Chitosan derivatives, and more specifically, glycosylated derivatives, are nowadays attracting much attention within the scientific community due to the fact that this set of engineered polysaccharides finds application in different sectors, spanning from food to the biomedical field. Overcoming chitosan (physical) limitations or grafting biological relevant molecules, to mention a few, represent two cardinal strategies to modify parent biopolymer; thereby, synthetizing high added value polysaccharides. The present review is focused on the introduction of oligosaccharide side chains on the backbone of chitosan. The synthetic aspects and the effect on physical-chemical properties of such modifications are discussed. Finally, examples of potential applications in biomaterials design and drug delivery of these novel modified chitosans are disclosed.
Mounting evidences have recognized that dual cross‐link and double‐network gels can promisingly recapitulate the complex living tissue architecture and overcome mechanical limitations of conventional scaffolds used hitherto in regenerative medicine. Here, dual cross‐link gels formed of a bioactive lactose‐modified chitosan reticulated via both temporary (boric acid‐based) and permanent (genipin‐based) cross‐linkers are reported. While boric acid rapidly binds to lactitol flanking diols increasing the overall viscosity, a slow temperature‐driven genipin binding process takes place allowing for network strengthening. Combination of frequency and stress sweep experiments in the linear stress–strain region shows that ultimate gel strength, toughness, and viscoelasticity depend on polymer‐to‐genipin molar ratio. Notably, herewith it is demonstrated that linear stretching correlates with strain energy dissipation through boric acid binding/unbinding dynamics. Strain‐hardening effect in the nonlinear regime, along with good biocompatibility in vitro, points at an interesting role of present system as biological extracellular matrix substitute.
Natural tissues and extracellular matrices (ECMs) are not purely elastic materials but exhibit dissipative properties. Although it has recently emerged as a novel regulator of cellular responses, the contribution of material dissipation to guiding cell‐fate decisions is still in its infancy. Here, a strategy for tuning the dissipation rate of viscoplastic substrates while precisely regulating linear elasticity is reported. Semi‐interpenetrating substrates consisting of a rigid hydrogel network intertwined with a branched biopolymer are described. The release of these weak physical entanglements under loading dissipates the applied stress and leads to the extension of the linear elasticity. These results reveal a crucial link between this material property and cell response in 2D cultures, impacting cell migration mode and speed, vinculin‐dependent focal adhesion geometry and size, F‐actin organization, the transmission of forces, and Yes‐associated protein nuclear translocation. It is shown that cells require joint actomyosin contractility and microtubule tension to probe the substrate and decide whether or not to adhere, revealing a clear correlation between force transmission, substrate dissipation rate, and amount of anchoring points. Overall, these findings introduce linear elasticity as a novel design parameter for assembling tunable dissipative materials to study cell mechanosensing in 2D and possibly also in 3D cultures.
The present manuscript deals with the elucidation of the mechanism of genipin binding by primary amines at neutral pH. UV-VIS and CD measurements both in the presence of oxygen and in oxygen-depleted conditions, combined with computational analyses, led to propose a novel mechanism for the formation of genipin derivatives. The indications collected with chiral and achiral primary amines allowed interpreting the genipin binding to a lactose-modified chitosan (CTL or Chitlac), which is soluble at all pH values. Two types of reaction and their kinetics were found in the presence of oxygen: (i) an interchain reticulation, which involves two genipin molecules and two polysaccharide chains, and (ii) a binding of one genipin molecule to the polymer chain without chain–chain reticulation. The latter evolves in additional interchain cross-links, leading to the formation of the well-known blue iridoid-derivatives.
Spheroids based on chondrocytes are gaining interest
in the treatment
of injured cartilage tissue due to their regenerative potential. In
this study, chondrocyte-based aggregates were formed by culturing
cells on a polymeric coating of a lactose-modified chitosan (CTL)
and their evolution was followed for 14 days of culture. Morphological
analyses through scanning electron microscopy indicated that these
cell aggregates formed by a process of cell aggregation rather than
proliferation, resulting in structures with an irregular morphology
that were up to 1 mm in size. Chondrocytes interact very closely with
CTL. In the early days of cellular aggregation, CTL is distributed
among the cells, while in later stages, it is localized in the inner
part of the aggregates, forming an amorphous matrix. The initial outer
position of the polymer is replaced over time by an increased matrix
deposition whose main component is type II collagen. Transmission
electron microscopy pointed out that the chondrocytes internalized
the polymer during the first days of culture. The presence of CTL
does not affect the ability of cells to migrate from chondro-aggregates
when transferred to uncoated wells, mimicking the ability of cells
to colonize a cartilage defect. Overall, these results suggest that
CTL plays a role as a temporary matrix for chondrocytes aggregation
during chondro-aggregates formation. This opens up innovative therapeutic
approaches for cartilage regeneration without the need to use a scaffold
to deliver cells to the damaged site.
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