BIOMATERIALS
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2021
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IF 12.479
Xianzhen Dong,Ping Wu,Lesan Yan,Kun Liu,Wenying Wei,Qiang Cheng,Xinyue Liang,Yun Chen,Honglian Dai
Delayed injured nerve regeneration remains a clinical problem, partly ascribing to the lack of regulation of regenerative microenvironment , topographical cues, and blood nourishment. Functional electrospun conduits have been established as an efficacious strategy to facilitate nerve regeneration by providing structural guidance, regulating the regenerative immune microenvironment, and improving vascular regeneration. However, the synthetic polymers conventionally used to fabricate electrospinning scaffolds, such as poly(L-lactic acid), poly(glycolic acid), and poly(lactic-co-glycolic acid), can cause aseptic inflammation due to acidic degradation products . Therefore, a poly[3(S)-methyl-morpholine-2,5-dione- co -lactic] [P(MMD- co -LA)] containing alanine units with good mechanical properties and reduced acid degradation products, was obtained by melt ring-opening polymerization (ROP). Here, we aimed to explore the effect of oriented nanofiber/Deferoxamine (DFO, a hydrophilic angiogenic drug) scaffold in the rapid construction of a favorable regenerative microenvironment, including cell bridge, polarized vascular system, and immune microenvironment. In vitro studies have shown that the scaffold can sustainably release DFO, which accelerates the migration and tube formation of human umbilical vein endothelial cells (HUVECs), as well as the expression of genes related to angiogenesis . The physical clues provided by the arranged nanofibers can regulate the polarization of macrophages and reduce the expression of inflammatory factors. Furthermore, the in vivo results demonstrated a higher M2 polarization level of the oriented nanofibrous scaffold treatment group with reducedinflammation reaction in the injured nerve. Moreover, the in-situ release of DFO up-regulated the expression of HIF1-α and SDF-1α genes, as well as the expression of HIF1-α′s target gene VEGF, further promoting revascularization and enhancing nerve regeneration at the defect site . The obtained results provide essential insights on accelerating the creation of the nerve regeneration microenvironment by combining the physiological processes of nerve regeneration with topographical cues and chemical signal induction.
研究领域:
生物材料
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组织工程
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再生医学
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神经科学
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免疫学
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血管生成
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
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2022
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IF 10.761
Lei Han,Xianzhen Dong,Tong Qiu,Zhaona Dou,Lin Wu,Honglian Dai
Wallerian degeneration after peripheral nerve injury (PNI), that is, the autonomous degeneration of distal axons, leads to an imbalance of iron homeostasis and easily induces oxidative stress caused by iron overload. Inspired by the process of nerve degeneration and regeneration, the design of a functional electrospinning scaffold with iron chelating ability exhibited the importance of reconstructing a suitable microenvironment. Here, an electrospinning scaffold based on deferoxamine and poly(3(S)-methyl-morpholine-2,5-dione -co- lactone) (PDPLA/DFO) was constructed. This work aims to explore the promotion of nerve regeneration by the physiological regulation of the scaffold. In vitro , PDPLA/DFO films mitigated the reduction of glutathione and the inactivation of Glutathione peroxidase 4 caused by iron overload. In addition, they decreased reactive oxygen species, relieve the stress of the endoplasmic reticulum and mitochondria, and reduce cell apoptosis. In vivo , PDPLA/DFO conduits constructed the anti-inflammatory microenvironment and promoted cell survival by alleviating iron overload and organelle stress. In conclusion, PDPLA/DFO guidance conduits targeted the distal iron overload and promoted nerve regeneration. It provides novel ideas for designing nerve conduits targeting the distal microenvironment.
研究领域:
神经科学
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材料科学
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再生医学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Materials Interfaces
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2023
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IF 5.4
Weixing Wang,Yifeng Yu,Hao Zhang,Zhiwei Wang,Honglian Dai,Aixi Yu
To solve the problem of tendon adhesion after an operation, an anti-adhesion membrane is designed, which can inhibit the exogenous healing of tendons and promote endogenous healing. Here, poly[3(S)-methyl-morpholine-2,5-dione- co -lactic acid] P(MMD- co -LA) containing alanine units is obtained by melt ring-opening polymerization (ROP). It can effectively reduce the production of acidic degradation products that cause aseptic inflammation. Then a kind of oriented P(MMD- co -LA)/deferoxamine (DFO) anti-adhesion membrane with good mechanical properties, cell adhesion properties, and induced macrophage polarization properties is constructed by electrospinning. In vitro and in vivo studies have shown that oriented fibrous membranes can down-regulate the expression of inflammatory cytokines. In addition, the fibrous membrane can up-regulate the expression of angiogenesis-related genes, namely HIF1-α, SDF-1α, and VEGF, by releasing DFO in situ, thus promoting the revascularization of tendon defects and providing nutritional support for endogenous tendon healing. This method provides a new barrier strategy to reduce tendon adhesion through anti-inflammation combined with vascularization to inhibit exogenous tendon healing while promoting tendon endogenous healing. The results provide essential insights into the corresponding regulation of the tendon healing microenvironment.
研究领域:
生物医学工程
·
组织工程
·
材料科学
·
再生医学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）