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基于拉蓬黏土纳米颗粒的硅烷化羟丙基甲基纤维素作为一种可注射增强互穿网络水凝胶用于软骨组织工程。

Laponite nanoparticle-associated silated hydroxypropylmethyl cellulose as an injectable reinforced interpenetrating network hydrogel for cartilage tissue engineering.

机构信息

Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes F-44042, France; Université de Nantes, UFR Odontologie, Nantes F-44042, France.

Inserm, UMR 1229, RMeS, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes F-44042, France; Université de Nantes, UFR Odontologie, Nantes F-44042, France; SC3M, SFR Santé F. Bonamy, FED 4203, UMS Inserm 016, CNRS 3556, Nantes F-44042, France.

出版信息

Acta Biomater. 2018 Jan;65:112-122. doi: 10.1016/j.actbio.2017.11.027. Epub 2017 Nov 8.

DOI:10.1016/j.actbio.2017.11.027
PMID:29128532
Abstract

UNLABELLED

Articular cartilage is a connective tissue which does not spontaneously heal. To address this issue, biomaterial-assisted cell therapy has been researched with promising advances. The lack of strong mechanical properties is still a concern despite significant progress in three-dimensional scaffolds. This article's objective was to develop a composite hydrogel using a small amount of nano-reinforcement clay known as laponites. These laponites were capable of self-setting within the gel structure of the silated hydroxypropylmethyl cellulose (Si-HPMC) hydrogel. Laponites (XLG) were mixed with Si-HPMC to prepare composite hydrogels leading to the development of a hybrid interpenetrating network. This interpenetrating network increases the mechanical properties of the hydrogel. The in vitro investigations showed no side effects from the XLG regarding cytocompatibility or oxygen diffusion within the composite after cross-linking. The ability of the hybrid scaffold containing the composite hydrogel and chondrogenic cells to form a cartilaginous tissue in vivo was investigated during a 6-week implantation in subcutaneous pockets of nude mice. Histological analysis of the composite constructs revealed the formation of a cartilage-like tissue with an extracellular matrix containing glycosaminoglycans and collagens. Overall, this new hybrid construct demonstrates an interpenetrating network which enhances the hydrogel mechanical properties without interfering with its cytocompatibility, oxygen diffusion, or the ability of chondrogenic cells to self-organize in the cluster and produce extracellular matrix components. This composite hydrogel may be of relevance for the treatment of cartilage defects in a large animal model of articular cartilage defects.

STATEMENT OF SIGNIFICANCE

Articular cartilage is a tissue that fails to heal spontaneously. To address this clinically relevant issue, biomaterial-assisted cell therapy is considered promising but often lacks adequate mechanical properties. Our objective was to develop a composite hydrogel using a small amount of nano reinforcement (laponite) capable of gelling within polysaccharide based self-crosslinking hydrogel. This new hybrid construct demonstrates an interpenetrating network (IPN) which enhances the hydrogel mechanical properties without interfering with its cytocompatibility, O diffusion and the ability of chondrogenic cells to self-organize in cluster and produce extracellular matrix components. This composite hydrogel may be of relevance for the treatment of cartilage defects and will now be considered in a large animal model of articular cartilage defects.

摘要

未加说明

关节软骨是一种结缔组织,不会自发愈合。为了解决这个问题,人们研究了生物材料辅助细胞疗法,取得了有希望的进展。尽管在三维支架方面取得了重大进展,但缺乏强有力的机械性能仍然令人担忧。本文的目的是开发一种使用少量纳米增强粘土(称为锂皂石)的复合水凝胶。这些锂皂石能够在硅丙基甲基纤维素(Si-HPMC)水凝胶的凝胶结构内自凝固。锂皂石(XLG)与 Si-HPMC 混合制备复合水凝胶,形成混合互穿网络。这种互穿网络增加了水凝胶的机械性能。体外研究表明,交联后 XLG 对复合水凝胶的细胞相容性或氧扩散没有副作用。在裸鼠皮下口袋中进行 6 周植入物研究后,研究了含有复合水凝胶和软骨细胞的杂交支架在体内形成软骨组织的能力。对复合结构的组织学分析显示,形成了一种具有含有糖胺聚糖和胶原蛋白的细胞外基质的软骨样组织。总的来说,这种新的混合结构证明了互穿网络的增强作用,提高了水凝胶的机械性能,同时不影响其细胞相容性、氧扩散或软骨细胞自组织成簇并产生细胞外基质成分的能力。这种复合水凝胶可能与关节软骨缺损的大动物模型中的软骨缺损治疗有关。

意义声明

关节软骨是一种不能自发愈合的组织。为了解决这个临床上相关的问题,生物材料辅助细胞疗法被认为很有前途,但往往缺乏足够的机械性能。我们的目标是开发一种使用少量纳米增强剂(锂皂石)的复合水凝胶,这种纳米增强剂能够在基于多糖的自交联水凝胶中凝胶化。这种新的混合结构证明了互穿网络(IPN)的增强作用,提高了水凝胶的机械性能,同时不影响其细胞相容性、O 扩散和软骨细胞自组织成簇并产生细胞外基质成分的能力。这种复合水凝胶可能与软骨缺损的治疗有关,现在将在关节软骨缺损的大动物模型中进行考虑。

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