Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, Shanghai, PR China.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, PR China.
Acta Biomater. 2020 May;108:87-96. doi: 10.1016/j.actbio.2020.03.039. Epub 2020 Apr 5.
Because of poor self-repair capacity, the repair of cartilage defect is always a great challenge in clinical 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 °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 mature 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 promising scaffold for cartilage regeneration with defined shapes in vitro and in vivo. STATEMENT OF SIGNIFICANCE: Because 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 moldable thermosensitive HPCH hydrogel could serve as a promising scaffold for in vitro and in vivo cartilage regeneration with different shapes.
由于自我修复能力差，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。水凝胶一直被认为是一种理想的软骨再生支架。然而，迄今为止，基于水凝胶的体外软骨再生尚未取得满意的效果。本研究探索了基于可模塑的热敏性羟丙基壳聚糖（HPCH）水凝胶进行体外 3D 软骨再生的可行性及其体内命运。制备并表征了热敏性 HPCH 水凝胶。将山羊耳廓软骨细胞包封到 HPCH 水凝胶中形成软骨细胞-水凝胶构建体。将构建体皮下注射到裸鼠体内，或模制成不同形状进行体外软骨生成培养，然后进行体内植入。结果表明，HPCH 水凝胶具有满意的胶凝性能（37°C 时凝胶时间<18s）、生物相容性（一周内细胞数量几乎翻了一番），并且可作为一种可注射的水凝胶用于软骨再生。所有体外培养的构建体基本保持其原始形状（体外到初始：110.8%），并显示出典型的软骨特征，具有丰富的腔隙和软骨特异性基质沉积。这些体外样本随着体内植入时间的延长变得更加成熟，并且在很大程度上保持了原始形状（体内到体外：103.5%）。这些结果表明，可模塑的热敏性 HPCH 水凝胶可作为一种有前途的支架，用于体外和体内具有规定形状的软骨再生。
由于软骨的血管和神经缺乏特征，体外再生在重建软骨功能方面起着重要作用。水凝胶一直被认为是一种理想的软骨再生支架。然而，迄今为止，基于水凝胶的体外软骨再生尚未取得满意的结果。本研究表明，高密度包封在热敏性 HPCH 水凝胶中的软骨细胞所产生的软骨细胞-水凝胶构建体，可以成功地在体外再生出具有规定形状的典型软骨样组织，并在体内植入后进一步成熟为具有原始形状的同质软骨。本研究表明，可模塑的热敏性 HPCH 水凝胶可作为一种有前途的支架，用于体外和体内具有不同形状的软骨再生。
