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一种新型复合水凝胶,将胶原蛋白的生物特性与超分子支架的机械特性结合起来,用于骨组织工程。

A new composite hydrogel combining the biological properties of collagen with the mechanical properties of a supramolecular scaffold for bone tissue engineering.

机构信息

Laboratoire BIOTIS, Inserm U1026, Université de Bordeaux, Bordeaux, France.

Lab. for Biomaterials & Bioengineering (CRC-I), Dept. Min-Met-Materials Engineering & Research Center CHU de Québec, Laval University, Québec City, Canada.

出版信息

J Tissue Eng Regen Med. 2018 Mar;12(3):e1489-e1500. doi: 10.1002/term.2569. Epub 2017 Dec 10.

Abstract

Tissue engineering is a promising alternative to autografts, allografts, or biomaterials to address the treatment of severe and large bone lesions. Classically, tissue engineering products associate a scaffold and cells and are implanted or injected into the lesion. These cells must be embedded in an appropriate biocompatible scaffold, which offers a favourable environment for their survival and differentiation. Here, we designed a composite hydrogel composed of collagen I, an extracellular matrix protein widely used in several therapeutic applications, which we associated with a physical hydrogel generated from a synthetic small amphiphilic molecule. This composite showed improved mechanical and biological characteristics as compared with gels obtained from each separate compound. Incorporation of the physical hydrogel prevented shrinkage of collagen and cell diffusion out of the gel and yielded a gel with a higher elastic modulus than those of gels obtained with each component alone. The composite hydrogel allowed cell adhesion and proliferation in vitro and long-term cell survival in vivo. Moreover, it promoted the differentiation of human adipose-derived stem cells in the absence of any osteogenic factors. In vivo, cells embedded in the composite gel and injected subcutaneously in immunodeficient mice produced lamellar osteoid tissue and differentiated into osteoblasts. This study points this new composite hydrogel as a promising scaffold for bone tissue engineering applications.

摘要

组织工程是一种有前途的替代自体移植物、同种异体移植物或生物材料的方法,可用于治疗严重和大面积的骨损伤。传统上,组织工程产品将支架和细胞结合在一起,并将其植入或注射到病变部位。这些细胞必须嵌入在合适的生物相容性支架中,为其生存和分化提供有利的环境。在这里,我们设计了一种由 I 型胶原组成的复合水凝胶,I 型胶原是一种在多种治疗应用中广泛使用的细胞外基质蛋白,我们将其与一种由合成小分子两亲性分子生成的物理水凝胶结合在一起。与单独使用每种化合物获得的凝胶相比,这种复合水凝胶表现出更好的机械和生物学特性。物理水凝胶的掺入可防止胶原收缩和细胞从凝胶中扩散,并产生具有比单独使用每种成分获得的凝胶更高弹性模量的凝胶。复合水凝胶允许细胞在体外黏附和增殖,并在体内长期存活。此外,它在没有任何成骨因子的情况下促进了人脂肪来源干细胞的分化。在体内,注射到免疫缺陷小鼠皮下的复合凝胶中的细胞产生板层状类骨质组织并分化为成骨细胞。这项研究表明这种新型复合水凝胶是一种有前途的骨组织工程应用支架。

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