Chasing the Dream of the Dermal Regenerator

By Julia Simpson

Adventures exploring the Final Frontier make for entertaining television – the enduring success of Star Trek since the original series’ airing (1966-1969)1 testifies to that – but for the characters navigating often tumultuous interspecies politics, adventure can be a dangerous business. Fortunately for those characters, by the time Star Trek: The Next Generation (1987-1994)1 graced the silver screen, showrunners and scriptwriters had stitched a critical piece of fictional medical technology into the fabric of the show. This device, called the “dermal regenerator,” had the incredibly useful power to effectively suture plotlines as well as skin. Subsequent decades of Star Trek canon have seen the dermal regenerator used to heal minor-to-moderate lacerations, treat burns, remove scars, and regrow skin, not to mention accelerate healing time so that fan-favorite Federation officers can bounce back from grievous injuries between action sequences2. While our twenty-first century society does not (yet) resemble the twenty-third century vision for humanity laid out by original Star Trek producer Gene Roddenberry, recent advances in wound healing and regenerative medicine could mean significant steps towards a future with “dermal regenerator”-like technology. Here, I’d like to call attention to three papers published in the last two years that exemplify this progress.

Big Idea 1: A matrix made of silkworm and spider silk are able to improve healing of diabetic wounds

In one of the Star Trek television shows, a dermal regenerator is used to heal a superficial hand wound. The look of the regenerator is re-invented with each new iteration of the show, but the basic concept (a hand-held healing device that somehow mediates wound healing via its light emissions) is always the same. Photo Credit: https://memory-alpha.fandom.com/wiki/Dermal_regenerator

In June 2019, an exciting study reported the wound healing capabilities of bioactive silkworm silk mats combined with spider silk proteins3. Silk from Antheraea assama (Aa) silkworms was processed and synthesized into a nanofibrous mat called silk fibroin (AaSF). Two spider silk fusion proteins were studied – one contained a fragment of fibronectin (FN), which helps with cell binding, and the other contained a piece of lactoferrin (Lac), an antimicrobial molecule. Researchers specifically sought ways to improve wound healing in diabetic individuals, in whom chronic wounds can be so severe that they require limb amputation. To address this, authors used diabetic rabbits as a model to test the effectiveness of their silkworm and spider silk wound dressings. 

To start, authors compared healing speeds of wounds treated with different combinations of silkworm and spider silk. The dressing composed of the silkworm silk plus both the FN- and Lac-containing spider silk fusion proteins, a matrix called AaSF-FN-Lac, yielded the fastest healing time3. Next, they wanted to measure angiogenesis, an important part of the healing process where new blood capillaries form to replace those that may have been destroyed during an injury. These capillaries are essential because they are the regenerating tissue’s only supply line of nutrients and oxygen. Wounds treated with AaSF-FN-Lac had markedly higher numbers of new blood capillaries3, demonstrating that their matrix was effective at promoting construction of those critical tissue repair “supply lines.” Further experiments also proved that treatment with their silk nanofibrous mats caused wounds to express more collagen, a key component for stability of the dermal layer during healing3. These findings are an important contribution to the field because the silk matrix described presents a safe, effective method to heal typically tough-to-treat diabetic wounds.

Big Idea 2: A biomaterial made with photosynthetic microalgae promotes wound healing by improving oxygen flow and eliminating infectious bacteria

In a July 2020, a paper published in Advanced Therapeutics described the development of a new kind of wound healing hydrogel. The hydrogel is composed of Spirulina platensis (SP), a kind of photosynthetic bacteria coated in chitosan, a biocompatible hydrogel with infection-fighting capabilities. Putting the two together allowed the SP gel to stick longer to wounded skin4. SP bacteria contain high amounts of chlorophyll, the same component present in green plants that allows conversion of sunlight into food via photosynthesis. A key by-product of photosynthesis is oxygen. Authors sought to take advantage of SP’s photosynthetic, oxygen-producing capability and use it in a directed manner to combat hypoxia in wounded tissues.

First, the researchers identified the precise wavelength of light that maximized SP photosynthesis and performed a series of experiments on human skin cells to determine whether treating “wounds” in the cell culture with SP gel + light would produce enough oxygen to combat hypoxia in the cells. To model wounds in a cell culture, they performed a scratch assay, a kind of test in which a layer of cells grown in a petri dish are “injured” when the researcher creates a short scratch through them. Results showed that treating the wounded cells with SP gel + light did, in fact, stimulate oxygen production4. Researchers then asked whether the SP gel + light treatment could kill bacterial colonies in petri dishes, which they suspected was possible because laser-stimulated SP can produce “reactive oxygen species” that kill bacteria. The tests demonstrated that SP gel + light had antibacterial properties4. Authors built on this work by testing their treatment in mice. Tissue analysis revealed that laser-stimulated SP gel treatments to wounds mitigated hypoxia, and further experiments demonstrated that this treatment triggered a high immune response against invading bacteria4. Of note, SP gel is inexpensive to produce and convenient to use, making it an exciting candidate for accelerating wound healing in the future4.

Big Idea 3: Tweaking the orientation of proteins in a hydrogel scaffold activates the adaptive immune system to trigger wound healing

Just this month (April 2021), a study was published describing how, by switching certain

protein building blocks to mirror-images of their original states (called “flipping the chirality”), a team of researchers was able to improve the wound healing capabilities of a previously developed biomaterial5. This material is called a “microporous annealed particle” (MAP) scaffold, and in earlier studies, they showed that it has wound healing abilities. Here, the researchers’ goal was to slow down the degradation of the MAP scaffold after application to a wound, theorizing that this would give regenerating tissues more time to utilize the micropores in the scaffold as a guiding mesh for healing.

Unexpectedly, they found that treating wounds with D-MAP (the flipped version of the scaffold) actually sped up degradation of the scaffold – but, instead of impairing wound healing in test mice, the D-MAP treatment improved it, through activation of specific immune system responses5. The secret to this surprising discovery was that, when implanted in mouse wounds, the D-MAP hydrogel scaffold recruited myeloid cells5, which are foot soldiers of the immune system deployed to eliminate foreign invaders when infection or other breaches of bodily barriers are detected. Experiments further characterized the reaction as a type 2 immune response, which is the same class of response that deals with allergens and parasites5. Authors also looked at the tensile strength of wounds treated with D-MAP or its unaltered predecessor, L-MAP, and found that presence of D-MAP could enhance tensile strength of regenerated tissues by up to 80%5. All in all, this study makes waves by a) improving on an already promising wound healing biomaterial, and b) showing how the adaptive immune system facilitates D-MAP’s effectiveness.

Creative speculation that reimagines the scope of the possible is an essential element of the science fiction genre. In Star Trek, the dermal regenerator looks like a grocery store barcode scanner; it fires a bright colored laser at a wound, and minor injuries are healed in a matter of seconds. Modern medical technology is not yet at the state illustrated in the twenty-third and twenty-fourth centuries of Roddenberry’s imagination, but with more scientific advancements like the ones discussed above being made all the time, perhaps a device like the dermal regenerator isn’t so far-fetched after all.


Citations

  1. https://en.wikipedia.org/wiki/Star_Trek
  2. https://memory-alpha.fandom.com/wiki/Dermal_regenerator
  3. https://pubs.acs.org/doi/pdf/10.1021/acsbiomaterials.9b00514
  4. https://onlinelibrary.wiley.com/doi/full/10.1002/adtp.202000107
  5. https://www.nature.com/articles/s41563-020-00844-w

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