Thadomal Shahani Engineering College
Worldwide, haemorrhage is responsible for up to 40% of trauma deaths. First aid like bandages are used to cover up wounds and pressure is applied to reduce the bleeding. But this does not promote or improve blood clotting, it simply creates a physical barrier to reduce blood flow.
In trauma cases, effective and instantaneous hemostasis is crucial to avoid death due to excessive bleeding. Recent studies have led to the development of chitosan-based hydrogels. The main component of the hydrogel-chitosan has been studied for its excellent hemostatic properties. These hydrogels have unique biological properties that contribute to drug delivery systems and wound healing.
Chitosan is obtained from chitin which is procured from crustaceans, insects and fungi. Due to high level of acetylated groups in chitin and poor solubility in aqueous solutions it cannot be used directly. Therefore, chitin is partially deacetylated to obtain chitosan.
The chitosan hydrogel is prepared by cross linking of chitosan polymers, which improves the stability of the polymer. Methods such as photopolymerization, ionic cross linking etc. are used for cross linking of polymers.
Hemostatic mechanism of chitosan
1. Aggregation of RBCs:
Chitosan is a natural cationic alkaline polysaccharide; the positive charge of NH3+ on chitosan chain electrostatically interacts with the anions on the surface of RBCs, leading to intensive aggregation of RBCs around the wound site to form blood clots which quickly stops bleeding. The study done by Zhang et al. on the chitosan-based composite material shows that the ability of chitosan to initiate coagulation was related to the percent of deacetylation, and also dependent on the number of protonated amine groups.
2. Stimulation of platelets:
The study done by Zhang et al. on the chitosan-based composite material also shows that chitosan could enhance the activation of platelets and accelerate the adhesion and aggregation of platelets. This plays an important role in the haemostatic process.
3. Contact system activation:
The contact of biomaterial surface with blood directly affects blood coagulation by modifying the protein function after adsorption, which is called the contact activation pathway.
4. Formation of partial network structure:
Chitosan is a linear glycosaminoglycan which makes it easy to construct a network structure, thus promoting the interaction of blood components with chitosan and facilitating strong blood clotting.
Why use chitosan-based hydrogel?
1. Most of the medical waste is incinerated to avoid the risk of contamination and infection. This increases air pollution to some extent. Therefore, biodegradability of chitosan is an important factor as it can be disposed off without much harm to the environment.
2. The chitosan-based polymers are biocompatible. They do not have a toxic effect on living tissue.
3. It is non antigenic in nature.
4. It has antimicrobial activity which is essential as the wounds may get infected after being exposed to air.
5. Chitosan acts like a biological adhesive and helps to stop the bleeding at a faster rate than normal clotting process.
6. The amino and hydroxyl groups in chitosan polymers can be easily reacted and chemically modified, thus allowing a high chemical versatility.
i. The primary application of such a hydrogel would be for military purposes and emergencies. It is believed that first few minutes after a severe injury are crucial because bleeding out may lead to death. The chitosan based hydrogel will stop the bleeding almost instantaneously.
ii. Drug delivery:- Due to the cationic nature of chitosan, it can adhere to negatively charged biological surface. This significantly improves the residence time of the drug-loaded system and is beneficial for localized drug delivery. Most common applications are oral drug delivery, ocular drug delivery and nasal drug delivery.
iii. Tissue engineering:-Chitosan hydrogels were used as scaffolds for tissue engineering, they can be used for regeneration of various tissues such as bone, cartilage, skin and nerves.
Based on the study of chitosan, a wound dressing gel was created by a company in Brooklyn called Cresilon. Their product Vetigel acts as a haemostatic agent and stops the bleeding instantaneously. This product is
approved to be used only on animals. Studies are being conducted on its modification and use on humans.
Other commercially available product is HemCon bandage. HemCon can stop severe bleeding by attaching to negatively charged cells of tissue as well as attracting negatively charged red blood cells and forming a tight seal over the wound.
Yet another important application of the gel is for surgical procedures where the internal bleeding can be controlled and stopped. Almost 2 million lives are lost every year due to bleeding out. The use of chitosan based hydrogels might just be the solution to reduce these fatalities.