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Pakistani Scientists Develop Low-Cost Skin Substitute to Heal Deep Burn Wounds

Most synthetic skin substitutes available in market are often unstable under normal storage conditions and fail to facilitate formation of new blood vessels
by Sohail Yusuf

A team of Pakistani scientists has developed a low-cost nanoparticle that can heal burned skin and chronic ulcer wounds.

Dr Muhammad Yar and his team at the Interdisciplinary Research Centre in Biomedical Materials (IRCBM) at COMSATS Institute of Information Technology (CIIT) have successfully tested the technique on chicken egg shells and rat skin. The skin substitute is made of a hydrogel filled with zinc oxide and zinc peroxide nanoparticles to support formation of blood vessels needed to heal burn wounds.

The findings have recently been published in Materials and Design, an internationally-reputed scientific journal.

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A World Health Organization (WHO) report published in 2016 had estimated that 265,000 deaths are caused by burns every year – the vast majority of these were reported from lower and middle-income countries.

The only FDA-approved skin for burn patients available in the market is named Integra – a dermal regeneration template. A four centimeter square patch of Integra costs around Rs80,000.

Most other synthetic skin substitutes available in the market for tissue regeneration are equally expensive but are often unstable under normal storage conditions. Another problem is that these products often fail to support angiogenesis – formation of new blood vessels in the affected part of the skin. Angiogenesis is crucial in healing of deep wounds as it facilitates growth of natural routes for oxygen and delivery of other nutrients to cells enabling tissue regeneration.

The skin substitute prepared by Dr Yar has the potential to overcome these problems. It supports blood vessels formation and is based on affordable indigenous raw materials. The hydrogel has been prepared by crosslinking two naturally occurring biopolymers.

Successful experiments with chicken eggs and rat skin

The research team introduced the hydrogels to an eight-day-old fertilized chicken eggs hatched in an incubator. The egg shells were cut and the hydrogel patch was applied onto the chorioallantoic membrane (CAM) in order to investigate its angiogenic potential. The eggs were then sealed carefully and placed inside the incubator at 37 degrees centigrade and 55 per cent humidity. On 14th day, angiogenesis was quantified by taking light microscope pictures. The results showed that the hydrogels containing zinc peroxide nanoparticles had better angiogenic activity and encouraged formation of new blood vessels.

Later, they grafted the material on a rat with deep wounds and saw positive results.

The healing hydrogels

The hydrogels were prepared from a matrix of biopolymers and nanoparticles. These polymers can hold large amounts of water due to their physical qualities. The team used plant cellulose, which is a non-toxic and inexpensive polymer. In addition, another biopolymer extracted from marine shells and often discarded as waste in Pakistan was utilized to prepare these hydrogels. Finally, the hydrogels were loaded with zinc oxide and zinc peroxide nanoparticles. The synthetic graft was then made to undergo various chemical and biological tests.

Synthetic Skin substitute synthesized at IRCBM.

The zinc oxide and zinc peroxide particles used in the graft were a few nanometers in size, making them roughly one billionth part of a meter. Due to this size factor, the nanoparticles provide high surface area and hence, enhanced bioactivity.

Both metal oxides are being widely used in various fields from industrial applications to use in medicines. Zinc oxide is an antibacterial agent. Its nanoparticles have been used in biomaterials to heal wounds and are being studied widely for use in tissue engineering. Zinc peroxide is more easily available making it a potential candidate for preparation of affordable materials needed in tissue engineering applications.

Right to left: Samreen Ahtzaz, Dr Muhammad Yar, Lubna Shahzadi

The image shows biopolymer based synthetic skin graft which successfully triggered new blood vessels in lab experiments. The technology is promising – it can provide relief to patients with deep wounds from burns or accidents. Image courtesy by Dr Muhammad Yar et al from IRCBM.

From research to application

The next step involves conducting human trials for the synthesized skin substitute grafts. The research team is also looking for potential investors to market their product. “The most challenging part of the research was the development of an inexpensive but effective synthetic skin for burn patients. This was made possible by using indigenous materials,” says Dr Muhammad Yar, while talking to MIT Technology Review Pakistan.

He says his team was working with some plastic surgeons to further investigate the findings of their research. “It has worked perfectly on standard animal models by healing the wounds. The next step is to pass human trials,” he says.

Dr Mustehsan Bashir, an associate professor and head of the Plastic and Burn Unit at Lahore’s Mayo Hospital, hails the findings of the research as promising. The research has been published by a prestigious journal which in itself is a certificate but more tests are still needed before proceeding to the human clinical trial stage, he says.
“Dr. Muhammad Yar hails from an interdisciplinary team of more than 20 international PhD scientists at IRCBM. This young team focuses on bone repair, soft tissue regeneration, dental materials, sensors and biosensors for health applications. Support in the form of collaborations and capital is something that will help them translate their research from the bench to bedside,” says Dr. Aqif Anwar Chaudhry, associate professor and the head of the IRCBM at COMSATS Institute of Information Technology.

Muhammad Yar’s team has filed applications to Pakistani and US authorities to get a patent for their invention. The research had been made possible by a grant of Rs14 million by the Higher Education Commission (HEC) under its Technology Development Fund.