Breakthroughs In 3D Printed Skin Grafts

Overview

From once being a distant sci-fi concept, 3D bioprinting of organs has now become a very current area of medical exploration. Traditional treatment methods like skin grafting after severe skin loss have been the mainstay treatment for potentially restoring function to damaged skin and improving aesthetic appearance after severe burns, deep wounds, or persistent skin infections. This method involves removing undamaged skin from the body to replace the damaged skin. However, this ‘cutting and pasting’ method of skin grafts leads to secondary wounds at the donor site (where the undamaged skin is taken from) and increases the risk of infection. the revolutionary technology of 3D-printed skin grafts provides a safer alternative to skin grafting. This is done by printing layers of skin that are customised to the patient, making extensive skin loss treatment more seamless than ever. In recent years, there have been many breakthroughs in this cutting-edge technology, with the promise of reshaping the future of skin restoration. 

What is the purpose of skin grafts? 

The skin is the biggest organ in the body, and it is needed for heat regulation, immune function and acting as a physical barrier to harmful substances like UV radiation or infections.¹ However, your skin is also the most exposed organ, making it more susceptible to damage. The skin can usually repair itself, but in cases of extensive skin damage or loss, patients typically receive a skin graft, which involves removing undamaged skin from part of the body and placing it over the damaged area.² This is done to replace the lost skin, improve the appearance of the damaged skin and restore skin function.³

Skin grafts can help those who have extensive skin loss due to: 

• Burns 
• Deep or slow-healing wounds
• Infections 
• Venous, pressure (bedsores) 
• diabetic ulcers
• Skin cancer removal surgery (like Mohs surgery).³

However, traditional 3D-printed skin grafts have potential complications. The removal of skin for the skin graft leads to a secondary wound, which can also get infected and leave scarring. In some cases, very extensive skin damage can mean there is not enough undamaged skin available for the skin graft. There is also a risk of the skin graft being rejected by the person's immune system.^3,4

What are 3D-printed skin grafts? 

3D bioprinting is like the sibling of traditional 3D printing, running on the same concept of creating layers of material to produce a 3D structure. However, instead of using materials such as metals or plastics, it uses bio-inks, which are substances containing living cells, proteins and other biological materials.^2,3 These bioinks mimic the body’s environment, allowing skin to grow and eventually resemble real skin.²

Advancements in 3D-printed skin grafts 

regenerative medicine and 3D-printed skin grafts are constantly evolving due to several research advancements in recent years. 

Personalisation 

Have you ever tried wrapping an oddly-shaped parcel with wrapping paper? That is what the process of skin grafting is often like. 3D-printed skin comes in rectangular sheets, thus, grafting it on irregularly shaped wounds can be difficult. However, current research is investigating how this could be overcome. Imaging scans, such as MRIs or CT scans, can be used to create a 3D image of the wound site, which can then be used to create a custom skin graft in the exact shape of the wound. This would reduce the need for suturing, reduce the duration of surgery and lead to a better aesthetic outcome. This method has been implemented sucessfully on mice, with the hope of being successful on humans too.⁵

In addition to this, using a patient’s own cells in the bio-ink improves the integration of skin to the wound area and reduces the risk of rejection by the body’s immune system.¹

In-situ skin grafting

Scientists have discovered a method of printing the skin graft directly on the wound site and letting the skin mature at the wound site. This method is known as in-situ skin grafting. This would allow cells to be placed exactly where they are needed, saving time and reducing the need for multiple surgeries, as the skin would not have to mature in a lab before transplanting.¹

Skin grafts containing blood vessels

In order for 3D-printed skin grafts to survive post-transplantation, blood vessel networks need to form in the new skin. This is because the skin graft cells can get the oxygen and nutrients they need to survive. Today, scientists have created a layer of skin filled with blood vessels. Scientists are also researching different techniques to stimulate blood vessel growth in 3D-printed skin grafts, such as creating skin graft structures with pre-designed channels for blood to flow through them or containing pro-angiogenic factors (substances that stimulate the growth of blood vessels) or stem cells (special types of cells that promote blood vessel growth). These methods help prolong the survival of skin graft after the transplant.^1,2

Skin grafts containing hair follicles and sweat glands

Once the skin has been significantly damaged, it cannot regenerate hair follicles and sweat glands, which can have a significant impact on a patient’s quality of life. The absence of sweat glands significantly reduces the patient’s ability to regulate their body temperature, whereas hair follicles contribute to an individual’s physical appearance and are important for mental well-being. Scientists are developing methods of generating skin grafts that can grow hair and regenerate sweat glands. They are attempting to achieve this through methods such as the use of stem cells, which are specialised cells that can be used for creating specific microenvironments that have the ideal conditions for growth and regeneration.¹

Benefits of 3D printed skin grafts 

3D printed grafts offer a more suitable alternative for those suffering from extensive skin damage, alongside having other potential uses. Some benefits of 3D-printed skin grafts include: 

• Customised shaped skin grafts: 3D-printed skin grafts can be printed to match the exact shape of the wound, improving healing outcomes. 
• No secondary wounds: Unlike traditional skin transplants, there is no need to harvest another area of the patient’s skin, which reduces pain, risks complications, and scarring at the secondary site. 
• Reduced rejection risk: Using a patient’s own cells in the bio-ink can reduce the chance of rejection by the immune system. 
• Faster healing: 3D-printed skin grafts have the optimal conditions for cell growth and regeneration, which can speed up recovery time. 
• Fewer surgeries and shorter hospital stays: In-situ skin grafting, where the skin graft is applied directly to the wound site, speeds up the grafting process. 
• Cost-effectiveness accessibility: Artificial production of skin that can be used for grafts can reduce the cost of surgical operations. This method also provides a solution for people who do not have enough healthy skin for a traditional skin graft.  
• Medical research: Realistic skin produced via 3D bioprinting can be used in research to test drugs or cancer treatments. 
• Cosmetic testing: 3D-printed skin can be used to test cosmetics and reduce testing on animals.^1,2,3

Limitations 

While there has been significant progress in the field of 3D bioprinting and skin grafts, scientists and researchers still face significant challenges, with the implantation of 3D bioprinted skin not yet being trialled on humans. Producing the optimum bio-ink that accurately mimics human skin and producing skin grafts that contain blood vessels, hair follicles, sweat glands, and nerves are areas that scientists are currently exploring but have not yet achieved.^1,3

In addition to this, there are also ethical, financial and production concerns about 3D skin bioprinting. The use of human cells, such as stem cells, raises ethical concerns, and there are issues with the large-scale production and preservation of 3D-printed skin grafts. whilst there are cost benefits in the future, the cost of bioprinting and bioinks alongside the expertise required to produce these skin grafts is quite significant.⁶

Future outlook 

In the future, we hope that 3D printing technology will be readily used on humans for burns and wound reconstruction. Alongside successful skin transplantation using this technology, 3D printed skin can be used for testing drugs and treatments for various skin conditions, ultimately animal studies. This technology may even be used to create other functioning organs, such as hearts or kidneys, which could significantly reduce the need to find a donor. 3D printing technology can  potentially create fully functioning skin at a reduced cost and in less time.²

Summary 

The field of 3D bioprinting of skin grafts aims to revolutionise the way we treat severe skin damage to achieve more painless, aesthetic and faster treatments. For those suffering from severe burns, deep wounds or serious infections, this new method of skin transplantation can drastically improve their quality of life. Unlike traditional ‘cut and paste’ style skin graft methods, 3D bioprinting does not create secondary wounds and has a lower rejection risk. Furthermore, 3D skin bioprinting can produce customised skin grafts by using patient-specific bio-inks based on a 3D modelling of the wound site. 

Despite progress, 3D-printed skin grafts have a long journey ahead before they can be used on humans, and these challenges remain. Ethical, financial and production issues around the use of human cells need to be addressed with significant expertise and resources. However, scientists are currently overcoming obstacles faced by 3D bioprinted skin, such as producing skin with blood vessels, hair follicles and sweat glands, which are crucial steps towards synthesising a fully functional human skin graft. 

Overall, the future of 3D printing technology looks promising, with the potential to make drastic improvements in burn treatment, wound reconstruction and testing drugs and cosmetics. This technology has the potential to even create other organs, like the heart or kidneys. 3D printing technology will  improve patient outcome on a huge scale, particularly in organ transplantation.