Eric de Mulder graduated 2013 June 10th, after which he left the ORL.
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To Thesis: Meniscus Tissue Engineering
T: +31 (0)
I graduated in dec 2007 as Master of Science in biomedical sciences at the Radboud University Nijmegen. In april 2008 I started as a phd-student at the ORL.
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Due to trauma’s, mainly as a result of sports activities, menisci can get torn. In addition, with increasing age degenerative changes might occur. In the past (partial) menisectomy was performed, however in time this leads to osteoarthritis. Since the avascularity of the meniscus affects its self-repair capacity, there is an increasing demand for total meniscus replacement. There are limited options available, namely, meniscus transplantation (allo- and xenografts) and scaffolds for the partial replacement of the damaged meniscus (ACTIfit™ and Menaflex™). However, allografts are poorly available and for the available implants based on scaffolds the long-term cartilage protection is unknown. To avoid the limitations related to the replacement techniques mentioned above, our long-term aim is to generate a completely new meniscus by tissue engineering.
In general, tissue engineered constructs should, in time, result in a copy of the original tissue. As mentioned above, the native meniscus is an anisotropic tissue. However, to our best knowledge the meniscus scaffolds described in literature are all isotropic porous scaffolds. To generate a meniscus like tissue, this would involve degradation of the scaffold and, if possible, reorientation of the extracellular matrix (ECM) to an anisotropic structure. To bypass this reorientation of the ECM we propose a conceptual negative anisotropic scaffold for tissue engineering.
The proposed scaffold would be semilunar, wedge shaped. Instead of an isotropic porous structure, the scaffold has no macropores but macrotubular channels in a circumferential direction (as the orientation of collagen type I fibers in the native meniscus). Based on the diameter of the collagen fibers in the meniscus we propose an optimal diameter of these channels between 100 and 300 microns with interconnected micropores of 30 microns (Fig 1). This will allow a fast tissue ingrowth where collagen will be guided into the circumferential channels, similar to the native meniscus.
Pre-seeding a scaffold with meniscal cells can lead into an increased incorporation of the scaffold into the body. With dynamic cell seeding and bioreactor culture techniques it is possible to control and direct ECM production. By adding growth factors, i.e. TGF-β1, IGF-1, FGF, PDGF-AB, cell proliferation and ECM production can be increased. Incorporation of growth factors into the scaffold by collagen and heparin binding/cross-linking can lead to a controlled slow release of growth factors, thereby enhancing tissue and/ or ECM formation. In summary, we propose that a negative anisotropic scaffold with circumferential macrotubules could be ideal for meniscus tissue engineering. When cell-seeded, growth factor loaded, scaffolds are cultured in bioreactors it could be possible to direct and enhance neotissue formation. Ultimately, the construct would closely resemble the native meniscus.
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