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An Injectable Hydrogel Scaffold Loaded with Dual-Drug/Sustained-Release PLGA Microspheres for the Regulation of Macrophage Polarization in the Treatment of Intervertebral Disc Degeneration

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单位: [1]Department of Orthopedics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,1095 Jiefang Avenue,Wuhan 430030,China [2]State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Biomedical Materials and Engineering Research Center of Hubei Province, Wuhan University of Technology, Wuhan 430070, China [3]Department of Pathology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,1095 Jiefang Avenue,Wuhan 430030,China
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关键词: drug delivery hydrogel intervertebral disc degeneration immune regulation kartogenin

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Due to the unique physical characteristics of intervertebral disc degeneration (IVDD) and the pathological microenvironment that it creates, including inflammation and oxidative stress, effective self-repair is impossible. During the process of intervertebral disc degeneration, there is an increase in the infiltration of M1 macrophages and the secretion of proinflammatory cytokines. Here, we designed a novel injectable composite hydrogel scaffold: an oligo [poly (ethylene glycol) fumarate]/sodium methacrylate (OPF/SMA) hydrogel scaffold loaded with dual-drug/sustained-release PLGA microspheres containing IL-4 (IL-4-PLGA) and kartogenin (KGN-PLGA). This scaffold exhibited good mechanical properties and low immunogenicity while also promoting the sustained release of drugs. By virtue of the PLGA microspheres loaded with IL-4 (IL-4-PLGA), the composite hydrogel scaffold induced macrophages to transition from the M1 phenotype into the M2 phenotype during the early induced phase and simultaneously exhibited a continuous anti-inflammatory effect through the PLGA microspheres loaded with kartogenin (KGN-PLGA). Furthermore, we investigated the mechanisms underlying the immunomodulatory and anti-inflammatory effects of the composite hydrogel scaffold. We found that the scaffold promoted cell proliferation and improved cell viability in vitro. While ensuring mechanical strength, this composite hydrogel scaffold regulated the local inflammatory microenvironment and continuously repaired tissue in the nucleus pulposus via the sequential release of drugs in vivo. When degenerative intervertebral discs in a rat model were injected with the scaffold, there was an increase in the proportion of M2 macrophages in the inflammatory environment and higher expression levels of type II collagen and aggrecan; this was accompanied by reduced levels of MMP13 expression, thus exhibiting long-term anti-inflammatory effects. Our research provides a new strategy for promoting intervertebral disc tissue regeneration and a range of other inflammatory diseases.

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出版当年[2022]版:
大类 | 2 区 生物学
小类 | 2 区 化学:综合 3 区 生化与分子生物学
最新[2025]版:
大类 | 3 区 生物学
小类 | 3 区 生化与分子生物学 3 区 化学:综合
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出版当年[2021]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q2 CHEMISTRY, MULTIDISCIPLINARY
最新[2023]版:
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q2 CHEMISTRY, MULTIDISCIPLINARY

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

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第一作者单位: [1]Department of Orthopedics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,1095 Jiefang Avenue,Wuhan 430030,China
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