Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue engineering

Abstract

A series of thermosensitive copolymer hydrogels, aminated hyaluronic acid-g-poly(Nisopropylacrylamide) (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-gPNIPAAm 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 ~30°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°C was 12.3% and 37.6% over 28 days, respectively. Equilibrium swelling ratios of AHA-gPNIPAAm 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-gPNIPAAm 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.

Enhanced and sustained topical ocular delivery of cyclosporine A in thermosensitive hyaluronic acid-based in situ forming microgels

“…20 As shown in the spectrum, the peaks at 1.1 ppm ( Figure 3C) and 3.9 ppm ( Figure 3D) are assigned to −CH 3 and −NH-groups, respectively. The DS values of PNIPAAm controlled by the feed mole ratio of PNIPAAm-COOH are shown in Table 1.…”

“…A prior study has demonstrated the usefulness of hyaluronic acid-g-poly(N-isopropylacrylamide) (HAg-PNIPAAm) microgels as an injectable hydrogel for adipose tissue engineering. 20 However, as far as we know, very little work has been done regarding the use of HA-g-PNIPAAm microgels for ophthalmic application.…”

Evaluation of Alginate and Hyaluronic Acid for Their Use in Bone Tissue Engineering

“…Its high, tissue-like water content and porous structure allows the influx of low molecular weight solutes and nutrients crucial to cellular viability, as well as the transport of cellular waste out of the hydrogel [3]. As biomaterials, the use of injectable hydrogels also allows the administration of the material through minimally invasive techniques, to fill any area with a good physical integration into the defect, to incorporate cells or various therapeutic agents (e.g., growth factors) with a facile and homogenous distribution within any defect [4][5][6][7]. Therefore, hydrogels have been identified to be suitable as bone and cartilage repair materials because they can be carriers for growth and morphogenetic factors to exert host cell chemotaxis, proliferation, differentiation and new tissue formation at the site of injury or defect [8].…”

Regeneration of Pulp/Dentin-Like Tissue in Immature Necrotic Permanent Dog Teeth Using Adipose Tissue-Derived Mesenchymal Stem Cells

“…Furthermore, they can be processed under relatively mild conditions and delivered in a minimally invasive manner. Chitosan also inhibits the growth of many types of fungi, yeasts, and bacteria [35][36][37][38]. All these features make it an attractive option for several applications, such as in food and nutrition, medicine, microbiology, immunology, agriculture, and veterinary medicine.…”