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Stem Cell Therapy Could Be Breakthrough Against Type 1 Diabetes

WEDNESDAY, Oct. 4, 2023 — People with type 1 diabetes lack functional islet cells in their pancreas to produce the hormone insulin and must take daily insulin via injections or a continuous pump to compensate.

Stem Cells and the Search For a Type 1 Diabetes Cure

But if new research pans out, some folks with type 1 diabetes may no longer need to take insulin. The study of six people with type 1 diabetes found that an investigational off-the-shelf form of islet stem cell therapy improves blood sugar control and slashes insulin needs, with three people no longer needing any daily insulin.

Given via an infusion, VX-880 are stem cell-derived, insulin-producing islet cells that essentially replace the dysfunctional islet cells in people with type 1 diabetes. The study was funded by VX-880 maker Vertex Pharmaceuticals.

“Islet cells have the potential to cure diabetes, and I believe this study is a huge step forward in that direction,” said study author Dr. Trevor Reichman, surgical director of the Pancreas and Islet Transplant Program at University Health Network’s Ajmera Transplant Center in Toronto, Canada.

Type 1 diabetes occurs when the pancreas produces little to no insulin. Insulin is needed to help blood sugar, or glucose, enter the cells, where it is used for energy. When insulin is in short supply, glucose can build up, causing such symptoms as extreme fatigue, blurry vision, weight loss and confusion.

Stem cells can multiply exponentially and morph into different types of cells. The cells used in VX-880 are grown in a lab. Once implanted, they morph into islet cells and can produce insulin.

“They are essentially off-the-shelf but do take several weeks to produce prior to infusion,” Reichman said.

In the new study, all six people treated with VX-880 had improved glycemic control, as shown by elimination of severe low blood sugar reactions, improved HbA1c (a snapshot of blood sugar levels over time), and the amount of time their blood sugar levels were in the recommended range within three months.

As a result, these patients needed less insulin or none at all.

“The impact … was truly life-changing,” Reichman said. “All of these patients had long-standing, difficult-to-manage type 1 diabetes with life-threatening complications, which included severe hypoglycemic unawareness.” Hypoglycemia unawareness means a person can’t tell when their blood glucose gets low, so they don’t know they need to treat it.

Within three months, this was eliminated in all study participants.

Exactly how long these effects will last is not yet known.

“The longest patient in follow-up is now at two years and maintains insulin independence,” Reichman said. The research is ongoing.

The study showed VX-880 is safe, and no serious side effects were reported.

People do need to take immunosuppressant drugs to prevent rejection, which Reichman called a potential roadblock for broader use.

“The future goal is to create a version of the treatment that does not require immunosuppressive therapy,” he said.

The study is limited to people aged 18 through 65 years of age, but in the future, kids may be included.

The findings were presented Tuesday at a meeting of the European Association for the Study of Diabetes, in Hamburg, Germany. Findings presented at medical meetings should be considered preliminary until they are published in a peer-reviewed journal.

Dr. John Buse is the director of the Diabetes Care Center at the University of North Carolina, Chapel Hill.

“The important thing here is that people do not need organ donors to have a source of insulin-producing cells for transplant,” said Buse, who reviewed the findings.

The new stem cell treatment seems to work “pretty well,” he added.

“The patients have to take immunosuppression but they had severe hypoglycemia beforehand so that is a reasonable trade-off for having to take insulin,” Buse said.

Sources

  • Trevor Reichman, MD, surgical director, Pancreas and Islet Transplant Program, University Health Network&rsquo
  • s Ajmera Transplant Center, Toronto, Ontario, Canada
  • John Buse, MD, PhD, director, University of North Carolina Diabetes Care Center, Chapel Hill, N.C.
  • presentation, European Association for the Study of Diabetes meeting, Hamburg, Germany, Oct. 3, 2023
ارور انسداد دستگاه وکیوم تراپی زخم

Blockage Error in Simplex III wound vacuum therapy device

In this educational video, we will talk about one of the alarms of the wound vacuum therapy devices produced by Teb Tajhiz Paya Engineering Company: Blockage Error

When the Blockage error appears, the dressing is not vacuumed on the wound bed and the suction of the device is blocked, the reasons of this alarm will be explained in this clip.

  1. kink of SPP tube
  2. Closed SPP pipe clamp
  3. The smaller size of the foam compared to the SPP in small wounds, in this case, with the suction of the vacuum therapy device, the foam is drawn into the knee of the SPP and causes the path to be blocked.

Therefore, care should be taken to ensure that the size of the foam is 2 to 3 cm larger than the SPP cup in small wounds.

4. Keep in mind that in all wounds, the height or thickness of the foam should be 2-3 cm higher than the surface of the wound.

زخم سوختگی

Introduction and treatment of burn wounds

There are many types of burn wounds caused by thermal, radiation, chemical, or electrical contact.

  • Thermal burnsThese burns are due to heat sources which raise the temperature of the skin and tissues and cause tissue cell death or charring. Hot metals, scalding liquids, steam, and flames, when coming into contact with the skin, can cause thermal burns.

 

  • Radiation burns. These burns are due to prolonged exposure to ultraviolet rays of the sun, or to other sources of radiation such as X-ray.

 

  • Chemical burns. These burns are due to strong acids, alkalies, detergents, or solvents coming into contact with the skin or eyes.

 

  • Electrical burns. These burns are from electrical current, either alternating current (AC) or direct current (DC).

 

What are the classifications of burns?

Burns are classified as first-, second-, or third-degree, depending on how deep and severely they penetrate the skin’s surface.

  • First-degree (superficial) burns
    First-degree burns affect only the epidermis, or outer layer of skin. The burn site is red, painful, dry, and with no blisters. Mild sunburn is an example. Long-term tissue damage is rare and usually involves an increase or decrease in the skin color.

 

  • Second-degree (partial thickness) burns
    Second-degree burns involve the epidermis and part of the dermis layer of skin. The burn site appears red, blistered, and may be swollen and painful.

 

  • Third-degree (full thickness) burns
    Third-degree burns destroy the epidermis and dermis. Third-degree burns may also damage the underlying bones, muscles, and tendons. When bones, muscles, or tendons are also burned, this may be referred to as a fourth-degree burn. The burn site appears white or charred. There is no feeling in the area since the nerve endings are destroyed.

 

wound vacuum therapy in burn wound

Third degree burns, after adequate debridement, may benefit from NPT, which may be applied as an adjuvant in bed preparation for subsequent skin grafting, or as a method of optimizing the integration of skin grafts. Patients with electrical trauma, which generally cause deep burn wounds with extensive tissue destruction and progressive tissue damage, are also NPT candidates. The increase in blood perfusion secondary to NPT use is beneficial to burn injury. Kamolz et al. observed this in 2003, in a prospective study comparing the blood perfusion of burned hands that underwent conservative therapy and NPT. In the conservatively treated group, the authors observed reduced limb blood perfusion, which did not occur in the NPT-treated group.

زخم تروماتیک

wound vacuum therapy in traumatic wounds

Traumatic wounds include a group of acute, generally extensive, wounds with loss of cutaneous lining, associated or not with fractures. They are represented by degloving wounds, exposed fractures, wounds associated with muscular crushing, and others, affecting predominantly patients of economically active age.

The stimulation to the formation of granulation tissue in these wounds may be responsible for the reduction in the complexity of the reconstruction option. For example, NPT can promote the coverage of exposed bones and tendons by granulation tissue, allowing wound closure by means of skin grafting, rendering unnecessary the use flaps, with and without concomitant use dermal matrices.

In 2012, Blum et al. evaluated the effect of NPT on the rate of infection in 220 patients with exposed tibial fractures, through a multicenter retrospective cohort study. The infection rate of the NTP group was lower (8.4% x 20.6%, p=0.01) compared with the group receiving conventional moist dressing. In 2006, Yang et al. evaluated the efficacy of NPT in the Treatment of 34 patients with fasciotomy wounds after traumatic compartment syndrome. The mean time to final wound closure was 6.7 days for the NPT group and 16.1 days for the conventional moist dressing group (p<0.05).

In 2013, Milcheski et al. studied 178 patients with traumatic lower limb wounds, most of them represented by degloving wounds. NPT significantly reduced the morbidity and healing time when compared with the previously used conventional dressings. According to the authors, NPT is useful in the treatment of acute traumatic wounds, acting as a bridge between emergency treatment and definitive cutaneous coverage.

زخم فشاری

Negative pressure therapy for the pressure ulcers

Pressure ulcers (PU) are caused by the pressure maintained between a bone prominence and the patient’s bed, leading to ischemia and necrosis of the involved tissues. They are common in patients with some mobility restriction, such as spinal cord injuries (paraplegic and quadriplegic) and patients under prolonged sedation. The most frequent sites of their development are the sacral, sciatic, trochanteric, calcaneal and occipital regions, among others.

The application of wound vacuum therapy in these wounds has the main objective of improving the local conditions for a later repairing surgery to obtain definitive cutaneous cover. This sequence is valid mainly in the cases of Pressure ulcers stages III and IV of the National Pressure Ulcer Advisory Panel (NPUAP), represented by deeper wounds, with muscular or bone exposure. Clinical reports such as that performed by Batra and Asseja19, however, show that even more complex wounds, when acute, could be treated only with NPT.

In 2002, Ford et al conducted a randomized, controlled study with 41 patients with deep Pressure ulcers, comparing NPT with topical healing promoter gels. The mean percentage reduction in ulcer volume was higher in the NPT group (51.8% vs. 42.1%, p=0.46). The mean number of capillaries per wound bed field was also higher in the NPT group (p=0.75). The authors stated that NPT promotes healing and neovascularization when compared to topical gel treatment20.

Ashby et al., in 2012, conducted a randomized controlled trial in patients with pressure ulcers grades III and IV, showing superior benefits of NTP in comparison with moist dressing.

source: https://www.scielo.br/j/rcbc/a/W6qy4BFN9DkdTRsGy6jrfkk/?lang=en&format=html#

skin equivalent

Printing technique creates effective skin equivalent, heals wounds

Chronic wounds are deep and difficult to repair. Often, the top of the injury heals before the bottom, so the wound collapses in on itself. Over time, this can result in scar tissue and reduced skin function. Skin equivalent is a new way for healing wounds.

In APL Bioengineering, by AIP Publishing, researchers from the University of Birmingham and University of Huddersfield developed an approach to print skin equivalents. The material may play a future role in facilitating the healing of chronic wounds.

print skin equivalents technique

The technique is the first of its kind to simulate three layers of skin: the hypodermis, or fatty layer, the dermis, and the epidermis.

“You effectively have three different cell types. They all grow at different speeds,” said author Alan Smith. “If you try to produce tri-layered structures, it can be very difficult to provide each of the requirements of each different layer.”

To solve this problem, the scientists used suspended layer additive manufacturing (SLAM). They created a gel-like material to support the skin equivalent, twisting and altering the structure of the gel as it formed to create a bed of particles that can then support a second phase of gel injection.

During printing, the skin layers are deposited within the support gel, which holds everything in place. After printing, the team washed away the support material, leaving behind the layered skin equivalent.

If the researchers moved a needle through the supporting gel, it repaired itself faster than other similar techniques. This results in higher resolution printing than previous methods and allows for the printing of complicated skin structures.

The authors tested the skin substitute by cutting a hole in pig tissue and printing a skin equivalent to fill the hole. After culturing the model system for 14 days, they saw signs of wound repair.

“We used a stain that allowed us to quantify the integration we got between original material and tissue,” said author Liam Grover. “We were able to demonstrate some integration even after a short period of time.”

The team cannot assess chronic wound healing with the skin substitute because that process takes more time than their model allowed, which was only 14-21 days. However, their next step is to test longer, appropriate models for chronic deep wounds. The ultimate goal is to repair human skin and reduce scarring for all patient scenarios.


Story Source:

Materials provided by American Institute of PhysicsNote: Content may be edited for style and length.

انتخاب میزان فشار

Choose pressure level for all types of wounds with Simplex III devices

In the following cases, a pressure more than -125 mmHg and less than -150 mmHg can be used:

  1. High secretions wounds
  2. Vacuum therapy using white foam
  3. Vacuum therapy using abdovac kit

In the following cases, pressures less than -125 mmHg is recommended:

  1. Diabetic foot ulcers
  2. Damaged vessels
  3. Patients with a lower pain threshold

Note: In case of skin grafts, pressure of -50 to -80 mmHg should be used.

پانسمان

Finding the optimal wound dressing

The ultimate goal of wound care is to accelerate healing and prevent acute wounds from becoming chronic. Part of this process involves choosing a wound dressing that complements the characteristics of the wound.

The $6.6-billion market for advanced wound dressings offers dozens of variations. Both alginate dressings, composed of seaweed or kelp, and foam dressings, made of polymer solutions, can absorb exudate and keep wounds moist; collagen or silicone-based dressings help stimulate new tissue and blood vessel growth; and hydrogels and hydrocolloids allow wounds to retain moisture (Front Bioeng Biotechnol 2020. doi:10.3389/fbioe.2020.00182).

Each category of dressing may contain additional substances—calcium, honey or silver, for example—to enhance antimicrobial activity (Cellulose 2020;27:385-400. doi.org/ 10.1007/ s10570-019-02795-1). Given the array of possibilities, how do experts choose the best option for each patient?

“In an ideal world, the wound dressing literature would help us choose among the many products, but unfortunately, we have minimal evidence to support the use of one product over another,” said Alex Wong, MD, the chief of plastic surgery at City of Hope Comprehensive Cancer Center, just outside Los Angeles.

High-quality trials comparing the efficacy of different wound dressings are hard to come by. According to a 2014 review that examined the effectiveness of wound dressings, experts found the literature contained “much conflicting data,” with few randomized controlled trials clearly demonstrating the advantage of particular materials or categories of wound dressings (Adv Wound Care [New Rochelle] 2014;3[8]:511-529).

Although the literature provides few definitive answers, “no wound or patient is the same,” and thus no single wound dressing will provide a “magic bullet” for everyone, Dr. Wong said.

Like dressings, wounds come in many forms (venous skin and diabetic foot ulcers, pressure sores, radiation-related injuries, or burns), with a range of characteristics (necrotic or infected tissue, exposed bone, or excessive exudate). Patient factors, including diabetes, peripheral artery disease, cancer and smoking, also affect wound healing.

“I can purchase all of the most expensive wound dressings out there, but they won’t help if I don’t know the patient factors contributing to poor wound healing,” said Jeffrey Chang, MD, MS, an assistant clinical professor in the Division of Plastic Surgery at City of Hope. “You have to understand and treat both.”

That’s why Dr. Chang begins each visit with a thorough patient exam and history: Does the patient have diabetes or hypertension? Does he have a condition that suppresses his immune system?

After identifying patient risk factors, Dr. Chang focuses on the wound itself, relying on four fundamental principles of wound care to guide his decision making. These principles, developed almost two decades ago, are represented by the acronym TIME:

  • Tissue
  • Infection/Inflammation
  • Moisture
  • Edges

When examining the wound, he looks for dead or infected tissue, moisture content, and how far apart the wound edges are.

For infected wounds, Dr. Chang may prefer a dressing with antimicrobial properties. If a wound is too wet, he will opt for a product that can absorb excess exudate. If the edges are far apart, he will use a leg wrap or abdominal binder to help close the wound. “By going through these stages, I can navigate my way to a more optimal dressing,” Dr. Chang noted.

Jennifer Powers, MD, an associate professor of dermatology at the University of Iowa Carver College of Medicine, in Iowa City, uses a similar process to determine the most appropriate dressing. “I don’t just zoom in on the wound; I analyze my patient from head to toe to understand the multifactorial reasons for poor healing,” she said. “I look at the skin over the entire body, I do blood work to assess kidney and liver function, as well as other factors, that may cause a wound to fester.”

The wound itself can point Dr. Powers toward a particular type of dressing. “I’ve had patients walk into my clinic with a diaper taped to their leg because of the exudate coming off the wound,” she said. In this case, Dr. Powers would likely go for an alginate or foam dressing to help manage the exudate.

The question then becomes which variation of alginate or foam dressing is optimal. Alginate dressings, for instance, have dozens of spinoffs—some embedded with silver, others with calcium or zinc calcium.

Fortunately, experts do not need to sort through dozens of options. Wound dressing choice is often driven by a hospital’s formulary, which will vary from institution to institution.

“Most hospitals will have one to two options in any given class of products because stocking much more than that will be a big financial loss for an institution,” said Geoffrey Gurtner, MD, a professor of surgery and the inaugural vice chairman of surgery for innovation at Stanford University School of Medicine, in California. “I just use whatever wound dressings are available among those options.”

Dr. Wong agreed that staying flexible with wound dressing choice is important. “Your hospital may not be willing or able to purchase a specific wound dressing for you, which is why I do not rely on any product in particular,” he said.

When choosing among an institution’s offerings, personal experience and cost also may influence decision making. To avoid surgery, Ernest S. Chiu, MD, a plastic and reconstructive surgeon at NYU Langone Health, in New York City, often uses skin substitutes to treat chronic, slow-healing wounds, but he questions whether the potential to accelerate wound healing by a few days justifies the higher price tag of these products. Skin substitutes can cost hundreds, even thousands of dollars, but it’s not clear whether these products are cost-effective (Adv Wound Care [New Rochelle] 2014;3[8]:511-529).

The challenge for the wound care industry will be to veer away from developing more “me-too” products with slight variations and instead focus on pushing the boundaries of wound care. Dr. Chiu highlighted early work that uses artificial intelligence–based predictive algorithms to help clinicians make diagnoses and predictions about the wound healing process (JAMA Netw Open 2021;4:e217234).

Dr. Chang sees promise in biologic dressings. A recent systematic review of 25 studies found that diabetic foot ulcers treated with biologic skin substitutes were 1.67 times more likely to heal by 12 weeks compared with standard-of-care dressings (Ann Plast Surg 2019;83[4S suppl 1]:S31-S44).

Other experts are investigating the use of stem cells in wound care. Although the evidence to date focuses on animal models, combining hydrogel dressings with adipose-derived stem cells, for instance, could help accelerate the healing process (J Biomed Mater Res B Appl Biomater 2019;107[2]:278-285).

“It’s still early days but I think we’re heading more toward biologic-based wound dressings embedded with growth factors that can help jump-start the wound healing process as well as understanding the molecular basis of a wound in order to optimize the treatment,” Dr. Chang said.

However, Dr. Chang added, “even without wound dressing products, as long as the TIME principles are followed—no dead tissue, no infection, moist environment—the body will heal. Having advanced wound dressings in our tool box helps but means we need to find the right balance between a product that is appropriate and a cost that is reasonable.”

choose therapy mode

choose therapy mode in wound vacuum therapy

Variable therapy mode is a useful combination from increasing and decreasing blood flow.

Increasing blood flow:

  • Facilitate oxygenation
  • Nutrient supply

Decreasing blood flow

  • stimulation angiogenesis
  • Granulation tissue formation

 

Comparison variable pressure and continuous pressure

  • Variable pressure results more granulation tissue formation than continuous pressure.
  • Repeated mechanical simulations due pressure changes cause enhanced regeneration of wound edges so wound contraction in vacuum therapy with variable pressure is more than continuous pressure

 

Contraindications of variable therapy mode:

Applying variable pressure in some wound types can be harmful(contraindication):

*Continuous pressure can be used for all types of wounds without risk.

کرم ترمیم کننده زخم بدون اسکار

The first human trials of scarless wound healing cream

Researchers from The University of Western Australia (UWA; Perth, Australia) have partnered with industry to conduct a world-first study to investigate a new product—a topical scareless wound healing cream containing the drug PXS-6302 (Pharmaxis)—that has the potential to prevent or reduce scars forming after trauma and particularly following burn injury.

This research have started in Australia.

Kylie Sandy-Hodgetts, Mark Fear, and Fiona Wood, all from UWA Medical School and the Skin Integrity Research Institute UWA, are working with industry partner pharmaceutical company Pharmaxis, clinical trials facility Linear Clinical, the Burn Injury Research Unit, and Burns Service at Fiona Stanley Hospital.

Sandy-Hodgetts says skin scars placed a substantial physical and psychological burden on patients. “Current treatments aim to rectify the scar in the acute phase, such as during wound healing and scar maturation, through options such as compression therapy, silicone gel sheeting, or when the scar is established by cryotherapy, scar revision, or laser with limited outcomes at times,” she adds. “This new compound may potentially avoid the need for invasive procedures such as further surgery or laser procedures.”

The world-first human trial, led by Wood and Sandy-Hodgetts, aims to determine the safety and tolerability of the product in healthy volunteers, which will lead to further trials in burns and surgical patients.

“Scar formation following surgery has a huge impact on patient wellbeing and how they feel about themselves,” Sandy-Hodgetts comments.

“What we are hoping is that this new scarless wound healing cream may have the potential to improve scar outcomes in patients following surgery.”

Wood notes that it was exciting for the research team to explore a novel path to reduce scarring and to be moving closer to that goal: “Scar-less healing is the vision that has motivated our work over many decades”.

Pharmaxis CEO Gary Phillips says that the company is also very excited to see its expertise in fibrosis being applied to help patients with scarring.

“We have had a long and productive collaboration with researchers at UWA and this world-first trial of our drug PXS-6302 will establish whether the remarkable results seen in the pre-clinical models can be replicated in patients,” he states.

“Scarring can have a devastating and life-long impact on people who have suffered traumatic injuries. A topical cream to reduce scarring would have a significant role in treatment”.

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