Cho, J.H., Kim, S.-H., Park, K.D., Jung, M.C., Yang, W.I., Han, S.W., Noh, J.Y. and Lee, J.W. (2004) Chondrogenic differentiation of human mesenchymal stem cells using a thermosensitive poly(Nisopropylacrylamide) and watersoluble chitosan copolymer. Biomaterials, 25, 5743-5751. doi:10.1016/j.biomaterials.2004.01.051

has been cited by the following article:

• TITLE: Poly(N-isopropylacrylamide-co-N-tert-butylacrylamide)- grafted hyaluronan as an injectable and self-assembling scaffold for cartilage tissue engineering

  AUTHORS: Kazuaki Muramatsu, Yuji Saito, Takuya Wada, Hiroyuki Hirai, Fujio Miyawaki

  KEYWORDS: Thermally Responsive Material; Cartilage Tissue Engineering; Biocompatibility; Mesenchymal Cells

  JOURNAL NAME: Journal of Biomedical Science and Engineering, Vol.5 No.11, November 26, 2012

  ABSTRACT: Novel poly(N-isopropylacrylamide-co-N-tert-butylacrylamide)-grafted hyaluronan [P(NIPAAm-co-NtBAAm)-g-HA] has been developed as a modified derivative to improve phase-transition characteristics of PNIPAAm-g-HA, which has a lower critical solution temperature (LCST) of approximately 32°C. This promising self-assembling biomaterial has potential as an injectable scaffold for in situ cartilage tissue engineering. LCST of the P(NIPAAm-co-NtBAAm)-g-HA decreased to approximately 3.6°C compared to that of the original PNIPAAm-g-HA. This modification enabled self-assembly at body temperatures lower than the temperature of the parental PNIPAAm-g-HA molecule. Cytotoxicity and acute systemic toxicity assays revealed that P(NIPAAm-co-NtBAAm)-g-HA was not hazardous. The DNA content of chondrogenic differentiated mesenchymal stem/stromal cells (MSCs) embedded in the gels was higher than that of biomaterial-free aggregates during the culture periods. Cartilage-related genes were also expressed in chondrogenic differentiated MSCs embedded in the P (NIPAAm-co-NtBAAm)-g-HA hydrogel. Specifically, an increased expression of SRY-related HMG box-containing gene 9 (Sox9) observed in the hydrogel group compared to controls. These data suggest that P(NIPAAm-co-NtBAAm)-g-HA is a promising injectable scaffold with thermoresponsive properties suitable for in situ cartilage tissue engineering.