Self-crosslinkable hyaluronate-based hydrogels as a soft tissue filler.

With increasing interest in aging and skin care, the use of fillers to increase the volume of soft tissue volume is increasing globally. However, the side effects caused by the residual chemical crosslinking agents present in these fillers limit the effective application of commercialized filler products. Therefore, the development of a novel crosslinking system with a non-toxic chemical crosslinking agent is required to overcome the limitations of commercial hyaluronate (HA)-based fillers. In this paper, a new injectable hydrogel with enhanced mechanical properties, tissue adhesion, injectability, and biocompatibility is reported. The HA derivatives modified with catechol groups (HA-DA) were crosslinked by self-oxidation under in vivo physiological conditions (pH 7.4) without chemical crosslinkers to form hydrogels, which can be further accelerated by the dissolved oxygen in the body. The fabricated HA-DA filler showed excellent mechanical properties and could be easily injected with a low injection force. Further, the HA-DA filler stably attached to the injection site due to the tissue adhesion properties of the catechol groups, thus leading to an improved displacement stability. In addition, the HA-DA filler showed excellent cell viability, cell proliferation, and biocompatibility. Therefore, the HA-DA hydrogel is a novel soft tissue filler with great potential to overcome the limitations of commercial soft tissue fillers.

Visible-light-induced hyaluronate hydrogel for soft tissue fillers.

Hyaluronic acid (HA) is widely used as a filler owing to its excellent biocompatibility and biodegradability. However, commercial HA-based filler products have some limitations and can cause side effects due to the presence of residual chemical crosslinking agents. In this study, tyramine (Tyr) was introduced into HA to impart photocrosslinking ability to HA, and a photocrosslinked hydrogel was formed using a less toxic vitamin B2 derivative as a photoinitiator. For injection, an injectable filler was prepared by converting the photocrosslinked hydrogel to a microgel form. The crosslinking of the tyramine-modified HA (HA-Tyr) hydrogel, which can be applied as a soft tissue filler, increased with an increase in the irradiation time, and the crosslinked hydrogel showed excellent mechanical strength, elastic recovery rate, and injectability. It also showed non-cytotoxicity and cell proliferation behavior in fibroblasts. Therefore, injectable HA hydrogels have great potential as an alternative to conventional commercial dermal fillers.

Long-lasting and bioactive hyaluronic acid-hydroxyapatite composite hydrogels for injectable dermal fillers: Physical properties and in vivo durability.

Hyaluronic acid (HAc)-hydroxyapatite (HAp) composite hydrogels were developed to improve the biostability and bioactivity of HAc for dermal filler applications. Two kinds of HAc-HAp composite fillers were generated: HAcmicroHAp and HAc-nanoHAp composites. HAc-microHAp was fabricated by mixing HAp microspheres with HAc hydrogels, and HAc-nanoHAp was made by in situ precipitation of nano-sized HAp particles in HAc hydrogels. Emphasis was placed on the effect of HAp on the durability and bioactivity of the fillers. Compared with the pure HAc filler, all of the HAc-HAp composite fillers exhibited significant improvements in volumetric maintenance based on in vivo tests owing to their reduced water content and higher degree of biointegration between the filler and surrounding tissues. HAc-HAp composite fillers also showed noticeable enhancement in dermis recovery, promoting collagen and elastic fiber formation. Based on their long-lasting durability and bioactivity, HAc-HAp composite fillers have great potential for soft tissue augmentation with multifunctionality.