Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering

• Published in: Biomaterials 2009-12, Vol.30 (36), p.6844-6853
• Main Authors: Tan, Huaping, Ramirez, Christina M, Miljkovic, Natasa, Li, Han, Rubin, J. Peter, Marra, Kacey G
• Format: Article
• Language: English
• Subjects: Acrylic Resins - chemistry; Adipose Tissue - cytology; Adipose Tissue - metabolism; Adipose-derived stem cells; Advanced Basic Science; Animals; Biocompatible Materials - chemistry; Cells, Cultured; Dentistry; Humans; Hyaluronic acid; Hyaluronic Acid - chemistry; Hydrogels - chemistry; Implants, Experimental; Injectable hydrogels; Injections; Materials Testing; Mice; Mice, Nude; Molecular Structure; Polymers - chemistry; Surface Properties; Temperature; Thermosensitive; Tissue Engineering - instrumentation; Tissue Engineering - methods
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2009.08.058

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. 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 by1 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 ∼30 °C by rheological analysis, regardless of the grafting degrees. Enzymatic resistance of AHA-g-PNIPAAm hydrogels with 28% and 53% of PNIPAAm in 100 U/mL hyaluronidase/PBS at 37 °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 °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.