A moldable thermosensitive hydroxypropyl chitin hydrogel for 3D cartilage regeneration in vitro and in vivo
A moldable thermosensitive hydroxypropyl chitin hydrogel for 3D cartilage regeneration in vitro and in vivo
复制标题
用于体外和体内 3D 软骨再生的可塑热敏羟丙基甲壳素水凝胶
DOI：
10.1016/j.actbio.2020.03.039
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发表时间：
2020-05-01
影响因子：
9.7
通讯作者：
Cao, Yilin
中科院分区：
文献类型：
--
作者：
Xu, Yawen;Xu, Yong;Cao, Yilin
由于软骨自身修复能力差，软骨缺损的修复一直是临床治疗的一大挑战。体外软骨再生为软骨缺损的功能重建提供了一种潜在的策略。水凝胶是理想的软骨再生支架材料。然而，迄今为止，基于水凝胶的体外软骨再生尚未取得令人满意的结果。本研究探讨了基于可模塑的温敏羟丙基甲壳素（HPCH）水凝胶的体外3D软骨再生的可行性及其在体内的命运。制备了温敏HPCH水凝胶并对其进行了表征。将山羊耳廓软骨细胞包封到HPCH水凝胶中以形成软骨细胞-水凝胶构建体。将构建体皮下注射到裸鼠体内或塑造成不同的形状用于体外软骨形成培养，随后进行体内植入。结果表明，HPCH水凝胶具有令人满意的凝胶化性质（在37 ℃下凝胶化时间< 18 s）、生物相容性（细胞量在一周内几乎翻了一番）以及作为可注射水凝胶应用于软骨再生的能力。所有体外培养的结构基本保持其原始形状（体外：初始：110.8%），并显示出典型的软骨特征，具有丰富的陷窝和软骨特异性基质沉积。这些体外样品随着体内植入时间的延长而变得更加成熟，并且基本上保持了原始形状（体内与体外：103.5%）。结果表明，可塑形的温敏性HPCH水凝胶可作为一种有前途的软骨再生支架材料，在体内外均具有一定的形态学特征。水凝胶是理想的软骨再生支架材料。然而，迄今为止，基于水凝胶的体外软骨再生尚未取得令人满意的结果。目前的研究表明，由高密度软骨细胞包封到温敏HPCH水凝胶中产生的软骨细胞-水凝胶构建体可以成功地在体外再生具有限定形状的典型软骨样组织，并在体内植入后进一步成熟以形成具有其原始形状的均匀软骨。目前的研究表明，可模压的温敏HPCH水凝胶可以作为一个有前途的支架，在体外和体内不同形状的软骨再生。(C)2020 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Because of poor self-repair capacity, the repair of cartilage defect is always a great challenge in clini-cal treatment. In vitro cartilage regeneration provides a potential strategy for functional reconstruction of cartilage defect. Hydrogel has been known as an ideal cartilage regeneration scaffold. However, to date, in vitro cartilage regeneration based on hydrogel has not achieved satisfactory results. The current study explored the feasibility of in vitro 3D cartilage regeneration based on a moldable thermosensitive hydroxypropyl chitin (HPCH) hydrogel and its in vivo fate. The thermosensitive HPCH hydrogel was prepared and characterized. Goat auricular chondrocytes were encapsulated into the HPCH hydrogel to form a chondrocyte-hydrogel construct. The constructs were injected subcutaneously into nude mice or molded into different shapes for in vitro chondrogenic culture followed by in vivo implantation. The results demonstrated that the HPCH hydrogel possessed satisfactory gelation properties (gelation time < 18 s at 37 degrees C), biocompatibility (cell amount almost doubled within one week), and the ability to be applied as an injectable hydrogel for cartilage regeneration. All the constructs of in vitro culture basically maintained their original shapes (in vitro to initial: 110.8%) and displayed typical cartilaginous features with abundant lacunae and cartilage specific matrix deposition. These in vitro samples became more ma-ture with prolonged in vivo implantation and largely maintained the original shape (in vivo to in vitro: 103.5%). These results suggested that the moldable thermosensitive HPCH hydrogel can serve as a promis-ing scaffold for cartilage regeneration with defined shapes in vitro and in vivo.Statement of significanceBecause of avascular and non-nervous characteristic of cartilage, in vitro regeneration plays an important role in reconstructing cartilage function. Hydrogel has been known as an ideal cartilage regeneration scaffold. However, to date, in vitro cartilage regeneration based on hydrogel has not achieved satisfactory results. The current study demonstrated that the chondrocyte-hydrogel construct generated by high density of chondrocytes encapsulated into a thermosensitive HPCH hydrogel could successfully regenerate in vitro typical cartilage-like tissue with defined shapes and further mature to form homogeneous cartilage with their original shapes after in vivo implantation. The current study indicated that the mold-able thermosensitive HPCH hydrogel could serve as a promising scaffold for in vitro and in vivo cartilage regeneration with different shapes. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.