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Open AccessArticle

In Vitro Evaluation of Novel Hybrid Cooperative Complexes in a Wound Healing Model: A Step Toward Improved Bioreparation

Department of Experimental Medicine, School of Medicine, University of Campania “Luigi Vanvitelli,” Via L. De Crecchio 7, 80138 Naples, Italy
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Int. J. Mol. Sci. 2019, 20(19), 4727; https://doi.org/10.3390/ijms20194727
Received: 7 August 2019 / Revised: 9 September 2019 / Accepted: 18 September 2019 / Published: 24 September 2019
(This article belongs to the Section Macromolecules)
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. View Full-Text
Keywords: wound healing; inflammation; hyaluronic acid; biorepair wound healing; inflammation; hyaluronic acid; biorepair
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MDPI and ACS Style

D’Agostino, A.; Maritato, R.; La Gatta, A.; Fusco, A.; Reale, S.; Stellavato, A.; Pirozzi, A.V.A.; De Rosa, M.; Donnarumma, G.; Schiraldi, C. In Vitro Evaluation of Novel Hybrid Cooperative Complexes in a Wound Healing Model: A Step Toward Improved Bioreparation. Int. J. Mol. Sci. 2019, 20, 4727. https://doi.org/10.3390/ijms20194727

AMA Style

D’Agostino A, Maritato R, La Gatta A, Fusco A, Reale S, Stellavato A, Pirozzi AVA, De Rosa M, Donnarumma G, Schiraldi C. In Vitro Evaluation of Novel Hybrid Cooperative Complexes in a Wound Healing Model: A Step Toward Improved Bioreparation. International Journal of Molecular Sciences. 2019; 20(19):4727. https://doi.org/10.3390/ijms20194727

Chicago/Turabian Style

D’Agostino, Antonella; Maritato, Rosa; La Gatta, Annalisa; Fusco, Alessandra; Reale, Sabrina; Stellavato, Antonietta; Pirozzi, Anna V.A.; De Rosa, Mario; Donnarumma, Giovanna; Schiraldi, Chiara. 2019. "In Vitro Evaluation of Novel Hybrid Cooperative Complexes in a Wound Healing Model: A Step Toward Improved Bioreparation" Int. J. Mol. Sci. 20, no. 19: 4727. https://doi.org/10.3390/ijms20194727

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