Abstract
The effectiveness of hyaluronic acid (HA), also called as hyaluronan, and its formulations on tissue regeneration and epidermal disease is well-documented. High-molecular-weight hyaluronan (HHA) is an efficient space filler that maintains hydration, serves as a substrate for proteoglycan assembly, and is involved in wound healing. Recently, an innovative hybrid cooperative complex (HCC) of high- and low-molecular-weight hyaluronan was developed that is effective in wound healing and bioremodeling. The HCC proposed here consisted of a new formulation and contained 1.6 ± 0.1 kDa HHA and 250 ± 7 kDa LHA (low molecular weight hyaluronic acid). We investigated the performance of this HCC in a novel in vitro HaCaT (immortalized human keratinocytes)/HDF (human dermal fibroblast) co-culture model to assess its ability to repair skin tissue lesions. Compared to linear HA samples, HCC reduced the biomarkers of inflammation (Transforming Growth Factor-β (TGF-β), Tumor Necrosis Factor receptor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8)), and accelerated the healing process. These data were confirmed by the modulation of metalloproteases (MMPs) and elastin, and were compatible with a prospectively reduced risk of scar formation. We also examined the expression of defensin-2, an antimicrobial peptide, in the presence of hyaluronan, showing a higher expression in the HCC-treated samples and suggesting a potential increase in antibacterial and immunomodulatory functions. Based on these in vitro data, the presence of HCC in creams or dressings would be expected to enhance the resolution of inflammation and accelerate the skin wound healing process.
Highlights
There is growing interest in unraveling the correlation between hyaluronan (HA) and inflammation in response to stress conditions or damaged tissue (i.e., wound healing (WH))
The present study aimed to evaluate novel hybrid cooperative complexes (HCCs) obtained through NaHyCo®technology [16] and containing both high- and low-molecular-weight hyaluronic acid (HHA ≈ 1600 kDa and low-molecular-weight HA (LHA) ≈ 220 kDa) for biomedical applications, especially topical wound treatment
The High-molecular-weight hyaluronan (HHA), LHA, and HCC samples were diluted to the concentration used for the biological experiments and investigated for their dynamic viscosity
Summary
There is growing interest in unraveling the correlation between hyaluronan (HA) and inflammation in response to stress conditions or damaged tissue (i.e., wound healing (WH)). HA is one of the most frequently used formulations for wounds, burns, and ulcer treatments, which often consist of specific hydrogels, such as alginate, carboxymethylcellulose, or chitosan [5,6]. The use of creams (foams and ointments) for infectious wounds is usually based on natural or synthetic biocompatible macromolecules with a higher viscosity, and often contain antibiotics and/or antibacterial agents [7,8,9,10,11,12,13]. Regarding commercial formulations containing HA, numerous products are reported to reduce ulcerous areas, which relieves symptoms related to skin burns and quickly decreases the wound size in general [14]
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