Development of bioinspired nanocomposite bioinks based on decellularized amniotic membrane and hydroxyethyl cellulose for skin tissue engineering.

Although hydrogels developed based on the decellularized amniotic membrane (dAM) hold great promise for tissue engineering and regenerative medicine, the development of printable bioinks faces serious limitations considering appropriate rheological behavior and shape fidelity after 3D printing. To improve the printability of dAM, we propose that hydroxyethyl cellulose (HEC) and silicate nanoplatelets (Laponite) can be used as a thickening agent and rheology modifier, respectively. It is shown that the Laponite operates as a physical crosslinking agent through reversible non-covalent interactions between nanoplatelets and the biopolymer matrix, thus improving the storage modulus of the bioink from 45 to 277 Pa at 1wt.% concentration. The decrease in pore size of the hydrogel network from 165 ± 45 to 130 ± 46 μm by the addition of 1 wt.% Laponite due to the increased crosslinking density is also observed. The enhanced crosslinking density and viscoelastic properties of hydrogels by the employment of nanoplatelets improved the printability of the bioinks. Nevertheless, the ion-containing HEC-dAM solution is prone to aggregate the silicate nanoplatelets, particularly at high concentrations, which may lead to degraded mechanical moduli (e.g., 125 Pa at 2 wt% concentration). The incorporation of 1 wt% Laponite offers improved biocompatibility by supporting the viability and proliferation of fibroblast cells. The developed nanocomposite bioinks also exhibit a promoting effect on the migration rate of fibroblast cells by about 2 times more than the Laponite-free counterpart, implying their in vitro wound healing potential. Overall, our nanoengineered formulation provides sufficient printability, structural stability, and biocompatibility for commensurate skin tissue engineering applications. [ABSTRACT FROM AUTHOR]