Frontiers in Medicine
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2025
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IF 3
Leidong Lian,Dingli Xu,Chaonan He,Zhe Luo,Han Yu,Botao Liu,Ke Zhou,Liangjie Lu,Kaifeng Gan
Introduction The natural polysaccharide-based injectable hydrogels have showed significant interest to use as 3D scaffolds for critical-sized bone defect repair. Methods Here, we incorporated ZnO nanoparticles (NPs) into a newly synthesized water-soluble phosphocreatine-functionalized chitosan (CSMP) water solution to form an injectable hydrogel (CSMP-ZnO) via supramolecular combination between phosphate groups in CSMP and Zinc in ZnO NPs. Results The phosphocreatine in this hydrogel not only provides sites to combine with ZnO NPs form supramolecular binding but also serves as the reservoir to control Zn 2+ release. The results show that the lyophilized CSMP-ZnO hydrogels presented a porous structure with some small holes in the pore wall, as shown by scanning electron microscopy. Rheological characterizations revealed that the mechanical properties of the hydrogels were almost maintained upon the addition of ZnO NPs. In vitro experiments showed that the CSMP-ZnO hydrogel exhibits excellent angiogenic and osteogenic properties compared with the CSMP hydrogel. The as-released Zn 2+ ions promote the high expression of osteoblast collagen 1 proteins and accelerate bone mineralization by activating the BMP2/SMAD signaling pathway. In vivo , the as-released Zn 2+ ions promot osteoblastic proliferation and the mineralization of osteoblasts inside the CSMP-ZnO scaffolds. Immunofluorescence for RUNX2, COL-1, and CD31, showed that stable vasculature could be formed inside the CSMP-ZnO scaffolds. Discussion Both the in vitro and in vivo results demonstrate that CSMP-ZnO hydrogel shows promise for bone regeneration, suggesting a new strategy for tissue engineering and regeneration in the future.
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2025
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IF 20.3
Tianyu Yu,Xun Sun,Yang Liu,Yiming Dou,Ye Tian,Yiming Zhang,Genghao Wang,Lianyong Wang,Jianmin Han,Xiaohong Li,Xigao Cheng,Honglong Li,Haobo Pan,Lei Yang,Yanhong Zhao,Qiang Yang
Focal articular cartilage defects often progress to osteoarthritis, imposing a substantial global health burden. Current neglect of cartilage developmental regulation and cartilage microenvironment compromises therapeutic efficacy. We developed an innovation CE-SKP/CPH/P2G3 scaffold which effectively repairs focal cartilage defects and emulates native cartilage ontogeny: the superficial CE-SKP hydrogel layer recruits SMSCs and promotes chondrogenesis; the middle CPH hydrogel layer induces chondrocyte hypertrophic calcification, forming cartilage calcified layer; and the basal P2G3 nanofiber membrane isolates subchondral cells, enforcing a top-down developmental sequence and preserving a localized hypoxic niche. In vitro characterization confirms that the porosity, swelling ratio, biodegradation rate, and biocompatibility are optimal for sequential SMSC recruitment, cartilage differentiation, hypertrophic mineralization, and cells isolation. In vivo , the biomimetic tri-layer scaffold promotes regeneration of both cartilage and calcified cartilage by recapitulating the native ontogenetic progression from cartilage to calcified cartilage within the in vivo microenvironment, successfully restoring the normal physiological structure of articular cartilage by 24 weeks post-implantation. ScRNA-seq revealed SMSCs and a novel chondrocyte subpopulation CHON_5 as key repair populations, SMSCs mediated early repair via hypoxia response and migration, while CHON_5 promoted ECM remodeling, synergistically enhancing regeneration in late repair stage. Furthermore, we identified FGF signaling (FGF2-FGFR1/2 and FGF18-FGFR1/2 pairs) was crucial for MSC-CHON_5 communication during sequential cartilage regeneration. Overall, by recapitulating native developmental dynamics and microenvironmental cues, this scaffold offers a novel and effective strategy for functional cartilage regeneration and osteoarthritis treatment.
研究领域:
组织工程
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再生医学
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生物医学材料
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发育生物学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）