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具有固有生物学特性的多功能赖氨酸树枝状接枝物和聚乙二醇水凝胶:体外细胞行为调控及体内生物相容性

Versatile lysine dendrigrafts and polyethylene glycol hydrogels with inherent biological properties: in vitro cell behavior modulation and in vivo biocompatibility.

作者信息

Carrancá Mariana, Griveau Louise, Remoué Noëlle, Lorion Chloé, Weiss Pierre, Orea Valérie, Sigaudo-Roussel Dominique, Faye Clément, Ferri-Angulo Daniel, Debret Romain, Sohier Jérôme

机构信息

Laboratory of Tissue Biology and Therapeutic Engineering, IBCP, CNRS Université, Lyon, France.

Laboratory for Materials Engineering and Science, CNRS INSA, Villeurbanne, France.

出版信息

J Biomed Mater Res A. 2021 Jun;109(6):926-937. doi: 10.1002/jbm.a.37083. Epub 2020 Sep 18.

Abstract

Poly(ethylene glycol) (PEG) hydrogels have been extensively used as scaffolds for tissue engineering applications, owing to their biocompatibility, chemical versatility, and tunable mechanical properties. However, their bio-inert properties require them to be associated with additional functional moieties to interact with cells. To circumvent this need, we propose here to reticulate PEG molecules with poly(L-lysine) dendrigrafts (DGL) to provide intrinsic cell functionalities to PEG-based hydrogels. The physico-chemical characteristics of the resulting hydrogels were studied in regard of the concentration of each component. With increasing amounts of DGL, the cross-linking time and swelling ratio could be decreased, conversely to mechanical properties, which could be tailored from 7.7 ± 0.7 to 90 ± 28.8 kPa. Furthermore, fibroblasts adhesion, viability, and morphology on hydrogels were then assessed. While cell adhesion significantly increased with the concentration of DGL, cell viability was dependant of the ratio of DGL and PEG. Cell morphology and proliferation; however, appeared mainly related to the overall hydrogel rigidity. To allow cell infiltration and cell growth in 3D, the hydrogels were rendered porous. The biocompatibility of resulting hydrogels of different compositions and porosities was evaluated by 3 week subcutaneous implantations in mice. Hydrogels allowed an extensive cellular infiltration with a mild foreign body reaction, histological evidence of hydrogel degradation, and neovascularization.

摘要

聚乙二醇(PEG)水凝胶因其生物相容性、化学多功能性和可调机械性能,已被广泛用作组织工程应用的支架。然而,其生物惰性特性要求它们与额外的功能部分结合以与细胞相互作用。为了规避这一需求,我们在此提出用聚(L-赖氨酸)树枝状接枝物(DGL)使PEG分子交联,为基于PEG的水凝胶提供内在的细胞功能。根据各组分的浓度研究了所得水凝胶的物理化学特性。随着DGL含量的增加,交联时间和溶胀率可降低,而机械性能则相反,可在7.7±0.7至90±28.8 kPa范围内进行调整。此外,还评估了成纤维细胞在水凝胶上的粘附、活力和形态。虽然细胞粘附随着DGL浓度的增加而显著增加,但细胞活力取决于DGL与PEG的比例。然而,细胞形态和增殖似乎主要与水凝胶的整体刚性有关。为了使细胞能够在三维空间中浸润和生长,使水凝胶具有多孔性。通过在小鼠体内进行3周的皮下植入,评估了不同组成和孔隙率的所得水凝胶的生物相容性。水凝胶允许大量细胞浸润,伴有轻微的异物反应、水凝胶降解的组织学证据和新血管形成。

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