Physical properties imparted by genipin to chitosan for tissue regeneration with human stem cells: A review

•The quality of genipin (GEN) produced with green technology is instrumentally assessed.•Minor amounts of GEN impart to chitosan (CHI) stability, stiffness, sensitivity to stimuli, fluorescence.•Stem cells, growth factors, morphogenetic proteins are incorporated in CHI | GEN for tissue regeneration.•Enhanced osteogenesis is obtained via osteoblast modulation with CHI | GEN in the presence of inorganics.•Cartilage is regenerated by fibroblasts growing uniformly in porous CHI | GEN | collagen.

Genipin is a fully assessed non-cytotoxic crosslinking compound. The chitosan | genipin physical properties such as morphology, roughness, porosity, hydrophilicity, ζ-potential, surface area and surface energy exert control over cell adhesion, migration, phenotype maintenance and intracellular signaling in vitro, and cell recruitment at the tissue-scaffold interface in vivo. For example a therapy using fucose | chitosan | genipin nanoparticles encapsulating amoxicillin, based on the recognition of fucose by H. pylori, leads to sharply improved clinical results. A bioactive scaffold sensitive to environmental stimuli provides an alternative approach for inducing adipose stem cell chondrogenesis: the expression of specific genes, the accumulation of cartilage-related macromolecules and the mechanical properties are comparable to the original cartilage-derived matrix (CDM), thus making the CDM | genipin a contraction-free biomaterial suitable for cartilage tissue engineering. For the regeneration of the cartilage, chitosan | genipin permits to modulate matrix synthesis and proliferation of chondrocytes by dynamic compression; chondrocytes cultured on the composite substrate produce much more collagen-II and sulfated GAG. The main advantages gained in the bone regeneration area with chitosan | genipin are: acceleration of mineral deposition; enhancement of adhesion, proliferation and differentiation of osteoblasts; promotion of the expression of osteogenic differentiation markers; greatly improved viability of human adipose stem cells.