Use of autologous whole blood clot in the treatment of complex surgical wounds: a case series.

OBJECTIVE: Dehiscence and infection of hard-to-heal surgical wounds results in an increased risk of complications and mortality. A hard-to-heal surgical wound will present decreased levels of growth factors along with increased levels of debris and matrix metalloproteinases, resulting in the destruction of the extracellular matrix (ECM). ActiGraft (RedDress Ltd., Israel) is an autologous whole blood clot treatment, created at a point of care, to promote wound healing. We hereby present the efficacy of ActiGraft in a case series of hard-to-heal surgical wounds. METHOD: A registry study of patients with surgical wounds was conducted in private clinics and hospitals across the US and Israel (NCT04699305). Autologous whole blood clot was created at point of care using the patient's own blood. RESULTS: A total of 14 patients took part in the study. Autologous whole blood clot treatment resulted in a mean percent wound area reduction of 72.33% at four weeks, with 33.33% of wounds achieving complete closure by week 4. At week 12, 78.54% of the wounds achieved complete closure. CONCLUSION: Surgical wounds in patients with comorbidities may fail to initiate the natural wound healing mechanism which in turn may cause deterioration of the wound into a hard-to-heal stage. In this case series, autologous whole blood clot treatment was able to restore wound healing, avoiding the risk of infection and amputation of an affected limb. The properties of autologous whole blood clot as an ECM reduce the risk of infection, causing the wound to progress from the inflammatory phase to the proliferative phase. Autologous whole blood clot treatment in hard-to-heal surgical wounds was found to be an effective approach, reducing the risk of infection and promoting cell granulation, resulting in wound closure.

Proposed Mechanism of Action of Topically Applied Autologous Blood Clot Tissue.

BACKGROUND: Chronic wounds, especially in patients with diabetes, often represent clinical challenges. Recently, the use of a topically applied blood clot has garnered significant interest. This stromal matrix contains viable cells that are autologous, biocompatible, biological, and consistent with a metabolically active scaffold. It has been shown to be safe, effective, and cost-efficient. However, the mechanism of action of this modality remains elusive. We sought to identify a potential mechanism of action of an autologous blood clot. METHODS: Review of clinical and scientific literature hypothesizes on how autologous blood clots may stimulate healing and facilitate the movement of critical substrates while lowering bioburden and fostering angiogenesis. RESULTS: Blood serves as a carrier for many components: red blood cells, white blood cells, platelets, proteins, clotting factors, minerals, electrolytes, and dissolved gasses. In response to tissue injury, the hemostatic mechanism uses a host of vascular and extravascular responses initiating primary, secondary, and tertiary hemostasis. The scaffold created by the autologous blood clot tissue provides a medium in which the body can transform the wound from a nonhealing chronic condition into a healing acute condition. The autologous blood clot tissue also creates a protective setting for the body to use its own mechanisms to promote wound healing in an organized manner. This transient scaffold recruits surrounding fibroblasts and promotes cell ingrowth to foster granulation tissue remodeling. Cells in this matrix sense not only soluble factors but also their physical environments. This well-orchestrated mechanism includes signals from soluble molecules, from the substrate/matrix to which the cell is adherent, from the mechanical or physical forces acting on it, and from contact with other cells. Topically applied autologous blood clot tissue can lower bacterial bioburden while stimulating angiogenesis and fostering the movement of keratinocytes and fibroblasts. CONCLUSIONS: Topically applied autologous blood clot tissue is a formidable cellular and tissue-based therapy that has been shown to be safe and effective. Although the central component of this therapy is blood, the autologous clot tissue creates a scaffold that performs as a biological delivery system that functions to control the release of growth factors and cytokines over several days.

Utilization of a topical autologous blood clot for treatment of pressure ulcers.

Management and treatment of pressure ulcers (PUs) are met with great difficulty due to various factors that cause vulnerability of the soft tissue such as location, limited mobility, increased friction and shearing forces, as well as other comorbidities that may delay or halt wound healing. The topical autologous blood clot therapy (TABCT) is a point-of-care treatment used as a blood clot to assist in recreating and repairing the extracellular matrix (ECM). The mechanism of action consists of reconstruction of the ECM by incorporating into the ulcer, providing protection from further external destruction, while assisting in advancement through the wound healing phases via interaction of necessary growth factors, mediators, and chemokines. This study aims to assess the efficacy of the TABCT in the treatment of PUs in comparison to standard of care (SOC) treatment. Twenty-four patients, 18 years or older, with PUs ranging from stage 1 to 4, were included in this study. TABCT was created by using the patient's own peripheral blood in a point of care setting. Efficacy in percent area reduction (PAR) on weeks 4 and 12 with TABCT over SOC was assessed. Treatment using TABCT in PUs resulted in 77.9% of the patients achieving a 50% PAR on week 4. The mean PAR on week 12 was 96.23% with 45% of the wounds treated with TABCT achieving complete wound closure. TABCT exhibited efficacy in PAR of PUs. In addition, TABCT use prompted granulation tissue formation over vital structures, such as bone, which is often present in later stage PUs. The potential of bringing an affordable, cost-effective, advanced biologic bedside treatment that is efficacious in resolution of these complex wounds has the potential to drastically reduce the burden of treatment on the health system.

Innovative treatment utilizing an autologous blood clot for diabetic foot ulcers.

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 (ClinicalTrials.gov: 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.

Design, construction, and optimization of a novel, modular, and scalable incubation chamber for continuous viral inactivation.

We designed, built or 3D printed, and screened tubular reactors that minimize axial dispersion to serve as incubation chambers for continuous virus inactivation of biological products. Empirical residence time distribution data were used to derive each tubular design's volume equivalent to a theoretical plate (VETP) values at a various process flow rates. One design, the Jig in a Box (JIB), yielded the lowest VETP, indicating optimal radial mixing and minimal axial dispersion. A minimum residence time (MRT) approach was employed, where the MRT is the minimum time the product spends in the tubular reactor. This incubation time is typically 60 minutes in a batch process. We provide recommendations for combinations of flow rates and device dimensions for operation of the JIB connected in series that will meet a 60-min MRT. The results show that under a wide range of flow rates and corresponding volumes, it takes 75 ± 3 min for 99% of the product to exit the reactor while meeting the 60-min MRT criterion and fulfilling the constraint of keeping a differential pressure drop under 5 psi. Under these conditions, the VETP increases slightly from 3 to 5 mL though the number of theoretical plates stays constant at about 1326 ± 88. We also demonstrated that the final design volume was only 6% ± 1% larger than the ideal plug flow volume. Using such a device would enable continuous viral inactivation in a truly continuous process or in the effluent of a batch chromatography column. Viral inactivation studies would be required to validate such a design. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:954-965, 2017.