Abstract
Fibrin is a protein-based hydrogel formed during blood coagulation. It can also be produced in vitro from human blood plasma, and it is capable of resisting high deformations. However, after each deformation process, it loses high amounts of water, which subsequently makes it mechanically unstable and, finally, difficult to manipulate. The objective of this work was to overcome the in vitro fibrin mechanical instability. The strategy consists of adding silica or chitosan-silica materials and comparing how the different materials electrokinetic-surface properties affect the achieved improvement. The siliceous materials electrostatic and steric stabilization mechanisms, together with plasma protein adsorption on their surfaces, were corroborated by DLS and ζ-potential measurements before fibrin gelling. These properties avoid phase separation, favoring homogeneous incorporation of the solid into the forming fibrin network. Young's modulus of modified fibrin hydrogels was evaluated by AFM to quantitatively measure stiffness. It increased 2.5 times with the addition of 4 mg/mL silica. A similar improvement was achieved with only 0.7 mg/mL chitosan-silica, which highlighted the contribution of hydrophilic chitosan chains to fibrinogen crosslinking. Moreover, these chains avoided the fibroblast growth inhibition onto modified fibrin hydrogels 3D culture observed with silica. In conclusion, 0.7 mg/mL chitosan-silica improved the mechanical stability of fibrin hydrogels with low risks of cytotoxicity. This easy-to-manipulate modified fibrin hydrogel makes it suitable as a wound dressing biomaterial.
Highlights
Obtention of biomaterials from natural polymers that can be used in the wound healing process is an important field of study
Silica (S) and hybrid chitosan-silica (CS) materials were synthesized by the Stober [17] and biomimetic [18] procedures, respectively. ey were characterized by Dynamic Light Scattering (DLS) and ζ-potential, before and after exposure to the precursor of the fibrin hydrogel (67% human plasma, traces of NaCl and tranexamic acid). ese results were the basis for rationalizing the effects of the addition of these materials on the evaluated mechanical characteristics of the fibrin hydrogels and cytotoxicity behavior
Aqueous suspensions of S material exhibited DLS monomodal hydrodynamic diameter distribution (Figures 1(a) and 1(b)) and negative ζ-potential values (Figure 1(d)) at neutral pH. ese characteristics are due to the deprotonated silanol groups in the surface, which caused the electrostatic repulsions between particles [31]. e mean size value was around 261.4 ± 70.1 nm independent of the material concentration (Figure 1(c)), with the highest variation for the 20 mg/mL S suspension. e high variation at this concentration is because the probability of particle collisions increases at a higher concentration due to the less negative ζ value (Figure 1(d))
Summary
Obtention of biomaterials from natural polymers that can be used in the wound healing process is an important field of study. It could be an efficient and cost-effective way to reduce morbidity in wound care around the world, especially in developing countries [1, 2]. Fibrin is a biopolymer of interest in tissue engineering for building grafts that can be used in wound healing. It is formed during a blood coagulation cascade. Functional grafts for wound healing can be obtained by modifying hydrogels with cells [7,8,9], biomolecules such as antioxidants, antimicrobial acids, and peptides [10,11,12] among others
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