Bionic peptide scaffold in situ polarization and recruitment of M2 macrophages to promote peripheral nerve regeneration

Pengxiang Yang; Yong Peng; Xiu Dai; Jing Jie; Deling Kong; Xiaosong Gu; Yumin Yang

doi:10.1016/j.bioactmat.2023.07.003

Bionic peptide scaffold in situ polarization and recruitment of M2 macrophages to promote peripheral nerve regeneration

Bioact Mater. 2023 Jul 26:30:85-97. doi: 10.1016/j.bioactmat.2023.07.003. eCollection 2023 Dec.

Authors

Pengxiang Yang^{1

2}, Yong Peng¹, Xiu Dai¹, Jing Jie³, Deling Kong⁴, Xiaosong Gu¹, Yumin Yang¹

Affiliations

¹ Key Laboratory of Neuroregeneration of Jiangsu Province and Ministry of Education, Co-Innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, 226001, Nantong, PR China.
² Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin Medical University, 150081, Harbin, PR China.
³ Department of Clinical Laboratory, The Second Affiliated Hospital of Nantong University, 226001, Nantong, PR China.
⁴ State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, 300071, PR China.

Abstract

Tissue regeneration requires exogenous and endogenous signals, and there is increasing evidence that the exogenous microenvironment may play an even more dominant role in the complex process of coordinated multiple cells. The short-distance peripheral nerve showed a spontaneous regenerative phenomenon, which was initiated by the guiding role of macrophages. However, it cannot sufficiently restore long-distance nerve injury by itself. Based on this principle, we firstly constructed a proinflammatory model to prove that abnormal M2 expression reduce the guidance and repair effect of long-distance nerves. Furthermore, a bionic peptide hydrogel scaffold based on self-assembly was developed to envelop M2-derived regenerative cytokines and extracellular vesicles (EVs). The cytokines and EVs were quantified to mimic the guidance and regenerative microenvironment in a direct and mild manner. The bionic scaffold promoted M2 transformation in situ and led to proliferation and migration of Schwann cells, neuron growth and motor function recovery. Meanwhile, the peptide scaffold combined with CX3CL1 recruited more blood-derived M2 macrophages to promote long-distance nerve reconstruction. Overall, we systematically confirmed the important role of M2 in regulating and restoring the injury peripheral nerve. This bionic peptide hydrogel scaffold mimicked and remodeled the local environment for M2 transformation and recruitment, favoring long-distance peripheral nerve regeneration. It can help to explicate regulative effect of M2 may be a cause not just a consequence in nerve repair and tissue integration, which facilitating the development of pro-regenerative biomaterials.

Keywords: Bionic peptide scaffolds; Conditional media; Immune microenvironment; Macrophages; Peripheral nerve regeneration.