Nerve ECM and PLA-PCL based electrospun bilayer nerve conduit for nerve regeneration

Xiaoyan Mao; Ting Li; Junqiu Cheng; Meihan Tao; Zhiyuan Li; Yizhan Ma; Rabia Javed; Jie Bao; Fang Liang; Weihong Guo; Xiaohong Tian; Jun Fan; Tianhao Yu; Qiang Ao

doi:10.3389/fbioe.2023.1103435

Nerve ECM and PLA-PCL based electrospun bilayer nerve conduit for nerve regeneration

Front Bioeng Biotechnol. 2023 Mar 2:11:1103435. doi: 10.3389/fbioe.2023.1103435. eCollection 2023.

Authors

Xiaoyan Mao¹, Ting Li^{1

2}, Junqiu Cheng³, Meihan Tao¹, Zhiyuan Li¹, Yizhan Ma¹, Rabia Javed¹, Jie Bao¹, Fang Liang¹, Weihong Guo⁴, Xiaohong Tian¹, Jun Fan¹, Tianhao Yu⁵, Qiang Ao^{1

3

6}

Affiliations

¹ Department of Tissue Engineering, China Medical University, Shenyang, China.
² Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
³ National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China.
⁴ Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁵ Liaoning Provincial Key Laboratory of Oral Diseases, The VIP Department, School and Hospital of Stomatology, China Medical University, Shenyang, China.
⁶ Institute of Regulatory Science for Medical Device, Sichuan University, Chengdu, China.

Abstract

Introduction: The porcine nerve-derived extracellular matrix (ECM) fabricated as films has good performance in peripheral nerve regeneration. However, when constructed as conduits to bridge nerve defects, ECM lacks sufficient mechanical strength. Methods: In this study, a novel electrospun bilayer-structured nerve conduit (BNC) with outer poly (L-lactic acid-co-ε-caprolactone) (PLA-PCL) and inner ECM was fabricated for nerve regeneration. The composition, structure, and mechanical strength of BNC were characterized. Then BNC biosafety was evaluated by cytotoxicity, subcutaneous implantation, and cell affinity tests. Furthermore, BNC was used to bridge 10-mm rat sciatic nerve defect, and nerve functional recovery was assessed by walking track, electrophysiology, and histomorphology analyses. Results: Our results demonstrate that BNC has a network of nanofibers and retains some bioactive molecules, including collagen I, collagen IV, laminin, fibronectin, glycosaminoglycans, nerve growth factor, and brain-derived neurotrophic factor. Biomechanical analysis proves that PLA-PCL improves the BNC mechanical properties, compared with single ECM conduit (ENC). The functional evaluation of in vivo results indicated that BNC is more effective in nerve regeneration than PLA-PCL conduit or ENC. Discussion: In conclusion, BNC not only retains the good biocompatibility and bioactivity of ECM, but also obtains the appropriate mechanical strength from PLA-PCL, which has great potential for clinical repair of nerve defects.

Keywords: ECM; bilayer structure; electrospun; nerve conduit; peripheral nerve regeneration.

Grants and funding

This work was supported by Sichuan Science and Technology Program (grant number 2020YFH0008); National Natural Science Foundation of China (grant number 81771351); National Key R&D Program of China (grant number 2017YFA0105802); Liaoning Provincial Natural Science Foundation of China (grant number 2022-MS-194; grant number 2021-M-208); Shengjing Hospital 345 Talent Project; China Postdoctoral Science Foundation (grant number 2022MD713819); and National Natural Science Foundation of China (grant number 82201544).