Tannic Acid-Modified Decellularized Tendon Scaffold with Antioxidant and Anti-Inflammatory Activities for Tendon Regeneration.

ABSTRACT

Tendon regeneration is greatly influenced by the oxidant and the inflammatory microenvironment. Persistent inflammation during the tendon repair can cause matrix degradation, tendon adhesion, and excessive accumulation of reactive oxygen species (ROS), while excessive ROS affect extracellular matrix remodeling and tendon integration. Herein, we used tannic acid (TA) to modify a decellularized tendon slice (DTS) to fabricate a functional scaffold (DTS-TA) with antioxidant and anti-inflammatory properties for tendon repair. The characterizations and cytocompatibility of the scaffolds were examined in vitro. The antioxidant and anti-inflammatory activities of the scaffold were evaluated in vitro and further studied in vivo using a subcutaneous implantation model. It was found that the modified DTS combined with TA via hydrogen bonds and covalent bonds, and the hydrophilicity, thermal stability, biodegradability, and mechanical characteristics of the scaffold were significantly improved. Afterward, the results demonstrated that DTS-TA could effectively reduce inflammation by increasing the M2/M1 macrophage ratio and interleukin-4 (IL-4) expression, decreasing the secretion of interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), as well as scavenging excessive ROS in vitro and in vivo. In summary, DTS modified with TA provides a potential versatile scaffold for tendon regeneration.