-hydrogel treatment onto the epicardial surface following epicardial abrasion

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Stapleton, L.M., Steele, A.N., Wang, H. et al. Use of a supramolecular polymeric hydrogel as an effective post-operative pericardial adhesion barrier. Nat Biomed Eng 3, 611–620 (2019). https://doi.org/10.1038/s41551-019-0442-z

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