Acta Biomaterialia
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2018
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IF 6.383
Xiaopeng Zhou,Jingkai Wang,Weijing Fang,Yiqing Tao,Tengfei Zhao,Kaishun Xia,Chengzhen Liang,Jianming Hua,Fangcai Li,Qixin Chen
Nucleus pulposus (NP) degeneration is usually the origin of intervertebral disc degeneration and consequent lower back pain. Although adipose-derived stem cell (ADSC)-based therapy is regarded to be promising for the treatment of degenerated NP, there is a lack of viable cell carriers to transplant ADSCs into the NP while maintaining cell function. In this study, we developed a type II collagen/chondroitin sulfate (CS) composite hydrogel-like ADSC (CCSA) delivery system with genipin as the cross-linking agent. The induction effect of the scaffold on ADSC differentiation was studied in vitro , and a rat coccygeal vertebrae degeneration model was used to investigate the regenerative effect of the CCSA system on the degenerated NP in vivo . The results showed that the CCSA delivery system cross-linked with 0.02% genipin was biocompatible and promoted the expressions of NP-specific genes. After the injection of the CCSA system, the disc height, water content, extracellular matrix synthesis, and structure of the degenerated NP were partly restored. Our CCSA delivery system uses minimally invasive approaches to promote the regeneration of degenerated NP and provides an exciting new avenue for the treatment of degenerative disc disease. Statement of Significance Nucleus pulposus (NP) degeneration is usually the origin of intervertebral disc degeneration and consequent lower back pain. Stem cell-based tissue engineering is a promising method in NP regeneration, but there is a lack of viable cell carriers to transplant ADSCs into the NP while maintaining cell function. In this study, we developed a type II collagen/chondroitin sulfate (CS) composite hydrogel-like ADSC (CCSA) delivery system with genipin as the cross-linking agent. Although several research groups have studied the fabrication of injectable hydrogel with biological matrix, our study differs from other works. We chose type II collagen and CS, the two primary native components in the NP, as the main materials and combined them according to the natural ratio of collagen and sGAG in the NP. The delivery system is preloaded with ADSCs and can be injected into the NP with a needle, followed by in situ gelation . Genipin is used as a cross-linker to improve the bio-stability of the scaffold, with low cytotoxicity. We investigated the stimulatory effects of our scaffold on the differentiation of ADSCs in vitro and the regenerative effect of the CCSA delivery system on degenerated NP in vivo .
研究领域:
组织工程
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干细胞生物学
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再生医学
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骨科
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生物医学材料
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产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
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2017
·Vol. 32
·期 3
·e4126
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IF 1.613
Fuguo Shi,Hong Pan,Yi Li,Linyan Huang,Qin Wu,Yuanfu Lu
Genipin (GP), an active metabolite of geniposide (GE), exhibits more potent pharmacological effects than its parent compound. In this paper, a sensitive LC-MS/MS method was developed and fully validated for the simultaneous determination of GE and GP in rat plasma. We found that GP degraded rapidly in rat plasma at room temperature as a result of irreversible binding with the endogenous nucleophiles in plasma. GP was stable when the sample's pH was ≤4.0. The degradation of GP in rat plasma was well prevented by immediate addition of 5% glacial acetic acid to the freshly collected plasma. The detection was performed on a tandem mass spectrometer coupled with electrospray ionization source in negative mode. Quantification was conducted by multiple reaction monitoring of the transitions [M + CH 3 COO] − m/z 447.3 → 225.3 for GE and [M − H] − m/z 225.2 → 123.1 for GP. The method exhibited high sensitivity (LLOQ 1 ng/mL for GE and 0.2 ng/mL for GP) by selecting the acetate adduct ions as the precursor ions for GE. The robust developed method was successfully applied to a pharmacokinetic study in rats after oral administration of GE.
研究领域:
药物分析
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药理学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2019
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IF 4.471
Dian Chen,Tonghe Zhu,Wei Fu,Haibo Zhang
Purpose A promising vascular scaffold must possess satisfying mechanical properties, great hemocompatibility, and favorable tissue regeneration. Combining natural with synthetic materials is a popular method of creating/enhancing such scaffolds. However, the effect of additional modification on the materials requires further exploration. Materials and methods We selected polycaprolactone (PCL), which has excellent mechanical properties and biocompatibility and can be combined with collagen. Electrospun fibers created using a PCL/collagen solution were used to fashion mixed nanofibers, while separate syringes of PCL and collagen were used to create separated nanofibers, resulting in different pore sizes. Mixed and separated nanofibers were cross-linked with glutaraldehyde (GA), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), and genipin; hence, we named them as mixed GA, mixed EDC (ME), mixed genipin (MG), separated GA, separated EDC (SE), and separated genipin (SG). Results Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction showed that cross-linking did not affect the main functional groups of fibers in all groups. ME, MG, SE, and SG met the requisite mechanical properties, and they also resisted collagenase degradation. In hemocompatibility assays, only ME and MG demonstrated ideal safety. Furthermore, ME and MG presented the greatest cytocompatibility. For vascular scaffolds, rapid endothelialization helps to prevent thrombosis. According to human umbilical vein endothelial cell migration on different nanofibers, ME and MG are also successful in promoting cell migration. Conclusion ME and MG may be promising candidates for vascular tissue engineering. The study suggests that collagen cross-linked by EDC/ N -hydroxysuccinimide or genipin facilitates endothelial cell regeneration, which could be of great benefit in tissue engineering of vascular scaffolds.
研究领域:
材料科学
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组织工程
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生物材料
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生物医学工程
✓ 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）