Regenerative Orthopedics

Research lines

The Tryfonidou group focusses on three research lines:

1. Local controlled drug delivery for prolonged pain relief in joints

Upon an intra-articular or intra-discal application, biomaterials enabling controlled release of anti-inflammatory medication harness inflammation and mitigate pain. Through a unique preclinical platform employing small animal models and ultimately the veterinary patients suffering from osteoarthritis or back pain, we have been able to develop these strategies. 

To feed these strategies with the appropriate biomolecules, we employ developmental biology and the divergence seen within the canine species to identify and validate regenerative targets by means of “omics”. Within this context, we also study how joint distraction facilitates intrinsic cartilage repair.



2. Cell-based therapies to regenerate intervertebral discs and reverse disease

Long-lasting reduction of back pain can only be achieved via regeneration of tissue and restoration of the biomechanical function of the disc. However, stem cell-therapies exert short-lived analgesic effects and do not regenerate the disc. In this research line, we employ notochordal cell biology and their regenerative and anti-inflammatory potential.

Within the H2020 iPSpine consortium, we focus on differentiating induced pluripotent stem cells (iPS) into notochordal cells, the cells that reside in juvenile discs. These iPS-NCs, combined with smart biomaterial, are geared to rejuvenate the degenerate disc. Initial studies in preclinical testing platforms will culminate in a proof-of-concept study in canine patients suffering from chronic back pain.  



3. Personalized 3D-printed implants.

In collaboration with the University Medical Centre and the Field lab 3DMedical we implement personalized implants to treat complicated veterinary orthopaedic cases. In addition, we are currently further developing a safe and straightforward surgical approach to treat hip dysplasia in human and veterinary patients with a personalized 3D-printed titanium implant.  This treatment should prevent the development of debilitating secondary hip osteoarthritis and prevent last resort surgical treatment in severe cases involving femoral head and neck resection or hip joint replacement.








Additional info
Marianna TryfonidouProfessorm.a.tryfonfidou[at]uu.nlPrincipal Investigator, group leader.
Björn MeijProfessorb.p.Meij[at]uu.nlVeterinary orthopedics surgeon. Implement personalized 3D-printed implants for the treatment of hip dysplasia.
Frances BachPostdocf.c.bach[at]uu.nlIVD regeneration strategies with extracellular vesicles derived from notochordal cells, large animal models (H2020 iPSpine project).
Deepani Poramba-LiyanagePostdocd.w.l.porambaliyanage[at]uu.nlepigenetics and iPSC differentiation, single cell sequencing of disc cells (H2020 iPSpine project).
Lizette UtomoScientific Project & Research managerl.utomo[at]uu.nlProject manager for H2020 iPSpine and scientifically involved in the research line: “local controlled drug delivery”.
Joost von HegedusPostdocj.h.vonhegedus[at]uu.nlNew Therapeutic Targets for Osteoarthritis, Equine Musculoskeletal Biology, Lipid Signaling, Cell Biology and Immunology. Involved in William Hunter, Jointsphere, Regmed, Eurostar projects.
Amir KamaliPostdocA.S.Kamali[at]uu.nlBiomimetic disc prosthesis in collaboration with TU/e, BioAID Project
Michelle TeunissenPhD candidatem.teunissen[at]uu.nlchondrogenesis & osteoarthritis, knee joint distraction, canine models (NWO Perspectief; William Hunter Revisited project).
Lisanne LaaglandPhD candidatel.t.laagland[at]uu.nlIVD regeneration strategies with iPSCs and notochordal cells (H2020 iPSpine project).
Josette van MaanenPhD candidatej.c.vanmaanen[at]uu.nlRegenerative and anti-inflammatory effects of extracellular vesicles derived from notochordal cells (H2020 iPSpine project).
Xiaole TongPhD candidatex.tong[at]uu.nlEpigenetics and iPSC differentiation for disc regeneration, iPS-based reporter lines (H2020 iPSpine project).
Frank RiemersBioinformaticianF.M.Riemers[at]uu.nlExpertise in bioinformatics, R programming, single cell RNAseq, and qPCR.
Saskia PlompSenior technicianS.G.M.Plomp[at]uu.nlExpertise in cell culture, histology, immunohistochemistry, biochemical assays
Adel MedzikovicTechniciana.medzikovic[at]uu.nlExpertise in iPS and notochordal cell culture, qPCR, immunofluorescence
Lianne SnelTechnicianl.snel[at]uu.nlExpertise in biomolecular research, iPS cell culture, histology



"Old Drugs, New Tricks" - Local controlled drug release   systems for treatment of degenerative joint disease. Tryfonidou   MA, de Vries G, Hennink WE, Creemers LB. Adv Drug Deliv Rev. 2020 Oct   27;160:170-185.   
Notochordal-cell   derived extracellular vesicles exert regenerative effects on canine and human   nucleus pulposus cells. Bach F, Libregts S, Creemers L, Meij B, Ito K, Wauben   M, Tryfonidou M.
Oncotarget. 2017 Oct 4;8(51):88845-88856. doi:   10.18632/oncotarget.21483.   
Tellegen AR, Dessing AJ, Houben K, Riemers FM, Creemers   LB, Mastbergen SC, et al. Dog as a Model for Osteoarthritis: The FGF4 Retrogene   Insertion May Matter. J Orthop Res.   2019;37(12):2550-60.   
Rudnik-Jansen I, Tellegen AR, Pouran B, Schrijver K,   Meij BP, Emans PJ, et al. Local controlled release of corticosteroids extends   surgically induced joint instability by inhibiting tissue healing. Br J Pharmacol. 2019;176(20):4050-64.   
Tellegen AR, Rudnik-Jansen I, Beukers M, Miranda-Bedate   A, Bach FC, de Jong W, et al. Intradiscal delivery of celecoxib-loaded microspheres   restores intervertebral disc integrity in a preclinical canine model. J Control Release. 2018;286:439-50.   
Bach FC, Tellegen AR, Beukers M, Miranda-Bedate A,   Teunissen M, de Jong WAM, et al. Biologic canine and human intervertebral   disc repair by notochordal cell-derived matrix: from bench towards bedside. Oncotarget. 2018;9(41):26507-26.   
Tellegen AR, Rudnik-Jansen I, Pouran B, de Visser HM,   Weinans HH, Thomas RE, et al. Controlled release of celecoxib inhibits inflammation,   bone cysts and osteophyte formation in a preclinical model of osteoarthritis.   Drug Deliv. 2018;25(1):1438-47.   
Krouwels A, Melchels FPW, van Rijen MHP, Ten Brink CBM,   Dhert WJA, Cumhur Oner F, et al. Focal adhesion signaling affects   regeneration by human nucleus pulposus cells in collagen- but not   carbohydrate-based hydrogels. Acta Biomater.   2018;66:238-47.   
Teunissen M, Riemers FM, van Leenen D, Groot Koerkamp   MJA, Meij BP, Alblas J, et al. Growth plate expression profiling: Large   and small breed dogs provide new insights in endochondral bone formation. J Orthop Res. 2018;36(1):138-48.   





Additional info
Maurits Olthof   
PhD Thesis Defended: 2019   
Imke Rudnik-Jansen   
PhD Thesis Defended: 2019   
Anna Tellegen   
PhD Thesis Defended: 2019   
Anita Krouwels   
PhD Thesis Defended: 2019   
Luc Smolders   
PhD Thesis Defended: 2013   


Contact for internships

Prof. Dr. Marianna Tryfonidou, Principal investigator, m.a.tryfonfidou[at]