journal article·2024-12Open access

A Single‐Cell RNA Sequencing Guided Multienzymatic Hydrogel Design for Self‐Regenerative Repair in Diabetic Mandibular Defects

Peihua Lin, Zhouyang Qian, Shanbiao Liu, Xin Ye, Pengpeng Xue, Yangjie Shao, Jing Zhao, Yunan Guan, Zhichao Liu, Yuhua Chen, Qiyue Wang, Zhigao Yi, Mingjian Zhu, Mengfei Yu, Daishun Ling, Fangyuan Li

Advanced Materials· Volume 36· Issue 50

Abstract

Abstract Conventional bone tissue engineering materials struggle to reinstate physiological bone remodeling in a diabetic context, primarily due to the compromised repolarization of proinflammatory macrophages to anti‐inflammatory macrophages. Here, leveraging single‐cell RNA sequencing (scRNA‐seq) technology, the pivotal role of nitric oxide (NO) and reactive oxygen species (ROS) is unveiled in impeding macrophage repolarization during physiological bone remodeling amidst diabetes. Guided by scRNA‐seq analysis, we engineer a multienzymatic bone tissue engineering hydrogel scaffold (MEBTHS) composed is engineered of methylpropenylated gelatin hydrogel integrated with ruthenium nanozymes, possessing both Ru 0 and Ru 4+ components. This design facilitates efficient NO elimination via Ru 0 while simultaneously exhibiting ROS scavenging properties through Ru 4+ . Consequently, MEBTHS orchestrates macrophage reprogramming by neutralizing ROS and reversing NO‐mediated mitochondrial metabolism, thereby rejuvenating bone marrow‐derived mesenchymal stem cells and endothelial cells within diabetic mandibular defects, producing newly formed bone with quality comparable to that of normal bone. The scRNA‐seq guided multienzymatic hydrogel design fosters the restoration of self‐regenerative repair, marking a significant advancement in bone tissue engineering.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Advanced Nanomaterials in Catalysis · Immune cells in cancer · Extracellular vesicles in disease

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Frontiers Science Center for Transformative Molecules School of Chemistry and Chemical Engineering School of Biomedical Engineering National Center for Translational Medicine Zhang Jiang Institute for Advanced Study Shanghai Jiao Tong University Shanghai 200240 China

Songjiang Research Institute Shanghai Key Laboratory of Emotions and Affective Disorders (LEAD) Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 201600 China

Key Laboratory of Oral Biomedical Research of Zhejiang Province Stomatology Hospital School of Stomatology Zhejiang University School of Medicine Hangzhou China

Institute of Pharmaceutics College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China

Suzhou Institute of Biomedical Engineering and Technology Chinese Academy of Science (CAS) Suzhou 215163 China

Funding

National Natural Science Foundation of China · Fundamental Research Funds for the Central Universities · National Key Research and Development Program of China · Natural Science Foundation of Zhejiang Province · Science and Technology Commission of Shanghai Municipality

References (51)

Show source-provided references
1. 10.1038/s41584-022-00887-010.1038/s41584-022-00887-0 ↗
2. 10.1038/s41368-022-00179-z10.1038/s41368-022-00179-z ↗
3. 10.1038/s41574-021-00575-110.1038/s41574-021-00575-1 ↗
4. 10.1016/j.immuni.2021.12.01310.1016/j.immuni.2021.12.013 ↗
5. 10.1038/s41574-019-0286-310.1038/s41574-019-0286-3 ↗
6. 10.1038/s41578-020-0204-210.1038/s41578-020-0204-2 ↗
7. 10.1038/s41578-020-0209-x10.1038/s41578-020-0209-x ↗
8. 10.1038/s41572-021-00289-810.1038/s41572-021-00289-8 ↗
9. 10.1038/s41580-020-00279-w10.1038/s41580-020-00279-w ↗
10. 10.1038/ncb313910.1038/ncb3139 ↗
11. 10.1016/j.actbio.2018.04.00810.1016/j.actbio.2018.04.008 ↗
12. 10.1016/j.bone.2020.11561810.1016/j.bone.2020.115618 ↗
13. 10.1016/j.bioactmat.2022.05.02110.1016/j.bioactmat.2022.05.021 ↗
14. 10.1002/adfm.20200943210.1002/adfm.202009432 ↗
15. 10.1002/advs.20230325910.1002/advs.202303259 ↗
16. 10.1016/j.cell.2022.06.01010.1016/j.cell.2022.06.010 ↗
17. 10.1038/s41467-020-14433-710.1038/s41467-020-14433-7 ↗
18. 10.1016/j.celrep.2016.09.00810.1016/j.celrep.2016.09.008 ↗
19. 10.1126/sciadv.abb738910.1126/sciadv.abb7389 ↗
20. 10.1038/cr.2015.6810.1038/cr.2015.68 ↗
21. 10.1021/acs.nanolett.3c0102310.1021/acs.nanolett.3c01023 ↗
22. 10.1038/cr.2013.610.1038/cr.2013.6 ↗
23. 10.1038/nri.2017.7610.1038/nri.2017.76 ↗
24. 10.1038/s44222-023-00132-710.1038/s44222-023-00132-7 ↗
25. 10.1038/s41573-023-00688-410.1038/s41573-023-00688-4 ↗
26. 10.1002/anie.20201322810.1002/anie.202013228 ↗
27. 10.1007/s10456-007-9084-y10.1007/s10456-007-9084-y ↗
28. 10.1038/s41467-024-46308-610.1038/s41467-024-46308-6 ↗
29. 10.1002/advs.20200411510.1002/advs.202004115 ↗
30. 10.1002/EXP.2021000510.1002/EXP.20210005 ↗
31. 10.1021/acs.analchem.1c0449210.1021/acs.analchem.1c04492 ↗
32. 10.1016/j.cej.2021.12943110.1016/j.cej.2021.129431 ↗
33. 10.1002/smll.20220480910.1002/smll.202204809 ↗
34. 10.1039/C8CS00718G10.1039/C8CS00718G ↗
35. 10.1038/s41467-022-32411-z10.1038/s41467-022-32411-z ↗
36. 10.1021/acs.chemrev.8b0067210.1021/acs.chemrev.8b00672 ↗
37. 10.1016/j.addr.2023.11477810.1016/j.addr.2023.114778 ↗
38. 10.1002/adma.20230038710.1002/adma.202300387 ↗
39. 10.1016/j.biomaterials.2020.11984810.1016/j.biomaterials.2020.119848 ↗
40. 10.1002/smll.20220155810.1002/smll.202201558 ↗
41. 10.1016/j.cej.2021.12854310.1016/j.cej.2021.128543 ↗
42. 10.1021/acsenergylett.2c0020710.1021/acsenergylett.2c00207 ↗
43. 10.1021/acs.jpcc.6b0928010.1021/acs.jpcc.6b09280 ↗
44. 10.3389/fimmu.2022.99045710.3389/fimmu.2022.990457 ↗
45. 10.1016/j.carbpol.2016.08.06810.1016/j.carbpol.2016.08.068 ↗
46. 10.3390/antiox1002031310.3390/antiox10020313 ↗
47. 10.1038/s41578-023-00591-910.1038/s41578-023-00591-9 ↗
48. 10.1016/j.cej.2024.15063110.1016/j.cej.2024.150631 ↗
49. 10.1016/j.drudis.2021.03.00210.1016/j.drudis.2021.03.002 ↗
50. 10.3390/antiox1102031810.3390/antiox11020318 ↗
51. 10.1038/s41581-018-0021-710.1038/s41581-018-0021-7 ↗