Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering

作者: Huaping Tan , Christina M. Ramirez , Natasa Miljkovic , Han Li , J. Peter Rubin

DOI: 10.1016/J.BIOMATERIALS.2009.08.058

关键词: Polymer chemistryPolymerizationPeptide bondLower critical solution temperatureHyaluronidaseHyaluronic acidMaterials scienceTissue engineeringCopolymerSelf-healing hydrogelsChemical engineering

摘要: Abstract A series of thermosensitive copolymer hydrogels, aminated hyaluronic acid-g-poly(N-isopropylacrylamide) (AHA-g-PNIPAAm), were synthesized by coupling carboxylic end-capped PNIPAAm (PNIPAAm-COOH) to AHA through amide bond linkages. was prepared grafting adipic dihydrazide the HA backbone and PNIPAAm-COOH via a facile thermo-radical polymerization technique NIPAAm using 4,4′-azobis(4-cyanovaleric acid) as an initiator, respectively. The structure AHA-g-PNIPAAm determined 1H NMR. Two copolymers with different weight ratios on applicability injectable hydrogels characterized. lower critical solution temperature (LCST) in PBS measured ∼30 °C rheological analysis, regardless degrees. Enzymatic resistance 28% 53% 100 U/mL hyaluronidase/PBS at 37 °C 12.3% 37.6% over 28 days, Equilibrium swelling 21.5, significantly decreased 13.3 37 °C. Results from SEM observations confirm porous 3D hydrogel interconnected pores after freeze-drying and the pore diameter depends PNIPAAm. Encapsulation human adipose-derived stem cells (ASCs) within showed noncytotoxic preserved viability entrapped cells. preliminary vivo study demonstrated usefulness for adipose tissue engineering. This newly described thermoresponsive attractive properties serve cell or pharmaceutical delivery vehicles variety engineering applications.

参考文章(38)
Li-Qun Wang, Kehua Tu, Yuping Li, Jie Zhang, Liming Jiang, Zhihua Zhang, Synthesis and characterization of temperature responsive graft copolymers of dextran with poly(N-isopropylacrylamide) Reactive and Functional Polymers. ,vol. 53, pp. 19- 27 ,(2002) , 10.1016/S1381-5148(02)00126-8
Yong Doo Park, Nicola Tirelli, Jeffrey A. Hubbell, Photopolymerized hyaluronic acid-based hydrogels and interpenetrating networks Biomaterials. ,vol. 24, pp. 893- 900 ,(2003) , 10.1016/S0142-9612(02)00420-9
Shinichi Ibusuki, Yasuo Fujii, Yukihide Iwamoto, Takehisa Matsuda, Tissue-engineered cartilage using an injectable and in situ gelable thermoresponsive gelatin: fabrication and in vitro performance. Tissue Engineering. ,vol. 9, pp. 371- 384 ,(2003) , 10.1089/107632703764664846
Jeanie L. Drury, David J. Mooney, Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials. ,vol. 24, pp. 4337- 4351 ,(2003) , 10.1016/S0142-9612(03)00340-5
Jennie B. Leach, Kathryn A. Bivens, Chelsea N. Collins, Christine E. Schmidt, Development of photocrosslinkable hyaluronic acid‐polyethylene glycol‐peptide composite hydrogels for soft tissue engineering Journal of Biomedical Materials Research Part A. ,vol. 70, pp. 74- 82 ,(2004) , 10.1002/JBM.A.30063
Qingpu Hou, Paul A. De Bank, Kevin M. Shakesheff, Injectable scaffolds for tissue regeneration Journal of Materials Chemistry. ,vol. 14, pp. 1915- 1923 ,(2004) , 10.1039/B401791A
Tatsuya Shimizu, Masayuki Yamato, Yuki Isoi, Takumitsu Akutsu, Takeshi Setomaru, Kazuhiko Abe, Akihiko Kikuchi, Mitsuo Umezu, Teruo Okano, Fabrication of Pulsatile Cardiac Tissue Grafts Using a Novel 3-Dimensional Cell Sheet Manipulation Technique and Temperature-Responsive Cell Culture Surfaces Circulation Research. ,vol. 90, pp. 363- 363 ,(2002) , 10.1161/HH0302.105722
Alison B. Pratt, Franz E. Weber, Hugo G. Schmoekel, Ralph Müller, Jeffrey A. Hubbell, Synthetic extracellular matrices for in situ tissue engineering. Biotechnology and Bioengineering. ,vol. 86, pp. 27- 36 ,(2004) , 10.1002/BIT.10897
Yong Qiu, Kinam Park, Environment-sensitive hydrogels for drug delivery Advanced Drug Delivery Reviews. ,vol. 53, pp. 321- 339 ,(2001) , 10.1016/S0169-409X(01)00203-4