MiRNA 24-3p-rich exosomes functionalized DEGMA-modified hyaluronic acid hydrogels for corneal epithelial healing

Xiaomin Sun; Wenjing Song; Lijing Teng; Yongrui Huang; Jia Liu; Yuehai Peng; Xiaoting Lu; Jin Yuan; Xuan Zhao; Qi Zhao; Yingni Xu; Jingjie Shen; Xiaoyun Peng; Li Ren

doi:10.1016/j.bioactmat.2022.07.011

MiRNA 24-3p-rich exosomes functionalized DEGMA-modified hyaluronic acid hydrogels for corneal epithelial healing

Bioact Mater. 2022 Jul 15:25:640-656. doi: 10.1016/j.bioactmat.2022.07.011. eCollection 2023 Jul.

Authors

Xiaomin Sun^{1

2

3

4

5}, Wenjing Song^{1

2

3

4

5}, Lijing Teng⁶, Yongrui Huang^{1

2

3

4

5}, Jia Liu^{1

2

3

4

5}, Yuehai Peng^{2

3

4

5

7}, Xiaoting Lu^{2

3

4

5

7}, Jin Yuan⁸, Xuan Zhao⁸, Qi Zhao^{1

2

3

4

5}, Yingni Xu^{1

2

3

4

5}, Jingjie Shen^{1

2

3

4

5}, Xiaoyun Peng^{1

2

3

4

5}, Li Ren^{1

2

3

4

5

9

10}

Affiliations

¹ School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510006, China.
² National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou, 510006, China.
³ Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou, 510006, China.
⁴ Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, 510006, China.
⁵ Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China.
⁶ School of Biology and Engineering, Guizhou Medical University, Guiyang, Guizhou, 550025, China.
⁷ School of Biological Science and Engineering, South China University of Technology, Guangzhou, 510006, China.
⁸ State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510623, China.
⁹ Sino-Singapore International Joint Research Institute, Guangzhou, 510555, China.
¹⁰ Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, 510005, China.

Abstract

The damage of corneal epithelium may lead to the formation of irreversible corneal opacities and even blindness. The migration rate of corneal epithelial cells directly affects corneal repair. Here, we explored ocu-microRNA 24-3p (miRNA 24-3p) that can promote rabbit corneal epithelial cells migration and cornea repair. Exosomes, an excellent transport carrier, were exacted from adipose derived mesenchymal stem cells for loading with miRNA 24-3p to prepare miRNA 24-3p-rich exosomes (Exos-miRNA 24-3p). It can accelerate corneal epithelial migration in vitro and in vivo. For application in cornea alkali burns, we further modified hyaluronic acid with di(ethylene glycol) monomethyl ether methacrylate (DEGMA) to obtain a thermosensitive hydrogel, also reported a thermosensitive DEGMA-modified hyaluronic acid hydrogel (THH) for the controlled release of Exos-miRNA 24-3p. It formed a highly uniform and clear thin layer on the ocular surface to resist clearance from blinking and extended the drug-ocular-epithelium contact time. The use of THH-3/Exos-miRNA 24-3p for 28 days after alkali burn injury accelerated corneal epithelial defect healing and epithelial maturation. It also reduced corneal stromal fibrosis and macrophage activation. MiRNA 24-3p-rich exosomes functionalized DEGMA-modified hyaluronic acid hydrogel as a multilevel delivery strategy has a potential use for cell-free therapy of corneal epithelial regeneration.

Keywords: Cell migration; Corneal epithelium; Exosome; Thermosensitive hydrogel; miRNA 24-3p.