<p>Newly emerging 3D bioprinting technologies promise appealing prospects for regenerative medicine, but they still need solutions of some bottleneck problems such as the vascularization of printed tissues. Here, we propose a novel concept of “sacrificial” 3D bioprinting, enabling the production of tissue structures with complex geometries. For this purpose, HEK293T cell spheroids were grown in the presence or absence of photoactive LaB<sub>6</sub> or Ti<sub>3</sub>AlC<sub>2</sub> nanoparticles, prepared by methods of pulsed laser ablation in liquids, and assembled together to form a flower-like tissue construct. Then, the whole tissue construct was irradiated by a near infrared (NIR-I) laser radiation to locally induce death of nanoparticles-loaded spheroid in the center of the construct and eliminate it from the structure. We found that the nanoparticle-loaded spheroids experienced photothermally induced overheating under laser irradiation leading to their death, while the nanoparticles themselves demonstrated a very low toxicity. An increase of Young’s modulus of spheroids improved their elimination from the construct, which rendered possible the creation of flower-like complex tissues structures with a void in the center. When arranged in a line, such voids can be used to engineer complex tissue structures such as vascular constructs. The proposed “sacrificial” concept opens new directions for 3D bioprinting of biological tissues.</p> Graphical Abstract <p></p>

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Smart Engineering of Complex Structural Tissue Constructs in 3D Bioprinting Via Photoinduced Nanoparticle-Mediated Spheroid Elimination

  • Artem Iliasov,
  • Arina Baranova,
  • Gleb Tikhonowski,
  • Elizaveta Koudan,
  • Ivan V. Zelepukin,
  • Anton A. Popov,
  • Daniil Tselikov,
  • Gleb Tselikov,
  • Alexey Kopylov,
  • Ekaterina Gosteva,
  • Vladimir Mironov,
  • Sergey M. Deyev,
  • Sergey M. Klimentov,
  • Andrei V. Kabashin

摘要

Newly emerging 3D bioprinting technologies promise appealing prospects for regenerative medicine, but they still need solutions of some bottleneck problems such as the vascularization of printed tissues. Here, we propose a novel concept of “sacrificial” 3D bioprinting, enabling the production of tissue structures with complex geometries. For this purpose, HEK293T cell spheroids were grown in the presence or absence of photoactive LaB6 or Ti3AlC2 nanoparticles, prepared by methods of pulsed laser ablation in liquids, and assembled together to form a flower-like tissue construct. Then, the whole tissue construct was irradiated by a near infrared (NIR-I) laser radiation to locally induce death of nanoparticles-loaded spheroid in the center of the construct and eliminate it from the structure. We found that the nanoparticle-loaded spheroids experienced photothermally induced overheating under laser irradiation leading to their death, while the nanoparticles themselves demonstrated a very low toxicity. An increase of Young’s modulus of spheroids improved their elimination from the construct, which rendered possible the creation of flower-like complex tissues structures with a void in the center. When arranged in a line, such voids can be used to engineer complex tissue structures such as vascular constructs. The proposed “sacrificial” concept opens new directions for 3D bioprinting of biological tissues.

Graphical Abstract