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Pirfenidone-loaded hyaluronic acid methacryloyl hydrogel for preventing epidural adhesions after laminectomy

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Abstract

It is inevitable that scar formation occurs between the spinal dura and surrounding tissues after laminectomy. While extensive epidural fibrosis, which results in limited nerve root activity and severe pain, is the main cause of postoperative failed-back surgery syndrome. Novel biomaterial loading effective drugs based on reasonable design are eagerly needed for the safe and effective prevention of epidural adhesions. We filtrated a suitable dose of pirfenidone (PFD) to load hyaluronic acid methacryloyl (HAMA) hydrogel in vitro. And then, we compare PFD-loaded HAMA hydrogel with only using PFD or HAMA hydrogels after laminectomy by in vivo studies in rats. We describe a safe and efficient anti-adhesive PFD-loaded HAMA hydrogel that prevents epidural fibrosis through the stable and sustained release of PFD. It was shown that the PFD-loaded HAMA hydrogel effectively inhibited cell penetration and suppressed collagen I/III expression. Thus, it effectively prevented the formation of adhesions through pharmacological and physical processes. The PFD-loaded HAMA hydrogel can effectively prevent adhesion formation in both pharmacological and physical barrier effects.

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Acknowledgements

This research was supported by the Postgraduate Research & Practice Innovation Program of Jiangsu Province (SJCX21-1472), the Health Commission of Jiangsu Province (H2018026), the Jiangsu Provincial Key Medical Center (YXZA2016001), and the Nantong Municipal Science and Technology Plan (JCZ20107).

Funding

Postgraduate Research and Practice Innovation Program of Jiangsu Province (SJCX21-1472), Health Commission of Jiangsu Province (H2018026), Jiangsu Provincial Key Medical Center (YXZA2016001); Nantong Municipal Science and technology Plan (JCZ20107). Nantong science and technology development foundation (Grant No. JC2021175).

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Author notes

  1. Jiawei Ji and Jiaqi Cheng equally contributed to this study.

Authors and Affiliations

  1. Department of Spine Surgery, Affiliated Hospital and Medical School of Nantong University, Nantong University, Jiangsu Province, 226001, Nantong, China

    Jiawei Ji, Jiaqi Cheng, Cheng Chen, Yang Lu, Xiaoqing Chen & Feng Zhang

  2. Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China

    Jiawei Ji, Jiaqi Cheng & Yang Lu

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  1. Jiawei Ji
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  2. Jiaqi Cheng
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  6. Feng Zhang
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Contributions

Jiawei Ji: Methodology, formal analysis, data curation, visualization, and writing—original draft. Xiaoqing Chen: Conceptualization, writing—reviewing and editing, and supervision. Jiaqi Cheng: Resources, validation, animal experiment, resources, and software. Cheng Chen: Animal experiment and data curation. Yang Lu: Validation and investigation. Feng Zhang: Conceptualization, validation, writing—reviewing and editing, and project administration.

Corresponding authors

Correspondence to Xiaoqing Chen or Feng Zhang.

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Ethics approval and consent to participate

The animals received care in compliance with the principles of the guidelines of the Chinese Society of Laboratory Animals on animal welfare, and the experimental protocol was approved by the Standard Operating Procedures for Laboratory Animal Center of Nantong University (no. S20220103-921).

Consent for publication

We submit the manuscript entitled: Pirfenidone-loaded Hyaluronic Acid Methacryloyl Hydrogel for Preventing Epidural Adhesions after Laminectomy. All authors would like to have it considered exclusively for publication in Drug Delivery and Translational Research. We hope our manuscript will have the opportunity to be published in it.

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The authors declare no competing interests.

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Ji, J., Cheng, J., Chen, C. et al. Pirfenidone-loaded hyaluronic acid methacryloyl hydrogel for preventing epidural adhesions after laminectomy. Drug Deliv. and Transl. Res. 13, 770–781 (2023). https://doi.org/10.1007/s13346-022-01236-0

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