Abstract
BackgroundRecent studies have reported the roles of Hyaluronic acid (HA) chains of diverse length in wound repair, especially considering the simultaneous occurrence in vivo of both high- (H-HA) and low-molecular weight (L-HA) hyaluronan at an injury site. It has been shown that HA fragments (5 ≤ MW ≤ 20 kDa) usually trigger an inflammatory response that, on one hand, is the first signal in the activation of a repair mechanism but on the other, when it’s overexpressed, it may promote unwanted side effects. The present experimental research has aimed to investigate H-HA, L-HA and of a newly developed complex of the two (H-HA/L-HA) for stability (e.g. hyaluronidases digestion), for their ability to promote wound healing of human keratinocytes in vitro and for their effect on cellular biomarker expression trends.ResultsTime-lapse video microscopy studies proved that the diverse HA was capable of restoring the monolayer integrity of HaCat. The H-HA/L-HA complex (0.1 and 1%w/v) proved faster in regeneration also in co-culture scratch test where wound closure was achieved in half the time of H-HA stimulated cells and 2.5-fold faster than the control. Gene expression was evaluated for transformation growth factor beta 1 (TGF-β1) proving that L-HA alone increased its expression at 4 h followed by restoration of similar trends for all the stimuli. Depending on the diverse stimulation (H-HA, L-HA or the complex), metalloproteinases (MMP-2, -9, -13) were also modulated differently. Furthermore, type I collagen expression and production were evaluated. Compared to the others, persistence of a significant higher expression level at 24 h for the H-HA/L-HA complex was found.ConclusionsThe outcomes of this research showed that, both at high and low concentrations, hybrid complexes proved to perform better than HA alone thus suggesting their potential as medical devices in aesthetic and regenerative medicine.
Highlights
Recent studies have reported the roles of Hyaluronic acid (HA) chains of diverse length in wound repair, especially considering the simultaneous occurrence in vivo of both high- (H-HA) and low-molecular weight (L-HA) hyaluronan at an injury site
In the earliest phase of wound healing (WH) in vivo, there is a sharp increase in HA right after injury: in particular, high molecular weight HA (H-HA) accumulates and binds fibrinogen that is fundamental for clot formation
Thereafter, in the inflammatory stage, there is an accumulation of low molecular weight HA (L-HA), which is generated from degradation of H-HA, inducing cytokine response and stimulating angiogenesis [8]
Summary
Recent studies have reported the roles of Hyaluronic acid (HA) chains of diverse length in wound repair, especially considering the simultaneous occurrence in vivo of both high- (H-HA) and low-molecular weight (L-HA) hyaluronan at an injury site. It has been well established that HA is associated with tissue repair [2,3,4,5] This macromolecule participates in many different biological processes during regeneration, detailed action mechanisms have still not been thoroughly unravelled. In the earliest phase of wound healing (WH) in vivo, there is a sharp increase in HA right after injury: in particular, high molecular weight HA (H-HA) accumulates and binds fibrinogen that is fundamental for clot formation. Many reports have studied the effects of exogenous H-HA or L-HA to obtain information on the role of HA in wound healing and to design innovative pharmaceutical/cosmeceutical formulations based on HA size [9,10,11,12,13,14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
