Journalpaper

Developement of a combined drug release and scaffold system for articular cartilage regeneration

Abstract

Degenerative and rheumatic diseases as well as trauma are the main reasons for articular cartilage damage. On its own, cartilage has a limited capacity for organotypic regeneration, which generally results in a mechanically and biologically inferior tissue. Consequently, tissue-engineered cell constructs and scaffold materials are of major interest in regenerative medicine to support the healing process. The chemical, physicochemical, structural, mechanical and biological properties of tissue engineered materials have a high impact on the differentiation and proliferation of seeded cells. Therefore, several strategies exist to design biocompatible scaffolds and to improve their inherent properties. In our own studies we were able to demonstrate that scaffold structure is a key element in successful tissue engineering. Among other structural parameters, the overall porosity, pore directionality and difference between woven and non-woven scaffolds were investigated. Another important scaffold parameter is the chemical composition of the material. To determine the effect of chemical composition, a protein-derived scaffold, a composite scaffold of a protein and a ceramic phase and a commercial synthetic polymer scaffold were investigated. Furthermore, scaffold properties can be enhanced by incorporating active agents to promote cellular differentiation or proliferation. In this report we discuss the prolonged release kinetics of active agents encapsulated in polymeric microspheres, which could be incorporated into tissue engineered scaffolds. Finally, the morphological and histochemical characterization of tissue engineered materials offer a basis for the understanding of the interaction between cells and materials. The most common methodology for the characterization of tissue engineered materials is the evaluation of sectioned and stained specimens, either by conventional histology, by immunohistochemistry or electron microscopy. A new innovative methodology for structural characterization which we have extensively utilized is synchrotron μ-tomography. This methodology is currently exerting increasing impact in the field of tissue engineering. It allows for the complete three-dimensional characterization of biological samples with spatial resolutions below 1.0 μm. In our studies we were able to characterize not only tissue engineered scaffolds for articular cartilage regeneration in their three-dimensional morphological aspects, but also the cellular distribution on cell seeded materials and compare these findings with tomographic data from native tissues. In conclusion, new innovative strategies in tissue engineering and in thecharacterization of tissue engineered materials shows promise in improving cartilage repair strategies.
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