基于赖氨酸树枝状突起作为交联剂的生物活性水凝胶:定制弹性特性以影响 hMSC 成骨分化。

IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS
Michele Valeo, Sébastien Marie, Murielle Rémy, Tiphaine Menguy, Cédric Le Coz, Michael Molinari, Cécile Feuillie, Fabien Granier and Marie-Christine Durrieu
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引用次数: 0

摘要

树枝状聚合物是一种多价高分子,与树枝状聚合物相比,其拓扑结构的有序性较差,分支较多。第五代聚 L-赖氨酸树枝状连接体(DGL G5)具有高密度的末端胺,可形成具有可定制交联密度和表面改性的水凝胶。本研究将 DGL G5 作为生物仿生 PEG 水凝胶中的多功能交联剂,以促进人类间充质干细胞(hMSCs)的成骨分化。DGL G5 与二羧酸 PEG 链的反应生成了刚度可变的酰胺网络,可在宏观和表面纳米尺度上测量。振荡流变仪和压缩法得出了一致的杨氏模量值,从 8 千帕增加到 30 千帕以上,并与 DGL G5 的浓度相关。在表面层面,原子力显微镜测量也显示出同样的趋势,但杨氏模量值更高,分别从约 15 千帕增至 100 千帕以上。为了促进细胞粘附和分化,用 GRGDSPC 肽和骨形态发生蛋白 2(BMP-2)的生物模拟物对水凝胶进行了功能化处理,确保了相同的移植浓度(2.15 ± 0.54 和 2.28 ± 0.23 pmols mm-2),但水凝胶的硬度不同。在无血清培养基中的功能化水凝胶上播种 6 小时后,hMSC 在较硬的凝胶上显示出新生粘附,并且比在有血清的玻璃对照上有更大的扩散。在成骨培养基中培养两周后,与对照组相比,在较硬的凝胶上播种的 hMSC 表现出更大的扩散性、更多的多边形形态和更高水平的骨生成素(一种成骨细胞标记物),在 22 kPa 凝胶上达到峰值。这些结果共同证明,DGL G5-PEG 水凝胶的生物活性可影响 hMSCs 的粘附、扩散和早期承诺。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Bioactive hydrogels based on lysine dendrigrafts as crosslinkers: tailoring elastic properties to influence hMSC osteogenic differentiation†

Bioactive hydrogels based on lysine dendrigrafts as crosslinkers: tailoring elastic properties to influence hMSC osteogenic differentiation†

Dendrigrafts are multivalent macromolecules with less ordered topology and higher branching than dendrimers. Exhibiting a high density of terminal amines, poly-L-lysine dendrigrafts of the fifth generation (DGL G5) allow hydrogel formation with tailorable crosslinking density and surface modification. This work presents DGL G5 as multifunctional crosslinkers in biomimetic PEG hydrogels to favour the osteogenic differentiation of human mesenchymal stem cells (hMSCs). DGL G5 reaction with dicarboxylic-acid PEG chains yielded amide networks of variable stiffness, measured at the macro and surface nanoscale. Oscillatory rheometry and compression afforded consistent values of Young's modulus, increasing from 8 to more than 30 kPa and correlating with DGL G5 concentration. At the surface level, AFM measurements showed the same tendency but higher E values, from approximately 15 to more than 100 kPa, respectively. To promote cell adhesion and differentiation, the hydrogels were functionalised with a GRGDSPC peptide and a biomimetic of the bone morphogenetic protein 2 (BMP-2), ensuring the same grafting concentrations (between 2.15 ± 0.54 and 2.28 ± 0.23 pmols mm−2) but different hydrogel stiffness. 6 h after seeding on functionalised hydrogels in serum-less media, hMSC showed nascent adhesions on the stiffer gels and greater spreading than on glass controls with serum. After two weeks in osteogenic media, hMSC seeded on the stiffer gels showed greater spreading, more polygonal morphologies and increased levels of osteopontin, an osteoblast marker, compared to controls, which peaked on 22 kPa-gels. Together, these results demonstrate that DGL G5-PEG hydrogel bioactivity can influence the adhesion, spreading and early commitment of hMSCs.

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来源期刊
Journal of Materials Chemistry B
Journal of Materials Chemistry B MATERIALS SCIENCE, BIOMATERIALS-
CiteScore
11.50
自引率
4.30%
发文量
866
期刊介绍: Journal of Materials Chemistry A, B & C cover high quality studies across all fields of materials chemistry. The journals focus on those theoretical or experimental studies that report new understanding, applications, properties and synthesis of materials. Journal of Materials Chemistry A, B & C are separated by the intended application of the material studied. Broadly, applications in energy and sustainability are of interest to Journal of Materials Chemistry A, applications in biology and medicine are of interest to Journal of Materials Chemistry B, and applications in optical, magnetic and electronic devices are of interest to Journal of Materials Chemistry C.Journal of Materials Chemistry B is a Transformative Journal and Plan S compliant. Example topic areas within the scope of Journal of Materials Chemistry B are listed below. This list is neither exhaustive nor exclusive: Antifouling coatings Biocompatible materials Bioelectronics Bioimaging Biomimetics Biomineralisation Bionics Biosensors Diagnostics Drug delivery Gene delivery Immunobiology Nanomedicine Regenerative medicine & Tissue engineering Scaffolds Soft robotics Stem cells Therapeutic devices
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