Enzymatically Bioactive Nucleus Pulposus Matrix Hydrogel Microspheres for Exogenous Stem Cells Therapy and Endogenous Repair Strategy to Achieve Disc Regeneration
Enzymatically Bioactive Nucleus Pulposus Matrix Hydrogel Microspheres for Exogenous Stem Cells Therapy and Endogenous Repair Strategy to Achieve Disc Regeneration
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酶活性髓核基质水凝胶微球用于外源性干细胞治疗及内源性修复策略实现椎间盘再生
DOI：
10.1002/advs.202304761
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发表时间：
2023-12
期刊：
影响因子：
15.1
通讯作者：
Yizhong Peng;Xuanzuo Chen;Qimin Zhang;Sheng Liu;Wei Wu;Kanglu Li;Hui Lin;Xiangcheng Qing;Yan Xiao;Baichuan Wang;Daping Quan;Shiqing Feng;Zilong Rao;Ying Bai;Zengwu Shao
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文献类型：
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作者：
Yizhong Peng;Xuanzuo Chen;Qimin Zhang;Sheng Liu;Wei Wu;Kanglu Li;Hui Lin;Xiangcheng Qing;Yan Xiao;Baichuan Wang;Daping Quan;Shiqing Feng;Zilong Rao;Ying Bai;Zengwu Shao
外源性干细胞治疗和内源性修复在椎间盘再生中显示出巨大的潜力。然而，有限的营养和乳酸的积累在很大程度上损害了移植干细胞和内源性髓核细胞（NPCs）的存活和再生能力。本研究通过微流控系统将乳酸氧化酶(LOX) -二氧化锰（MnO2）纳米酶（LM）浸入富含葡萄糖的脱细胞髓核水凝胶微球（GDNPs）中，制备了一种可注射水凝胶微球（LMGDNPs）。LMGDNPs表现出LOX的延迟释放特征和令人满意的消耗乳酸的酶促能力。LMGDNPs处理的间充质干细胞（MSCs）比GelMA和脱细胞髓核微球（DNP）处理的间充质干细胞（MSCs）表现出更好的细胞活力，且NPCs表型明显增加。LMGDNPs抑制MSCs和NPCs死亡，并通过释放乳酸促进细胞外基质合成。我们确定LMGDNPs通过激活转化生长因子β2重叠转录物1 (TGFB2‐OT1)，依赖于纳米酶促进npc自噬。在体内，MSCs装载的LMGDNPs在很大程度上保留了椎间盘的水化作用，减轻了基质的降解。综上所述，LMGDNPs通过TGFB2‐OT1及其下游通路提供营养供应、消耗乳酸和激活自噬，从而促进细胞存活和基质再生，可能是外源性干细胞治疗和内源性修复的理想递送系统。
Exogenous stem cell therapy and endogenous repair has shown great potential in intervertebral disc regeneration. However, limited nutrients and accumulation of lactate largely impair the survival and regenerative capacity of implanted stem cells and endogenous nucleus pulposus cells (NPCs). Herein, an injectable hydrogel microsphere (LMGDNPs) have been developed by immersing lactate oxidase (LOX)‐manganese dioxide (MnO2) nanozyme (LM) into glucose‐enriched decellularized nucleus pulposus hydrogel microspheres (GDNPs) through a microfluidic system. LMGDNPs showed a delayed release profile of LOX and satisfactory enzymatic capacity in consuming lactate. Mesenchymal stem cells (MSCs) plated on LMGDNPs exhibited better cell viability than cells on GelMA and decellularized nucleus pulposus microspheres (DNP) and showed a obviously increased NPCs phenotype. LMGDNPs prevented MSCs and NPCs death and promoted extracellular matrix synthesis by exhausting lactate. It is determined that LMGDNPs promoted NPCs autophagy by activating transforming growth factor β2 overlapping transcript 1 (TGFB2‐OT1), relying on the nanozyme. MSCs‐loaded LMGDNPs largely preserved disc hydration and alleviated matrix degradation in vivo. Summarily, LMGDNPs promoted cell survival and matrix regeneration by providing a nutrient supply, exhausting lactate, and activating autophagy via TGFB2‐OT1 and its downstream pathway and may serve as an ideal delivery system for exogenous stem cell therapy and endogenous repair.