Eye on Medical Innovations: WOUND HEALING and the ARTIFICIAL SKIN

By definition, WOUND HEALING refers to the regeneration of damaged or destroyed skin/tissue by newly produced tissue. Upon a traumatic event to the body causing a breach or tear in the epithelial layer, a national and expected cascade of biochemical events is activated to repair the damage to form a protective barrier from the outside environment.  This is our body's way of protecting itself from infection, bacteria or further injury. The process of wound-healing may encounter unforeseen failure in its natural regenerative process, leading to chronic disease and further wounds (ie. diabetic wounds or diabetic ulcers).  This can lead to more serious infections and reinjury. 

BARDDIAGNOSTICS has joined the technological movement to advance wound healing science through real-time 3D ultrasound monitoring and laser thermographics. This aids the mitigation of the wound recovery process by immediately identifying the depth of the injury and the extent of the damage (neurological, vascular, circulatory) underneath.

A PARADIGM SHIFT IN WOUND CARE

Dr. Jose L. Ramirez-GarciaLuna

Polymedics Innovations (https://polymedics.com/) is a German company based in Stuttgart and is the leading medical device company specializing in synthetic skin substitutes for wound and burn care. Their flagship products, Suprathel and Supra SDRM, are designed to promote better and more rapid wound healing and improve patient outcomes in challenging clinical scenarios. These polymeric synthetic skin substitutes provide a controlled environment conducive to tissue regeneration and minimize the risks associated with traditional biological grafts. The products are composed 75% of poly-lactic acid, which is a safe biological material approved by the FDA since the '50s and widely used in sutures, implantable devices and prosthetic joints, and 25% other FDA-approved structural polymers.

Being fully synthetic means the products do not contain human or animal tissue, cells, proteins, peptides, or growth factors. They are designed and engineered in the company's lab; therefore, unlike biological materials, there is consistency in every single batch of products. Also, because they are devoid of a biological origin, they can easily be applied to people who cannot be treated with human or porcine-derived products due to personal or religious preferences. Finally, the skin substitutes are composed of large chain polymers, meaning that there is virtually no risk of allergy or immunological reactions to the material.

While fully synthetic, Polymedics' skin substitutes exert profound biological effects through their degradation. As these products integrate and get degraded by the native tissue in the wound bed, their polylactic acid chains get cleaved down to lactide monomers, which in turn are metabolized to lactate by surrounding cells. Lactate has traditionally been regarded as a waste product of cellular metabolism; however, mounting evidence demonstrates it exerts potent effects: 1) it induces the formation of new blood vessels (neo-angiogenesis); 2) it promotes cell survival, proliferation, and deposition of extracellular matrix; 3) it regulates the inflammatory environment; and 4) acidifies the extracellular environment through the conversion f lactate into lactic acid. Taken together, these effects are translated into faster and better wound healing.

Suprathel, a synthetic, resorbable epidermal membrane, is commonly used to treat superficial and partial-thickness burns and donor sites for skin grafts. Its flexible, transparent structure conforms closely to wound surfaces, providing effective protection while allowing gas exchange and maintaining moisture balance. This creates an optimal microenvironment for healing, significantly reduces pain, and eliminates the need for frequent dressing changes, significantly improving patient comfort. Clinical studies have shown that Suprathel supports rapid re-epithelialization, reduces scarring compared to traditional dressings, and reduces the need for opioid medication in burn patients.

Supra SDRM (Synthetic Dermal Regeneration Matrix) expands on these advantages for deeper injuries, complex soft tissue defects due to infection or trauma, and chronic wounds such as venous leg ulcers and diabetic ulcers. Its high porosity is ideally suited to enhance cell adhesion, angiogenesis, and extracellular matrix deposition, leading to healing soft tissue and dermal structures. Clinical evidence demonstrates that Supra SDRM reduces by half the time needed to achieve the complete closure of chronic wounds while lowering costs and providing a higher quality of life.

After cleaning and debridement, the wounded areas were covered with Suprathel® membranes. Suprathel® initially looks white and opaque, but as it heats up to the body's temperature, it becomes translucent, allowing the visualization of the wound bed and monitoring of wound healing. It is designed to stay in place for 10 to 14 days, after which it self-degrades and may require re-application. Shortly after application, the patient reported a significant decrease in the associated pain. The material self-adheres only to wounds and conforms to the wound bed, as seen in the image. Supra Net(R) was then used as a non-adhesive, non-contact layer to protect the graft. Supra Net(R) is a highly porous silicon-nylon mesh with good adherence to intact skin and very low adherence to Suprathel and wounded areas. It is ideal for ensuring intimate contact of the synthetic skin to the wound bed and allowing fluid exchange. These layers are then covered by a secondary dressing that can be changed as often as needed until the next visit to the clinic.

SUPRATHEL® is purely synthetic and therefore does not bear any residual risks as is the case with biological products of human or animal origin. Literature suggests that lactate may stimulate the healing process by supporting angiogenesis1-6 and the re-building of the dermis. The potential of lactate to act as a free radical scavenger and therefore to be able to reduce oxidative stress.

These synthetic skin substitutes represent a paradigm shift in wound care. Their ability to mimic the biological functions of human skin, combined with the bioactive properties of components like lactate, makes them a versatile and effective option for treating burns and chronic wounds. They improve healing outcomes while reducing complications and treatment costs.

EPILOGUE

By: Dr. Robert Bard

As a clinical researcher and a medical validator, my unique commitment to explore new medical innovations often introduces me to some of the most ground-breaking technologies and the best and brightest clinical or engineering minds behind them.  I am tasked to validate their efficacy with medical imaging and report on their ability to integrate with our current modalities.  

In the spring of 2024, I traveled to Montreal Canada (McGill University) to meet Dr. Jose Ramirez-GarciaLuna, "The Wound Scientist"- who was undergoing dedicated clinical evaluation efforts to measure the severity of burn wounds. Helped me uncover the intricacies of wound healing and the many resources that comprise this highly valued study.  His work led to the use of infrared thermography to identify soft tissue viability to assess burn depth.  In support of this project, he also introduced the impressive properties and effects of the highly developed SYNTHETIC SKIN- what is obviously a major game-changer in burn care and traumatic injuries.  

It was here that my attention was drawn to an exciting avenue of clinical care and an area where my diagnostic prowess and imaging expertise could contribute to furthering its advancement. The application of this critical care science has come a long way in the managing of burns, extreme skin disorders or post-surgical lacerations.  Dr. GarciaLuna and I had great discussions about the many possibilities of integrating regenerative technologies to optimizing the healing of bodily damage, and our collaboration continues to grow at this present day.

DR. JOSE L. RAMIREZ-GARCIALUNA earned his MD and an MSc in epidemiology and biostatistics from Universidad Autonoma de San Luis Potosi, in Mexico. He practiced for five years as an emergency and critical care physician before earning a Ph.D. in experimental surgery at McGill University, Canada. In addition, he holds graduate diplomas in surgical innovation, machine learning, and data science. Dr. Ramirez-GarciaLuna's areas of expertise include wound healing research, the immunology of wound healing, surgical innovation, and e-Health. For the past 10-years, he has used spectral imaging, infrared thermography, machine learning, and artificial intelligence for a plethora of surgical problems, including wound healing and COVID-19 infection detection. He has authored over 80 peer-reviewed articles, and his research has been awarded multiple accolades, including McGill University's Rising Star Award and the distinction as a Fellow of the Mexican National Council for Science and Technology. Dr. Ramirez-Garcialuna is the Director of Medical Affairs for Polymedics Innovations, a company focused on developing synthetic skin substitutes, and is a medical and scientific consultant for several biotech companies. He is also affiliated with the Division of Experimental Surgery of McGill University, Canada and as an Adjunct Professor in the Department of Surgery of Universidad Autonoma de San Luis Potosi, Mexico.

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Part 2:

MULTI-IMAGING REVIEW FOR WOUND HEALING & INFLAMMATORY SKIN DISORDERS

From a recorded interview with DR. ROBERT L. BARD (of BardDiagnostics lab)

INTRODUCTION: The following is an abridged private performance study of a multi-diagnostic reporting paradigm of thermographic imaging (FLIR) and ultrasound/ 3D Doppler microvascular blood flow imaging (CANON) to report on various wound healing applications.  Dr. Robert Bard, functional diagnostic imaging specialist partnered with Dr. Jose Garcialuna in the implementation of image-guided treatments of a traumatic and inflammatory skin disorders and the application of synthetic skin.   This study was performed in a closed setting under strict monitoring of the patient’s time-based progress. The collaboration between the diagnostic team and Dr. Garcialuna supports the use of multi-factorial data to detect treatment efficacy and improved recovery time alongside the severity of the pathological condition of the subject/patient. Comparison of the bilateral inflammatory changes on this patient with hemolytic autoimmune anemia (which flared after trauma to the dorsum of the left foot) shows that the lower tibial area is wet and inflamed - a so-called weeping or active wound.  The left foot, whose magnification [image #1] shows that the wounds are dry as compared to the weeping wound.

ABSTRACT: Inflammatory disease of the skin, which includes burns and diseases like psoriasis demonstrates thickened epidermis and dermis with increased intra and subdermal vascularity - all of which are measured by the out flow imaging and verified by other micro-imaging device technologies to confirm the epidermal and dermal extent of the disease. The blood flow, quantified either by 4-D ultrasound or by the optical vascular imaging may be used as a marker of treatment and noninvasive guide to adjust therapy without biopsy. 

For example, when the wound heals, there is less blood flow.  The inflamed skin at 1200 magnification on the vivo light microscopic camera used for high resolution imaging captures surface texture irregularity.

THERMOGRAPHY represents healing wound physiology as follows: inflamed areas are higher temperature (lighter color) while healing tissue or are starting to ‘fibrose’ and scar down are identified as darker colors. These measurements serve as treatment guides of inflammation before, during, and after treatment as part of a noninvasive methodology to follow up in post-care. [Image #3] Thermographic imaging (with a high resolution FLIR or infrared camera) indicates specific areas that appear dark, indicating that the wound is starting to fibrose due to elevated blood supply.

[Image #4 R-L] REFLECTANCE CONFOCAL MICROSCOPY shows inflammatory disease neovascularity with cutaneous lupus. The red and black scans (#4-L) with high resolution OCT or OPTICAL COMPUTED TOMOGRAPHY images of the inflammatory blood supply documents, which subsides in intensity as the wound is healing. 

[Image #5] 3D DOPPLER ULTRASOUND IMAGING represents the dermal edema (arrow) and the subcutaneous tissues with hypervascularity.  This includes a major vessel that is hypertrophied - supplying the inflamed tissues in the center right with a bright yellow image of the blood flow surrounded by a darker area of inflammatory edematous inflammatory disease is focused at the deeper level, which is impossible to see with the human eye and certainly best image with 3D, ultrasound and doppler. 

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Part 3:

BURNS AND DERMAL TRAUMAS

Written by: Dr. Robert L. Bard of the Bard Diagnostic Imaging Center

For most emergency responders and physicians, identifying the degree of any burn or dermal trauma cases starts with a visual assessment.  With professional training and enough experience, the professional eye can differentiate between first, second and third degree burns to initiate the proper treatment process. First-degree burns commonly show redness, and swelling only on the outermost skin layer; second-degree burns show surface injury to the underlying layer with blistering and Third-degree burns affect up to the deep layers of the skin.

As standard practices continue to evolve, diagnosing any advanced burns are now calling for new considerations for the prevention of burn-related complications.  As more and more after-effects from high degree burns have left patients with lasting (and sometimes fatal) results, it may no longer be enough to drive a treatment protocol based on surface topical healing. 

BURN SCANNING TECHNOLOGY: ASSURANCE AGAINST COMPLICATIONS

Second and third-degree burns may show blisters and red skin but with today’s many non-invasive subdermal technologies, you can now identify the depth of the burn and what the injury truly means under the skin. Identifying the exact DEPTH of the internal injury as well as monitoring (visually) its internal impact/effect on the body may uncover and predict other potential health issues such as:

-        Scarring and unrecoverable dead tissues

-        Damage to Nerve endings /neuropathy

-        Inflammation

-        Temporary to permanent loss of skin

-        Damage to underlying bones, muscles and tendons

-        Bacterial infections (from the broken skin) like tetanus

-        Internal Shock

-        Hypovolemia (low blood volume/ unusual blood loss from a burn)

According to Image 1A, high resolution sonogram used a standard probe for skin imaging showing the black area, which is just below the white line of the surface and the black fluid corresponds to the blister seen on the specimen of the burned area. Now below it you see the skin with the first vertical blue dotted line and it goes to the fascial plain white line, which shows swelling of the tissues. The normal skin measures 1.3 millimeters or thin as a dime and the depth of the burn itself measured is twice that, 2.6 millimeters. So we have a way of seeing the fluid. We have a way of checking the depth of the burn, which is clinically difficult because the eyes cannot see below the skin.   You can see the blister is basically gone because that's the tiny black area above the tissue line- showing almost no fluid left (represented In the blackish area)

Upon review of Day 9 diagram, see "burn healing" on the left side of this diagram where it says dermis on day 9, you can see the bottom white line under the lettering dermis, which shows the bottom of the skin, which last time was 1.3 millimeters. Then to the right of that the dermis tissue is starting to have the red and blue healing blood vessels that's coming in marked by the red arrow. And then to the right of that where it says decreased vascularity, the larger blood vessels have not yet come in, but at least we know the skin has viable feeding blood flow. So it's more likely than not to heal.

** These images are scanned with the GE Ultrasound Voluson E8.  Any machine over 15 megahertz can be used on burns- however, devices with higher the resolution improves the scan experience to get the best data.

REVIEW OF THE BLOOD FLOW INNOVATION

Today’s imaging devices cover a wide range of functions on the market carrying specific features to fit their many users specific needs.  This scan was generated by the General Electric Voluson E8 system which uses an 18 mhz probe outputting 1/10 of a millimeter of resolution.  The benefit of using this GE 3D Doppler system enables the ability to measure the depth of the burn as well as identify and record the exact amount of fluid in the surface of the burn, which is the blister. 

For many diagnostic applications, the real-time scanning ability of VASCULAR ULTRASOUND has greatly advanced the way injuries are read, identified and managed.  Vascular ultrasound uses sound waves to evaluate the body's circulatory system.  It also helps identify blockages in the arteries and veins and detect blood clots.  This innovation is not radiation based, leaving no harmful side effects and out-performs many of today’s current counterparts including accuracy in scanning soft tissues that does not appear in x-rays. 

BLOOD FLOW technology is the “diagnostician’s storyteller”.  It allows you to see which part of the skin is alive by the indication of active blood flow through the area- versus the skin that is dead or dying with no blood flow. In cases of burns, the margin of injury can extend once the burn has been completely cooled down. Since vascular ultrasound is safe sound waves, you can conduct frequent scans to monitor healing and progress every hour/every day until resolution.

The paradigm of studying blood flow allows any diagnostician to review whether the tissue is curing or not.  In the case of performing a possible skin graft, the blood flow around an injury gives more data as far as the behavior of the burn or injury as well as the condition of healthy tissue to attach to the burn.

Any inflammatory skin disease is caused by inflammatory blood vessels, which is not evident by the naked eye. This scanning modality allows you to quantify the degree of inflammation and the response to all the new treatments available. Where widely accepted optical technologies work well,  they are limited to 1/2 of a millimeter depth, so they are surface only.

SKIN LIFE VS. SCARS 

If the tissue doesn't heal with normal skin, it will scar. The scar tissue appears as black in ultrasound imaging, almost like the fluid- but with zero blood flow.  Any kind of trauma can result in healing tissue or dead tissue, which will either get infected or scar down. Imaging can also show if the area is getting inflamed as it indicates irregular volume of the blood vessels resulting in cellulitis or the inflamed skin.

Scar tissue is dead skin.  Doppler Imaging can be useful as it shows the thickness of the scar to determine if it can be treated, either with steroids, laser or any of a number of current scar treatment technologies.  The depth and the hardness of the scar determines which option to use and all these can be resolved by the various ultrasound technologies. Ultrasound is the new ‘weapon of choice’ to show depth, thickness of the scar, type of scar, how hard or elastic it is  (also see elastography).  It also allows the surgeon to clearly identify the margins you wish to attach the graph to.  

[IMAGE 2] In this image, we have a burn that came from a charcoal grill. This burn leaves a white coating (surface singe) to the red skin. (A) This white surface outline with the black arrows is the ash from the grill or the burning surface. The small yellow circle is the blister that immediately broke from the heat. So the blister burst and opened up causing the teardrop-shaped opening in the skin, which could get infected. 

Diagram B shows the two yellow arrows pointing to the white area, it's got a top white, a medium dark, and a bottom white area.  That's the appearing ash visible only on the surface but not penetrating deep (thus it is not a third-degree burn). Upon further interactive review of the burn, it was only surface ash from the surface of the charcoal grill which was easily removable. On the same image (B), we are also looking at external tendon, 1 mm wide. 

Diagram C indicates the blood vessels and the normal tissue on the side of the burn. Though the burn goes deep into the skin, it is not a complete third-degree burn in the whole area (B). Comparing B and C, the injury to the burned tissue is marked by the red arrow on top and also the tendon that raises the finger pushes 1 mm wide is completely unaffected by the dark burn area. Now below that since we weren't sure if it was a third-degree burn or we wanted to see if there was viable skin next to it, we did the blood flow technology which shows the micro vessels or the capillaries that are in the adjacent skin, so if you ever needed to graft it you'd have normal skin and also the fact that you have normal skin in the red area means that the burn in that area is a first degree or not really burned at all.

“IT’S ALL ABOUT THE PROBES”

The GE Doppler scanner can go deeper under the skin - at an estimated 5x the resolution than the average ultrasound probe (at 1/10mm resolution). The higher the megahertz, the deeper and sharper the image (like 70mhz has 1/50 of a millimeter resolution).  Such a probe is much better for imaging tendons and skin and the regular 18 or 20 megahertz (such as the GE) that we use routinely use has 1/10 of a millimeter resolution. You have better detail for seeing tendons and blood vessels.

Overall, each probe determines a specific depth, the width & range of the scan, the level of blood flow while the hardware & diagnostic software itself communicates with the probe to translate all data into recognizable images in real time.

PRE-OPERATIVE (AND RISK REDUCTION) PROTOCOL

Among its many uses, cosmetic surgeons can benefit from dermal imaging by mapping the nerves and the arteries before cutting. Also, you can find the dead skin as compared to the normal skin for doing reconstructive surgery. 

Emergency departments can more easily treat nerve trauma, burns, tendon injuries with the help of visual analysis of any affected area.  As an example,  you can see if the tendon is partly or completely torn with ultrasound more easily and effectively. you are able to move the finger because it won't be any movement of the torn part. If you move the tendon when you open up the finger from a closed fist position.

ABOUT THE AUTHOR-

ROBERT L. BARD, MD, PC, DABR, FASLMS - Advanced Imaging & Diagnostic Specialist
Having paved the way for the study of various cancers both clinically and academically, Dr. Robert Bard co-founded the 9/11 CancerScan program to bring additional diagnostic support to all first responders from Ground Zero. His main practice in midtown, NYC (Bard Diagnostic Imaging- www.CancerScan.com) uses the latest in digital Imaging technology has been also used to help guide biopsies and in many cases, even replicate much of the same reports of a clinical invasive biopsy. Imaging solutions such as high-powered Sonograms, Spectral Doppler, sonofluoroscopy, 3D/4D Image Reconstruction and the Spectral Doppler are safe, noninvasive, and does not use ionizing radiation. It is used as a complement to find anomalies and help diagnose the causes of pain, swelling and infection in the body’s internal organs while allowing the diagnostician the ability to zoom and ‘travel’ deep into the body for maximum exploration.

References

https://www.cdc.gov/masstrauma/factsheets/public/burns.pdf’’

https://stanfordhealthcare.org/medical-conditions/skin-hair-and-nails/burns/stages.html

https://www.intechopen.com/books/hot-topics-in-burn-injuries/burn-etiology-and-pathogenesis

  

https://www.healthline.com/health/burns#complications

https://www.radiologyinfo.org/en/info.cfm?pg=vascularus

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Part 4:

Wound Healing & Exosomes for the Skin

INTRODUCTION
Our publication's first interaction with Dr. Jordan Plews was during HealthTech Reporter's pilot program where Dr. Robert Bard conducted a performance test of the ELEVAI Exosomes product (Image R).  Dr. Plews, CEO of Elevai collaborated with BardDiagnostics to explore quantifiable  effects of the skin regenerative product, offering a new way of monitoring the progress of a topical serum.  This "test drive" employed the use of hospital-grade 3D Ultrasound, showing remarkable epidermal and subdermal progress with Dr. Plews' exosomes' during a limited time period.

The exploratory relationship continued to grow as both clinical minds entertained other potential benefits of extracellular vesicles (EVs) for its directed use and beyond. The expansion of regenerative medicine brought Drs. Bard and Plews a common appreciation for each others' work in the spirit of publishing new findings for the progress of exosome science as future co-investigators.  This is also evident in this latest report on "Wound Healing & Exosomes for the Skin"- where Dr. Plews brings a clear path of understanding about the regenerative potential for platelet-derived extracellular vesicles.

UNVEILING THE POWER OF CELLULAR COMMUNICATION 
 Written by: Jordan R. Plews, PhD

As a biochemical engineer, molecular biologist, and stem cell researcher, I'm constantly fascinated by the body's intricate communication networks. One particularly exciting area is the field of exosomes, tiny extracellular vesicles released by cells that act as messengers, carrying vital cargo to influence the behavior of recipient cells. In the realm of dermatology, exosomes hold immense potential for promoting and supporting skin health and regeneration. However, it's crucial to understand not only the source of these messengers but also the specific content they deliver for optimal results.

Exosomes: Nature's Nanoscale Communication Network
Exosomes are naturally occurring, membrane-bound nanoparticles (30-150 nm) secreted by various cell types. They carry a rich cargo of proteins, lipids, and genetic material, including messenger RNA (mRNA), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) [1]. This molecular payload allows exosomes to act as intercellular signaling units, influencing the behavior of recipient cells.

In the context of skin, exosomes play a vital role in various processes. They contribute to wound healing, tissue regeneration, immune modulation, and even pigmentation regulation [2, 3]. However, it's important to differentiate between exosomes derived from different cell sources.

Plant vs. Human Exosomes: A Tale of Two Kingdoms
The recent surge in interest in exosomes has led to the exploration of plant-derived options. While plant exosomes may possess intriguing properties, it's crucial to recognize the fundamental limitations. Human and plant cells belong to distinct biological kingdoms with vastly different cellular structures, signaling pathways, and metabolic processes [4]. Therefore, plant exosomes might not be well-suited for addressing human skin concerns. Their cargo may not effectively interact with our cellular machinery, hindering their ability to deliver the desired effects.

Platelets vs. MSCs: Unveiling the Superior Source for Skin Rejuvenation
Platelet-derived extracellular vesicles (EVs) have garnered considerable attention in aesthetics. However, as a stem cell researcher, I find them to be a limited source for comprehensive skin rejuvenation. While platelet EVs offer some beneficial growth factors, their cargo is comparatively restricted compared to exosomes derived from mesenchymal stem cells (MSCs) [5].

MSCs are multipotent adult stem cells with the remarkable potential to differentiate into various cell types. Importantly, MSCs can be isolated from numerous adult tissues, including bone marrow, adipose tissue, and even umbilical cord and placenta [6].

The Power of Younger Sources: Unveiling a Superior Exosome Profile
Interestingly, the source of MSCs significantly impacts the exosome profile. Human MSCs derived from younger sources, such as umbilical cord (hUMSCs) and placenta exhibit several advantages over those from bone marrow or adipose tissue [7, 8]. Here's why:

1. Enhanced Proliferative Capacity: Younger MSC sources possess a higher proliferation rate, leading to a greater yield of exosomes for therapeutic applications, and have been shown to improve the function of older MSCs [9].

2. Superior miRNA and Growth Factor Profile: hUMSCs secrete exosomes rich in specific miRNAs and growth factors known to promote cell proliferation, migration, and tissue regeneration [10, 11]. These factors include vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF), all crucial players in the wound healing cascade.

3. Potent Anti-Inflammatory and Immunomodulatory Effects: Exosomes from younger MSC sources display pronounced anti-inflammatory and immunomodulatory properties [12]. This is particularly beneficial for addressing conditions like chronic wounds or acne, where inflammation plays a key role.

Harnessing the Power of Exosomes for Skin Regeneration: The 4-Phase Wound Healing Cascade

The human body possesses a remarkable ability to heal wounds through a well-defined, four-phase process:

● Hemostasis (0-1 day): This initial phase focuses on stopping bleeding through platelet aggregation and clot formation.

● Inflammation (1-3 days): The body initiates an inflammatory response to remove damaged tissue and prepare for repair.

● Proliferation (3-21 days): New blood vessels are formed, and fibroblasts migrate to the wound site to synthesize collagen, the building block of new tissue.

● Remodeling (~14 days – 2 years): The newly formed tissue matures and strengthens, eventually returning the skin to its pre-injury state [13].

Exosomes sourced from young MSCs, such as human umbilical mesenchymal stem cells (hUMSCs), hold tremendous potential to support each phase of this process. Their cargo of growth factors can accelerate the proliferation phase, while their anti-inflammatory properties can shorten the inflammatory phase. Additionally, miRNAs contained within these exosomes can regulate gene expression to promote tissue repair and regeneration [14].

Conclusion

In conclusion, exosomes represent a promising frontier in dermatology. However, it is crucial to select the right exosome source for optimal results. While plant-derived exosomes may offer some benefits, human-derived exosomes, particularly those from younger MSC sources, provide a superior profile of bioactive molecules to more effectively address a broad array of skin concerns, as many trace back to lack of completion of the canonical four phases of wound healing. By understanding the science behind exosomes and the intricacies of the wound healing cascade, we can harness their power to promote healthier, younger-looking skin.

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ABOUT THE AUTHOR

Dr. Jordan R. Plews is an expert at the intersection of biochemical engineering, stem cell research, and regenerative medicine with a particular focus on the cellular and molecular mechanisms of aging and human longevity. He graduated with 1st class honors in Biochemical Engineering from the University of London and completed doctorate research in Molecular Biology and Stem Cell Research at University College London, specializing in Somatic Cell Reprogramming. After working as part of Pfizer's bioprocess development group in bioprocess design and scale up, he conducted postdoctoral research at Stanford, looking at ways to apply stem cells in inventive and practical ways to treat disease. He held key roles at med/biotech companies like Velos, Becton Dickinson, and Xytogen Biotech, where he developed innovative products for researchers, clinicians, and consumers. At Natera, he lead the launch of Signatera, a personalized genomics based cancer diagnostic. In 2020, he co-founded ELEVAI, creating advanced skincare solutions using human stem cell exosomes. His research, published in leading journals, explores the relationship between stem cells, aging, and disease to enhance and extend healthy lifespan.

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References

1. Raposo, G., & Stoorvogel, W. (2013). Extracellular vesicles: exosomes, microvesicles, and friends. Journal of Cell Biology, 200(4), 373-383.  

2. Qin, Xinchi, et al. "The functions and clinical application potential of exosomes derived from mesenchymal stem cells on wound repair: a review of recent research advances." Frontiers in Immunology 14 (2023): 1256687.

3. Liu, Ying, Haidong Wang, and Juan Wang. "Exosomes as a novel pathway for regulating development and diseases of the skin." Biomedical reports 8.3 (2018): 207-214.

4. Bloemendal, S., Kück, U. Cell-to-cell communication in plants, animals, and fungi: a comparative review. Naturwissenschaften 100, 3–19 (2013). https://doi.org/10.1007/s00114-012-0988-z

5. Anderson JD, Johansson HJ, Graham CS, Vesterlund M, Pham MT, Bramlett CS, Montgomery EN, Mellema MS, Bardini RL, Contreras Z, Hoon M, Bauer G, Fink KD, Fury B, Hendrix KJ, Chedin F, El-Andaloussi S, Hwang B, Mulligan MS, Lehtiö J, Nolta JA. Comprehensive Proteomic Analysis of Mesenchymal Stem Cell Exosomes Reveals Modulation of Angiogenesis via Nuclear Factor-KappaB Signaling. Stem Cells. 2016 Mar;34(3):601-13. doi: 10.1002/stem.2298. Epub 2016 Feb 19. PMID: 26782178; PMCID: PMC5785927.

6. Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D. E., ... & Horwitz, E. M. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8(4), 315-317.  

7. Teng L, Maqsood M, Zhu M, Zhou Y, Kang M, Zhou J, Chen J. Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Accelerate Diabetic Wound Healing via Promoting M2 Macrophage Polarization, Angiogenesis, and Collagen Deposition. Int J Mol Sci. 2022 Sep 9;23(18):10421. doi: 10.3390/ijms231810421. PMID: 36142334; PMCID: PMC9498995.

8. Wang, Zg., He, Zy., Liang, S. et al. Comprehensive proteomic analysis of exosomes derived from human bone marrow, adipose tissue, and umbilical cord mesenchymal stem cells. Stem Cell Res Ther 11, 511 (2020). https://doi.org/10.1186/s13287-020-02032-8

9. Zhang, N., Zhu, J., Ma, Q. et al. Exosomes derived from human umbilical cord MSCs rejuvenate aged MSCs and enhance their functions for myocardial repair. Stem Cell Res Ther 11, 273 (2020). https://doi.org/10.1186/s13287-020-01782-9

10. Zhang, Z., Mi, T., Jin, L. et al. Comprehensive proteomic analysis of exosome mimetic vesicles and exosomes derived from human umbilical cord mesenchymal stem cells. Stem Cell Res Ther 13, 312 (2022). https://doi.org/10.1186/s13287-022-03008-6

11. Bian, D., Wu, Y., Song, G. et al. The application of mesenchymal stromal cells (MSCs) and their derivative exosome in skin wound healing: a comprehensive review. Stem Cell Res Ther 13, 24 (2022). https://doi.org/10.1186/s13287-021-02697-9

12. Yari, H., Mikhailova, M.V., Mardasi, M. et al. Emerging role of mesenchymal stromal cells (MSCs)-derived exosome in neurodegeneration-associated conditions: a groundbreaking cell-free approach. Stem Cell Res Ther 13, 423 (2022). https://doi.org/10.1186/s13287-022-03122-5

13. Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res. 2009 Sep-Oct;37(5):1528-42. doi: 10.1177/147323000903700531. PMID: 19930861.

14. Toghiani, R., Azimian Zavareh, V., Najafi, H. et al. Hypoxia-preconditioned WJ-MSC spheroid-derived exosomes delivering miR-210 for renal cell restoration in hypoxia-reoxygenation injury. Stem Cell Res Ther 15, 240 (2024). https://doi.org/10.1186/s13287-024-03845-7

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