Anti-inflammatory therapy for cartilage preservation (CartRegen)

ARI Exploratory Research
S Grad, Z Li

Background

Osteoarthritis (OA) is affecting a large proportion of the population and is associated with significant burden on patients and health care systems. Traumatic joint injury is a major risk factor for the development of OA. Early anti-inflammatory and chondroprotective treatment may halt or even reverse the deteriorating process.

Safranin O/Fast Green staining on sections of unstimulated and IL-1β- and TNF-α-stimulated osteochondral explants from human femoral heads. (A) Representative staining images of explants. Scale bars, 200 μm. (B) Safranin O-unstained area normalized to the control group of each donor as 1 (n=3). Means +SD. *p < 0.05, **p < 0.01, ****p < 0.0001.

Goal

The aim is to evaluate the chondroprotective and anti-inflammatory activity of small molecule compounds in an inflammatory 3D pellet culture system and inflammatory osteochondral explant model.

  • Presentation

    Zhang P, Ziadlou R, Basoli V, Li Z, Grad S. In vitro and ex vivo models to test the anti-inflammatory and regenerative effects of small molecules in osteoarthritis. 2020 GR forscht virtual (poster)

    Zhang P, Basoli V, Wang X, Alini M, Grad S, Li Z. Anti-inflammatory and regenerative effects of small molecules for osteoarthritis – in vitro and ex vivo evaluation. 
    2021 ORS virtual (oral)

    Li KH, Zhu Y, Zhang P, Alini M, Grad S, Li Z.Anti-inflammatory and pro-anabolic effects of 5-aminosalicylic acid on inflammatory human osteoarthritic chondrocytes in vitro. 2022 eCM (oral)

    Ossendorff R, Börger V, Wirtz DC, Grad S, Giebel B, Schildberg FA. Extracellular Vesicles (MSC-EV) - influence on cartilage regeneration in osteoarthritic surroundings. 2022 eCM (oral)

     
  • Publication

    Meng X, Ziadlou R, Grad S, Alini M, Wen C, Lai Y, Qin L, Zhao Y, Wang X. Animal Models of Osteochondral Defect for Testing Biomaterials. Biochem Res Int. 2020 Jan 28;2020:9659412. doi: 10.1155/2020/9659412. eCollection 2020

    Ziadlou R, Barbero A, Martin I, Wang X, Qin L, Alini M, Grad S. Anti-Inflammatory and Chondroprotective Effects of Vanillic Acid and Epimedin C in Human Osteoarthritic Chondrocytes. Biomolecules. 2020 Jun 19;10(6):E932. doi: 10.3390/biom10060932.

    Vainieri ML, Alini M, Yayon A, van Osch GJVM, Grad S. Mechanical stress inhibits early stages of endogenous cell migration: a pilot study in an ex vivo osteochondral model. Polymers (Basel). 2020 Aug 6;12(8):1754. doi: 10.3390/polym12081754.

    Meng X, Grad S, Wen C, Lai Y, Alini M, Qin L, Wang X. An impaired healing model of osteochondral defect in papain-induced arthritis. J Orthop Transl 2020.

    Ziadlou R, Rotman S, Teuschl A, Salzer E, Barbero A, Martin I, Alini M, Eglin D, Grad S. Optimization of hyaluronic acid-tyramine/silk-fibroin composite hydrogels for cartilage tissue engineering and delivery of anti-inflammatory and anabolic drugs. Materials Science and Engineering C 2021.

    Zhang P, Liu X, Guo P, Li X, He Z, Li Z, Stoddart MJ, Grad S, Tian W, Chen D, Zou X, Zhou Z, Liu S. Effect of cyclic mechanical loading on immunoinflammatory microenvironment in biofabricating hydroxyapatite scaffold for bone regeneration. Bioact Mater. 2021;6(10):3097-108. https://doi.org/10.1016/j.bioactmat.2021.02.024 

    Li K, Zhang P, Zhu Y, Alini M, Grad S, Li Z. Establishment of an ex vivo inflammatory osteoarthritis model with human osteochondral explants. Front Bioeng Biotechnol. 2021;9:787020. https://dx.doi.org/10.3389/fbioe.2021.787020

    Zhang P, Li K, Kamali A, Ziadlou R, Ahmad P, Wang X, Richards RG, Alini M, Basoli V, Li Z,Grad S. Small molecules of herbal origin for osteoarthritis treatment: In vitro and in vivo evidence. Arthritis Res Ther. 2022;24:105. https://doi.org/10.1186/s13075-022-02785-y

    Du J, Garcia JP, Bach FC, Tellegen AR, Grad S, Li Z, Castelein RM, Meij BP, Tryfonidou MA, Creemers LB. Intradiscal injection of human recombinant BMP-4 does not reverse intervertebral disc degeneration induced by nuclectomy in sheep. J Orthop Translat. 2022;37:23-36. https://doi.org/10.1016/j.jot.2022.08.006 

    Gao M, Liu X, Guo P, Wang J, Li J, Wang W, Stoddart MJ, Grad S, Li Z, Wu H, Li B, He Z, Zhou G, Liu S, Zhu W, Chen D, Zou X, Zhou Z. Deciphering postnatal limb development at single-cell resolution. iScience. 2023;26(1):105808. https://doi.org/10.1016/j.isci.2022.105808 

    Li K, Zhu Y, Zhang P, Alini M, Grad S, Li Z. Anti-inflammatory and pro-anabolic effects of 5-aminosalicylic acid on human inflammatory osteoarthritis models. 
    J Orthop Translat. 2023;38:106-16. https://doi.org/10.1016/j.jot.2022.10.003 

    Vainieri ML, Grad S. Osteochondral Explant Isolation and Culture Under a Compression and Shear Bioreactor. Methods Mol Biol. 2023;2598:325-36. https://www.doi.org/10.1007/978-1-0716-2839-3_23 

    Li K. Establishment of ex vivo osteoarthritis models and their application in the evaluation of the effects of 5-aminosalicylic acid. 2023 Central South University (Z. Li) – PhD Thesis

    Li K, Basoli V, Li Z, Grad S. The importance of mechanical stimulation in cartilage formation: applications of bioreactors. in: Eslaminejad MB, Hosseini S, editors. Cartilage: From Biology to Biofabrication, 2023; Springer Singapore, p. 97-123. https://doi.org/10.1007/978-981-99-2452-3_5 (book chapter)

     

     

     



  • Partner

    Wang X (Prof), Shenzhen Institute of Advanced Technology, Shenzhen, China

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