Injectable Shape-Memorizing Three-Dimensional Hyaluronic Acid Cryogels for Skin Sculpting and Soft Tissue Reconstruction

Abstract

Introduction: Hyaluronic acid (HA)-based fillers are used for various cosmetic procedures. However, due to filler migration and degradation, reinjections of the fillers are often required. Methacrylated HA (MA-HA) can be made into injectable shape-memorizing fillers (three-dimensional [3D] MA-HA) aimed to address these issues. In this study, shape retention, firmness, and biocompatibility of 3D MA-HA injected subcutaneously in mice were evaluated. Materials and Methods: Fifteen mice, each receiving two subcutaneous injections in their back, were divided into four groups receiving HA, MA-HA, 3D MA-HA, or saline, respectively. Digital imaging, scanning electron microscope (SEM) and in vivo imaging system (IVIS), durometry, and histology were utilized to evaluate in vitro/ vivo degradation and migration, material firmness, and the angiogenic (CD31) and immunogenic (CD45) response of the host tissue toward the injected materials. Results: Digital imaging, SEM, and IVIS revealed that 3D MA-HA fillers maintained their predetermined shape for at least 30 days in vitro and in vivo. Little volume effects were noted in the saline and other control groups. There were no differences in skin firmness between the groups or over time. Histology showed intact skin architecture in all groups. Three-dimensional MA-HA maintained its macroporous structure with significant angiogenesis at the 3D MA-HA/skin interfaces and throughout the 3D MA-HA. There was no significant inflammatory response to any of the injected materials. Conclusion: 3D MA-HA showed remarkable tissue compatibility, compliance, and shape predictability, as well as retention, and thus might be suitable for various skin sculpting and soft tissue reconstruction purposes.

Injectable Hyaluronic Acid-co-Gelatin Cryogels for Tissue-Engineering Applications

“…Our results further confirmed that HA, although a naturally derived and non-immunogenic polymer, which can be formed into an injectable cryogel, has poor cell adhesion properties [31]. Previous reports on incorporating different types of polymers or peptides with HA showed improved bioadhesive properties [32,35,48,49,80].…”

“…Furthermore, HA can play an important role in angiogenesis and wound healing [ 12 , 29 ]. The polysaccharide is composed of d -glucuronic acid and D- N -acetyl glucosamine repeating units that can be degraded by hyaluronidase enzyme [ 30 , 31 ]. Hydrogel scaffolds mimicking various tissues have been made using HA [ 31 , 32 ].…”

“…The polysaccharide is composed of d -glucuronic acid and D- N -acetyl glucosamine repeating units that can be degraded by hyaluronidase enzyme [ 30 , 31 ]. Hydrogel scaffolds mimicking various tissues have been made using HA [ 31 , 32 ]. These biomaterials have been shown to exhibit a rapid ability to absorb body fluids, a high moisture content, a long-term water-retention ratio, and good flexibility [ 33 ].…”

In situ forming injectable hydrogels for drug delivery and wound repair

“…Cryogel materials have been successfully applied to a wide range of both cosmetic and regenerative therapies. In one study, Cheng et al demonstrated that cryogels synthesized from methacrylated HA (cryo-MA-HA) could be utilized as improved fillers for soft-tissue reconstruction due to their relatively high stability in vivo 146 . Pre-formed cryo-Me-HA gels injected subcutaneously in mice retained their shape for 30 days, remained situated at the injection site and demonstrated no adverse inflammatory effects over the course of the study.…”

Needle-injectable microcomposite cryogel scaffolds with antimicrobial properties

“…These cryogels have shape-memory properties and can undergo injection through hypodermic needles without any structural damage, allowing their minimally invasive delivery into the body 17 , 33 , 46 , 47 . A variety of biopolymers have been used to fabricate biomimetic cryogels for tissue engineering applications 48 – 53 .…”