4.8 Article

Dynamically Responsive Scaffolds from Microfluidic 3D Printing for Skin Flap Regeneration

Journal

ADVANCED SCIENCE
Volume 9, Issue 22, Pages -

Publisher

WILEY
DOI: 10.1002/advs.202201155

Keywords

3D printing; microfluidics; photothermal; regeneration; scaffold; vascularization

Funding

  1. National Key Research and Development Program of China [2020YFA0908200]
  2. National Natural Science Foundation of China [52073060, 61927805]
  3. Shenzhen Fundamental Research Program [JCYJ20190813152616459, JCYJ20210324133214038]
  4. China Postdoctoral Science Foundation [2021M700141]

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In this study, a responsive MX-HF scaffold is proposed to improve skin flap survival by promoting vascularization and skin flap regeneration. The scaffold demonstrates near-infrared responsiveness through the photothermal conversion capacity of MXene nanosheets and the temperature-responsive ability of poly(NIPAM) hydrogels, facilitating cell penetration into scaffold channels. Additionally, controlled delivery of vascular endothelial growth factor (VEGF) in the scaffold enhances angiogenesis.
Biological scaffolds hold promising perspectives for random skin flap regeneration, while the practical application is greatly limited by their insufficient vascularization ability and the lack of responsiveness during the dynamical healing process. Herein, a novel MXene-incorporated hollow fibrous (MX-HF) scaffold with dynamically responsive channels is presented for promoting vascularization and skin flap regeneration by using a microfluidic-assisted 3D printing strategy. Benefiting from the photothermal conversion capacity of the MXene nanosheets and temperature-responsive ability of poly(NIPAM) hydrogels in the MX-HF scaffolds, they display a near-infrared (NIR)-responsive shrinkage/swelling behavior, which facilitates the cell penetration into the scaffold channels from the surrounding environment. Moreover, by incorporating vascular endothelial growth factor (VEGF) into the hydrogel matrix for controllable delivery, the MX-HF scaffolds can achieve promoted proliferation, migration, and proangiogenic effects of endothelial cells under NIR irradiation. It is further demonstrated in vivo that the NIR-responsive VEGF@MX-HF scaffolds can effectively improve skin flap survival by promoting angiogenesis, decreasing inflammation, and attenuating apoptosis in skin flaps. Thus, it is believed that such responsive MX-HF scaffolds are promising candidates for clinical random skin flap regeneration as well as other diverse tissue engineering applications.

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