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Microengineered 3D cell‐laden thermoresponsive hydrogels for mimicking cell morphology and orientation in cartilage tissue engineering
Author(s) -
Mellati Amir,
Fan ChiaMing,
Tamayol Ali,
Annabi Nasim,
Dai Sheng,
Bi Jingxiu,
Jin Bo,
Xian Cory,
Khademhosseini Ali,
Zhang Hu
Publication year - 2017
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.26061
Subject(s) - self healing hydrogels , chondrogenesis , cartilage , tissue engineering , mesenchymal stem cell , chemistry , glycosaminoglycan , biomedical engineering , biophysics , materials science , nanotechnology , microbiology and biotechnology , anatomy , polymer chemistry , biology , biochemistry , medicine
Mimicking the zonal organization of native articular cartilage, which is essential for proper tissue functions, has remained a challenge. In this study, a thermoresponsive copolymer of chitosan‐g‐poly(N‐isopropylacrylamide) (CS‐g‐PNIPAAm) was synthesized as a carrier of mesenchymal stem cells (MSCs) to provide a support for their proliferation and differentiation. Microengineered three‐dimensional (3D) cell‐laden CS‐g‐PNIPAAm hydrogels with different microstripe widths were fabricated to control cellular alignment and elongation in order to mimic the superficial zone of natural cartilage. Biochemical assays showed six‐ and sevenfold increment in secretion of glycosaminoglycans (GAGs) and total collagen from MSCs encapsulated within the synthesized hydrogel after 28 days incubation in chondrogenic medium. Chondrogenic differentiation was also verified qualitatively by histological and immunohistochemical assessments. It was found that 75 ± 6% of cells encapsulated within 50 μm wide microstripes were aligned with an aspect ratio of 2.07 ± 0.16 at day 5, which was more organized than those observed in unpatterned constructs (12 ± 7% alignment and a shape index of 1.20 ± 0.07). The microengineered constructs mimicked the cell shape and organization in the superficial zone of cartilage whiles the unpatterned one resembled the middle zone. Our results suggest that microfabrication of 3D cell‐laden thermosensitive hydrogels is a promising platform for creating biomimetic structures leading to more successful multi‐zonal cartilage tissue engineering. Biotechnol. Bioeng. 2017;114: 217–231. © 2016 Wiley Periodicals, Inc.