Vanillin-based functionalization strategy to construct multifunctional microspheres for treating inflammation and regenerating intervertebral disc

Intervertebral disc degeneration (IVDD) is one of the main causes of low back pain. Although local delivery strategies using biomaterial carriers have shown potential for IVDD treatment, it remains challenging for intervention against multiple adverse contributors by a single delivery platform. In t...

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Main Authors: Zhuang Zhu, Qifan Yu, Hanwen Li, Feng Han, Qianping Guo, Heng Sun, He Zhao, Zhengdong Tu, Zhuang Liu, Caihong Zhu, Bin Li
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2023-10-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X23001494
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author Zhuang Zhu
Qifan Yu
Hanwen Li
Feng Han
Qianping Guo
Heng Sun
He Zhao
Zhengdong Tu
Zhuang Liu
Caihong Zhu
Bin Li
author_facet Zhuang Zhu
Qifan Yu
Hanwen Li
Feng Han
Qianping Guo
Heng Sun
He Zhao
Zhengdong Tu
Zhuang Liu
Caihong Zhu
Bin Li
author_sort Zhuang Zhu
collection DOAJ
description Intervertebral disc degeneration (IVDD) is one of the main causes of low back pain. Although local delivery strategies using biomaterial carriers have shown potential for IVDD treatment, it remains challenging for intervention against multiple adverse contributors by a single delivery platform. In the present work, we propose a new functionalization strategy using vanillin, a natural molecule with anti-inflammatory and antioxidant properties, to develop multifunctional gelatin methacrylate (GelMA) microspheres for local delivery of transforming growth factor β3 (TGFβ3) toward IVDD treatment. In vitro, functionalized microspheres not only improved the release kinetics of TGFβ3 but also effectively inhibited inflammatory responses and promoted the secretion of extracellular matrix (ECM) in lipopolysaccharide-induced nucleus pulposus (NP) cells. In vivo, functionalized platform plays roles in alleviating inflammation and oxidative stress, preserving the water content of NP and disc height, and maintaining intact structure and biomechanical functions, thereby promoting the regeneration of IVD. High-throughput sequencing suggests that inhibition of the phosphatidylinositol 3-kinase (PI3K)-Akt signaling might be associated with their therapeutic effects. In summary, the vanillin-based functionalization strategy provides a novel and simple way for packaging multiple functions into a single delivery platform and holds promise for tissue regeneration beyond the IVD.
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spelling doaj.art-5a9d89de7c284cbdbb736890bb90b1922023-07-25T04:15:17ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2023-10-0128167182Vanillin-based functionalization strategy to construct multifunctional microspheres for treating inflammation and regenerating intervertebral discZhuang Zhu0Qifan Yu1Hanwen Li2Feng Han3Qianping Guo4Heng Sun5He Zhao6Zhengdong Tu7Zhuang Liu8Caihong Zhu9Bin Li10Orthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215007, ChinaOrthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215007, ChinaOrthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215007, ChinaOrthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215007, ChinaOrthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215007, ChinaOrthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215007, ChinaChildren's Hospital of Soochow University, Pediatric Research Institute of Soochow University, Suzhou, Jiangsu, 215123, ChinaOrthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215007, ChinaInstitute of Functional Nano & Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu, 215123, China; Corresponding author.Orthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215007, China; Corresponding author.Orthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Biology & Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215007, China; Corresponding author. Rm 201 Bldg Jiwu, Soochow University (North Campus), 178 Ganjiang Rd, Suzhou, Jiangsu, 215007, China.Intervertebral disc degeneration (IVDD) is one of the main causes of low back pain. Although local delivery strategies using biomaterial carriers have shown potential for IVDD treatment, it remains challenging for intervention against multiple adverse contributors by a single delivery platform. In the present work, we propose a new functionalization strategy using vanillin, a natural molecule with anti-inflammatory and antioxidant properties, to develop multifunctional gelatin methacrylate (GelMA) microspheres for local delivery of transforming growth factor β3 (TGFβ3) toward IVDD treatment. In vitro, functionalized microspheres not only improved the release kinetics of TGFβ3 but also effectively inhibited inflammatory responses and promoted the secretion of extracellular matrix (ECM) in lipopolysaccharide-induced nucleus pulposus (NP) cells. In vivo, functionalized platform plays roles in alleviating inflammation and oxidative stress, preserving the water content of NP and disc height, and maintaining intact structure and biomechanical functions, thereby promoting the regeneration of IVD. High-throughput sequencing suggests that inhibition of the phosphatidylinositol 3-kinase (PI3K)-Akt signaling might be associated with their therapeutic effects. In summary, the vanillin-based functionalization strategy provides a novel and simple way for packaging multiple functions into a single delivery platform and holds promise for tissue regeneration beyond the IVD.http://www.sciencedirect.com/science/article/pii/S2452199X23001494Intervertebral disc degenerationMicrosphereVanillinTransforming growth factor β3Regeneration
spellingShingle Zhuang Zhu
Qifan Yu
Hanwen Li
Feng Han
Qianping Guo
Heng Sun
He Zhao
Zhengdong Tu
Zhuang Liu
Caihong Zhu
Bin Li
Vanillin-based functionalization strategy to construct multifunctional microspheres for treating inflammation and regenerating intervertebral disc
Bioactive Materials
Intervertebral disc degeneration
Microsphere
Vanillin
Transforming growth factor β3
Regeneration
title Vanillin-based functionalization strategy to construct multifunctional microspheres for treating inflammation and regenerating intervertebral disc
title_full Vanillin-based functionalization strategy to construct multifunctional microspheres for treating inflammation and regenerating intervertebral disc
title_fullStr Vanillin-based functionalization strategy to construct multifunctional microspheres for treating inflammation and regenerating intervertebral disc
title_full_unstemmed Vanillin-based functionalization strategy to construct multifunctional microspheres for treating inflammation and regenerating intervertebral disc
title_short Vanillin-based functionalization strategy to construct multifunctional microspheres for treating inflammation and regenerating intervertebral disc
title_sort vanillin based functionalization strategy to construct multifunctional microspheres for treating inflammation and regenerating intervertebral disc
topic Intervertebral disc degeneration
Microsphere
Vanillin
Transforming growth factor β3
Regeneration
url http://www.sciencedirect.com/science/article/pii/S2452199X23001494
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