Mesenchymal Stem Cell Exosome-Integrated Antibacterial Hydrogels for Nasal Mucosal Injury Treatment

Author:

Li Min12ORCID,Liu Rui1,Chen Guopu1,Wang Handong1,Wang Jinglin1,Kong Bin34,Yu Chenjie12

Affiliation:

1. Department of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.

2. Department of Otolaryngology Head and Neck Surgery, Affiliated Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, Nanjing 210008, China.

3. Guangdong Key Laboratory of Biomedical Measurements and Ultrasound Imaging, Department of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518000, China.

4. Department of Neurosurgery, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong 518035, China.

Abstract

Hydrogels have emerged as appealing prospects for wound healing due to their superior biocompatible qualities. However, the integration of antibacterial active substances into hydrogels for effective wound repair remains challenging. Here, we present a novel double-network hydrogel for nasal mucosal injury repair with antibacterial and self-healing capabilities. This hydrogel is the result of mixing aldehyde polyethylene glycol (PEG) and a carboxymethyl chitosan (CMCS)-based hydrogel with a photocured methylacrylate gelatin (GelMA) hydrogel to envelop mesenchymal stem cell exosomes (MSC-Exos). CMCS is rich in amino groups and facilitates antibacterial repair. Given the dynamically reversible Schiff base connections between the amino group of chitosan and the aldehyde group of modified PEG, the hydrogel can be easily injected into the lesion site because of its excellent injection and shear thinning properties. GelMA introduces an additional network layer for the hydrogel, which enhances its strength and extends the duration of stem cell exosomes on the wound surface. On the basis of these characteristics, we provide evidence that this compound hydrogel can substantially increase cell proliferation and regeneration, inhibit scar hyperplasia, and stimulate angiogenesis in rabbit nasal septum mucosa trauma models. These results suggest that MSC exosome-loaded hydrogels (ME-Gel) have substantial clinical potential for the repair and regeneration of nasal mucosa after surgery or trauma.

Funder

Innovative Research Group Project of the National Natural Science Foundation of China

the Shenzhen Science and Technology Program

Instituto Nacional de Ciência e Tecnologia Centro de Estudos das Adaptações da Biota Aquática da Amazônia

Jiangsu Provincial Medical Key Discipline Laboratory

Postgraduate Research & Practice Innovation Program of Jiangsu Province

Nanjing Medical Science and Technique Development Foundation

the Shenzhen Medical Research Fund

Publisher

American Association for the Advancement of Science (AAAS)

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