https://www.army.mil/article/129584

https://www.army.mil/article/129584

Our skin is arguably our most important organ; the first line of defense separating us from the external environment. The elasticity of our skin allows us to move without it tearing like paper, and its phenomenal sensory network allows us to negotiate our environment and protects us from sources of danger before we may even be aware of a risk. In short, our skin is our armour, hydrator, and a lifelong protector from the external world of the unknown.

Dangerous then, is the possibility that our skin may be irreversibly damaged. Thankfully, 3D bioprinting is offering possibilities for solutions to restore tissue and minimize damage.

A step beyond standard 3D printing of synthetic components, bioprinting achieves fabrication of a layered construct of biocompatible tissue equal to or similar to the layers present in our own organs.

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A. Burns

A burn signifies a heat-related injury to the tissue, with more serious injuries damaging the neural and vascular networks in the dermis. Once the dermis is damaged, there is no feeling in the actual area of injury, but the areas surrounding are unbelievably painful and sensitive. It is imperative to restore living tissue as soon as possible to avoid infection and restore protection to the body.

Burns are classified in grades from one through four. While grades one and two are more superficial, grade three burns extend through both dermal layers (epidermis, dermis), and grade four burns indicate damage beyond the dermis into muscle and bone. Grade three and four burns are generally irreversible, and require graft of living tissue to heal.

In addition, there is a phenomenon called conversion, where superficial burns convert into third degree burns following the initial injury. While the cause it is still only partially understood, studies have shown that earlier treatment may prevent conversion.

 

B. Burns Treatment:

Standard treatment of 3rd degree burns involve grafts, painful excisions of viable tissue from a different part of the body. In burns covering a large percentage of a victim, this is often difficult because there is little viable tissue and the body is already allocating much energy toward healing the initial wound. In order for a graft to be successful, it must include the restore the vascular and neural networks that are normally in the dermal layer which make our skin viable.

C. Bioprinting

Bioprinting offers much promise for fabricating grafts. For the purpose of skin grafts, this can be done through biomimicry or autonomous self-assembly, where non-differentiated cells are printed and develop into viable skin cells. This is vital and promising for any organ or tissue injury, particularly burns, where large patches of damaged skin lead to cell death due to decreased vascularization.

The military is often at the forefront of research due to immediate need, and given the extent of burns and other exterior wounds in combat there is great need for timely solutions to dermal damage. Wake Forest Institute for Regenerative Medicine is in the later stages of developing skin for use on military personnel.  During this process, a bioprinter scans and prints new skin directly onto the burn site while determining the types of cells to place onto the site.

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One example of how bioprinting is applied for skin repair. Image source.

 

D. Induced pluripotent stem cells

The creation of induced pluripotent stem cells (iPSC’s) in the laboratory has been well outlined in several studies and there are many hopeful plans for their application in tissue and organ repair.  Derived from the patient themselves, these undifferentiated cells are able to regenerate into any adult cell to recreate potentially any tissue or organ. Unlike previously used embryonic stem cells, are less likely to be rejected by a patient’s immune system during transfer as they are derived from the patient themselves and not an embryo. Differentiation of these cells is then directed by internal or laboratory-induced factors. This has huge implications for patient specific therapy by decreasing risk and time to receive treatment.

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Inkjet bioprinting. source

 

E. Types of bioprinting techniques
There are several methods generally used when printing biological materials with varying speeds, adapted to the type of cells being produced and ensuring minimum damage to the cells during transfer. While the methods below have been used in research, most developing bioprinting companies are inspired by certain techniques while surpassing traditional methods.

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Inkjet:

Ink in cartridge is biological material. A nozzle is heated, forcing the material droplets through onto target surface. Because the heat used in traditional inkjet printing may damage the cells being printed, these companies using inkjet-inspired technology while still keeping biological material viable:

 

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Organovo

 

Aspect Biosystem

Aspect Biosystems

PrintAlive Bioprinter

PrintAlive

 

Microextrusion:

Temperature-controlled printing of biological material that assemble after printing. Continuous droplets of material are pushed through a dispensing system by pneumatics or mechanical forces.

Laser Assisted:

Lasers are used as the energy to push biological material onto a collecting area.

 

The developments for types of cells, methods of printing, and applications are developing. The potential for improved healing time, tissue restoration, and ultimately improved quality of life are massive with the growth of bioprinting.

 

An example of the inkjet-inspired bioprinting technique can be viewed below on the PrintAlive bioprinter site, where a team is developing printing sheets of pre-dermal and epidermal cells for grafts:

 

 

 

References:

  1. Murphy S, Atala A. 3D bioprinting of tissues and organs. Nature Biotechnology. 2014; 32 (8): 773-785.
  2. Singh V, Devgan L, Bhat S, Milner, S. The pathogenesis of burn wound conversion. Annals of Plastic Surgery. 2007; 59(1): 109-115
  3. Wake Forest School of Medicine. Printing skin cells on burn wounds. http://www.wakehealth.edu/Research/WFIRM/Research/Military-Applications/Printing-Skin-Cells-On-Burn-Wounds.htm
  4. Faulkner-Jones A, Fyfe C, Cornelissen D-J et al. Bioprinting of human pluripotent stem cells and their directed differentiation into hepatocyte-like cells for the generation of mini-livers in 3D. Biofabrication. Biofabrication. 2015 (7); 10.1088/1758-5090/7/4/044102
  5. Boston Children’s Hospital. Pluripotent stem cells 101: http://stemcell.childrenshospital.org/about-stem-cells/pluripotent-stem-cells-101/
  6. Boston Children’s Hospital. Turning pluripotent stem cells into treatment. http://stemcell.childrenshospital.org/about-stem-cells/pluripotent-stem-cells-101/how-do-pluripotent-stem-cells-get-turned-into-treatments/
  7. Canadian Business.The 3d printed organ is coming, and Canadian firms are leading the way. http://www.canadianbusiness.com/innovation/the-3d-printed-organ-is-coming-and-canadian-firms-are-leading-the-way/

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About the author:

Dr. Anna Sternin is a trained physical therapist, and has a strong interest in wearable technology andbiotechnology. Recently she also began PhysioRobotics Consulting, a clinical consulting business, to bridge the gap between healthcare and tech. She graduated with a Doctorate of Physical Therapy from Columbia University.

 

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