Hyaluronic acid colloidal gels as self‐assembling elastic biomaterials

Abstract

Hyaluronic acid (HA) is a naturally occurring biodegradable polymer with a variety of applications in medicine. The use of HA as a filler or scaffold for regenerating tissues often requires improving the elastic properties of HA. This is conventionally accomplished via chemical crosslinking, which might require the generation of toxic free radicals. Although the mechanical properties of the resulting gel material can be tuned, these types of materials are static and susceptible to mechanical failure. The aim of this study was to develop a colloidal system for scaffold fabrication that is held together by physical interactions between HA nanoparticles. HA nanoparticles composed of 17 kDa HA suspended in water at different concentrations (15%, 30%, and 45% w/v, respectively) formed a stable three-dimensional (3D) colloidal gel as a result of physical entanglement of free polymer chains on the surfaces of nanoparticles. The swelling ratio, shear moduli (G), compressive failure properties, and viscosity of colloidal gels were concentration dependent. The colloidal gels also were found to exhibit dynamic and recoverable properties, thus suggesting that these "self-associating colloids" offer characteristics distinct arising from crosslinked polymers or high concentration colloids.

Enabling Surgical Placement of Hydrogels Through Achieving Paste-Like Rheological Behavior in Hydrogel Precursor Solutions

“…14 HAnp were prepared using carbodiimide crosslinking chemistry using EDC with adipic acid dihydrazide (AAD) as the crosslinker. 7 Briefly, 300 mg HA (16 kDa) was dissolved in 120 mL DI water in a 500 mL round flask stirring at 300 rpm. Then, 200 mL acetone was added to the flask and stirred for 15 min.…”

“…4, 23–25 Our recent work has shown that colloidal gels with shear-thinning rheological behavior can be made out of solutions of hyaluronic acid (HA) nanoparticles. 7 These HA-based colloidal gels also have the ability to fully recover after compression to high strains and also after physically destroying and reassembling the gel, which may be attractive for applications such as for cartilage regeneration. 7 However, preliminary work demonstrated that these colloidal gels do not retain their integrity over time in culture.…”

“…7 These HA-based colloidal gels also have the ability to fully recover after compression to high strains and also after physically destroying and reassembling the gel, which may be attractive for applications such as for cartilage regeneration. 7 However, preliminary work demonstrated that these colloidal gels do not retain their integrity over time in culture. Therefore, we have created a platform system that combines the HA colloidal gels systems with traditional crosslinked HA hydrogels to form a hydrogel suitable for load-bearing applications that is paste-like prior to crosslinking for effective delivery in situ .…”

“…Although other systems, including dermal fillers, employ HA particles with traditional crosslinked HA hydrogels, 9–13, 20, 21 or use alternate means to induce a set strength in injectable materials, 5, 15 our HA nanoparticles (HAnp) are fabricated with a specific molecular weight (MW) designed to achieve paste-like rheological behavior and a yield stress and they have never before been encapsulated within crosslinked HA hydrogels. 7 This yield stress is especially desirable to enable a surgeon to mold the material into the defect site without the concern that the material will flow or leak from the defect, which is the main concern for traditional hydrogel precursor solutions. The HAnp will also allow the surgeon to mold the hydrogel precursor solution to obtain appropriate contouring of the defect site, which in some cases may not be possible with traditional hydrogel precursor solutions.…”

Effect of molecular weight of hyaluronic acid (HA) on viscoelasticity and particle texturing feel of HA dermal biphasic fillers

“…In its natural state, hyaluronic acid (HA) exhibits poor biomechanical properties as a dermal fillers due to the poor viscoelasticity and the short half-life of HA when injected into normal skin [1–11]. To provide the ability to lift and fill wrinkles in the skin, chemical modification is required to improve its mechanical properties.…”