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. 2022 Feb;34(5):e2106564.
doi: 10.1002/adma.202106564. Epub 2021 Dec 16.

Self-Healing Hydrogel Embodied with Macrophage-Regulation and Responsive-Gene-Silencing Properties for Synergistic Prevention of Peritendinous Adhesion

Chuandong Cai  1 , Xinshu Zhang  1 , Yuange Li  1 , Xuanzhe Liu  1 , Shuo Wang  1 , Mingkuan Lu  1 , Xiong Yan  2 , Lianfu Deng  3 , Shen Liu  1 , Fei Wang  3 , Cunyi Fan  1
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Self-Healing Hydrogel Embodied with Macrophage-Regulation and Responsive-Gene-Silencing Properties for Synergistic Prevention of Peritendinous Adhesion

Chuandong Cai et al. Adv Mater. 2022 Feb.

Abstract

Antiadhesion barriers such as films and hydrogels used to wrap repaired tendons are important for preventing the formation of adhesion tissue after tendon surgery. However, sliding of the tendon can compress the adjacent hydrogel barrier and cause it to rupture, which may then lead to unexpected inflammation. Here, a self-healing and deformable hyaluronic acid (HA) hydrogel is constructed as a peritendinous antiadhesion barrier. Matrix metalloproteinase-2 (MMP-2)-degradable gelatin-methacryloyl (GelMA) microspheres (MSs) encapsulated with Smad3-siRNA nanoparticles are entrapped within the HA hydrogel to inhibit fibroblast proliferation and prevent peritendinous adhesion. GelMA MSs are responsively degraded by upregulation of MMP-2, achieving on-demand release of siRNA nanoparticles. Silencing effect of Smad3-siRNA nanoparticles is around 75% toward targeted gene. Furthermore, the self-healing hydrogel shows relatively attenuated inflammation compared to non-healing hydrogel. The mean adhesion scores of composite barrier group are 1.67 ± 0.51 and 2.17 ± 0.75 by macroscopic and histological evaluation, respectively. The proposed self-healing hydrogel antiadhesion barrier with MMP-2-responsive drug release behavior is highly effective for decreasing inflammation and inhibiting tendon adhesion. Therefore, this research provides a new strategy for the development of safe and effective antiadhesion barriers.

Keywords: hydrogels; macrophages; responsive-gene-silencing properties; self-healing hydrogels; tendons.

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