Bio-engineered thermo-sensitive alginate/PNIA-g-CS co-polymeric injectable hydrogel laden with GDF-5 to stimulate nucleus pulposus for IVD regeneration
Abstract Chronic back pain and disability are primarily caused by intervertebral disc degeneration (IDD) that requires novel therapies to regenerate the nucleus pulposus (NP) and restore disc function. In this study, a bioengineered thermo-sensitive injectable hydrogel composed of co-polymeric poly-...
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BMC
2025-05-01
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| Series: | Journal of Biological Engineering |
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| Online Access: | https://doi.org/10.1186/s13036-025-00520-0 |
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| author | Guangnan Chen Chong Bian Xiangyang Cheng Jun Xu Kaifeng Zhou Yiming Zhang |
| author_facet | Guangnan Chen Chong Bian Xiangyang Cheng Jun Xu Kaifeng Zhou Yiming Zhang |
| author_sort | Guangnan Chen |
| collection | DOAJ |
| description | Abstract Chronic back pain and disability are primarily caused by intervertebral disc degeneration (IDD) that requires novel therapies to regenerate the nucleus pulposus (NP) and restore disc function. In this study, a bioengineered thermo-sensitive injectable hydrogel composed of co-polymeric poly-N-isopropyl acrylamide-grafted-chondroitin sulfate cross-linked with sodium alginate microspheres (PNIA-g-CS-NaA Ms: denote HMs) loaded with growth differentiation factor 5 (GDF-5), to stimulate Nucleus Pulposus cells (NPCs) activity and promote intervertebral disc (IVD) regeneration. The Low critical solution temperature (LCST) of PNIA-g-CS was 31.8 and 32.3 °C at 5% (w/v) and 15% (w/v), respectively. In the in vitro study, GDF-5-loaded hydrogel (1 mg/mL) marginally enhanced NPC proliferation and reduced inflammatory cytokines (TNF-α, IL-6, IL-1β) after 24 h. HMs-GDF-5 combined with Adipose-Derived Mesenchymal Stem Cells (ADMSCs) was delivered to NP tissue using a minimally invasive technique, promoting NP regeneration in rats. At 8 weeks, significant upregulation of COL-II and ACAN proteins and mRNA expressions was observed. X-ray imaging showed disc height recovery and increased water content, while histology revealed partial restoration of NPCs and matrix. The outcomes show that the biodegradable hydrogel could be used as a potential therapeutic agent for IVD repair. |
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| institution | OA Journals |
| issn | 1754-1611 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
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| series | Journal of Biological Engineering |
| spelling | doaj-art-26c1dda6d5e54fc28b5c08f866a0d5a02025-08-20T02:34:17ZengBMCJournal of Biological Engineering1754-16112025-05-0119111810.1186/s13036-025-00520-0Bio-engineered thermo-sensitive alginate/PNIA-g-CS co-polymeric injectable hydrogel laden with GDF-5 to stimulate nucleus pulposus for IVD regenerationGuangnan Chen0Chong Bian1Xiangyang Cheng2Jun Xu3Kaifeng Zhou4Yiming Zhang5Department of Orthopedics Surgery, Minhang Hospital, Fudan UniversityDepartment of Orthopedics Surgery, Minhang Hospital, Fudan UniversityDepartment of Orthopedics Surgery, Minhang Hospital, Fudan UniversityDepartment of Orthopedics Surgery, Minhang Hospital, Fudan UniversityDepartment of Orthopedics Surgery, Minhang Hospital, Fudan UniversityDepartment of Orthopedics Surgery, Minhang Hospital, Fudan UniversityAbstract Chronic back pain and disability are primarily caused by intervertebral disc degeneration (IDD) that requires novel therapies to regenerate the nucleus pulposus (NP) and restore disc function. In this study, a bioengineered thermo-sensitive injectable hydrogel composed of co-polymeric poly-N-isopropyl acrylamide-grafted-chondroitin sulfate cross-linked with sodium alginate microspheres (PNIA-g-CS-NaA Ms: denote HMs) loaded with growth differentiation factor 5 (GDF-5), to stimulate Nucleus Pulposus cells (NPCs) activity and promote intervertebral disc (IVD) regeneration. The Low critical solution temperature (LCST) of PNIA-g-CS was 31.8 and 32.3 °C at 5% (w/v) and 15% (w/v), respectively. In the in vitro study, GDF-5-loaded hydrogel (1 mg/mL) marginally enhanced NPC proliferation and reduced inflammatory cytokines (TNF-α, IL-6, IL-1β) after 24 h. HMs-GDF-5 combined with Adipose-Derived Mesenchymal Stem Cells (ADMSCs) was delivered to NP tissue using a minimally invasive technique, promoting NP regeneration in rats. At 8 weeks, significant upregulation of COL-II and ACAN proteins and mRNA expressions was observed. X-ray imaging showed disc height recovery and increased water content, while histology revealed partial restoration of NPCs and matrix. The outcomes show that the biodegradable hydrogel could be used as a potential therapeutic agent for IVD repair.https://doi.org/10.1186/s13036-025-00520-0HydrogelSodium alginateGrowth differentiation factorStem cellsNucleus pulposusIntervertebral disc regeneration |
| spellingShingle | Guangnan Chen Chong Bian Xiangyang Cheng Jun Xu Kaifeng Zhou Yiming Zhang Bio-engineered thermo-sensitive alginate/PNIA-g-CS co-polymeric injectable hydrogel laden with GDF-5 to stimulate nucleus pulposus for IVD regeneration Journal of Biological Engineering Hydrogel Sodium alginate Growth differentiation factor Stem cells Nucleus pulposus Intervertebral disc regeneration |
| title | Bio-engineered thermo-sensitive alginate/PNIA-g-CS co-polymeric injectable hydrogel laden with GDF-5 to stimulate nucleus pulposus for IVD regeneration |
| title_full | Bio-engineered thermo-sensitive alginate/PNIA-g-CS co-polymeric injectable hydrogel laden with GDF-5 to stimulate nucleus pulposus for IVD regeneration |
| title_fullStr | Bio-engineered thermo-sensitive alginate/PNIA-g-CS co-polymeric injectable hydrogel laden with GDF-5 to stimulate nucleus pulposus for IVD regeneration |
| title_full_unstemmed | Bio-engineered thermo-sensitive alginate/PNIA-g-CS co-polymeric injectable hydrogel laden with GDF-5 to stimulate nucleus pulposus for IVD regeneration |
| title_short | Bio-engineered thermo-sensitive alginate/PNIA-g-CS co-polymeric injectable hydrogel laden with GDF-5 to stimulate nucleus pulposus for IVD regeneration |
| title_sort | bio engineered thermo sensitive alginate pnia g cs co polymeric injectable hydrogel laden with gdf 5 to stimulate nucleus pulposus for ivd regeneration |
| topic | Hydrogel Sodium alginate Growth differentiation factor Stem cells Nucleus pulposus Intervertebral disc regeneration |
| url | https://doi.org/10.1186/s13036-025-00520-0 |
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