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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Delivering cells via ECM mimetic hydrogel microspheres for promoting the reconstruction of rat lumbar nucleus pulposus

Hao Liu,Xin Tian,Chenyang Jin,Yangfeng Li,Xuesong Zhu,Ming Pei,Tao Liu,Huilin Yang,Yong Xu,Fan He

Nucleus pulposus (NP) discectomy is a clinical procedure for the treatment of late-stage intervertebral disc (IVD) degeneration; however, it is associated with the potential for serious complications. The reconstruction of the NP tissue presents challenges due to its avascular structure and prolonged compression within the IVD. In this study, we have developed a novel biomimetic hydrogel microsphere composed of gelatin methacryloyl (GelMA) and fucoidan, a polysaccharide derived from marine brown seaweed, to mimic the extracellular matrix (ECM) of the native NP. The GelMA and fucoidan (GelMA@FD) hydrogel microspheres demonstrate favorable cytocompatibility and significantly enhance the synthesis of matrix components in nucleus pulposus cells (NPCs), including aggrecan and type II collagen. Transcriptome sequencing analysis demonstrates a correlation between the augmentation of matrix synthesis and the enrichment of genes and pathways related to mitochondrial function. Subsequent molecular investigations provide evidence that NPCs cultured on GelMA@FD exhibit enhanced mitochondrial functions, including elevated adenosine triphosphate production and respiratory chain factor expression, alongside a reduction in mitochondrial reactive oxygen species. When implantated into rat lumbar IVDs that have undergone discectomy, the incorporation of NPCs within GelMA@FD hydrogel microspheres facilitates the regeneration of the NP and reinstates its structural and biomechanical properties. This is substantiated by the observed augmentation in IVD disc height and water content within the NP compartment. Collectively, these results demonstrate the potential of employing cell-laden GelMA@FD hydrogel microspheres as a promising strategy for NP regeneration in degenerated IVDs.

CAS / MDL: 760-93-0
研究领域: 生物材料 · 组织工程 · 再生医学 · 骨科
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ADVANCED MATERIALS · 2025 · IF 26.8

Janus Graphene Oxide Nanoplatform with Oppositely Functionalized Adhesion and Lubrication Enables Local Sustained Fenofibrate Release to Synergistically Halt Osteoarthritis

Xi Chen,Hongfu Cao,Haoyuan Lei,Na Li,Ping Song,Yi Cao,Weilin Tian,Xiaolin Cui,Tun Yuan,Jie Liang,Qiguang Wang,Yujiang Fan,Xingdong Zhang

Osteoarthritis (OA) progresses via a destructive cycle involving cartilage damage, friction, lubrication loss, and chondrocyte senescence. Current therapies, limited to temporary lubrication or pain relief, fail to halt OA due to their inability to repair cartilage or restore innate lubrication. To address this challenge, an asymmetric Janus graphene oxide (MGO) nanoplatform is engineered and functionalized with the anti-senescence agent Fenofibrate (FN), creating the MGO-FN system. This integrated design features one side providing robust cartilage adhesion and the opposing side offering superior lubrication, while simultaneously delivering the therapeutic FN. Critically, the nanoscale MGO-FN effectively infiltrates and fills micro-damage on the cartilage surface, enabling localized and sustained FN release. This maximizes drug bioavailability at the target site by minimizing diffusion distances. In vitro, MGO-FN demonstrated potent synergistic effects, significantly enhancing chondrocyte proliferation and extracellular matrix synthesis, reducing senescence, and upregulating the lubrication marker PRG4 more effectively than either component alone. In vivo OA rat studies, supported by transcriptomics analysis, validated MGO-FN's potent therapeutic effects, including reduced cartilage degradation, mitigated inflammation, promoted matrix regeneration, and restored innate lubrication. These findings underscore MGO-FN as a promising multifaceted therapeutic strategy to halt OA progression by concurrently restoring cartilage integrity and lubricating function.

研究领域: 纳米医学 · 骨科 · 药物递送 · 组织工程 · 风湿病学
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Materials Today Bio · 2023 · IF 8.2

Melatonin-loaded self-healing hydrogel targets mitochondrial energy metabolism and promotes annulus fibrosus regeneration

Xiayu Hu,Xin Tian,Chunju Yang,Feng Ling,Hao Liu,Xuesong Zhu,Ming Pei,Huilin Yang,Tao Liu,Yong Xu,Fan He

Intervertebral disc (IVD) herniation is a major cause of chronic low back pain and disability. The current nucleus pulposus (NP) discectomy effectively relieves pain symptoms, but the annulus fibrosus (AF) defects are left unrepaired. Tissue engineering approaches show promise in treating AF injury and IVD degeneration; however, the presence of an inflammatory milieu at the injury site hinders the mitochondrial energy metabolism of AF cells, resulting in a lack of AF regeneration. In this study, we fabricated a dynamic self-healing hydrogel loaded with melatonin (an endocrine hormone well-known for its antioxidant and anti-inflammatory properties) and investigate whether melatonin-loaded hydrogel could promote AF defect repair by rescuing the matrix synthesis and energy metabolism of AF cells. The protective effects of melatonin on matrix components (e.g. type I and II collagen and aggrecan) in AF cells were observed in the presence of interleukin (IL)-1β. Additionally, melatonin was found to activate the nuclear factor erythroid 2-related factor signaling pathway, thereby safeguarding the mitochondrial function of AF cells from IL-1β, as evidenced by the increased level of adenosine triphosphate, mitochondrial membrane potential, and respiratory chain factor expression. The incorporation of melatonin into a self-healing hydrogel based on thiolated gelatin and β-cyclodextrin was proposed as a means of promoting AF regeneration. The successful implantation of melatonin-loaded hydrogel has been shown to facilitate in situ regeneration of AF tissue, thereby impeding IVD degeneration by preserving the hydration of nucleus pulposus in a rat box-cut IVD defect model. These findings offer compelling evidence that the development of a melatonin-loaded dynamic self-healing hydrogel can promote the mitochondrial functions of AF cells and represents a promising strategy for IVD regeneration.

CAS / MDL: 4781-83-3
研究领域: 组织工程 · 再生医学 · 生物医学工程 · 骨科 · 药理学
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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Acupoint Therapy with Injectable, Pro-Healing Stem Cell-Loaded Hydrogel Microspheres Promotes Skin Wound Healing

Yinqiu Yan,Liling Chen,Liwen Zheng,Gen Wang,Hongmei Zhang,Xing Feng,Yaxian Liu,Lan Li,Yu Shrike Zhang,Ping Ji,Ximu Zhang

Wound repair is a complex and dynamic process, involving stages of hemostasis, inflammation, proliferation, and remodeling. Standard methods currently used for clinical treatment of skin defects remain unsatisfying and alternative treatments have emerged including acupuncture mostly relying on the conventional needle method. It is applied sustained acupuncture therapy with bioengineered stem cell-loaded hydrogel microspheres (A-SGC), where the data gathered through transcriptomics, metabolomics, and single-cell omics analyses are used to construct a comprehensive multi-omics map underlying the wound regeneration process with such a therapy. Under the treatment of A-SGC, the interactions and Yin-Yang balance among fibroblasts, macrophages, endothelial cells, and keratinocytes facilitated skin regeneration instead of scarred healing. The genes related to the promotion of matrix synthesis and re-epithelialization played important roles in the transition from the inflammatory granulation phase to the stromal remodeling phase. This convergence use of hydrogel microspheres, stem cells, and sustained acupuncture therapy could have previously unattainable therapeutic implications for improved wound treatment.

CAS / MDL: 85073-19-4 760-93-0
研究领域: 生物医学工程 · 再生医学 · 伤口愈合 · 干细胞生物学 · 组学分析
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