Local drug delivery in cartilage and disc

Research lines

The articular joint cartilage and the intervertebral disc (IVD) are only partially accessible to therapeutics administered systemically, leading to an unfavourable trade-off between side effects and clinical effectivity. In the ongoing projects, biomaterial-based delivery for inhibition of degeneration and stimulation of regeneration of the IVD and articular cartilage includes small molecules, proteins, peptides and nucleic acids. Carriers vary from hydrogels and microparticles to nanoparticles. Research is done both in vitro and in vivo models, the latter ranging from rat to large animals. In addition to studying proof of concept of different targets and materials, also the mechanisms behind the discrepancy between in vitro and in vivo release is investigated to further the field towards the clinic. To this end, various biochemical, molecular and advanced imaging tools are being used.






Additional info
Joao Marques GarciaPostdocJ.P.MarquesGarcia@umcutrecht.nlIVD bioreactor, development of advanced imaging tools

Jie Du

PhD studentJ.Du-2@umcutrecht.nlIVD regeneration, in vitro and in vivo

Katrin Münzebrock

PhD studentK.A.Munzebrock@umcutrecht.nlNucleic acid delivery for regeneration of cartilage and IVD

Yeter Dilek

PhD studentY.Dilek@ umcutrecht.nlSmall molecule delivery targeting degeneration and pain in IVD

Jaqueline Rios

PostdocJ.L.Rios-2@umcutrecht.nlNanogel-mediated mRNA delivery in osteoarthritis
Carla Jorqueira

PhD student

C.Jorquera@umcutrecht.nlExosome-mediated delivery of miRNA in osteoarthritis
Adriano PontesPhD student (20Med)pontes@20medtx.comNanogel-mediated nucleic acid delivery in cartilage and IVD degeneration



Tryfonidou MA, de Vries G, Hennink WE, Creemers LB. "Old Drugs, New Tricks" - Local controlled drug release systems for treatment of degenerative joint disease. Adv Drug Deliv Rev. 2020 Oct 27;160:170-185
Rudnik-Jansen I, Tellegen AR, Pouran B, Schrijver K, Meij BP, Emans PJ, de Gendt E, Thomas RE, Kik MJL, de Visser HM, Weinans H, Egas A, van Maarseveen E, Woike N, Mihov G, Thies J, Tryfonidou MA, Creemers LB. Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing. Br J Pharmacol. 2019 Oct;176(20):4050-4064.
Garcia JP, Stein J, Cai Y, Riemers F, Wexselblatt E, Wengel J, Tryfonidou M, Yayon A, Howard KA, Creemers LB. Fibrin-hyaluronic acid hydrogel-based delivery of antisense oligonucleotides for ADAMTS5 inhibition in co-delivered and resident joint cells in osteoarthritis. J Control Release. 2019 Jan 28;294:247-258
Krouwels A, Melchels FPW, van Rijen MHP, Ten Brink CBM, Dhert WJA, Cumhur Öner F, Tryfonidou MA, Creemers LB. Focal adhesion signaling affects regeneration by human nucleus pulposus cells in collagen- but not carbohydrate-based hydrogels. Acta Biomater. 2018 Jan 15;66:238-247
Yang HY, van Ee R, Timmer K,  Craenmehr EGM, Huang JH, Öner FC, Dhert WJA, Kragten AHM, Willems N, Grinwis G, Tryfonidou MA, Papen-Botterhuis NE, Creemers LB. A novel injectable thermoresponsive and cytocompatible gel of poly (N-isopropylacrylamide) with layered double hydroxides facilitates siRNA delivery into chondrocytes in 3D culture. Acta Biomaterialia 2015 Sep 1;23:214-28
Vonk LA, Kragten AH, Dhert WJ, Saris DB, Creemers LB. Overexpression of hsa-miR-148a promotes cartilage production and inhibits cartilage degradation by osteoarthritic chondrocytes. Osteoarthritis Cartilage. 2014 Jan;22(1):145-53.


Contact for internships

Principal investigator