Circadian Clock Regulation via Biomaterials for Nucleus Pulposus

Chen, Wei; Zheng, Dandan; Chen, Hao; Ye, Tingjun; Liu, Zhihong; Qi, Jin; Shen, Hongxing; Ruan, Huitong; Cui, Wenguo; Deng, Lianfu

doi:10.1002/adma.202301037

Cited by 10 publications

(1 citation statement)

References 51 publications

(54 reference statements)

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“…In addition, Kim et al (2020) developed a leaf stack structural morphology that successfully and stably delivered human BMSCs and TGF-β3 to the IVD, which prevented cell leakage and provided a sustained supply of bioactive TGF-β3, inducing cell differentiation into cells resembling the NP. In another study, Chen et al (2023c) used an air-microfluidic technique to prepare circadian clock-regulating microspheres made of polyvinyl alcohol, cross-linked them with modified phenylboronic acid (PBA) connectors and loaded them with liposomes containing melatonin.…”

Section: Delivery Platforms For Therapeutic Factorsmentioning

confidence: 99%

Therapeutic factors and biomaterial-based delivery tools for degenerative intervertebral disc repair

Song,

Guo,

et al. 2024

Front. Cell Dev. Biol.

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Intervertebral disc degeneration (IDD) is the main cause of low back pain (LBP), which significantly impacts global wellbeing and contributes to global productivity declines. Conventional treatment approaches, encompassing conservative and surgical interventions, merely serve to postpone the advancement of IDD without offering a fundamental reversal. Consequently, there is an urgent demand for an effective approach to prevent the progression of IDD. Recent investigations focusing on the treatment of IDD utilizing diverse bioactive substances integrated within various biomaterials have exhibited promising outcomes. Various bioactive substances, encompassing conventional small molecule drugs, small molecule nucleic acids, and cell therapies, exhibit distinct capacities for repairing IDD. Additionally, various biological material delivery systems, such as nano micelles, microspheres, and hydrogels, possess diverse biological and release characteristics. Consequently, these diverse materials and drugs hold promise for advancing the treatment of IDD. This article aims to provide a concise overview of the IDD process and investigate the research advancements in biomaterials and bioactive substances for IDD treatment, delving into their mechanisms.

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Section: Delivery Platforms For Therapeutic Factorsmentioning

confidence: 99%

Therapeutic factors and biomaterial-based delivery tools for degenerative intervertebral disc repair

Song,

Guo,

et al. 2024

Front. Cell Dev. Biol.

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Injectable Hydrogel Based on Enzymatic Initiation of Keratin Methacrylate for Controlled Exosome Release in Intervertebral Disc Degeneration Therapy

Chen,

Peng,

Huang

et al. 2024

Adv Funct Materials

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The treatment of intervertebral disc degeneration (IVDD) using bone marrow mesenchymal stem cell‐derived exosomes has shown success in alleviating inflammation and restoring the extracellular matrix (ECM), however, challenges persist due to the deficiency in mechanical support and controlled release. Herein, a carbon‐carbon double bond modified keratin (KeMA) is synthesized by 2‐isocyanatoethyl modification for exosomes wrapping. This injectable KeMA hydrogel, initiated by a biocompatible glucose/ glucose oxidase/ horse radish peroxidase enzymatic cascade reaction with acetylacetone and N‐vinylpyrrolidone, displayed rapid gelation, resembling nucleus pulposus (NP) elasticity, and excellent cytocompatibility. In vitro studies showcased that the exosomes‐loaded KeMA hydrogel (Exo@KeMA) enhanced exosome release kinetics, suppressed inflammation, fostered extracellular matrix (ECM) regeneration, and reinstated NP biomechanics. RNA‐seq analysis indicated Exo@KeMA's effects involved PI3K‐Akt signaling for matrix regeneration and NF‐κB signaling inhibition for anti‐inflammation. In vivo IVDD rat models demonstrated Exo@KeMA attenuated inflammation, maintained NP water content, preserved disc height, and promoted structural regeneration. This research introduces an injectable KeMA hydrogel as a promising therapy for IVDD, by facilitating biomechanics restoration, anti‐inflammatory response, and ECM regeneration.

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Targeting Osteoblast‐Osteoclast Cross‐Talk Bone Homeostasis Repair Microcarriers Promotes Intervertebral Fusion in Osteoporotic Rats

Zheng,

Li,

Zhang

et al. 2024

Adv Healthcare Materials

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Balancing osteoblast‐osteoclast (OB‐OC) cross‐talk is crucial for restoring bone tissue structure and function. Current clinical drugs targeting either osteogenesis or osteoclastogenesis fail to effectively regulate cross‐talk, impeding efficient bone repair in osteoporosis patients. Ubiquitin‐specific protease 26 (USP26) is shown to coordinate OB‐OC cross‐talk by independently regulating β‐catenin and Iκb‐α. However, effective drugs for activating USP26 are still lacking. Here, they constructed bone homeostasis repair microcarriers (BHRC) that encapsulate Usp26 mRNA‐loaded lipid nanoparticles (mRNA@LNP) within MMPs‐responsive GelMA hydrogel microspheres. These microcarriers target the osteoporotic microenvironment and regulate OB‐OC cross‐talk, thereby facilitating intervertebral fusion in osteoporotic rats. Results demonstrate that mRNA@LNP exhibits uniform particle size and high transfection efficiency, while GelMA hydrogel microspheres possess excellent biocompatibility and MMP responsiveness, providing favorable cell survival space and controllable release of mRNA@LNP. The released LNP upregulates USP26 protein expression, effectively promoting osteogenesis while suppressing osteoclast formation. In vivo experiments show that injecting BHRC into the defect site of intervertebral discs in osteoporotic rats significantly promotes tail vertebrae fusion by responding to the microenvironment and regulating cell‐to‐cell cross‐talk. Thus, the BHRC holds great potential in regulating osteoporotic homeostasis, particularly in challenging bone defects such as intervertebral fusion in osteoporotic environments.

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Circadian Clock Regulation via Biomaterials for Nucleus Pulposus

Cited by 10 publications

References 51 publications

Therapeutic factors and biomaterial-based delivery tools for degenerative intervertebral disc repair

Therapeutic factors and biomaterial-based delivery tools for degenerative intervertebral disc repair

Injectable Hydrogel Based on Enzymatic Initiation of Keratin Methacrylate for Controlled Exosome Release in Intervertebral Disc Degeneration Therapy

Targeting Osteoblast‐Osteoclast Cross‐Talk Bone Homeostasis Repair Microcarriers Promotes Intervertebral Fusion in Osteoporotic Rats

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