Zheng Yi, Xue Borui, Wei Bin, Xia Bing, Li Shengyou, Gao Xue, Hao Yiming, Wei Yitao, Guo Lingli, Wu Haining, Yang Yujie, Gao Xueli, Yu Beibei, Zhang Yongfeng, Yang Shijie, Luo Zhuojing, Ma Teng, Huang Jinghui
Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
School of Ecology and Environment, Northwestern Polytechnical University, Xi'an, 710072, China.
Mater Today Bio. 2023 Jan 3;18:100535. doi: 10.1016/j.mtbio.2022.100535. eCollection 2023 Feb.
The repair of annulus fibrosus (AF) defect after discectomy in the intervertebral disc (IVD) has presented a challenge over the past decade. Hostile microenvironments in the IVD, including, compression and hypoxia, are critical issues that require special attention. Till date, little information is available on potential strategies to cope with the hypoxia dilemma in AF defect sites. In this study, perfluorotributylamine (PFTBA) core-shell fibers were fabricated by coaxial electrospinning to construct oxygen-releasing scaffold for promoting endogenous repair in the AF after discectomy. We demonstrated that PFTBA fibers (10% chitosan, chitosan: PCL, 1:6) could release oxygen for up to 144 h. The oxygen released from PFTBA fibers was found to protect annulus fibrosus stem cells (AFSCs) from hypoxia-induced apoptosis. In addition, the PFTBA fibers were able to promote proliferation, migration and extracellular matrix (ECM) production in AFSCs under hypoxia, highlighting their therapeutic potential in AF defect repair. Subsequent studies demonstrated that oxygen-supplying fibers were capable of ameliorating disc degeneration after discectomy, which was evidenced by improved disc height and morphological integrity in rats with the oxygen-releasing scaffolds. Further transcriptome analysis indicated that differential expression genes (DEGs) were enriched in "oxygen transport" and "angiogenesis", which likely contributed to their beneficial effect on endogenous AF regeneration. In summary, the oxygen-releasing scaffold provides novel insights into the oxygen regulation by bioactive materials and raises the therapeutic possibility of oxygen supply strategies for defect repair in AF, as well as other aerobic tissues.
在过去十年中,椎间盘(IVD)切除术之后纤维环(AF)缺损的修复一直是一项挑战。IVD中的不利微环境,包括压迫和缺氧,是需要特别关注的关键问题。迄今为止,关于应对AF缺损部位缺氧困境的潜在策略的信息很少。在本研究中,通过同轴静电纺丝制备了全氟三丁胺(PFTBA)核壳纤维,以构建用于促进椎间盘切除术后AF内源性修复的释氧支架。我们证明PFTBA纤维(10%壳聚糖,壳聚糖:聚己内酯,1:6)可以释放氧气长达144小时。发现从PFTBA纤维释放的氧气可保护纤维环干细胞(AFSCs)免受缺氧诱导的凋亡。此外,PFTBA纤维能够在缺氧条件下促进AFSCs的增殖、迁移和细胞外基质(ECM)产生,突出了它们在AF缺损修复中的治疗潜力。随后的研究表明,供氧纤维能够改善椎间盘切除术后的椎间盘退变,这在植入释氧支架的大鼠中通过椎间盘高度和形态完整性的改善得到证明。进一步的转录组分析表明,差异表达基因(DEGs)在“氧转运”和“血管生成”中富集,这可能有助于它们对AF内源性再生的有益作用。总之,释氧支架为生物活性材料的氧调节提供了新的见解,并提高了供氧策略对AF以及其他需氧组织缺损修复的治疗可能性。