Innovative Treatment Utilizing an Autologous Blood Clot for Diabetic Foot Ulcers

Marie Williams, DPM; David Davidson, DPM; Naz Wahab, MD; Jessie Hawkins, PhD; Chinenye D. Wachuku, DPM; Robert Snyder, DPM


Wounds. 2022;34(7):195-200. 

In This Article

Abstract and Introduction


Introduction: Diabetic foot ulcer is a complex wound that requires considerable effort to restart a stalled healing process. In this study, a TABCT product was used in a point-of-care setting to treat DFUs by reconstructing the ECM and adjusting intricate phenotypes and mechanisms of mediators to progress towards complete healing. The mechanism of action consists of reconstruction of the ECM, which protects the wound area from further destruction while it incorporates into the ulcer to promote granulation over exposed vital structures (ie, tendons, bone, and neurovascular structures).

Objective: The authors evaluated the efficacy of the TABCT product in the management of DFUs.

Materials and Methods: Study participants were wound care patients in hospitals and clinics across the United States and Israel as part of a registry study ( NCT04699305). Twenty-nine patients age 18 years or older with chronic DFUs were included. A blood clot was created using the patient's own peripheral blood in a point-of-care setting. An 18-mL blood sample was drawn from the patient and incorporated with calcium gluconate and kaolin to form a clot. Efficacy and superiority levels in PAR at week 4 and week 12 over the SOC treatment were established using the Agresti-Coull confidence interval.

Results: Treatment of DFUs using the TABCT product resulted in 22 patients (75.86%) achieving 50% PAR at week 4 and showed superiority when compared with SOC data in previously published studies. Complete closure was achieved in 28 wounds (95%) at week 12.

Conclusion: In the current study, TABCT exhibited superiority over SOC treatment and provided granulation over vital structures with a reduction in overall wound size in a timely manner via incorporation and stimulation of the body's own healing capabilities.


Diabetic foot ulcer is among the most common complications of uncontrolled diabetes and is associated with an increased risk of mortality.[1] The annual incidence of DFUs worldwide ranges between 9.1 million and 26.1 million.[1] It is estimated that approximately 15% to 25% of patients with diabetes will develop a DFU in their lifetime, resulting in increased incidence of hospitalizations and amputations.[1,2] In the United States, the total annual medical cost for the management of DFUs ranges between $9 billion and $13 billion.[3]

Diabetes alters the wound environment and negatively affects the ECM. Hyperglycemia causes an increase in advanced glycation end products, resulting in decreased ECM elasticity, which causes disruption of ECM-cell interactions and signaling.[4,5] Irregularity of the ECM occurs as a result of decreased collagen and elastin production; decreased levels of thrombospondin-1, angiopoietin-like 4, hyaluronan, and glycosaminoglycans; and increased levels of tissue fibronectin, thrombospondin-2, osteopontin, connective tissue growth factor, versican expression, and tenascin-C.[4] The alternating levels of these molecules are responsible for the irregular composition of the ECM and structure, which leads to further interruptions in ECM-cell interactions and compromised cell functions that prohibit proper cell migration, proliferation, and contraction. These adverse events induce a prolonged inflammatory phase, stalled healing process, and compromised neurovascular function, resulting in a chronic DFU.[6]

Effects of Chronicity on Ulcers

In the setting of chronic DFU, cellular events become dysfunctional, and crucial mediators are unable to activate and provide signaling for wound remodeling. Continued disruption of the ECM reduces signaling, adhesion, and activation of macrophages, growth factors, and various mediators, resulting in wound stagnation. Macrophages are essential not only in fostering a wound environment free of debris and bioburden, but in the initiation and progression of the healing cascade towards reepithelialization. Macrophages are involved in host defense, initiation and resolution of inflammation, growth factor production, phagocytosis, cellular proliferation, and tissue restoration in wounds.[7]

Under normal circumstances, owing to inflammation at the ulcerative site, macrophages are recruited to the area, where they engage in the polarization of various phenotypes that are mediated by cytokines, oxidants, lipids, and growth factors released by the same macrophages.[7] Once recruited, macrophages ingest neutrophils, thus initiating their phenotypic conversion into anti-inflammatory macrophages via mediators released by neutrophils. The conversion of macrophages from pro-inflammatory (M1 classically activated) to anti-inflammatory (M2 alternatively activated) is a major differentiating factor between an ulcer that heals vs one that becomes chronic. The M1 macrophages release interleukin 12 and promote strong proinflammatory Th1 immune responses early in the healing process with the main intention of host defense. The M2 macrophages release interleukin 10 to downregulate inflammation and promote repair of soft tissue.[7] Under chronic conditions, macrophages secreting interleukin 1 beta with an inflammatory phenotype are present in diabetic ulcers, which is part of a proinflammatory feedback loop that blocks the activation of M2 macrophages, preventing advancement towards tissue repair. Targeting the pathway of phenotypic modulations of macrophages is beneficial in generating new therapies. Development of a TABCT product (ActiGraft; RedDress Medical) assists in producing an environment in which phenotypic conversion from M1 to M2 macrophages can occur while repairing soft tissue deficits.

Treatment Modality of TABCT

Chronic DFU is often managed using SOC options such as initial offloading, debridement of necrotic and infected soft tissue, antibiotics, and wound care dressings. Wound care dressings must provide a moist wound environment in which proper wound healing may occur. Further developments have been made towards creating autologous therapeutic modalities that can provide a moist and bioburden-free wound environment, reconstruction of the ECM to provide an organized means of signaling and activating mediators that are capable of restoring the wound healing mechanisms, and regeneration and epithelialization of soft tissue. This study evaluates the efficacy of a TABCT product to treat hard-to-heal DFUs in a real-world setting.

The TABCT product can be used in either an outpatient or inpatient setting for safe and rapid preparation and administration of a whole blood clot matrix. The blood clot is derived from the patient's own peripheral blood and biologically delivers necessary growth factors and induces macrophages, cytokines, and mediators to promote the body's natural healing process for treatment of the wound. Each application of the blood clot provides a protective covering, allowing the formation of a scaffold and integration into the ulcer to devise an optimal environment for healing. The newly formed scaffold acts as a biocompatible wound/environment barrier to prevent further contamination of the wound while preventing interruption of advancement through the wound healing process.[16] While providing protection, the fibrin clot allows for remodeling and reconstruction of the ECM in an organized manner to assist with proper cell adhesion and signaling for recruitment of necessary factors and mediators to promote healing.