Tannic acid/Sr2+-coated silk/graphene oxide-based meniscus scaffold with anti-inflammatory and anti-ROS functions for cartilage protection and delaying osteoarthritis

Abstract

Tissue engineering method provides a promising solution for meniscus repair and regeneration. However, the inflammatory environment that persists after meniscus injury in the knee joint impedes meniscus tissue regeneration. The purpose of this study was to investigate the applicability of silk/graphene oxide (GO)-based meniscus scaffold modified with tannic acid (TA)/Sr²⁺ coating for the elimination of inflammatory cytokines and reactive oxygen species (ROS) under osteoarthritis (OA) environment along with cartilage protection by using a rat model. The self-assembled coating composed of a series of TA-Sr²⁺ complex concentrations was formed by a facile, rapid, and efficient method on the scaffold. The phenolic hydroxyl groups on the coating endowed the meniscus scaffold with excellent anti-inflammatory and ROS scavenging capacities. We also found that the coating could promote cell migration in a mock wound model and could increase extracellular matrix secretion in vitro. Moreover, the coating components at a certain concentration played an effective role in delaying OA and providing cartilage protection in the rat model. The expression of inflammation cytokines (e.g., IL-6, IL-8, and MMPs) in rat knee tissue was significantly downregulated, and cartilage degeneration and OA damage were also inhibited according to tissue staining results and the OARSI (Osteoarthritis Research Society International) scoring system. Combining these performances, we suggest that this silk/GO-based scaffold modified with TA/Sr²⁺ coating could have broader application prospects by virtue of its effective and user-friendly properties. STATEMENT OF SIGNIFICANCE: The biological properties of the meniscus play a role in activating and regulating the metabolic and inflammatory responses that influence the homeostasis of joint health and ultimately lead to knee osteoarthritis (OA). The inflammation condition of the knee joint may exacerbate the degeneration of meniscus and cartilage. The present study aimed to develop a functional coating composed of tannic acid/Sr²⁺ complex on a silk/graphene oxide-based meniscus scaffold and to endow the scaffold with anti-inflammatory and ROS elimination capacities during the meniscus regeneration process to protect cartilage and delay OA development. The in vitro cytocompatibility study and the in vivo rat OA model study revealed that the coating was effective in promoting cell migration, facilitating ECM secretion, inhibiting inflammation, and delaying OA development.

Keywords: Anti-inflammation/anti-ROS coating; Meniscus tissue engineering; Silk/graphene oxide-based scaffold; Sr ions; Tannic acid.