Homogeneously Cross-Linked Scaffolds Based on Clinical-Grade Alginate for Transplantation and Tissue Engineering

Abstract

Transplantation of therapeutic allogenic tissues or genetically manipulated cells without immunosuppression is a promising strategy for the long-term treatment of various hormone deficiencies and neuro-degenerative diseases in human [9, 8, 18]. To achieve this promise, host reactions against the transplants must be prevented by encapsulation in a microcapsule. A major problem of encapsulation is the precise adjustment of the numerous matrix- and host-related parameters to the need of immunoisolation, while not impeding simultaneously the inward transport of nutrients and oxygen and the release of the generated therapeutic factors from the microcapsule core. Numerous animal studies and recent pilot clinical trials have shown the feasibility of alginate-based microcapsules for long-term immunoisolated transplantation [5, 18]. Alginate also has many potential advantages as a tissue engineering matrix [2,14]. The primary challenge in the field of regenerative medicine is to promote formation of missing or non-functioning tissue by transplantation of specialized autologous cells. Repair of articular cartilage lesions by mesenchymal stem cells or chrondrocytes is one of the key applications. In this case, the alginate matrix serves as a three-dimensional scaffold for promotion of re-differentiation and formation of hyaline cartilage by in vitro expanded and de-differentiated cells.

We are very grateful to M. Behringer, P. Geßner and A. Steinbach for skillful technical assistance. This work was supported by grants from the Landesgewerbeanstalt (High-Tech-Offensive des Freistaates Bayern), the Deutsche Forschungsgemeinschaft (DFG, Zi 99/16-1) and the BMBF (VDI 16SV1329) given to U. Z., v\by grants from FONDECYT 1000044 to J.A.V., by grants from the Deutsche Forschungsgemeinschaft (He 2460/4-1) to C. H., by grant from BMBF (VDI 16SV1366/0) to H. Z., and by grants from IBMT to F.V.