Tailoring Thermoreversible Hyaluronan Hydrogels by “Click” Chemistry and RAFT Polymerization for Cell and Drug Therapy

Abstract

Thermoreversible hydrogels are promising matrices for tissue-engineered cartilage and spine constructs. They require specific properties during all the stages of a cell therapy (e.g., cell expansion, recovery, injection, delivery). Thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HA-PNIPAM) hydrogels with well-defined molecular architecture and properties were synthesized through RAFT polymerization and "click" chemistry. The effect of PNIPAM grafting length and density on HA-PNIPAM properties was evaluated by methods relevant for a cell therapy. It was found that reversibility of the PNIPAM gelling process was improved in the presence of HA. Increasing M(n) of PNIPAM decreased the viscosity at 20 degrees C and led to high G' at T > 30 degrees C; however, higher grafting density led to lower mechanical properties. Water uptake of the hydrogels was mainly dependent on PNIPAM M(n). All of the hydrogels and their degradation products were cytocompatible to hTERT-BJ1 fibroblasts. A composition with properties ideal for cell encapsulation was identified and characterized by a low viscosity at 20 degrees C, rapid gelling at 37 degrees C, absence of volume change upon gelling, and G' of 140 Pa at 37 degrees C.

The transpedicular approach for the study of intervertebral disc regeneration strategies: in vivo characterization

“…Indeed, tissue regeneration has made rapid progresses in recent years, making possible the synthesis of constructs that closely mimic the structure and properties of native tissues. Many new promising biomaterials have been recently described [23][24][25] and need to be tested in valuable animal models. Various agencies, such as Medicines and Healthcare products Regulatory Agency (MHRA), National Institute for Health and Clinical Excellence (NICE), Central Office for Research Ethics Committees (COREC) and US Food and Drug Administration (FDA), will require evidences of successful animal works, to sanitize any permissions given to proceed to human work [3].…”

Water‐Soluble Poly(N‐isopropylacrylamide)–Graphene Sheets Synthesized via Click Chemistry for Drug Delivery

“…[38][39][40] Meanwhile, it is water-soluble at room temperature and able to undergo a coilto-globule transition above 32 ° C (the low critical solution temperature, LCST). Thus, the combination of graphene with PNIPAM is promising to lead to thermoresponsive materials with unique properties for various applications.…”

Chemically Modified Natural Polysaccharides to Form Gels

“…Polysaccharide hydrogels can also be generated relying on an additional, typically synthetic polymer for providing the thermogelation property. Examples of this include graft polymers of alginate with poloxamer (a known synthetic thermogel containing blocks of polypropylene oxide and polyethylene oxide) (Chen et al 2011) and hyaluronic acid with poly(Nisopropylacrylamide) (PNIPAM) (Mortisen et al 2010). In both these situations, the polysaccharide provides general hydrophilicity as well as other desired properties (biodegradability, biocompatibility), while the thermogel (poloxamer or PNIPAM) provides the thermogelling property.…”