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Diabetic Foot Ulcers and PRF

By August 3, 2022April 16th, 2024No Comments

In 2021, it was estimated 537 million people worldwide are diabetic. 463 million people represent 9.3% of the global population ages 20-79. This number is expected to increase to 643 million in 2030 and 783 million by 2045

In the United States, in 2020, 34.2 million people of all ages (10.5% of the population) has diabetes, with Pacific Islanders and American Indians having the highest rate of Diabetes in the US.

China has the highest rate of diabetes world -wide and Lithuania, Estonia and Ireland the lowest at about 4%. Almost 240 million people world -wide are living with undiagnosed diabetes.

Diabetes is responsible for 6.7 million deaths in 2021-1 every 5 seconds. Diabetes caused at least USD 966 billion dollars in health expenditure- a increase of 316% over the last 15 years. In the US, 1 in 7 adults are living with diabetes. The number of adults in the US is expected to reach 57 million by 2030 and 63 million by 2045. 1 in 4 adults living with diabetes are not diagnosed

931,000 deaths caused by diabetes in 2021.

USD 415 billion spent on diabetes in 2021

Foot Ulcers in Diabetes

The annual incidence of foot ulcers world-wide is between 9.1 to 26.1%.

Around 15 to 25% of patients with diabetes mellitus will develop a foot ulcer during their lifetime.

The causes are peripheral neuropathy (nerve damage) and lower extremity ischemia (lack of blood flow) due to peripheral artery disease are the primary cause of diabetic foot ulcers. Patients with diabetic foot ulcers are commonly seen by a healthcare provider about 14 times a year and are hospitalized about 1.5 times a year. The cost to Medicare is about $33,00 yearly per patient.

Leg ulcers are commonly caused by venous disease accounting for almost 80% of all lower extremity ulcerations. Peak incidence is between 60-80 years of age. Approximately one third of patients with chronic venous insufficiency will develop venous ulcers before the age of 40.

Although there is no evidence that diabetes causes venous diseases like varicose veins or deep vein thrombosis, there is evidence that diabetes makes these patients more susceptible to diseases affecting the health of the veins in the lower extremity affecting overall vein health. Varicose veins, spider veins and DVT can then develop leading to venous ulcers.

Over time, high blood glucose levels can weaken the veins and damage blood vessels. These weakened vessels are then more susceptible to infection. The infection can lead to skin breakdown and ulcer development.

Signs of Diabetic Foot Problems

  • Changes in skin color
  • Changes in skin temperature
  • Swelling
  • Pain in the legs
  • Open sores that are slow or do not heal
  • Fungus in the nails
  • Dry cracking skin
  • Decreased sensation

Treatment of Diabetic Foot Ulcers

  • Primary Goal is to manage the blood sugar
  • Treatment and prevention of infection
  • Off Load the area- take pressure off
  • Debride the dead tissue
  • Apply covering to the area and medication

Treatment of Leg Ulcers

  • Cleaning the area of dead tissue- surgical debridement may be needed
  • Specialized wound dressings to augment the various stages of wound healing
  • Occlusive dressings


A Hydrogel is a hydrophilic polymer that does not dissolve in water. They are highly absorbent yet maintain well defined structure. The hydrogel was first used in 1894.

The polymers fall into two general categories:

  1. Chemical hydrogels which have strong covalent bonding. These bonds result in strong irreversible gels that may have harmful properties and are unfavorable for medical applications
  2. Physical hydrogels are not toxic and have biocompatibility and are favorable for medical use.

Hydrogels are prepared using a variety of materials and are further divided into two categories according to their origin:

  1. Natural polymers include hyaluronic acid, chitosan, heparin, alginate and fibrin
  2. Synthetic polymers include polyvinyl alcohol, polyethylene glycol, sodium polyacrylate, acrylate polymers and copolymers

Hydrogels from different materials can be used in the biomedical field such as regenerative medicine. Hydrogels can be derived from biologic materials. These hydrogels can incorporate protein polymers such as collagen, elastin and polysaccharide polymers like glycosaminoglycans or alginate. Introduction of decellularized tissues into hydrogel synthesis has several advantages compared to others. Preservation of natural molecules such as growth factors, glycans, bioactive peptides and natural proteins can promote cell growth, function, differentiation, angiogenesis, anti-angiogenesis, antimicrobial effects and chemotactic effects.

Uses of Hydrogels

  • Soft contact lenses
  • Breast implants
  • Disposable diapers that absorb urine
  • Dressings for burns and hard to heal wounds such as leg ulcers and diabetic foot ulcers

Natural Hydrogels have unique properties including biocompatibility, biodegradability, low cytotoxicity and the possibility to tailor the hydrogel to an injectable gel. These products are used to mimic the natural environment in human tissues. They are called “smart biomaterials” because they can adapt and interact with the cellular microenvironment. However, each material has limitations especially in the healing of leg ulcers and diabetic foot ulceration.

Platelet Rich Fibrin

Platelet Rich Fibrin is an autologous leukocyte and platelet rich fibrin biomaterial that is produced from the patients own blood and can be used for a variety of applications including wound/ulcer healing. It is well known and documented ,platelets participate in homeostasis, angiogenesis inflammation and tissue repair and regeneration. Growth factors released from platelets precipitate and stimulate the differentiation of mesenchymal stem cells involved in the healing process. The ability to provide super-physiologic doses of platelets to an area of tissue damage is the basis of platelet rich plasma and platelet rich fibrin.

The Platelet Rich Fibrin forms a dense fibrin network that enables slower degradation rate and therefore delayed release of growth factors to the surrounding tissue for healing and regeneration. The release of growth factors from PRF has been reported up to 7 days for the majority of applications and in one study ,the growth factors were elevated after 30 days.

In wound applications, the advantages of the combination of both platelet rich plasma and platelet rich fibrin are :

  • Completely autologous product with no antigenicity
  • No biochemical handling as in hydrogels
  • Contains growth factors and cytokines involved in wound healing
  • Has leukocytes present to fight infection
  • Highly flexible and elastic
  • PRF shows extended growth factor release
  • Cost is inexpensive vs. hydrogels


Curr Pharm Biotechnol 2012 Jun;13(7): 1145-1152  PMID 21740377

Purpose: Platelet concentrates for surgical use are tools of regenerative medicine designed for the local release of platelet growth factors into a surgical or wounded site in order to stimulate tissue healing or regeneration. In this demonstration, we highlight some outstanding differences in the growth factor and matrix protein release between the 2 families of platelet concentrate.

Conclusion: PRP completely dissolves in the culture in less than 5 days while the PRF are still intact after 7 days. This simple demonstration shows the final architecture of the fibrin matrix considerably influence the strength and growth factor trapping and release.

Clin Oral Investig 2016 Dec; 20(9): 2353-2360. PMID 26809431

Purpose: The use of platelet concentrates has gained increasing awareness in recent years for regenerative procedures. The aim of this study was to compare the growth factor release over time from PRP, PRF and Advanced-PRF (activated)

Conclusion: The results from the present study indicate that the various platelet products have quite different release kinetics. The advantages of PRP is the release of significantly higher proteins at earlier time points whereas PRF displayed a continual and steady release of growth factors over a 10 day period of time. It was also observed A-PRF release a significantly higher total quantities of growth factors when compared to traditional PRF.

ACS Appl Mater Interfaces 2020 Dec 16; 12(50): 55659-55674  PMID 33327053

Purpose: Diabetic skin ulcer is one of the severe complications of diabetes mellitus which has a high incidence and may cause death or disability. Platelet Rich Plasma is widely used in the treatment of diabetic wounds due to the effect of growth factors derived from it. In our study, we fabricated a self-healing hydrogel for promoting diabetic wound healing.

Conclusion: The results showed that it could promote the proliferation of repair cells in vitro. Moreover, it could enhance wound healing by expediting collagen deposition, angiogenesis and nerve repair in a type 2 diabetic rate model and rat skin defect model.

ACTA Biomater 2019 Mar 15;87:76-87  PMID 30665019

Purpose: This work focused on the optimization of a PEGylated platelet rich plasma hydrogel for the protracted release of cytokines, growth factors, and signaling molecules and also the delivery of a provisional framework for stem cell angiogenesis.

Conclusion: Our findings support an innovative means of cellular therapy intervention to improve surgical wound healing in a normal wound model. It could be an efficacious and completely autologous therapy for people who have poorly healing wounds caused by vascular insufficiency, previous radiation or full thickness burns. Because wound healing is a dynamic and complex process, the application of more than one growth factor with ASC demonstrates an advantageous way of improving healing.

Juventix Regenerative Medical is an industry leader in the regenerative medical field. Our Platelet Rich Plasma Kits are FDA approved and designed for safety and effectiveness. They are cost effective and very easy to use. Our kits provide consistency of concentrated product when obtained from the same source.

Juventix Regenerative Medical offers a patent pending LED Photo- Activator to activate the platelets and begin the regenerative process. The activation, a critical step in the release of cytokines and growth factors, is accomplished with light and not with the addition of other chemicals such as Calcium Chloride or Thrombin.

Juventix Regenerative Medical supplies a Bio-Incubator that transforms the Platelet Rich Plasma into an Injectable Platelet Rich Fibrin. The PRF, commonly called the “second generation of platelet products, has a broader range of clinical applications while providing outstanding outcomes.




Regenerative Regards,


Dr. Robert McGrath




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