Wednesday, March 13, 2019

New Hope for People With Skin Ulcers

It's probably safe to assume that you know we're in the midst of a diabetes epidemic.  While there are some very promising treatments that will reduce or eliminate the overt presentation of the most common forms of the disease, there are millions suffering right now.  Among the common diabetic complications are skin ulcers; miserable, painful open sores that require many treatments.  It has been reported that a single diabetic foot ulcer can cost approximately $50,000 to treat.

This week brings news via Machine Design that the Wake Forest Institute of Regenerative Medicine (WFIRM) has developed a new 3D bioprinting technique to help enhance treatment response time and create overall better skin graft results.  WFIRM published their results in Nature, which is currently allowing us to read and download the paper (pdf).  Due to the need for a sterile environment, the treatment is done in an operating theater.  The patient then lies in the printer while it sprays layers of cells onto their wound. The end result is that it builds up, layer by layer, what will function as a skin graft.
The new bioprinter from WFIRM combines the delivery systems of inkjet printers with mobility and the scanning capability of different topographies. The research team outlined its design and printing approach in the paper “Bioprinting of Autologous skin Cells Accelerates Wound Healing of extensive excisional Full-thickness Wounds.” The main components of the system are a handheld 3D scanner and a print head that can move in any XYZ direction. The print head contains eight 260 μm diameter nozzles, each driven by an independent dispensing motor. The printer components are mounted on a small frame which can be used in an operating room. The system is 79 cm wide (patient head-to-toe direction) by 77 cm deep (cross-patient direction). The system includes a robotic arm and, when fully extended, adds an additional 50 cm—combining for a full reach of 127 cm.

The scanner attached to the printer system is the ZScanner Z700 scanner from 3DSystems. As noted, the scanner is handheld and easy to use. It can capture the entire wound in one continuous scan which results in a computer model of the wound. The model is processed via Geomagic Studio and imported into Artcam 3D software to obtain the full volume and the nozzle path needed to print the fill volume. The wound is split into Z axis layers for its depth, corresponding to dermis and epidermis layers, and each Z-axis layers is overlaid with XY lines that cover the entire wound.
The printer uses the same sorts of techniques as inkjet printers: the delivery system is based on cartridges, and each cartridge contains a different type of sterile compound rather than a different colored ink.  Each nozzle is connected to a separate cartridge, and each cartridge contains a matrix of fibrinogen and collagen. Separate atomizing nozzles deposit thrombin on the fibrinogen matrix to produce fibrin simultaneously (clotting, to hold everything in place).  The system is just barely pressurized - a mere 1 pound per square inch difference drives the material.

Skin bioprinter prototype. (A) Schematic demonstrating scale, design, and components of the skin bioprinter. (B) The main components of the system consist of 260 µm diameter nozzles, driven by up to eight independently dispensing systems connected to a print-head with an XYZ movement system, in addition to the 3D wound scanner. All components are mounted on a frame small enough to be mobile in the operating room. (C) Skin bioprinting concept. Wounds are first scanned to obtain precise information on wound topography, which then guides the print heads to deposit specified materials and cell types in appropriate locations (Images courtesy of LabTV - National Defense Education Program, Washington, D.C.). (D) Example of skin bioprinting process, where markers that are placed around the wound area used as reference points: (a) prior to scanning with a hand-held ZScanner Z700 scanner (b). Geometric information obtained via scanning is then inputted in the form of an STL file to orient the scanned images to a standard coordinate system (c). The scanned data with its coordinate system is used to generate the fill volume and the path points for nozzle head to travel to print the fill volume (d). Output code is then provided to the custom bioprinter control interface for the generation of nozzle path needed to print fill volume (e, f). (E) This system facilitates the depositing of multiple cell types with high precision and control. The layering of fibroblasts (green) and keratinocytes (red) is shown.
Based off this delivery system, the keratinocytes [skin cells] and fibroblasts [cells which form the collagen matrix that supports the skin cells] are mixed into a hydrogel and delivered directly on top of the wound layer by layer, replicating the skin structure and accelerating the healing of normal skin and function. The research team has had successful results on mice in clinical trials. The new skin begins to form outward from the center of the wound and, by using the subject’s own unaffected cells for new cell delivery, it allowed the subject’s body to accept the new skin and prevent tissue rejection.

“The technology has the potential to eliminate the need for painful skin grafts that cause further disfigurement for patients suffering from large wounds or burns,” said WFIRM Director Anthony Atala, M.D., a co-author of the paper.

“If you deliver the patient’s own cells, they do actively contribute to wound healing by organizing up front to start the healing process much faster,” added James Yoo, M.D., Ph.D., who led the research team and co-authored the paper with Atala. “While there are other types of wound healing products available to treat wounds and help them close, those products do not actually contribute directly to the creation of skin.”  Note: anything in square brackets added by me - SiG
All work done so far has been done on experimental animals, as medical regulators demand.  The next step is to conduct a clinical trial on humans, and hopefully replace the traditional donor or artificial skin graft treatment with the patient’s own 3D-printed skin.


  1. As a Diabetic and one who also suffers through skin ulcers, this looks promising.

    1. It does. They give no real idea of how far away that is. I can't imagine it being sooner than five years.

  2. My ex-wife, a Type 1 diabetic, would have benefited greatly from this technology last year. Se cut the bottom of her foot late last summer while working in her garden. Instead of going to her Doctor or the local hospital to have the wound properly cleaned and attended to, she attended to it herself. Of course, it got infected and she still wouldn't go have it looked at. After two months, she was in such agony, she finally went to the doctor at the strong urging of one of our sons. Her doctor promptly hospitalized her. Next day a surgeon removed two of her toes and part of the bottom of her foot, all which had necrotic tissue. About a week later on a followup visit to the surgeon, he re-hospitalized her and removed two more toes and parts of the metatarsals in her foot. She then had a 3" x 6" open wound on her foot, which wasn't healing well. After another week or so and after daily transfusions of antibiotics, the surgeon decided that hyperbaric treatments were required to help promote healing. Those treatments finally worked in jump starting the healing process. She still, six months after the initial injury, has a 1" x 2" place on her foot that is not covered with skin, yet. It is continuing to heal with more skin coverage every time she goes to the surgeon for followup. The tech reported in this article would have greatly enhanced her recovery process.


    1. Quite a story, Nemo.

      Too many people minimize the how serious Type 1 is. Other than medical types (or us chronic researchers) few seem to realize that Type 1 was a death sentence not even 100 years ago. It wasn't until the isolation of insulin and its widespread availability that T1 diabetics could live normal lifespans. I think that was 1925.

    2. Diabetics that want to play doctor with extremity wounds are fools. I lost a good friend to that mindset. The last one was a bruise on his thigh from falling on his prosthetic. He had already lost both feet due to minor problems he couldn't fix. Lasted a week in the ICU with systemic poisoning, after ignoring it for a week. At his wake, I was told he had done this all his life. Now he won't get to watch his grandchildren growing up. I miss the guy.

  3. Aesop:
    Great news for people who can afford the technology, someday, maybe.
    New technology = somebody deservedly trying to recover their research costs.

    Diabetes ruthlessly culls the stupid and the lazy, and stupid and lazy people don't tend to accumulate wealth, so this will benefit a few, at best.

    The skin ulcerations of those who inject illicit narcotics tend to become a feature, not a bug, in their long-term prognosis, and their insurance prospects are even lower.

    The best prospects for this are for burn patients in general, and the occasional adventuring frostbite victim.

  4. Thanks for posting this, SiG. I never even imagined a biologic 3-D printer, thinking most structures and organs (skin _is_ an organ) were too complex, at least at this time. I'm glad to be wrong, even if it is still in the testing phase.