Improvement of long-term drug release and design of mechanically more stable encapsulation devices are still major challenges in the field of cell encapsulation. This may be in part due to the weak in vivo stability of calcium-alginate beads and to the use of inactive biomaterials and inert scaffolds that do not mimic the physiological situation of the normal cell milieu. We hypothesized that designing biomimetic cell-hydrogel capsules might promote the in vivo long-term functionality of the enclosed drug-secreting cells and improve the mechanical stability of the capsules. Biomimetic capsules were fabricated by coupling the adhesion peptide arginine glycine aspartic acid (RGD) to alginate polymer chains and by using an alginate-mixture providing a bimodal molecular weight distribution. The biomimetic capsules provide cell adhesion for the enclosed cells, potentially also leading to mechanical stabilization of the cell-polymer system. Strikingly, the novel cell-hydrogel system significantly prolonged the in vivo long-term functionality and drug release, providing a sustained erythropoietin delivery during 300 days without immunosuppressive protocols. Additionally, controlling the cell-dose within the biomimetic capsules enables a controlled in vitro and in vivo drug delivery. Biomimetic cell-hydrogel capsules provide a unique microenvironment for the in vivo long-term de novo delivery of drugs from immobilized cells.
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