pH-driven continuous stem cell production with enhanced regenerative capacity from polyamide/chitosan surfaces

Chia-Hsiang Yen; Nai-Chen Cheng; Hao-Ying Hsieh; Ching-Wen Tsai; An-Li Lee; Chien-Yi Lu; Yin-Tzu Chen; Tai-Horng Young

doi:10.1016/j.mtbio.2022.100514

pH-driven continuous stem cell production with enhanced regenerative capacity from polyamide/chitosan surfaces

Mater Today Bio. 2022 Dec 7:18:100514. doi: 10.1016/j.mtbio.2022.100514. eCollection 2023 Feb.

Authors

Chia-Hsiang Yen¹, Nai-Chen Cheng², Hao-Ying Hsieh^{1

3}, Ching-Wen Tsai⁴, An-Li Lee^{1

5

6}, Chien-Yi Lu¹, Yin-Tzu Chen¹, Tai-Horng Young^{1

7}

Affiliations

¹ Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Sec. 1, Jen-Ai Rd., Taipei, 100, Taiwan.
² Department of Surgery, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan S Rd., Taipei, 100, Taiwan.
³ Department of Dentistry, National Taiwan University Hospital, No. 7, Chung-Shan S Rd., Taipei, 100, Taiwan.
⁴ Taiwan Instrument Research Institute, National Applied Research Laboratories, No. 20, R&D Rd. VI, Hsinchu Science Park, Hsinchu, 300, Taiwan.
⁵ Department of Plastic and Reconstructive Surgery, MacKay Memorial Hospital, No. 92, Sec. 2, Chung-Shan N Rd., Taipei, 104, Taiwan.
⁶ Department of Medicine, MacKay Medical College, No. 46, Sec. 3, Zhong-Zheng Rd., New Taipei City, 252, Taiwan.
⁷ Department of Biomedical Engineering, National Taiwan University Hospital, No. 7, Chung-Shan S Rd., Taipei, 100, Taiwan.

Abstract

Adipose-derived stem cells (ASCs) have raised significant interest for their potential therapeutic applications in regenerative medicine. However, ASCs usually suffer from decreased pluripotency and functional plasticity during in vitro expansion. Herein, this study sought to develop a continuous cell production system that can mass-produce ASCs with sustained regenerative capacity. The strategy was blending pH-responsive chitosan (CS) with polyamide-66 (PA) to generate combined surface properties with controllable cell growth/detachment ability to achieve a repeated cell production process. From the collected data, all the polymer blends were capable of completing a minimum of four consecutive production cycles, wherein the PA17CS blend (PA:CS $=$ 1:7) outperformed with respect to the working effectiveness (average cell detachment ratio $=$ 88%) and the cell viability. Compared to the trypsin-based method, ASCs harvested from PA17CS exhibited superior stemness characteristics along with SDF-1-mediated CXCR4 chemotactic response for stem cell homing. Moreover, injection of ASCs generated from PA17CS blend could more effectively induce neovascularization and protect skin ﬂaps during an ischemic injury in a rat model.

Keywords: Cell therapy; Continuous cell production; Polyamide-66/chitosan; SDF-1/CXCR4 axis; pH-responsive surface.