Injectable Quercetin-Loaded Hydrogel with Cartilage-Protection and Immunomodulatory Properties for Articular Cartilage Repair

Abstract

Articular cartilage plays an important role in human body. How to repair articular cartilage defects when they appear due to various factors has always been a major clinical challenge. Recently, studies have shown that slowing the degradation of cartilage extracellular matrix (ECM) and modulating the inflammatory response of the host thereby promoting cartilage tissue regeneration are important in the cartilage repair process. In this study, a drug-loaded injectable hydrogel was constructed for repairing articular cartilage. This hydrogel could not only maintain the phenotype of chondrocytes but also regulate the inflammatory response of the host. The injectable sodium alginate (SA)/bioglass (BG) hydrogel was mixed with the injectable thermal-responsive SA/agarose (AG)/quercetin (Que) hydrogel to obtain an injectable hydrogel containing both Que and BG (Que-BG hydrogel) for articular cartilage regeneration. The Que-BG hydrogel has a proper swelling ratio that can promote integration between the formed tissue and host tissue, and it allows Que to release slowly in situ to improve its bioavailability. The Que-BG hydrogel could upregulate SRY-box 9 (SOX9), aggrecan (ACAN), and collagen type II alpha 1 chain (COL2A1) of normal chondrocytes to maintain the normal chondrocyte phenotype. In addition, it could promote macrophage M2 polarization, reduce inflammation, and inhibit ECM degradation by downregulating the expression of inducible nitric oxide synthase (iNOS), matrix metalloproteinase-13 (MMP13), and matrix metalloproteinase-1 (MMP1) in degenerative chondrocytes. After injecting the Que-BG hydrogel into a rat cartilage defect model, the formed tissue was observed to be similar to the normal tissue and was highly integrated with the surrounding tissue. Therefore, the injectable Que-BG hydrogel improves Que bioavailability, maintains chondrocyte phenotype, inhibits ECM degradation, and reduces inflammatory response.

Quercetin modified electrospun PHBV fibrous scaffold enhances cartilage regeneration

“…5 ). The results were consistent with the study on the encapsulation of QUE in hydrogel [ 30 ], suggesting that the chemical modification method did not abolish the functions of QUE. Moreover, the PHBV-g-QUE fibrous scaffold reduced the oxidative stress in chondrocytes and inhibited cell apoptosis by upregulating the transcription of Bcl-2, Nrf2, SOD1, and SOD2 and downregulating the transcription of APAF1 and CASP3 in chondrocytes (Fig.…”

“…Surface modification is an effective way to introduce bioactive substances into the surface of PHBV scaffolds [ 22 , 25 ]. QUE, as a bioactive phytomolecule, exhibits multiple functions, which benefit chondrocytes keeping chondrocytic activity and growth that result in efficient cartilage regeneration [ 30 , 31 , 44 ]. QUE modified PHBV scaffold may display both advantages of PHBV and QUE that make it more applicable in CTE.…”

“…[26][27][28][29]. Importantly, it has been reported that QUE loaded hydrogel maintains the chondrocytic phenotype, inhibits ECM degradation, and delays the progression of OA [30,31]. Hence, it may be a feasible way to improve the bioactivity of PHBV by surface modification with QUE that may significantly promote the regeneration of cartilage.…”

Structural and biological investigation of chitosan/hyaluronic acid with silanized-hydroxypropyl methylcellulose as an injectable reinforced interpenetrating network hydrogel for cartilage tissue engineering

“…Likewise, the quantitative data of fibronectin ( Figure 11(c) ) and elastin ( Figure 11(b) ) significantly enhanced in the CS/HA/Si-HPMC sample treatment when compared to the CS/HA and control groups, which demonstrated improved materials–cell interactions after implantations of prepared host materials. The values of TGFβ, β1, and β2 were estimated through ELISA kit showed comparable ranging results and no very significant difference from the control groups as shown in Figure 11(f) (Asadi et al., 2019 ; Chen et al., 2020 ; Yu et al., 2020 ).…”

Thermo-responsive injectable naringin-loaded hydrogel polymerised sodium alginate/bioglass delivery for articular cartilage

“…Often sport-related trauma and arthritis, birth defects, discomfort or exhaustion, and other causes are caused by articular cartilage defects. With indigenous cartilage modules in the range of 300–800 kPa, mechanical efficiency and structural stability are essential requirements of cartilage scaffold manufacturing (Li et al., 2017 ; Chen et al., 2020 ; Yu et al., 2020 ). Mainly because there are no vascular channels, the conversion of stable chondrocytes into deficient locations and low protein efficiency typical of the adjacent extracellular matrices are inadequate.…”