The Hemostatic and Wound Healing Effect of Chitosan Following Debridement of Chronic Ulcers

David H Keast, BSc, MSc, MD, FCFP(LM); Ashrafunissa Janmohammad, MBBS, MSc, MPH, CCRP

Disclosures

Wounds. 2021;33(8) 

In This Article

Abstract and Introduction

Abstract

Introduction: Chitosan has been proven to be helpful in wound care as a hemostatic agent. The hemostatic effect is due to the positively charged chitosan interacting with negatively charged red blood cell membranes, initiating the agglutination of red blood cells and platelets. This promotes the activation of thrombin, which activates the clotting pathway, leading to thrombus formation.

Objective: Based on the properties of chitosan as a rapidly acting hemostatic agent, the authors sought to determine if a chitosan gelling fiber wound dressing could control bleeding of freshly debrided wounds. The effect of the chitosan dressing on overall healing and patient and provider satisfaction was also evaluated.

Materials and Methods: Wounds of any etiology requiring sharp debridement in patients older than 18 years who were capable of consent were eligible. Wounds were sharply debrided by curettage, scalpel, electrosurgery, or a combination of methods. A chitosan dressing was applied to the freshly debrided wound with gentle pressure. The time from application to hemostasis as assessed by non-progression of blood pattern was measured. Other outcome measures also included digital photography, wound surface area, numerical pain scores, and Photographic Wound Assessment Tool (PWAT) scores. Patient and provider satisfaction were measured.

Results: Twenty patients with a variety of etiologies and ulcer types were evaluated. After debridement, wound bleeding was rated as mild (n=9), moderate (n=9), or severe (n=2). The mean time to hemostasis was 75 seconds ± 41 SD (range, 28–221 seconds). In 1 week, the mean wound area decreased from 6.9 cm2 ± 7.8 to 6.2 cm2 ± 7.9 and mean PWAT scores decreased from 17.7 ± 4.9 to 11.4 ± 5.0 (lower score indicates wound healing). Pain scores associated with wound debridement were reduced in all but 1 patient evaluated at week 1. Overall, the rating scores from the Patient Reported Acceptance Questionnaire (PRAQ) and Provider Acceptance Questionnaire (PAQ) developed by this research group were high. The mean total PRAQ score was 30.5 ± 3.9 out of 35 (35 being most satisfied). The PAQ score was 15 out of 15 for all but 1 patient (15 being most satisfied).

Conclusions: The chitosan gelling fiber wound dressing was simple to use and rapidly promoted hemostasis in fresh sharply debrided wounds. It was safe and easy to use in an outpatient setting and was highly rated by the patients.

Introduction

Chitin (poly-N-acetylglucosamine) is found in the shells of crustaceans and the exoskeletons of insects.[1] Chitin is the second most abundant biopolymer in nature, with cellulose being the most abundant.[2] In the late 1970s, there was a growing interest in chitin as an abundant source of chitosan because of its unique cationic properties.[3] The polysaccharide chitosan is a by-product of the alkaline deacetylation of chitin that occurs during seafood processing.[4] Chitosan and chitin have shown promise as wound dressing materials largely owing to their hemostatic properties and antimicrobial effects.[5–7]

Chitosan provides a nonprotein 3-dimensional extracellular matrix that stimulates fibroblast proliferation, natural hyaluronic acid synthesis, and tissue regeneration at the wound site.[8,9] In biopolymer gel form, chitosan offers hydrogel properties that are beneficial for keratinocyte delivery, which promotes skin healing and regulates burn wound exudate.[10] Chitosan-based hydrogels promote wound healing by providing a moist wound environment, protecting against infections, removing wound exudate, promoting wound reepithelization, and accelerating angiogenesis.[11] In addition, the hydrogel provides a biocompatible delivery system for growth factors, drug delivery, antibacterial agents, and mesenchymal stem cells. The antimicrobial and antifungal properties of chitosan make it a favorable option for accelerating wound healing.[12]

Use of a biocompatible hydrogel and biodegradable antibiotic delivery system to inhibit the growth of bacteria can improve patient outcomes following traumatic injury or surgery.[13] The antibiotic properties of chitosan and silver have been well-documented for use in wound healing.[14,15] In a pilot study of 10 children with partial-thickness burns, a chitosan-silver dressing was found to be optimal for moist wound management and wound healing without infections.[16] In 19 patients with donor site split-thickness skin graft (STSG), the effective use of a chitosan-based gelling fiber dressing with silver was demonstrated.[17] Use of the chitosan-based silver wound dressing resulted in markedly decreased pain between 1 and 14 days postoperatively at the STSG donor site. There were no donor site infections or adverse events, and acceptable quality of healing was achieved at the STSG donor site.

In a randomized, placebo-controlled, double-blind clinical trial, a 10% chitosan gel with isosorbide dinitrate spray combination therapy was used to treat 68 patients with diabetic foot ulcers.[18] Isosorbide dinitrate is a vasodilator, and the 10% chitosan gel provides hemostatic properties. Of 61 patients who completed the study, the mean wound closure percentage was 71% ± 30 for patients who received the combination therapy compared with a mean of 50% ± 16 for patients who received the placebo (P <.001). Combination therapy was not better than chitosan or isosorbide dinitrate alone, however.[18] In a study of 16 patients with venous leg ulcers, there was a mean 89% reduction in ulcer area (1.8 cm2 weekly) following treatment with chitosan and compression bandage.[19]

Vorbeck[20] discussed the use of chitosan or carboxymethylcellulose dressing to treat 10 patients with venous ulcers. Chitosan was shown to be superior to carboxymethylcellulose in reduced wound size, improved dressing integrity, improved periwound skin quality, and reduced dressing shrinkage. In a pilot study of 4 patients, the combination of autologous platelet-rich plasma with chitosan-alginate membranes was used in the management of chronic venous ulcers.[21] The ulcers were completely healed by an average of 5.4 months (range, 2–9 months) and accompanied by reduced pain, reduced exudate, and decreased bad smell for all 4 patients after the first treatment. In a different study, platelet adhesion to chitosan was enhanced in the presence of plasma and extracellular matrix proteins that resulted in activated platelets, indicating possible downstream effects on wound healing.[1]

Uncontrolled hemorrhage results in 30% of trauma-related deaths, more than half of which occur before emergency care is administered.[22] Since 2003, hemostatic dressings made of chitosan have been used to manage injuries in military and civilian emergency response settings, with promising results.[23,24] In an emergency medical services setting, a chitosan dressing controlled hemorrhage within 3 minutes of application in 27 of 34 cases (79%).[23] The failure rate of 21% (7 of 34 cases) was attributed to user error that was correctable with proper training and improved product design.

Chitosan has been found to reduce blood clotting time in vitro by 40% compared with blood alone.[1] Chitosan induces clotting, which also depends on the positive charge of the amino groups on the molecule; the positive charge interacts with the membranes of red blood cells, which have a negative charge.[25] A higher degree of deacetylation results in a higher positive charge, which positively influences coagulation.[26,27] The form of chitosan used, whether as a solid or as a solution, has also been shown to influence the level of coagulation. To investigate if a dose-related response exists between chitosan concentration and coagulation, chitosan samples of varying concentrations were incubated with heparinized human blood for 30 minutes.[28] A dose-related clotting response was found, with higher concentrations of chitosan leading to greater coagulation. Mechanistically, the adhesion of platelets to chitosan seems to be mediated primarily by αIIbβ3 integrins and P-selectin following platelet activation.[1]

Before autografting, adequate debridement, hemostasis, and infection control are critical to prepare the wound bed and prevent graft failure.[29] Significant blood loss can occur during debridement and excision, however.[29] In a study by Stone et al,[29] chitosan was shown to facilitate more rapid reepithelialization and nerve regeneration within the vascular dermis compared with conventional dressing. During wound debridement, excessive and prolonged bleeding may interfere with the wound healing process.[30] Compared with the use of gauze alone, the topical application of a chitosan-based dressing better controlled blood loss following wound debridement in a heparin-treated animal model.[30] For the current study of 20 patients with chronic wounds, the authors wanted to test if the same chitosan dressing would reduce bleeding in humans following wound debridement, with the subsequent result of decreased size of the wound area. In addition, the authors evaluated improvement in wound assessment scores, reduction in wound pain, and patient and provider satisfaction.

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