Spine Lab, Department of Orthopedic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou 310030, China.
Int J Biol Macromol. 2023 Mar 31;232:123479. doi: 10.1016/j.ijbiomac.2023.123479. Epub 2023 Jan 30.
Disc degeneration is the common pathology underlying various degenerative spinal disorders and currently there is no effective cure. Here, we found nucleus pulposus (NP) cell senescence was closely associated with the severity of disc degeneration, and exosomes (Exos) derived from mesenchymal stem cells (MSCs) ameliorated NP cell senescence and promoted extracellular matrix (ECM) deposition. As chitosan-based hydrogels have been widely used as vehicles to deliver Exos due to their prominent antibacterial capacity, biocompatibility, and biodegradability, we developed an Exos-laden hydrogel based on quaternized chitosan (QCS) and oxidized starch (OST) to treat disc degeneration. The synthesized QCS-OST hydrogel is injectable, self-healing, biocompatible, and demonstrated desirable pore size, injectable properties, and sustainable release of Exos. In a rat model of disc degeneration, the QCS-OST/Exos hydrogel was able to rejuvenate NP cell senescence, promote ECM remodeling, and partially restore the structures of NP and annulus fibrosis. Our findings suggested that the novel QCS-OST/Exos hydrogel is an effective therapeutic strategy for treating disc degeneration via alleviating NP cell senescence.
椎间盘退变是各种退行性脊柱疾病的共同病理基础，目前尚无有效的治疗方法。在这里，我们发现髓核（NP）细胞衰老与椎间盘退变的严重程度密切相关，间充质干细胞（MSCs）来源的外泌体（Exos）可改善 NP 细胞衰老并促进细胞外基质（ECM）的沉积。由于壳聚糖基水凝胶具有突出的抗菌能力、生物相容性和可生物降解性，已被广泛用作递送 Exos 的载体，我们开发了一种基于季铵化壳聚糖（QCS）和氧化淀粉（OST）的负载 Exos 的水凝胶来治疗椎间盘退变。合成的 QCS-OST 水凝胶具有可注射性、自修复性、生物相容性，并且表现出理想的孔径、可注射性和 Exos 的可持续释放。在椎间盘退变的大鼠模型中，QCS-OST/Exos 水凝胶能够使 NP 细胞衰老恢复活力，促进 ECM 重塑，并部分恢复 NP 和纤维环的结构。我们的研究结果表明，新型 QCS-OST/Exos 水凝胶是一种通过缓解 NP 细胞衰老来治疗椎间盘退变的有效治疗策略。
