Cartilage Regeneration in Preannealed Silk Elastin-Like Co-Recombinamers Injectable Hydrogel Embedded with Mature Chondrocytes in an Ex Vivo Culture Platform.

Tissue engineering for cartilage repair requires biomaterials that show rapid gelation and adequate mechanical properties. Although the use of hydrogel is the most promising biomaterial, it often lacks in rigidity and anchorage of cells when they are surrounded by synovial fluid while they are subjected to heavy loads. We developed and produced the Silk Elastin-Like co-Recombinamer (SELR), which contains both the physical interaction from elastin motifs and from silk motifs. In the first part of this work, we set up and optimized a preannealing treatment based on the evolution of silk motifs into ß-sheet structures in order to fulfill the required mechanical properties of hydrogels for cartilage repair. The new preannealed SELRs (pA(EIS)2-(I5R)6) were characterized with the combination of several experimental techniques (CD, TEM, SEM, and rheology) to provide a deep insight into the material features. Finally, the regeneration properties of the pA(EIS)2-(I5R)6 hydrogel embedded with chondrocytes were evaluated. After 4 weeks of culturing in a standardized and representative ex vivo model, the biochemical and histological analysis revealed the production of glycosaminglycans and collagen. Moreover, the immunohistochemistry showed the absence of fibro-cartilage and the presence of hyaline cartilage. Hence, we conclude that the pA(EIS)2-(I5R)6 hydrogel presents improved mechanical properties while conserving the injectability, which leads to successful regeneration of hyaline cartilage in an ex vivo model.

Elastin-like polypeptides in drug delivery.

The use of recombinant elastin-like materials, or elastin-like recombinamers (ELRs), in drug-delivery applications is reviewed in this work. Although ELRs were initially used in similar ways to other, more conventional kinds of polymeric carriers, their unique properties soon gave rise to systems of unparalleled functionality and efficiency, with the stimuli responsiveness of ELRs and their ability to self-assemble readily allowing the creation of advanced systems. However, their recombinant nature is likely the most important factor that has driven the current breakthrough properties of ELR-based delivery systems. Recombinant technology allows an unprecedented degree of complexity in macromolecular design and synthesis. In addition, recombinant materials easily incorporate any functional domain present in natural proteins. Therefore, ELR-based delivery systems can exhibit complex interactions with both their drug load and the tissues and cells towards which this load is directed. Selected examples, ranging from highly functional nanocarriers to macrodepots, will be presented.