Cells-Grab-on Particles: A Novel Approach to Control Cell Focal Adhesion on Hybrid Thermally Annealed Hydrogels

Abstract

Biomaterials engineered with specific cell binding sites, tunable mechanical properties, and complex architectures are essential to control cell adhesion and proliferation. The influence of the local properties, such as the local hardness and stability on the interaction with cells, has not been yet fully understood and exploited. This is particularly relevant for hydrogels, very promising materials with, unfortunately, poor cell adhesion properties, attributed mostly to their softness. Here, we propose a new approach for producing hybrid hydrogels by functionalizing them with particles and performing a thermal treatment. Exploring the interaction of cells with these materials we introduce a new concept, cells-grabbing-onto-particles, a facilitation of the cell adhesion through modulation of local properties. The approach is implemented on alginate hydrogels typically unsuitable for cell growth by turning them into a very effective cell culture growth platform. Specifically, alginate hydrogels are bio-mineralized with calcium carbonate (CaCO3) particles, where an additional thermal annealing (T-A) process has been applied. The local Young’s modulus of new T-A treated hybrid hydrogels has increased to over 3 MPa on areas of hydrogels containing particles and to around 1 MPa on areas without particles, which is drastically different from 130 to 180 kPa values for unmodified hydrogels. Intriguingly, our results show that enhancement of local mechanical properties alone is a necessary, but insufficient, condition; the particles must be stably fixed in gels for cell growth and proliferation. Extended for hydrogels functionalized with silica particles too, the cells-grab-on-particles concept is shown applicable to different materials and cells for cell biology and tissue engineering.

Self‐Assembled Liesegang Rings of Hydroxyapatite for Cell Culturing

“…Deposition of calcium phosphate may increase the stiffness of the sample surface as was show in the similar case with MC3T3‐E1 cells in work. [ 35 ] The second factor is HA that may serve as a source of the Ca 2+ and PO 4 3− for cells and accelerates their proliferation. [ 36–39 ] The cell density is about 30 times higher on the HA rings compared with the agar gel taken as a control one (Figure 7j).…”

Carbon Nanotubes Transform Soft Gellan Gum Hydrogels into Hybrid Organic–Inorganic Coatings with Excellent Cell Growth Capability

“…For example, it is possible to design hybrid materials [11] by incorporating various particles or networks [27], for example, microcapsules [28], bioglass particles [29], hydroxyapatite particles [30,31] calcium, and magnesium carbonate particles [32][33][34][35]. In this case, it is identified that the cell senses the environment and literally "grabs" hard particles at surfaces [33]. An overview of various interfaces allows us to conclude that many particles incorporated into polymeric coatings can promote cell adhesion [36][37][38].…”

Soft Actuated Hybrid Hydrogel with Bioinspired Complexity to Control Mechanical Flexure Behavior for Tissue Engineering

“…Notably, this study implies a significant novelty in the field, as no similar gels with this complexity have been designed or characterized before. We hypothesized that cell interaction can be established by functionalizing the coatings with proteins [ 43 ], while particles in hydrogel coatings can serve for establishing focal adhesion [ 44 , 45 ].…”