Su-Hwan Kima,1, Hak Rae Leeb,1, Seung Jung Yub, Min-Eui Hana, Doh Young Leec, Soo Yeon Kimc, Hee-Jin Ahnc, Mi-Jung Hanc, Tae-Ik Leed, Taek-Soo Kimd, Seong Keun Kwonc,2, Sung Gap Imb,2, and Nathaniel S. Hwanga,e,2
aInterdisciplinary Program in Bioengineering, Seoul National University, Seoul 151-742, Republic of Korea;
bDepartment of Chemical and Biomolecular Engineering & KI for the NanoCentury, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea;
cDepartment of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul 110-744, Republic of Korea;
dDepartment of Mechanical Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea;
eSchool of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 151-742, Republic of Korea
Abstract
In this study, we present a method for assembling biofunctionalized paper into a multiform structured scaffold system for reliable tissue regeneration using an origami-based approach. The surface of a paper was conformally modified with a poly(styrene-co-maleic anhydride) layer via initiated chemical vapor deposition followed by the immobilization of poly-l-lysine (PLL) and deposition of Ca2+. This procedure ensures the formation of alginate hydrogel on the paper due to Ca2+ diffusion. Furthermore, strong adhesion of the alginate hydrogel on the paper onto the paper substrate was achieved due to an electrostatic interaction between the alginate and PLL. The developed scaffold system was versatile and allowed area-selective cell seeding. Also, the hydrogel-laden paper could be folded freely into 3D tissue-like structures using a simple origami-based method. The cylindrically constructed paper scaffold system with chondrocytes was applied into a three-ring defect trachea in rabbits. The transplanted engineered tissues replaced the native trachea without stenosis after 4 wks. As for the custom-built scaffold system, the hydrogel-laden paper system will provide a robust and facile method for the formation of tissues mimicking native tissue constructs.
paper scaffolds, origami, tissue engineering, initiated chemical vapor deposition, hydrogel
1S.-H.K. and H.R.L. contributed equally to this work.
2To whom correspondence may be addressed.
Author contributions: S.-H.K., H.R.L., S.G.I., and N.S.H. designed research; S.-H.K., H.R.L., S.J.Y., M.E.H., and S.K.K. performed research; S.J.Y., D.Y.L., S.Y.K., H.-J.A., M.-J.H., T.-I.L., and T.-S.K. contributed new reagents/analytic tools; S.-H.K., H.R.L., S.J.Y., T.-S.K., S.K.K., S.G.I., and N.S.H. analyzed data; and S.-H.K., H.R.L., S.K.K., S.G.I., and N.S.H. wrote the paper.