Li–Mg–Si bioceramics provide a dynamic immuno-modulatory and repair-supportive microenvironment for peripheral nerve regeneration

Sun, Yiting; Zhang, Hongjian; Yu, Zhuang; Liu, Zheqi; He, Dedong; Xu, Wanlin; Li, Siyi; Zhang, Chenping; Zhang, Zhen

doi:10.1016/j.bioactmat.2023.05.013

Cited by 9 publications

(7 citation statements)

References 78 publications

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“…To evaluate the effects of macrophage polarization on the proliferation, migration, and myelination of RSC96 cells, the supernatants of LPS-treated RAW264.7 cells which were seeded on different membranes for 72 h were collected as the conditioned medium (CM). According to relative studies [ 13 , 17 , 25 ], RSC96 cells were seeded in 96-well plates and then treated with a mixture of DMEM and CM at a ratio of 1:1. After culturing for 1 and 3 days, respectively, the CCK-8 assay was performed to analyze the proliferation of RSC96 cells.…”

Section: Methodsmentioning

confidence: 99%

Electrical aligned polyurethane nerve guidance conduit modulates macrophage polarization and facilitates immunoregulatory peripheral nerve regeneration

Sun,

Zhang,

Guo

et al. 2024

J Nanobiotechnol

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Biomaterials can modulate the local immune microenvironments to promote peripheral nerve regeneration. Inspired by the spatial orderly distribution and endogenous electric field of nerve fibers, we aimed to investigate the synergistic effects of electrical and topological cues on immune microenvironments of peripheral nerve regeneration. Nerve guidance conduits (NGCs) with aligned electrospun nanofibers were fabricated using a polyurethane copolymer containing a conductive aniline trimer and degradable L-lysine (PUAT). In vitro experiments showed that the aligned PUAT (A-PUAT) membranes promoted the recruitment of macrophages and induced their polarization towards the pro-healing M2 phenotype, which subsequently facilitated the migration and myelination of Schwann cells. Furthermore, NGCs fabricated from A-PUAT increased the proportion of pro-healing macrophages and improved peripheral nerve regeneration in a rat model of sciatic nerve injury. In conclusion, this study demonstrated the potential application of NGCs in peripheral nerve regeneration from an immunomodulatory perspective and revealed A-PUAT as a clinically-actionable strategy for peripheral nerve injury.

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Section: Methodsmentioning

confidence: 99%

Electrical aligned polyurethane nerve guidance conduit modulates macrophage polarization and facilitates immunoregulatory peripheral nerve regeneration

Sun,

Zhang,

Guo

et al. 2024

J Nanobiotechnol

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“…This is only the general physiological process of peripheral nerve regeneration; a more detailed mechanism of regeneration remains to be determined in neuroscience and clinical specialties. The current research directions for peripheral nerve tissue engineering are (1) improving the proliferation and migration of Schwann cells [ 94 ]; (2) regulating the macrophage phenotype [ 95 ]; (3) inhibiting scar blocking induced by fibroblasts; and (4) promoting angiogenesis of newly regenerated nerve tissue [ 96 ]. The pore size, morphology, and porosity can affect the surface roughness, stiffness, and permeability of NGCs, affecting the biological functions of Schwann cells, fibroblasts, macrophages, and vascular endothelial cells ( Figure 4 ).…”

Section: Implications Of Porous Ngcs On Peripheral Nerve Regenerationmentioning

confidence: 99%

The Porous Structure of Peripheral Nerve Guidance Conduits: Features, Fabrication, and Implications for Peripheral Nerve Regeneration

Wan,

Wang,

Zhang

et al. 2023

IJMS

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Porous structure is an important three-dimensional morphological feature of the peripheral nerve guidance conduit (NGC), which permits the infiltration of cells, nutrients, and molecular signals and the discharge of metabolic waste. Porous structures with precisely customized pore sizes, porosities, and connectivities are being used to construct fully permeable, semi-permeable, and asymmetric peripheral NGCs for the replacement of traditional nerve autografts in the treatment of long-segment peripheral nerve injury. In this review, the features of porous structures and the classification of NGCs based on these characteristics are discussed. Common methods for constructing 3D porous NGCs in current research are described, as well as the pore characteristics and the parameters used to tune the pores. The effects of the porous structure on the physical properties of NGCs, including biodegradation, mechanical performance, and permeability, were analyzed. Pore structure affects the biological behavior of Schwann cells, macrophages, fibroblasts, and vascular endothelial cells during peripheral nerve regeneration. The construction of ideal porous structures is a significant advancement in the regeneration of peripheral nerve tissue engineering materials. The purpose of this review is to generalize, summarize, and analyze methods for the preparation of porous NGCs and their biological functions in promoting peripheral nerve regeneration to guide the development of medical nerve repair materials.

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“…In particular, Li et al and Pixley et al have used Mg metal wires in their studies, with positive effects on nerve repair [15,[20][21][22]. However, while many of the in vivo studies have targeted the effects on axons and inflammation, observing the nerve as a whole, few studies have specifically studied the effects on SCs [14,23], and the in vitro studies focused mainly on cytocompatibility [24,25] or did not consider the injury microenvironment [17,19]. In summary, there is a need for improved understanding of SC responses to Mg material degradation.…”

Section: Introductionmentioning

confidence: 99%

“…The enzyme GSK3β has been shown to influence SC functions such as autophagy and remyelination during nerve regeneration. Therefore, Li, an inhibitor of this enzyme, can influence nerve regeneration via its actions on GSK3β [23,30,37]. We propose that using Li as an alloying element combined with Mg metal could enhance the beneficial effects on nerve regeneration.…”

Section: Introductionmentioning

confidence: 99%

“…We propose that using Li as an alloying element combined with Mg metal could enhance the beneficial effects on nerve regeneration. Sun et al published a nerve regeneration study using Li-Mg-Si bioceramics, demonstrating beneficial effects both in vitro and in vivo [23]. They found that the material promoted the myelinating phenotype of SCs in a GSK3β/β-catenin dependent manner, suggesting that Mg-Li materials show promise for use in nerve regeneration.…”

Section: Introductionmentioning

confidence: 99%

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Influence of Magnesium Degradation on Schwannoma Cell Responses to Nerve Injury Using an In Vitro Injury Model

Bhat,

Hanke,

Helmholz

et al. 2024

JFB

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Nerve guidance conduits for peripheral nerve injuries can be improved using bioactive materials such as magnesium (Mg) and its alloys, which could provide both structural and trophic support. Therefore, we investigated whether exposure to Mg and Mg-1.6wt%Li thin films (Mg/Mg‑1.6Li) would alter acute Schwann cell responses to injury. Using the RT4-D6P2T Schwannoma cell line (SCs), we tested extracts from freeze-killed cells (FKC) and nerves (FKN) as in vitro injury stimulants. Both FKC and FKN induced SC release of the macrophage chemoattractant protein 1 (MCP-1), a marker of the repair SC phenotype after injury. Next, FKC-stimulated cells exposed to Mg/Mg‑1.6Li reduced MCP-1 release by 30%, suggesting that these materials could have anti-inflammatory effects. Exposing FKC-treated cells to Mg/Mg‑1.6Li reduced the gene expression of the nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), and myelin protein zero (MPZ), but not the p75 neurotrophin receptor. In the absence of FKC, Mg/Mg‑1.6Li treatment increased the expression of NGF, p75, and MPZ, which can be beneficial to nerve regeneration. Thus, the presence of Mg can differentially alter SCs, depending on the microenvironment. These results demonstrate the applicability of this in vitro nerve injury model, and that Mg has wide-ranging effects on the repair SC phenotype.

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Li–Mg–Si bioceramics provide a dynamic immuno-modulatory and repair-supportive microenvironment for peripheral nerve regeneration

Cited by 9 publications

References 78 publications

Electrical aligned polyurethane nerve guidance conduit modulates macrophage polarization and facilitates immunoregulatory peripheral nerve regeneration

Electrical aligned polyurethane nerve guidance conduit modulates macrophage polarization and facilitates immunoregulatory peripheral nerve regeneration

The Porous Structure of Peripheral Nerve Guidance Conduits: Features, Fabrication, and Implications for Peripheral Nerve Regeneration

Influence of Magnesium Degradation on Schwannoma Cell Responses to Nerve Injury Using an In Vitro Injury Model

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