Nature Communications
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2025
·Vol. 16
·期 1
·1-15
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IF 15.7
Xie Chang,Li Wenyue,Yao Xudong,Wu Boxuan,Fang Jinghua,Mao Renwei,Yan Yiyang,Meng Hongxu,Wu Yan,Zhang Xianzhu,Li Rui,Zhang Jie,Duan Wangping,Dai Xuesong,Wang Xiaozhao,Ouyang Hongwei
Growth plate (GP), a critical cartilaginous structure in amniotes, underpins longitudinal bone growth, yet the intricate mechanisms behind its polarized mineralization during evolution remain unclear. Herein, employing high-resolution analytical techniques, we reveal that the GP-epiphysis interface displays a sharp transition in tissue modulus, acting as a protective shell for the underlying GP, whereas the GP-metaphysis interface exhibits a gradual modulus increase, enabling efficient load redistribution to the metaphysis. This mechanical microenvironment contributes to unique microstructural and compositional transformations from GP to epiphysis and metaphysis. Notably, the GP-epiphysis interface acts as a mineralization inhibition zone while the GP-metaphysis serves as a mineralization promotion zone, orchestrated by a complex network of proteins. Proteins such as secreted phosphoprotein 1 (SPP1) and alpha-2-HS-glycoprotein (AHSG) at the GP-epiphysis interface inhibit mineralization, forming a defense line; while ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and alkaline phosphatase, biomineralization associated (ALPL), coexisting with SPP1 and AHSG, promote a sequential nucleation and assembly of calcium phosphate minerals at the GP-metaphysis. Such polarized mineralization patterns maintain the homeostasis of GPs and drive polarized bone elongation. Replicating this process in vitro, we synthesize stable amorphous calcium phosphate which shows highly controlled transformation into hydroxyapatite. This work provides a more comprehensive view of the structural integrity of human bone in development and offers strategies for controlled biomineralization.
研究领域:
发育生物学
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生物力学
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生物矿化
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分子生物学
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骨骼生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Guanlu Shen,Xinxin Si,Lei Qiang,Yihao Liu,Zhiyang Yin,Jing Shan,Pengfei Zheng
Growth plate injuries in children and adolescents often lead to bone bridge formation, resulting in limb deformities due to the limited self-repair capacity of the growth plate. The limitations of traditional treatments prompted interest in the role of the extracellular matrix (ECM) and mechanical environment in tissue repair. Recent research showed that 3D hydrogels could mimic ECM to regulate mesenchymal stem cells (MSCs) differentiation, with MSCs sensing matrix viscoelasticity via Piezo1 and responding through the ROCK signaling pathway. This study aimed to develop a 3D biomimetic hydrogel composed of acellular cartilage matrix methacryloyl (ACMMA) and gelatin methacryloyl (GelMA), with adjustable viscoelasticity via blue light crosslinking time. Hydrogels with low (5 s) and high (20s) modulus were fabricated and loaded with bone marrow mesenchymal stem cells (BMSCs). Results demonstrated that the 5 s hydrogel promoted chondrogenic differentiation and inhibited osteogenesis, effectively preventing bone bridge formation and enhancing growth plate repair in vivo . Mechanistic studies confirmed that the 5 s group did not activate the Piezo1-ROCK pathway, supporting its role in chondrogenic differentiation.
研究领域:
生物医学工程
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组织工程
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干细胞研究
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生物材料
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骨科
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xinxin Si,Quan Zhang,Bo Ning,Lei Qiang,Qiang Li,Yihao Liu,Minjie Fan,Jing Shan,Guanlu Shen,Zichen Lin,Pengfei Zheng
The growth plate is vital for childhood development, and most of the injuries can formation of bone bridges on it, which has negative impact on limb development. Current biomaterial scaffolds often lack essential cartilage matrix components, which hurdles to get an acceptable regeneration. Additionally, stem cell transplantation faces challenges including high apoptosis rates and uncertain differentiation. Then, we designed an injectable composite hydrogel (Exo-AMG) loaded with exosomes (Exo) and composed of methacrylate-modified acellular cartilage matrix (ACMMA) and gelatin methacrylate (GelMA) to repair the growth plate for children and adolescents. The hydrogel is administered via minimally invasive injection and undergoes in-situ photocrosslinking to fill the growth plate defects. It exhibited suitable mechanical properties, biodegradation rates; it also could sustain exosome release. Moreover, it promoted M2 macrophage polarization and secretion of anti-inflammatory factors, and it enhanced bone mesenchymal stem cells (BMSCs) proliferation and chondrogenic differentiation in vitro . In vivo study, this Exo-AMG induced growth plate cartilage regeneration without bone bridge formation. Therefore, this injectable and in-situ photocrosslinkable composite hydrogel is promising on growth plate injury repair by alleviating inflammation and promoting chondrogenic differentiation.
研究领域:
生物材料
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组织工程
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再生医学
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骨科
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·Vol. 35
·期 43
·2417743
·
IF 19
Junji Li,Gaohua Li,Pengfei Guan,Rikuan Tong,Haoyang Feng,Kai Ang,Zhen Kong,Zhaobo Zhu,Can Liu,Cheng Li,Hongliang Wu,Yongjian Sun
It is now understood that oxidative stress, characterized by an excess of reactive oxygen species (ROS) within growth plate injury sites, can impede cartilage repair through various mechanisms. Morinda officinalis (MO), a traditional Chinese herbal medicine, possesses potent antioxidant properties. Furthermore, extracellular vesicles (EVs) derived from plants exhibit comparable physical and chemical characteristics to their parent plants, along with favorable tissue permeability and biocompatibility. Herein, it develops a ROS-sensitive hydrogel by self-crosslinking two natural extracellular matrix (ECM)-derived components: polyvinyl alcohol (PVA) and chondroitin sulfate grafted with phenylboric acid (CSBA). The hydrogel is subsequently combined with MO-derived EVs (MO-EVs) to eliminate excess ROS from the damaged microenvironment and release MO-EVs as needed to facilitate growth plate damage healing. In vitro studies revealed that a CSBA-PVA hydrogel containing MO-EVs facilitated the restoration of chondrocyte mitochondrial function by activating the NRF2-HO-1/NQO1 pathway, thereby enhancing endogenous antioxidant capacity. Furthermore, in vivo results reveal that implantation of CSBA-PVA hydrogel loaded with MO-EVs significantly inhibited bone bridge development and facilitated cartilage restoration within the growth plate. CSBA-PVA@MO-EVs therapy brings huge prospects as a therapeutic approach, offering novel insights and therapeutic strategies for treating growth plate injuries.
研究领域:
生物医学工程
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再生医学
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植物药理学
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氧化应激生物学
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软骨组织工程
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纳米医学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）