Diabetic Wound Healing Approaches - An Update

Diabetic wounds are of profound clinical importance and are the common manifestations seen in case of diabetic patients. It is defined as per the International Working Group on the Diabetic Foot as  - Infection, ulceration or destruction of tissues of the foot associated with neuropathy and/or peripheral artery disease in the lower extremity of people with diabetes.

Diabetic foot is a complication involving non-healing chronic wounds that often lead to amputations thus resulting in disability and poor quality of life for the patient. Particularly, in developing countries such as India, this can mean job loss for the patient, increased financial burden for the patient's family and increased frequency of hospitalization for the patients, creating a vicious cycle of hospitalization until the demise of the individual.

About 25% of all diabetics in India develop diabetic foot ulcers, and within this group 20% will end up with amputations.Current approaches to wound healing from a diabetes perspective: An ideal agent for diabetic wound healing would have to stimulate the expression of growth factors and along with suppressing the expression of certain inflammatory markers. Unfortunately, till date there is no such agent, due to which there exists such a large percentage of cases where diabetics face limb amputations. Current approaches involve the use of antibiotics and surgical interventions or modified wound dressings. These are focused with the aim to contain and prevent infection, improve oxygenation of the wound, removal of necrotic tissue and exudate.

1. Surgery: Surgical interventions involve wound debridement. It involves the removal of dead and dying tissue to help promote re-epithelialization, infection control and revascularization. The use of an appropriate dressing is also recommended to allow the wound to remain moist and allow for healing. In extreme cases where there is significant necrosis, deep reaching infection to the bone, the limb itself may need amputation.

2. Skin substitutes from natural sources: This is an expensive approach where in a supporting mesh is coated with animal derived peptides or collagen or cells. One approach involves the use of human fibroblasts derived from new-born foreskin which are seeded on to a polyglactin scaffold. As the cells multiply, they release growth factors that are captured onto the extracellular matrix. When placed on the wound this entire system provides most of the mediators required for wound healing. This invention is called as Dermagraft which has been approved as a medical device in USA. The system of Dermagraft acts almost like a skin transplant. Yet another approach in this category would involve the use of autograft or allograft and even xenografts from aquamarine sources. It has been noted that the popular approach using fish grafts appear to heal faster when compared to wounds treated with dehydrated Human AMNION/Chorion Membrane (dHACM) and even porcine tissue.

3. Nonconventional forms of dressings: The function of a dressing is to prevent the loss of blood, protect the wound from the environment and prevent entry of microbes. They may be passive, active or interactive. Passive dressings protect the wounds from the elements and microbes. Active dressings help retain moisture to promote healing, whereas interactive dressings help improve the wound healing by interacting with the cells involved in the healing process. The dressings used traditionally are made from cotton fibres and are applied in some form of cotton pad and gauze combination.

4. Nanofibers based approach for diabetic wound healing is now an extensively investigated area within nanotechnology. The nanocomposite dressings are commonly made biocompatible materials, such as chitosan, collagen, gelation polyvinyl alcohol (PVA), among numerous other agents available. Newer forms of nanocomposite dressings combine a variety of agents such as quaternary ammonium salts with chitosan which provides the benefit of having innate antimicrobial properties. Dressings of other origin are also available for diabetic wounds as hydrogels, foam dressings, alginate dressings and hydrocolloid dressings.

5. Topical growth factor: One of the only marketed drugs specific for diabetic foot ulcers is Becaplermin (Regranex) gel which contains PGDF-BB. The agent works by accelerating rate of growth of the cells causing closure of the wound. In wound healing however often all the required growth regulators are reduced. The use of growth regulators for wound healing is not without its risks, since reports have claimed risk of cancer due to the use of PDGF-BB, due to which the product now carries a warning of malignancy even at sites distant from use.

6. Use of plant products: There are numerous plant compounds that can be tested for wound healing and unlike synthetic ones there is a higher likelihood of success. This is due to the possibility they may work in synergism with other compounds that may be present along with the primary active compound. There is also the possibility that these compounds may stimulate the expression and repression of the molecular markers of wound healing in the appropriate manner that is seen in the natural process of wound healing. Curcumin, a compound found commonly in Indian curry has been an agent that has been used historically for wound healing. It is thought to work by regulating the inflammatory processes. In the modern era, it has been tried and tested in various nano formulations. Apart, the nano-formulations of Syzygium cumini have been tested and found successful in healing the diabetic wounds. Naringin, a glycoside is another example that has been known to improve wound healing by regulating inflammation and promoting angiogenesis.

New Alternatives: Apart from the above-mentioned methods there are few alternative approaches available, and some are under development for managing diabetic wound healing as listed below. Approaches using the Stem cells - Use of nanotechnology, going beyond the dressings - Tapping the microbiome  Radio waves and plasma guns - Smart wound dressing

Conclusion: Diabetic wound research is in the infancy stages of development. There is yet lot of progress to be made, perhaps far more than other areas of medicine. Generation of cost-effective solution to manage wound healing as well as better tools for identification of the microbial infection of wound can help in better and faster treatment of the wound reducing the need for unnecessary amputations. These approaches have a huge potential to prevent loss of pay to the patient, a burden on the healthcare system and maintain the quality of life of the patients and their families.