Abstract
Hyaluronic acid (HA) is used in substitutive and aesthetic medicine with various applications. Ultrapure absorbable HA (Bioregen®) and a mix of reticulated and free low molecular weight HA (Regenyal Idea Bioexpander®) (both provided by Regenyal Laboratories Srl, San Benedetto del Tronto (AP), Italy) represent a reliable hydrating device and skin filler, useful for skin blemishes, lines and wrinkles, and lip widening, respectively. The commercial products are known for their safety, but data on the molecular, cellular, and tissue responses are lacking. We aimed to evaluate the bioavailability and the pro-angiogenic features of the products Bioregen® and Bioexpander® in vitro on cultured endothelial cells (ECs) and dermal fibroblasts in vivo when injected into experimental animals. When added to fibroblasts and ECs, Bioexpander® induced cell migration. The two HA preparations were well tolerated, while a transient proangiogenic behavior of Bioexpander®, when implanted subcutaneously in mice, was found. The neovascular response was evident in the first week with higher levels of VEGF and FGF-2 before undergoing regression. In conclusion, our data strengthen the safety of HA synthetic preparations both in vitro and in vivo. Even if a proangiogenic response is documented, it is modest and transient, leading to tissue recovery and absence of an inflammatory infiltrate.
Highlights
Hyaluronic acid (HA), glycans, and oligosaccharides exert different effects on the biological functions of cells and tissues, such as in the connective, epithelial, and neural tissues [1,2]
(A,B) Fibroblasts were exposed to increasing concentrations of the HA preparations Bioregen® (A) and Bioexpander® (B) (0.1–10 mg/mL) for 48 h in a medium containing
In Human umbilical vein endothelial cells (HUVEC) exposed to Bioregen®, we observed a significant increase in FGF-2 and a reduction of fibronectin and zonula occludens-1 (ZO-1) (Figure 4A,B), while Bioexpander® exerted milder effects (Figure 4C,D)
Summary
Hyaluronic acid (HA) (a nonsulfated glycosaminoglycan consisting of repeated disaccharide units of D-glucoronic acid and N-acetylglucosamine), glycans (nHA), and oligosaccharides (oHA) exert different effects on the biological functions of cells and tissues, such as in the connective, epithelial, and neural tissues [1,2]. HA is a naturally occurring glycosaminoglycan which, by virtue of its viscosity, elasticity, and other rheological properties ( for its biocompatibility), acts as a lubricating and shock absorbing fluid in skin and joints and as an ocular lubricant. The medical use of HA covers clinical use in ophthalmology, such as for cataract surgery, retinal reattachment, corneal transplantation, trabeculectomy in glaucoma, joint diseases ( osteoarthritis and rheumatoid arthritis), and adjuvant in wound healing [4]
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