Cells interact mechanically with their environment, exerting mechanical forces that probe the extracellular matrix (ECM). The mechanical properties of the ECM determine cell behavior and control cell differentiation both in 2D and 3D environments. Gelatin (Gel) is a soft hydrogel into which cells can be embedded. This study shows signifi cant 3D Gel shrinking due to the high traction cellular forces exerted by the cells on the matrix, which prevents cell differentiation. To modulate this process, Gel with hyaluronic acid (HA) has been combined in an injectable crosslinked hydrogel with controlled Gel-HA ratio. HA increases matrix stiffness. The addition of small amounts of HA leads to a signifi cant reduction in hydrogel shrinking after cell encapsulation (C2C12 myoblasts). We show that hydrogel stiffness counterbalanced traction forces of cells and this was decisive in promoting cell differentiation and myotube formation of C2C12 encapsulated in the hybrid hydrogels.
Gelatin–hyaluronic acid (Gel–HA)
hybrid hydrogels
have been proposed as matrices for tissue engineering because of their
ability to mimic the architecture of the extracellular matrix. Our
aim was to explore whether tyramine conjugates of Gel and HA, producing
injectable hydrogels, are able to induce a particular phenotype of
encapsulated human mesenchymal stem cells without the need for growth
factors. While pure Gel allowed good cell adhesion without remarkable
differentiation and pure HA triggered chondrogenic differentiation
without cell spreading, the hybrids, especially those rich in HA,
promoted chondrogenic differentiation as well as cell proliferation
and adhesion. Secretion of chondrogenic markers such as aggrecan,
SOX-9, collagen type II, and glycosaminoglycans was observed, whereas
osteogenic, myogenic, and adipogenic markers (RUNX2, sarcomeric myosin,
and lipoproteinlipase, respectively) were not present after 2 weeks
in the growth medium. The most promising matrix for chondrogenesis
seems to be a mixture containing 70% HA and 30% Gel as it is the material
with the best mechanical properties from all compositions tested here,
and at the same time, it provides an environment suitable for balanced
cell adhesion and chondrogenic differentiation. Thus, it represents
a system that has a high potential to be used as the injectable material
for cartilage regeneration therapies.
In the development of tissue engineering strategies to replace, remodel, regenerate, or support damaged tissue, the development of bioinspired biomaterials that recapitulate the physicochemical characteristics of the extracellular matrix has received increased attention. Given the compositional heterogeneity and tissue-to-tissue variation of the extracellular matrix, the design, choice of polymer, crosslinking, and nature of the resulting biomaterials are normally depended on intended application. Generally, these biomaterials are usually made of degradable or nondegradable biomaterials that can be used as cell or drug carriers. In recent years, efforts to endow reciprocal biomaterial-cell interaction properties in scaffolds have inspired controlled synthesis, derivatization, and functionalization of the polymers used. In this regard, elastin-like recombinant proteins have generated interest and continue to be developed further owing to their modular design at a molecular level. In this review, the authors provide a summary of key extracellular matrix features relevant to biomaterials design and discuss current approaches in the development of extracellular matrix-inspired elastin-like recombinant protein based biomaterials.
Intrinsically disordered protein polymers (IDPPs) have attracted a lot of attention in the development of bioengineered devices and use as molecular biology study models due to their biomechanical properties and stimuli-responsiveness. The present work aims to understand the effect of charge distribution on self-assembly of IDPPs. To that end, a library of recombinant IDPPs based on an amphiphilic diblock design with different charge distributions were bioproduced and their supramolecular assembly characterized on the nano-, meso-and microscale. Although phase transition was driven by the collapse of hydrophobic moieties, hydrophilic block composition strongly affected hierarchical assembly and, therefore, enabled the production of new molecular
Elastin polypeptides
based on -VPGVG- repeated motifs are widely
used in the production of biomaterials because they are stimuli-responsive
systems. On the other hand, glycine-rich sequences, mainly present
in tropoelastin terminal domains, are responsible for the elastin
self-assembly. In a previous study, we have recombinantly expressed
a chimeric polypeptide, named resilin, elastin, and collagen (REC),
inspired by glycine-rich motifs of elastin and containing resilin
and collagen sequences as well. Herein, a three-block polypeptide,
named (REC)
3
, was expressed starting from the previous
monomer gene by introducing key modifications in the sequence. The
choice was mandatory because the uneven distribution of the cross-linking
sites in the monomer precluded the hydrogel production. In this work,
the cross-linked polypeptide appeared as a soft hydrogel, as assessed
by rheology, and the linear un-cross-linked trimer self-aggregated
more rapidly than the REC monomer. The absence of cell-adhesive sequences
did not affect cell viability, while it was functional to the production
of a material presenting antiadhesive properties useful in the integration
of synthetic devices in the body and preventing the invasion of cells.
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