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Multifunctional injectable hydrogels with controlled delivery of bioactive factors for efficient repair of intervertebral disc degeneration.

ABSTRACT: Millions of people worldwide suffer from intervertebral disc degeneration (IVDD), which imposes a significant socioeconomic burden on society. There is an urgent clinical demand for more effective treatments for IVDD because conventional treatments can only alleviate the symptoms rather than preventing the progression of IVDD. Hydrogels, a class of elastic biomaterials with good biocompatibility, are promising candidates for intervertebral disc repair and regeneration. In recent years, various hydrogels have been investigated in vitro and in vivo for the repair of intervertebral discs, some of which are ready for clinical testing. This review summarizes the latest findings and developments in using bioactive factors-released bioactive injectable hydrogels for the repair and regeneration of intervertebral discs. It focuses on the analysis and summary of the use of multifunctional injectable hydrogels to delivery bioactive factors (cells, exosomes, growth factors, genes, drugs) for disc regeneration, providing guidance for future study. Finally, we discussed and analyzed the optimal timing for the application of controlled-release hydrogels in the treatment of IVDD to meet the high standards required for intervertebral disc regeneration and precision medicine.

SUBMITTER: Han H

PROVIDER: S-EPMC10665751 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Multifunctional injectable hydrogels with controlled delivery of bioactive factors for efficient repair of intervertebral disc degeneration.

Han Hao H Zhao Xiaoming X Ma Hongyun H Zhang Yingang Y Lei Bo B

Heliyon 20231031 11

Millions of people worldwide suffer from intervertebral disc degeneration (IVDD), which imposes a significant socioeconomic burden on society. There is an urgent clinical demand for more effective treatments for IVDD because conventional treatments can only alleviate the symptoms rather than preventing the progression of IVDD. Hydrogels, a class of elastic biomaterials with good biocompatibility, are promising candidates for intervertebral disc repair and regeneration. In recent years, various h ...[more]

PMID: 38027562

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Project description:Cell-based therapies have shown significant promise in tissue engineering with one key challenge being the delivery and retention of cells. As a result, significant efforts have been made in the past decade to design injectable biomaterials to host and deliver cells at injury sites. Intervertebral disc (IVD) degeneration, a major cause of back pain, is a particularly relevant example where a minimally-invasive cellular therapy could bring significant benefits specifically at the early stages of the disease, when a cell-driven process starts in the gelatinous core of the IVD, the nucleus pulposus (NP). In this present study we explore the use of graphene oxide (GO) as nano-filler for the reinforcement of FEFKFEFK (β-sheet forming self-assembling peptide) hydrogels. Our results confirm the presence of strong interactions between FEFKFEFK and GO flakes with the peptide coating and forming short thin fibrils on the surface of the flakes. These strong interactions were found to affect the bulk properties of hybrid hydrogels. At pH 4 electrostatic interactions between the peptide fibres and the peptide-coated GO flakes are thought to govern the final bulk properties of the hydrogels while at pH 7, after conditioning with cell culture media, electrostatic interactions are removed leaving the hydrophobic interactions to govern hydrogel final properties. The GO-F820 hybrid hydrogel, with mechanical properties similar to the NP, was shown to promote high cell viability and retained cell metabolic activity in 3D over the 7 days of culture and therefore shown to harbour significant potential as an injectable hydrogel scaffold for the in-vivo delivery of NP cells. STATEMENT OF SIGNIFICANCE: Short self-assembling peptide hydrogels (SAPHs) have attracted significant interest in recent years as they can mimic the natural extra-cellular matrix, holding significant promise for the ab initio design of cells' microenvironments. Recently the design of hybrid hydrogels for biomedical applications has been explored through the incorporation of specific nanofillers. In this study we exploited graphene oxide (GO) as nanofiller to design hybrid injectable 3Dscaffolds for the delivery of nucleus pulposus cells (NPCs) for intervertebral disc regeneration. Our work clearly shows the presence of strong interactions between peptide and GO, mimicking the mechanical properties of the NP tissue and promoting high cell viability and metabolic activity. These hybrid hydrogels therefore harbour significant potential as injectable scaffolds for the in vivo delivery of NPCs.

Project description:BackgroundPreceding intervertebral disc (IVD) degeneration, the cell phenotype in the nucleus pulposus (NP) shifts from notochordal cells (NCs) to chondrocyte-like cells (CLCs). Microarray analysis showed a correlation between caveolin-1 expression and the phenotypic transition of NCs to CLCs. With a clinical directive in mind, the aim of this study was to determine the role of caveolin-1 in IVD degeneration. As a scaffolding protein, caveolin-1 influences several signaling pathways, and transforming growth factor (TGF)-β receptors have been demonstrated to colocalize with caveolin-1. Therefore, the hypothesis of this study was that caveolin-1 facilitates repair by enhancing TGF-β signaling in the IVD.MethodsProtein expression (caveolin-1, apoptosis, progenitor cell markers, extracellular matrix, and phosphorylated Smad2 [pSmad2]) was determined in IVDs of wild-type (WT) and caveolin-1-null mice and canine IVDs of different degeneration grades (immunofluorescence, immunohistochemistry, and TUNEL assay). Canine/human CLC microaggregates were treated with chondrogenic medium alone or in combination with caveolin-1 scaffolding domain (CSD) peptide and/or caveolin-1 silencing RNA. After 28 days, gene and protein expression profiles were determined.ResultsThe NP of WT mice was rich in viable NCs, whereas the NP of caveolin-1-null mice contained more collagen-rich extracellular matrix and fewer cells, together with increased progenitor cell marker expression, pSmad2 TGF-β signaling, and high apoptotic activity. During canine IVD degeneration, caveolin-1 expression and apoptotic activity increased. In vitro caveolin-1 silencing decreased the CLC microaggregate glycosaminoglycan (GAG) content, which could be rescued by CSD treatment. Furthermore, CSD increased TGF-β/pSmad2 signaling at gene and protein expression levels and enhanced the anabolic effects of TGF-β1, reflected in increased extracellular matrix deposition by the CLCs.ConclusionsCaveolin-1 plays a role in preservation of the NC phenotype. Additionally, it may be related to CLC apoptosis, given its increased expression in degenerated IVDs. Nevertheless, CSD enhanced CLC GAG deposition in vitro, and hence the increased caveolin-1 expression during IVD degeneration may also facilitate an ultimate attempt at repair. Further studies are needed to investigate how caveolin-1 modifies other signaling pathways and facilitates IVD repair.

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Multifunctional injectable hydrogels with controlled delivery of bioactive factors for efficient repair of intervertebral disc degeneration.

Publications

Multifunctional injectable hydrogels with controlled delivery of bioactive factors for efficient repair of intervertebral disc degeneration.

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