水凝胶引导软骨形成与间充质干细胞成骨制备软骨组织

IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL
Jingming Chen, A. Chin, A. Almarza, J. Taboas
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引用次数: 13

摘要

用于软骨和软骨界面再生的水凝胶成分的理想组合是一个重大挑战,因为控制分化为多个谱系是必要的。需要稳定干细胞衍生软骨细胞的表型,以避免不希望的晚期肥大和组织矿化的进展。设计了一种由甲基丙烯酸聚乙二醇(PEG)、明胶和肝素(PGH)组成的新型三元共混水凝胶,用于指导骨髓间充质干细胞(BMSCs)的软骨形成和维持其软骨表型。与甲基丙烯酸明胶水凝胶(GEL)(一种用于软骨形成和成骨应用的传统生物墨水)相比,评估了水凝胶材料对BMSC软骨形成和骨形成分化的影响。PGH和GEL水凝胶负载山羊BMSCs,并在软骨和成骨培养基中体外培养6周。PGH在体外成骨环境中没有显示出矿物质沉积的迹象。为了进一步评估材料效果,将水凝胶负载成人BMSCs(hBMSCs)和转化生长因子β-3,并在小鼠皮下口袋中生长8周。与体外结果一致,与GEL相比,PGH在体内通过BMSC诱导软骨形成的潜力更大,软骨形成标记物的基因表达升高证明了这一点,支持了其稳定软骨工程的潜力。与凝胶相比,PGH还显示出更大百分比的GAG阳性细胞。与GEL不同,PGH水凝胶在体内表现出抗成骨作用,Von-Kossa阴性染色证明了这一点,并抑制了肥大和成骨标志物的基因表达。PGH和GEL单独通过其聚合物组成的性质调节BMSC向不同骨软骨谱系的分化。因此,PGH和GEL是很有前途的水凝胶,可以使用未分化的BMSC和分层支架设计原位再生分层软骨界面组织,如下颌髁表面。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hydrogel to guide chondrogenesis versus osteogenesis of mesenchymal stem cells for fabrication of cartilaginous tissues
The ideal combination of hydrogel components for regeneration of cartilage and cartilaginous interfaces is a significant challenge because control over differentiation into multiple lineages is necessary. Stabilization of the phenotype of stem cell derived chondrocytes is needed to avoid undesired progression to terminal hypertrophy and tissue mineralization. A novel ternary blend hydrogel composed of methacrylated poly(ethylene glycol) (PEG), gelatin, and heparin (PGH) was designed to guide chondrogenesis by bone marrow derived mesenchymal stem cells (BMSCs) and maintenance of their cartilaginous phenotype. The hydrogel material effects on chondrogenic and osteogenic differentiation by BMSCs were evaluated in comparison to methacrylated gelatin hydrogel (GEL), a conventional bioink used for both chondrogenic and osteogenic applications. PGH and GEL hydrogels were loaded with goat BMSCs and cultured in chondrogenic and osteogenic mediums in vitro over six weeks. The PGH showed no sign of mineral deposition in an osteogenic environment in vitro. To further evaluate material effects, the hydrogels were loaded with adult human BMSCs (hBMSCs) and transforming growth factor β-3 and grown in subcutaneous pockets in mice over eight weeks. Consistent with the in vitro results, the PGH had greater potential to induce chondrogenesis by BMSCs in vivo compared to the GEL as evidenced by elevated gene expression of chondrogenic markers, supporting its potential for stable cartilage engineering. The PGH also showed a greater percentage of GAG positive cells compared to the GEL. Unlike the GEL, the PGH hydrogel exhibited anti-osteogenic effects in vivo as evidenced by negative Von Kossa staining and suppressed gene expression of hypertrophic and osteogenic markers. By nature of their polymer composition alone, the PGH and GEL regulated BMSC differentiation down different osteochondral lineages. Thus, the PGH and GEL are promising hydrogels to regenerate stratified cartilaginous interfacial tissues in situ, such as the mandibular condyle surface, using undifferentiated BMSCs and a stratified scaffold design.
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来源期刊
Biomedical materials
Biomedical materials 工程技术-材料科学:生物材料
CiteScore
6.70
自引率
7.50%
发文量
294
审稿时长
3 months
期刊介绍: The goal of the journal is to publish original research findings and critical reviews that contribute to our knowledge about the composition, properties, and performance of materials for all applications relevant to human healthcare. Typical areas of interest include (but are not limited to): -Synthesis/characterization of biomedical materials- Nature-inspired synthesis/biomineralization of biomedical materials- In vitro/in vivo performance of biomedical materials- Biofabrication technologies/applications: 3D bioprinting, bioink development, bioassembly & biopatterning- Microfluidic systems (including disease models): fabrication, testing & translational applications- Tissue engineering/regenerative medicine- Interaction of molecules/cells with materials- Effects of biomaterials on stem cell behaviour- Growth factors/genes/cells incorporated into biomedical materials- Biophysical cues/biocompatibility pathways in biomedical materials performance- Clinical applications of biomedical materials for cell therapies in disease (cancer etc)- Nanomedicine, nanotoxicology and nanopathology- Pharmacokinetic considerations in drug delivery systems- Risks of contrast media in imaging systems- Biosafety aspects of gene delivery agents- Preclinical and clinical performance of implantable biomedical materials- Translational and regulatory matters
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