Anti-inflammatory therapy for cartilage preservation (CartRegen)
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 intervention after an acute injury may therefore prevent progressive joint deterioration. Cartilage defects occur frequently and predispose the joint to degradation and loss of function. To date no effective treatment is available to preserve cartilage function and joint homeostasis after damage. It is believed that the acute inflammatory response plays a major role in the progression towards the chronic painful condition. Early anti-inflammatory and chondroprotective treatment may halt or even reverse the deteriorating process. We found that small molecule compounds used in Traditional Chinese Medicine (TCM) showed significant anabolic and inflammation preventing effects on human osteoarthritic chondrocytes in vitro.
The aim of this project is to evaluate the chondroprotective and anti-inflammatory activity of these compounds in an inflammatory cartilage explant model under bioreactor controlled mechanical load. Bovine explants and human chondrocytes and explants from osteoarthritic cartilage will be used for compound evaluation. The overall goal is to generate pre-clinical ex vivo data for the use of small molecule compounds for OA prevention and treatment.
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
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)