Cell-encapsulated chitosan-collagen hydrogel hybrid nerve guidance conduit for peripheral nerve regeneration

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Cell-encapsulated chitosan-collagen hydrogel hybrid nerve guidance conduit for peripheral nerve regeneration Shun Itai 1 & Karin Suzuki 1 & Yuta Kurashina 1,2 & Hiroo Kimura 3 & Tsuyoshi Amemiya 3 & Kazuki Sato 4 & Masaya Nakamura 3 & Hiroaki Onoe 1 Accepted: 11 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Nerve guidance conduits (NGCs) composed of biocompatible polymers have been attracting attention as an alternative for autograft surgery in peripheral nerve regeneration. However, the nerve tissues repaired by NGCs often tend to be inadequate and lead to functional failure because of the lack of cellular supports. This paper presents a chitosan-collagen hydrogel conduit containing cells to induce peripheral nerve regeneration with cellular support. The conduit composed of two coaxial hydrogel layers of chitosan and collagen is simply made by molding and mechanical anchoring attachment with holes made on the hydrogel tube. A chitosan layer strengthens the conduit mechanically, and a collagen layer provides a scaffold for cells supporting the axonal extension. The conduits of different diameters (outer diameter approximately 2–4 mm) are fabricated. The conduit is bioabsorbable with lysozyme, and biocompatible even under bio absorption. In the neuron culture demonstration, the conduit containing Schwann cells induced the extension of the axon of neurons directed to the conduit. Our easily fabricated conduit could help the high-quality regeneration of peripheral nerves and contribute to the nerve repair surgery. Keywords Peripheral nerve regeneration . Nerve guidance conduit . Chitosan . Collagen . Cell culture

1 Introduction Peripheral nerve injuries often occur in traumatic injuries and torture patients with disorders (Robinson 2000). The degree of the nerve injury is classified into 3 levels by Seddon classification: neurapraxia (temporary conduction disorder without rupture of axons), axonotmesis (rupture of axons without rupture of an epineurium), and neurotmesis (total rupture of nerve fiber including axons and an epineurium) (Seddon 1942). In the case of neurapraxia and axonotmesis, the peripheral nerve would be able

* Hiroaki Onoe [email protected] 1

Department of Mechanical Engineering, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan

2

Department of Materials Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 4259 Nagatsutacho, Midori-Ku, Yokohama 226-8503, Japan

3

Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

4

Institute for Integrated Sports Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

to repair naturally (Evans 2001). In contrast, neurotmesis would not be repaired by itself because the scar formation at the surface of nerve stump disturbs the extension of axons (Burnett and Zager 2004). To repair the neurotmesis,