RESTORE strives towards delaying the onset of osteoartrithis (OA) and design an effective approach to manage the specific unmet clinical needs to treat chondral lesions by developing smart nano-biomaterial-based solutions. One approach this is developed within RESTORE is by using 3D bioprinting for cartilage repair. Results from the RESTORE project using 3D bioprinting in a true OA defect was recently published with the title “ Collagen 2A Type B Induction after 3D Bioprinting Chondrocytes In Situ into Osteoarthritic Chondral Tibial Lesion” in the journal Cartilage and have a high “Altemeric” score from the last three months. This means that the article has reached many readers. The bioink developed in RESTORE has been activated with both nano particles and cells for a result that mimic cartilage. This was recently published with the title “Generating functional cartilage tissue by 3D bioprinting stem cells– A team of Swedish researchers have devised an innovative method to produce functional cartilage by 3D bioprinting stem cells” in the scientific innovation network and You can find the special report article for further reading; https://www.innovationnewsnetwork.com/generating-functional-cartilage-tissue-by-3d-bioprinting-stem-cells/12623/ (Simonsson, 2021)Aggrecan (ACAN) is a protein found in mature cartilage and is also known as AGC1, AGCAN, CSPG1, CSPGCP, MSK16, SEDK, SSOAOD or chondroitin sulphate proteoglycan 1 or cartilage specific protein 1 (CSPCP) and in human coded by the ACAN gene. Its function is to withstand compression in cartilage tissue and the protein is found in the extra cellular matrix (ECM). It is a proteoglycan with a high molecular weight. To differentiate the cells to form cartilage tissue, we found 3 dimensional culture to be superior based on ACAN and collagen type II expression (Figure1) (Gatenholm, Lindahl, Brittberg, & Simonsson, 2020), and we optimized such protocols on a gold nanoparticle gradient that we attached the different growth factors, TGFβ1, TGFβ3, GDF5 or Activin A. These growth factors are known to function as morphogens. Organs and tissues, such as limb and cartilage, are formed early in life through concentration gradients of growth factors. We have recently published our findings with the title “GDF5 induces TBX3 in a concentration dependent manner-on a gold nanoparticle gradient” in the journal Heliyon (Andreasson, Evenbratt, & Simonsson, 2020) and title “Differentiation of induced pluripotent stem cells into definitive endoderm on Activin A-functionalized gradient surfaces.” In the journal Journal of Biotechnology (Andreasson, Evenbratt, Mobini, & Simonsson, 2020, 2021). Finally, RESTORE will be present at the 6th TERMIS (Tissue Engineering and Regenerative Medicine Society) world conference and our submitted abstract has been chosen for oral presentation, Abstract ID:864, Abstract title: “3D bioprinting with rejuventated cells and OA protective nano-ink in shape of an OA lesion”. Hope to see You there in November. https://www.termis.org/wc2021.
Figure1 3D is promoting differentiation of stem cells towards cartilage and increased cartilage specific aggrecan (ACAN) mRNA expression is seen in 3D milieu compare to 2D (Gatenholm et al., 2020).
Andreasson, L., Evenbratt, H., Mobini, R., & Simonsson, S. (2020). Differentiation of induced pluripotent stem cells into definitive endoderm on Activin A-functionalized gradient surfaces. J Biotechnol. doi:10.1016/j.jbiotec.2020.10.030
Andreasson, L., Evenbratt, H., Mobini, R., & Simonsson, S. (2021). Differentiation of induced pluripotent stem cells into definitive endoderm on Activin A-functionalized gradient surfaces. J Biotechnol, 325, 173-178. doi:10.1016/j.jbiotec.2020.10.030
Andreasson, L., Evenbratt, H., & Simonsson, S. (2020). GDF5 induces TBX3 in a concentration dependent manner – on a gold nanoparticle gradient. Heliyon, 6(6), e04133. doi:10.1016/j.heliyon.2020.e04133
Gatenholm, B., Lindahl, C., Brittberg, M., & Simonsson, S. (2020). Collagen 2A Type B Induction after 3D Bioprinting Chondrocytes In Situ into Osteoarthritic Chondral Tibial Lesion. Cartilage, 1947603520903788. doi:10.1177/1947603520903788
Simonsson, S. (Producer). (2021). Generating functional cartilage tissue by 3D bioprinting stem cells. INNOVATION NEWSNETWORK.