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
单位:[1]Department of Orthopedics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,1095 Jiefang Avenue,Wuhan 430030,China华中科技大学同济医学院附属同济医院外科学系骨科[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病理科华中科技大学同济医学院附属同济医院
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.
基金:
National Natural Science Foundation of China; [81974351]
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
通讯作者:
推荐引用方式(GB/T 7714):
Cheng Haozhe,Guo Qian,Zhao Hongjian,et al.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[J].INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES.2023,24(1):doi:10.3390/ijms24010390.
APA:
Cheng, Haozhe,Guo,Qian,Zhao, Hongjian,Liu, Kun,Kang, Honglei...&Fang,Zhong.(2023).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.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,24,(1)
MLA:
Cheng, Haozhe,et al."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".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 24..1(2023)