Many mammalian tissues adopt a specific cellular arrangement under stress stimulus that enables their unique function. However, conventional 3D encapsulation often fails to recapitulate the complexities of these arrangements, thus motivating the need for advanced cellular arrangement approaches. Here, an original 3D prestress bioprinting approach of directed tissues under the synergistic effect of static sustained tensile stress and molecular chain orientation, with an aid of slow crosslinking in bioink, is developed. The semi-crosslinking state of the designed bioink exhibits excellent elasticity for applying stress on the cells during the sewing-like process. After bioprinting, the bioink gradually forms complete crosslinking and keeps the applied stress force to induce cell-orientated growth. More importantly, multiple cell types can be arranged directionally by this approach, while the internal stress of the hydrogel filament is also adjustable. In addition, compared with conventional bioprinted skin, the 3D prestress bioprinted skin results in a better wound healing effect due to promoting the angiogenesis of granulation tissue. This study provides a prospective strategy to engineer skeletal muscles, as well as tendons, ligaments, vascular networks, or combinations thereof in the future.
Keywords: 3D bioprinting; cellular arrangement; controlled mechanical stimulation.
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