Huang Chongquan, Zhong Guoqing, Xiao Jin, Wang Xiaolan, Huang Weijuan, Chen Lingyun, Zhang Yu, Cheng Shi
Department of Orthopedics, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China.
Bioengineering (Basel). 2025 Apr 22;12(5):434. doi: 10.3390/bioengineering12050434.
Cartilage defects and injuries often lead to osteoarthritis, posing significant challenges for cartilage repair. Traditional treatments have limited efficacy, necessitating innovative therapeutic strategies. This study aimed to develop an injectable hydrogel-based tissue engineering construct to enhance cartilage regeneration by combining mesenchymal stem cells (MSCs) and the small molecule drug kartogenin (KGN).
An injectable hydrogel was synthesized by crosslinking carboxymethyl chitosan (CMC) with aldehyde-modified cellulose nanocrystals (DACNCs). KGN was incorporated into the hydrogel during crosslinking to achieve sustained drug release. Three hydrogels with varying CMC/DACNC molar ratios (MR = 0.11, 0.22, and 0.33) were developed and characterized for their structural, mechanical, and biocompatible properties. The hydrogel with the optimal ratio (MR = 0.33) was further evaluated for its ability to support MSC viability and differentiation in vitro. Additionally, signaling pathways (TGF-β, FOXO, and PI3K-AKT) were investigated to elucidate the underlying mechanisms. In vivo efficacy was assessed using a rabbit femoral trochlear cartilage defect model.
The hydrogel with a higher CMC/DACNC molar ratio (MR = 0.33) exhibited increased compressive modulus, a reduced swelling rate, and superior biocompatibility, effectively promoting MSC differentiation in vitro. Signaling pathway analysis revealed activation of the TGF-β, FOXO, and PI3K-AKT pathways, suggesting enhanced chondrogenic potential. In vivo experiments demonstrated that the KGN-MSC-encapsulated hydrogel significantly improved cartilage repair.
The injectable CMC/DACNC hydrogel, combined with KGN and MSCs, synergistically enhanced cartilage regeneration both in vitro and in vivo. This study highlights the potential of this hydrogel as a promising scaffold for cartilage tissue engineering, offering a novel therapeutic approach for cartilage defects and injuries.
软骨缺损和损伤常导致骨关节炎，给软骨修复带来重大挑战。传统治疗方法疗效有限，因此需要创新的治疗策略。本研究旨在开发一种基于可注射水凝胶的组织工程构建体，通过将间充质干细胞（MSCs）与小分子药物卡托金（KGN）相结合来增强软骨再生。
通过羧甲基壳聚糖（CMC）与醛基修饰的纤维素纳米晶体（DACNCs）交联合成可注射水凝胶。在交联过程中将KGN掺入水凝胶中以实现药物的持续释放。制备了三种具有不同CMC/DACNC摩尔比（MR = 0.11、0.22和0.33）的水凝胶，并对其结构、力学和生物相容性进行了表征。对具有最佳比例（MR = 0.33）的水凝胶进一步评估其在体外支持MSCs活力和分化的能力。此外，研究了信号通路（TGF-β、FOXO和PI3K-AKT）以阐明潜在机制。使用兔股骨滑车软骨缺损模型评估体内疗效。
具有较高CMC/DACNC摩尔比（MR = 0.33）的水凝胶表现出更高的压缩模量、更低的溶胀率和更好的生物相容性，有效地促进了体外MSCs的分化。信号通路分析显示TGF-β、FOXO和PI3K-AKT通路的激活，表明软骨生成潜力增强。体内实验表明，包裹KGN-MSCs的水凝胶显著改善了软骨修复。
可注射的CMC/DACNC水凝胶与KGN和MSCs相结合，在体外和体内均协同增强了软骨再生。本研究突出了这种水凝胶作为软骨组织工程有前景的支架的潜力，为软骨缺损和损伤提供了一种新的治疗方法。
