TY - JOUR
T1 - Aligned microfiber-induced macrophage polarization to guide schwann-cell-enabled peripheral nerve regeneration
AU - Dong, Xianhao
AU - Liu, Siyang
AU - Yang, Yueyue
AU - Gao, Shan
AU - Li, Wenlei
AU - Cao, Jiasong
AU - Wan, Ye
AU - Huang, Ziqi
AU - Fan, Guanwei
AU - Chen, Quan
AU - Wang, Hongjun
AU - Zhu, Meifeng
AU - Kong, Deling
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/5
Y1 - 2021/5
N2 - Mechanistic understanding of the topological cues delivered by biomaterials in promotion of oriented tissue regeneration (e.g., peripheral nerve regrowth) remains largely elusive. Here, we engineered nerve conduits composed of oriented microfiber-bundle cores and randomly organized nanofiber sheaths to particularly interrogate the regulatory mechanism of microfiber orientation on promoted peripheral nerve regeneration. With comprehensive yet systematic analyses, we were able to elucidate the intricate cascade of biological responses associated with conduit-assisted nerve regrowth, i.e., oriented microfibers facilitated macrophage recruitment and subsequent polarization toward a pro-healing phenotype, which in turn promoted Schwann cell (SC) migration, myelinization and axonal extension. Pronounced improvement of nerve regeneration in rat sciatic nerve injury was evidenced with enhanced electrophysiologic function, sciatic functional index and alleviated muscle atrophy 3 months post-implantation. The obtained results offer essential insights on the topological regulation of biomaterials in functional nerve tissue regeneration via immune modulation.
AB - Mechanistic understanding of the topological cues delivered by biomaterials in promotion of oriented tissue regeneration (e.g., peripheral nerve regrowth) remains largely elusive. Here, we engineered nerve conduits composed of oriented microfiber-bundle cores and randomly organized nanofiber sheaths to particularly interrogate the regulatory mechanism of microfiber orientation on promoted peripheral nerve regeneration. With comprehensive yet systematic analyses, we were able to elucidate the intricate cascade of biological responses associated with conduit-assisted nerve regrowth, i.e., oriented microfibers facilitated macrophage recruitment and subsequent polarization toward a pro-healing phenotype, which in turn promoted Schwann cell (SC) migration, myelinization and axonal extension. Pronounced improvement of nerve regeneration in rat sciatic nerve injury was evidenced with enhanced electrophysiologic function, sciatic functional index and alleviated muscle atrophy 3 months post-implantation. The obtained results offer essential insights on the topological regulation of biomaterials in functional nerve tissue regeneration via immune modulation.
KW - Macrophage polarization
KW - Nerve grafts
KW - Nerve regeneration
KW - Oriented microfiber
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U2 - 10.1016/j.biomaterials.2021.120767
DO - 10.1016/j.biomaterials.2021.120767
M3 - Article
C2 - 33813259
AN - SCOPUS:85103632355
SN - 0142-9612
VL - 272
JO - Biomaterials
JF - Biomaterials
M1 - 120767
ER -