title: Sustained release of collagen VI potentiates sciatic nerve regeneration by modulating macrophage phenotype.
abstract: Although the peripheral nervous system has an intrinsic ability for repair and regeneration after injury, bridging long peripheral nerve defects remains a challenge. Functional nerve regeneration depends on interactions among axons, Schwann cells, fibroblasts and immune cells. Macrophages, as immune cells recruited early in this process, show polarization toward phenotypes that are detrimental or beneficial to tissue remodeling depending on the microenvironment of the scaffolds. In this study, we investigated the effects of macrophage phenotypes modulated by collagen VI on axonal regeneration and functional recovery by bridging a 15-mm-long sciatic nerve defect in rats. Our results showed that local delivery of collagen VI within a polycaprolactone (PCL) electrospun conduit increased the recruitment of macrophages and their polarization toward the pro-healing (M2) phenotype. In addition, the axonal regeneration and neurologic functional recovery in the PCL/collagen VI conduit group are equivalent to that of an autograft. In conclusion, the present study confirmed that PCL/collagen VI conduits with sustained release of collagen VI in the local microenvironment may, through triggering macrophage M2 polarization to enhance the nerve regeneration, suggest that our combined biomaterial-immunomodulatory system may be an attractive candidate for peripheral nerve regeneration.
authors.affiliation: The graduate School, Tianjin Medical University, Tianjin, China.|Department of Orthopaedics, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, Tianjin, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Lv
authors.affiliation: Key Laboratory of Oral Diseases Research of Anhui Province (Anhui), Stomatologic Hospital & College, Anhui Medical University, Hefei, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Oral Diseases Research of Anhui Province (Anhui), Stomatologic Hospital & College, Anhui Medical University, Hefei, China.
authors.forename: Xianyu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Orthopaedic Oncology, Tianjin Hospital, Tianjin, 300210, China.
authors.forename: Yongcheng
authors.identifier: 0000-0001-5628-301X
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D024142:Collagen Type VI / Q000008:administration & dosage / Q000627:therapeutic use*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D057139:Nanofibers / Q000737:chemistry; D009416:Nerve Regeneration; D059348:Peripheral Nerve Injuries / Q000188:drug therapy*; D010641:Phenotype; D011091:Polyesters / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries
chemical_list: D024142:Collagen Type VI; D011091:Polyesters; C016240:polycaprolactone
keywords: axonal regeneration; collagen VI; macrophage; peripheral nerve injury