1. Introduction
Maltodextrin represents a polysaccharide that has been characterized for wound healing applications. Maltodextrin is a D- glucose polysaccharide obtained by starch hydrolysis with an average molecular weight of 3 kDa that is composed of small quantities of glucose and maltose. In clinical studies, topical application of a maltodextrin/ ascorbic acid to wounds and ulcers has shown to form a protective cover that regulates exudate and the invasion of microorganisms. The moist wound environment established by maltodextrin promotes tissue granulation and with the ascorbic acid, the maltodextrin/ ascorbic acid low pH exhibits a bacteriostatic activity.
2. Materials and methods
2.1. In-vitro “wound healing” assay of fibroblast cultures exposed to maltodextrin/ ascorbic acid
Cultures were treated until they close with 1% of maltodextrin/ ascorbic acid (Multidex® Powder, DeRoyal Inc. Tennessee, USA) in D-MEM supplemented with 1% FBS, 2 mM L-glutamine and antibiotic. D-MEM supplemented with 1% FBS or 10% FBS; both, in the presence of 2 mM L-glutamine and antibiotics were considered negative and positive controls, respectively. At 0, 8, 12, 24 and 30 h, images were acquired under a microscope (Axio Observer Z1; Carl Zeiss, Gottingen, Germany) € fitted with a monochromatic highspeed camera (AxioCam camera Carl Zeiss).
2.2. Collagen turnover and transforming growth factor (TGF)-b1 expression in fibroblast damaged cultures exposed to maltodextrin/ ascorbic acid
2.3. Human chronic wounds treated with maltodextrin/ ascorbic acid
We performed a bi-institutional, open, prospective, longitudinal, experimental, pilot study comparing the efficacy of maltodextrin/ ascorbic acid treatment of venous ulcers of the lower limbs vs. zinc oxide. All patients were appropriately informed about their venous disease and the purpose and procedures of the study.
Patients were allocated by simple random sampling to the maltodextrin/ ascorbic acid and zinc oxide groups by the staff of every wound care clinic. Treatment consisted of daily topical
application for 12 weeks of maltodextrin/ ascorbic acid powder or zinc oxide ointment.
2.4. Evaluation of wound closure and wound imaging
At the start of the study, 4, 8 and 12 weeks of treatment, the evolution of each patient's lesion was assessed. The area was measured by planimetry and all of the wounds were photographed and digitally processed to capture every lesion relief with the PhotoStudio 2000 software (ArcSoft, Inc.Fremont, California, USA) in order to distinguish the depth of each ulcer.
3. Results
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Scratch wound assay revealed that fibroblasts respond to maltodextrin/ ascorbic acid stimulation by increasing the growth and collagen turnover
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Maltodextrin/ ascorbic acid controlled the growth of most of colonizing microorganisms hosted in the ulcer and improved chronic wound repair
4. Discussion
Wound repair is a multifactorial process involving cells, extracellular matrix and humoral responses. From the plethora of substances and devices that stimulate wound healing, polysaccharides are some of the most ancient and popular materials, frequently administered from natural extracts, where the mechanism of action cannot be attributed to a particular molecule. On the other hand, maltodextrins are highly specific carbohydrates with an interesting potential to improve wound healing. In this work we assessed maltodextrin/ ascorbic acid in a preclinical in vitro wound healing model, as well as in vivo in venous leg ulcers. In vitro we found that cultures treated with maltodextrin/ ascorbic acid mimics the in vivo wound repair behavior related to MMP-1 and TIMP-1 expression, which are well known to be regulated by TGF-b1. Additionally, gelatinolytic activities, specifically 55 and 70 kDa, increased after 24 h, following repair of the fibroblast monolayer, suggesting that maltodextrin/ ascorbic acid stimulates fibroblast metabolism in order to promote collagen turnover (collagenase and gelatinases). In vivo evaluation demonstrated that patients treated with the maltodextrin/ ascorbic acid dressing experienced 3.7 times wound healing at 12 weeks with improvements in tissue morphology and cellular biomarkers compared to control treatment. These findings support the general efficacy of maltodextrin as a viable option for the treatment of chronic wounds.
In conclusion, the present observations indicate that maltodextrin/ ascorbic acid treatment favors wound repair in vitro and in vivo. We hypothesize that maltodextrin/ ascorbic acid improves healing by changing the wound environment from chronic to acute, promoting wound healing through stimulating the formation of granulation tissue and consequently epithelialization. At the rate of closure observed with 12 weeks of treatment, it can be projected through linear regression analysis (data not shown), that complete closure should be achieved in all maltodextrin/ ascorbic acidtreated patients by week 20 of treatment. In comparison, wound healing in patients treated with zinc oxide wound occur at week 28.
Further research is still required to fully establish clinical efficacy of maltodextrin/ ascorbic acid treatment as well as research to investigate other wound healing markers (i.e. IL-10, TNF-a, and PDGFAB) to fully understand the mechanisms of wound healing associated with maltodextrin/ ascorbic acid treatment. While further research is still required, the results from this study are the first to clearly relate clinical wound healing seen with maltodextrin/ ascorbic acid to specific established biomechanisms for wound healing.
Clinical images of two representative patients treated with zinc oxide ointment and maltodextrin/ ascorbic acid. The panels on the left show wounds treated with zinc oxide at
weeks 0, 8 and 12 and on the right wounds treated with maltodextrin (inside each panel, left images are photographs of wounds and right images show relief of the ulcer, in which
the depth of the wound at each time point can be observed).