High‐Performance Multi‐Dynamic Bond Cross‐Linked Hydrogel with Spatiotemporal siRNA Delivery for Gene–Cell Combination Therapy of Intervertebral Disc Degeneration
Abstract Chronic inflammatory diseases, such as intervertebral disc degeneration (IVDD), which affect the lives of hundreds of millions of people, still lack effective and precise treatments. In this study, a novel hydrogel system with many extraordinary properties is developed for gene–cell combina...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-06-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202206306 |
| _version_ | 1797804411790032896 |
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| author | Jiaxin Chen Haifeng Zhu Jiechao Xia Yutao Zhu Chen Xia Zehui Hu Yang Jin Ji Wang Yong He Jiayong Dai Zhijun Hu |
| author_facet | Jiaxin Chen Haifeng Zhu Jiechao Xia Yutao Zhu Chen Xia Zehui Hu Yang Jin Ji Wang Yong He Jiayong Dai Zhijun Hu |
| author_sort | Jiaxin Chen |
| collection | DOAJ |
| description | Abstract Chronic inflammatory diseases, such as intervertebral disc degeneration (IVDD), which affect the lives of hundreds of millions of people, still lack effective and precise treatments. In this study, a novel hydrogel system with many extraordinary properties is developed for gene–cell combination therapy of IVDD. Phenylboronic acid‐modified G5 PAMAM (G5‐PBA) is first synthesized, and therapeutic siRNA silencing the expression of P65 mixed with G5‐PBA (siRNA@G5‐PBA) is then embedded into the hydrogel (siRNA@G5‐PBA@Gel) based on multi‐dynamic bonds including acyl hydrazone bonds, imine linkage, π–π stacking, and hydrogen bonding interactions. Local and acidic inflammatory microenvironment‐responsive gene‐drug release can achieve spatiotemporal regulation of gene expression. In addition, gene‐drug release from the hydrogel can be sustained for more than 28 days in vitro and in vivo, greatly inhibiting the secretion of inflammatory factors and the subsequent degeneration of nucleus pulposus (NP) cells induced by lipopolysaccharide (LPS). Through prolonged inhibition of the P65/NLRP3 signaling pathway, the siRNA@G5‐PBA@Gel is verified to relieve inflammatory storms, which can significantly enhance the regeneration of IVD when combined with cell therapy. Overall, this study proposes an innovative system for gene–cell combination therapy and a precise and minimally invasive treatment method for IVD regeneration. |
| first_indexed | 2024-03-13T05:36:47Z |
| format | Article |
| id | doaj.art-abf4924d148e4a49aaf689893e357415 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-13T05:36:47Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-abf4924d148e4a49aaf689893e3574152023-06-14T07:18:56ZengWileyAdvanced Science2198-38442023-06-011017n/an/a10.1002/advs.202206306High‐Performance Multi‐Dynamic Bond Cross‐Linked Hydrogel with Spatiotemporal siRNA Delivery for Gene–Cell Combination Therapy of Intervertebral Disc DegenerationJiaxin Chen0Haifeng Zhu1Jiechao Xia2Yutao Zhu3Chen Xia4Zehui Hu5Yang Jin6Ji Wang7Yong He8Jiayong Dai9Zhijun Hu10Center for Plastic & Reconstructive Surgery Department of Plastic & Reconstructive Surgery Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College Hangzhou 310014 ChinaKey Laboratory of Musculoskeletal System Degeneration Regeneration Translational Research of Zhejiang Province Department of Orthopaedic Surgery Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou 310016 ChinaKey Laboratory of Musculoskeletal System Degeneration Regeneration Translational Research of Zhejiang Province Department of Orthopaedic Surgery Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou 310016 ChinaKey Laboratory of Musculoskeletal System Degeneration Regeneration Translational Research of Zhejiang Province Department of Orthopaedic Surgery Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou 310016 ChinaDepartment of Orthopedic Surgery Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College Hangzhou 310014 ChinaKey Laboratory of Musculoskeletal System Degeneration Regeneration Translational Research of Zhejiang Province Department of Orthopaedic Surgery Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou 310016 ChinaKey Laboratory of Musculoskeletal System Degeneration Regeneration Translational Research of Zhejiang Province Department of Orthopaedic Surgery Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou 310016 ChinaCenter for Plastic & Reconstructive Surgery Department of Plastic & Reconstructive Surgery Zhejiang Provincial People's Hospital Affiliated People's Hospital Hangzhou Medical College Hangzhou 310014 ChinaState Key Laboratory of Fluid Power and Mechatronic Systems College of Mechanical Engineering Zhejiang University Hangzhou 310027 ChinaKey Laboratory of Musculoskeletal System Degeneration Regeneration Translational Research of Zhejiang Province Department of Orthopaedic Surgery Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou 310016 ChinaKey Laboratory of Musculoskeletal System Degeneration Regeneration Translational Research of Zhejiang Province Department of Orthopaedic Surgery Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou 310016 ChinaAbstract Chronic inflammatory diseases, such as intervertebral disc degeneration (IVDD), which affect the lives of hundreds of millions of people, still lack effective and precise treatments. In this study, a novel hydrogel system with many extraordinary properties is developed for gene–cell combination therapy of IVDD. Phenylboronic acid‐modified G5 PAMAM (G5‐PBA) is first synthesized, and therapeutic siRNA silencing the expression of P65 mixed with G5‐PBA (siRNA@G5‐PBA) is then embedded into the hydrogel (siRNA@G5‐PBA@Gel) based on multi‐dynamic bonds including acyl hydrazone bonds, imine linkage, π–π stacking, and hydrogen bonding interactions. Local and acidic inflammatory microenvironment‐responsive gene‐drug release can achieve spatiotemporal regulation of gene expression. In addition, gene‐drug release from the hydrogel can be sustained for more than 28 days in vitro and in vivo, greatly inhibiting the secretion of inflammatory factors and the subsequent degeneration of nucleus pulposus (NP) cells induced by lipopolysaccharide (LPS). Through prolonged inhibition of the P65/NLRP3 signaling pathway, the siRNA@G5‐PBA@Gel is verified to relieve inflammatory storms, which can significantly enhance the regeneration of IVD when combined with cell therapy. Overall, this study proposes an innovative system for gene–cell combination therapy and a precise and minimally invasive treatment method for IVD regeneration.https://doi.org/10.1002/advs.202206306anti‐inflammatorygene silencingmulti‐dynamic bondsmultifunctional hydrogelstissue regeneration |
| spellingShingle | Jiaxin Chen Haifeng Zhu Jiechao Xia Yutao Zhu Chen Xia Zehui Hu Yang Jin Ji Wang Yong He Jiayong Dai Zhijun Hu High‐Performance Multi‐Dynamic Bond Cross‐Linked Hydrogel with Spatiotemporal siRNA Delivery for Gene–Cell Combination Therapy of Intervertebral Disc Degeneration Advanced Science anti‐inflammatory gene silencing multi‐dynamic bonds multifunctional hydrogels tissue regeneration |
| title | High‐Performance Multi‐Dynamic Bond Cross‐Linked Hydrogel with Spatiotemporal siRNA Delivery for Gene–Cell Combination Therapy of Intervertebral Disc Degeneration |
| title_full | High‐Performance Multi‐Dynamic Bond Cross‐Linked Hydrogel with Spatiotemporal siRNA Delivery for Gene–Cell Combination Therapy of Intervertebral Disc Degeneration |
| title_fullStr | High‐Performance Multi‐Dynamic Bond Cross‐Linked Hydrogel with Spatiotemporal siRNA Delivery for Gene–Cell Combination Therapy of Intervertebral Disc Degeneration |
| title_full_unstemmed | High‐Performance Multi‐Dynamic Bond Cross‐Linked Hydrogel with Spatiotemporal siRNA Delivery for Gene–Cell Combination Therapy of Intervertebral Disc Degeneration |
| title_short | High‐Performance Multi‐Dynamic Bond Cross‐Linked Hydrogel with Spatiotemporal siRNA Delivery for Gene–Cell Combination Therapy of Intervertebral Disc Degeneration |
| title_sort | high performance multi dynamic bond cross linked hydrogel with spatiotemporal sirna delivery for gene cell combination therapy of intervertebral disc degeneration |
| topic | anti‐inflammatory gene silencing multi‐dynamic bonds multifunctional hydrogels tissue regeneration |
| url | https://doi.org/10.1002/advs.202206306 |
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