Photo-crosslinked adhesive hydrogel loaded with extracellular vesicles promoting hemostasis and liver regeneration

Wuzheng Xia; Guanzhi Lai; Yichuan Li; Cong Zeng; Chengjun Sun; Pinzhe Zhang; Guanghao Zhu; Leping Li; Linwei Wu

doi:10.3389/fbioe.2023.1170212

Photo-crosslinked adhesive hydrogel loaded with extracellular vesicles promoting hemostasis and liver regeneration

Front Bioeng Biotechnol. 2023 May 10:11:1170212. doi: 10.3389/fbioe.2023.1170212. eCollection 2023.

Authors

Wuzheng Xia¹, Guanzhi Lai^{1

2}, Yichuan Li³, Cong Zeng^{4

5}, Chengjun Sun¹, Pinzhe Zhang^{1

2}, Guanghao Zhu^{1

6}, Leping Li^{1

2}, Linwei Wu^{1

2

6}

Affiliations

¹ Department of Organ Transplantation, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China.
² Shantou University Medical College, Shantou, China.
³ Department of Hepatobiliary and Pancreatic Surgery, People's Hospital of Guang'an City, West China-Guang'an Hospital, Sichuan University, Guang'an, China.
⁴ Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
⁵ Department of General Practice, Hospital of South China Normal University, Guangzhou, China.
⁶ The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.

Abstract

Hepatectomy is an effective surgical method for the treatment of liver diseases, but intraoperative bleeding and postoperative liver function recovery are still key issues. This study aims to develop a composite hydrogel dressing with excellent hemostatic properties, biocompatibility, and ability to promote liver cell regeneration. The modified gelatin matrix (GelMA, 10%) was mixed with equal volumes of sodium alginate-dopamine (Alg-DA) at concentrations of 0.5%, 1%, and 2%. Then a cross-linking agent (0.1%) was added to prepare different composite hydrogels under UV light, named GelMA/Alg-DA-0.5, GelMA/Alg-DA-1 and GelMA/Alg-DA-2, respectively. All the prepared hydrogel has a porous structure with a porosity greater than 65%, and could be stabilized in a gel state after being cross-linked by ultraviolet light. Physicochemical characterization showed that the elastic modulus, water absorption, adhesion, and compressibility of the composite hydrogels were improved with increasing Alg-DA content. Furthermore, the prepared hydrogel exhibits in vitro degradability, excellent biocompatibility, and good hemostatic function. Among all tested groups, the group of GelMA/Alg-DA-1 hydrogel performed the best. To further enhance its application potential in the field of liver regeneration, adipose-derived mesenchymal stem cell exosomes (AD-MSC-Exo) were loaded into GelMA/Alg-DA-1 hydrogel. Under the same conditions, GelMA/Alg-DA-1/Exo promoted cell proliferation and migration more effectively than hydrogels without extracellular vesicles. In conclusion, the prepared GelMA/Alg-DA-1 composite hydrogel loaded with AD-MSC-Exo has great application potential in liver wound hemostasis and liver regeneration.

Keywords: adhesive hydrogel; extracellular vesicles; hemostasis; liver regeneration; tissue repair.