Bi-directional cell-pericellular matrix interactions direct stem cell fate

Modifiable hydrogels have revealed tremendous insight into how physical characteristics of cells’ 3D environment drive stem cell lineage specification. However, in native tissues, cells do not passively receive signals from their niche. Instead they actively probe and modify their pericellular space to suit their needs, yet the dynamics of cells’ reciprocal interactions with their pericellular environment when encapsulated within hydrogels remains relatively unexplored. Here, we show that human bone marrow stromal cells (hMSC) encapsulated within hyaluronic acid-based hydrogels modify their surroundings by synthesizing, secreting and arranging proteins pericellularly or by degrading the hydrogel. hMSC’s interactions with this local environment have a role in regulating hMSC fate, with a secreted proteinaceous pericellular matrix associated with adipogenesis, and degradation with osteogenesis. Our observations suggest that hMSC participate in a bi-directional interplay between the properties of their 3D milieu and their own secreted pericellular matrix, and that this combination of interactions drives fate

New trends in the development of multifunctional peptides to functionalize biomaterials

Improving cell-material interactions is a major goal in tissue engineering. In thisregard, functionalization of biomaterials with cell instructive molecules from theextracellular matrix stands out as a powerful strategy to enhance their bioactivity andachieve optimal tissue integration. However, current functionalization strategies, likethe use of native full-length proteins, are associated with drawbacks, thus urging theneed of developing new methodologies. In this regard, the use of synthetic peptidesencompassing specific bioactive regions of proteins represents a promising alterna-tive. In particular, the combination of peptide sequences with complementary or syn-ergistic effects makes it possible to address more than one biological target at thebiomaterial surface. In this review, an overview of the main strategies using peptidesto install multifunctionality on biomaterials is presented, mostly focusing on the com-bination of the RGD motif with other peptides sequences. The evolution of theseapproaches, starting from simple methods, like using peptide mixtures, to moreadvanced systems of peptide presentation, with very well defined chemical proper-ties, are explained. For each system of peptide's presentation, three main aspects ofmultifunctionality—improving receptor selectivity, mimicking the extracellular matrixand preventing bacterial colonization while improving cell adhesion—are highlighted.Peer ReviewedPostprint (published version