Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering.
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. AHA was prepared by grafting adipic dihydrazide to the HA backbone and PNIPAAm-COOH copolymer was synthesized via a facile thermo-radical polymerization technique by polymerization of NIPAAm using 4,4'-azobis(4-cyanovaleric acid) as an initiator, respectively. The structure of AHA and AHA-g-PNIPAAm copolymer was determined by (1)H NMR. Two AHA-g-PNIPAAm copolymers with different weight ratios of PNIPAAm on the applicability of injectable hydrogels were characterized. The lower critical solution temperature (LCST) of AHA-g-PNIPAAm copolymers in PBS were measured as approximately 30 degrees C by rheological analysis, regardless of the grafting degrees. Enzymatic resistance of AHA-g-PNIPAAm hydrogels with 28% and 53% of PNIPAAm in 100U/mL hyaluronidase/PBS at 37 degrees C was 12.3% and 37.6% over 28 days, respectively. Equilibrium swelling ratios of AHA-g-PNIPAAm hydrogels with 28% of PNIPAAm were 21.5, and significantly decreased to 13.3 with 53% of PNIPAAm in PBS at 37 degrees C. Results from SEM observations confirm a porous 3D AHA-g-PNIPAAm hydrogel structure with interconnected pores after freeze-drying and the pore diameter depends on the weight ratios of PNIPAAm. Encapsulation of human adipose-derived stem cells (ASCs) within hydrogels showed the AHA-g-PNIPAAm copolymers were noncytotoxic and preserved the viability of the entrapped cells. A preliminary in vivo study demonstrated the usefulness of the AHA-g-PNIPAAm copolymer as an injectable hydrogel for adipose tissue engineering. This newly described thermoresponsive AHA-g-PNIPAAm copolymer demonstrated attractive properties to serve as cell or pharmaceutical delivery vehicles for a variety of tissue engineering applications.
Division of Plastic Surgery, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Huaping
H
Tan
Christina M
CM
Ramirez
Natasa
N
Miljkovic
Han
H
Li
J Peter
JP
Rubin
Kacey G
KG
Marra
D000180:Acrylic Resins / Q000737:chemistry; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002478:Cells, Cultured; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D020007:Implants, Experimental; D007267:Injections; D008422:Materials Testing; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry*; D013499:Surface Properties; D013696:Temperature; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods
D000180:Acrylic Resins; D001672:Biocompatible Materials; D020100:Hydrogels; D011108:Polymers; C052970:poly-N-isopropylacrylamide; D006820:Hyaluronic Acid