Management of Diabetic Foot Ulcer with MA–ECM (Minimally Manipulated Autologous Extracellular Matrix) Using 3D Bioprinting Technology – An Innovative Approach

Abstract

Chronic foot ulcers are the leading cause of prolonged hospitalization and loss of social participation in people with diabetes. Conventional management of diabetic foot ulcers (DFU) is associated with slow healing, high cost, and recurrent visits to the hospital. Currently, the application of autologous lipotransfer is more popular, as the regenerative and reparative effects of fat are well established. Herein we report the efficacy of minimally manipulated extracellular matrix (MA-ECM) prepared from autologous homologous adipose tissue by using 3D bioprinting in DFU (test group) in comparison to the standard wound care (control group). A total of 40 subjects were screened and randomly divided into test and control groups. In the test group, the customized MA-ECM was printed as a scaffold from the patient autologous fat using a 3D bioprinter device and applied to the wound directly. The control group received standard wound care and weekly follow-up was done for all the patients. We evaluated the efficacy of this novel technology by assessing the reduction in wound size and attainment of epithelialization. The patients in the test group (n = 17) showed complete wound closure with re-epithelialization approximately within a period of 4 weeks. On the other hand, most of the patients in the control group (n = 16) who received standard wound dressings care showed a delay in wound healing in comparison to the test group. This technique can be employed as a personalized therapeutic method to accelerate diabetic wound healing and may provide a promising potential alternative approach to protect against lower foot amputation a most common complication in diabetes.

Preclinical study of diabetic foot ulcers: From pathogenesis to vivo/vitro models and clinical therapeutic transformation

“…Tânia et al transplanted skin grafts made using 3D printing technology into an immunodeficient mouse wound model that could rapidly invade host microvasculature and epidermal tissue 130 . Rajesh et al topically applied an extracellular matrix prepared from autologous homologous adipose tissue using 3D bioprinting to the wounds of patients with DFU, revealing that it could accelerate epithelialization formation 131 …”

“…130 Rajesh et al topically applied an extracellular matrix prepared from autologous homologous adipose tissue using 3D bioprinting to the wounds of patients with DFU, revealing that it could accelerate epithelialization formation. 131 Capillaries can be formed and assembled in 3D printed scaffolds by encapsulating human blood-derived endothelial colony-forming cells and MSCs in 3D gelatin methacrylate (GelMA) to produce dense microvessel systems. Recently, Turner et al combined functionalized scaffolds with GelMA to generate a vascular structural body for improved wound healing, forming strips of natural micro vascularization in in vitro experiments of wound healing.…”

The 3D Bioprinted Scaffolds for Wound Healing

“…The burn wound healing results of employing cellularised materials were far more effective than acellularised treatments [235]. Meanwhile, it was reported that an autologous homologous adipose tissue, prepared employing 3D bioprinting, successfully accelerated diabetic wound healing with complete wound closure and re-epithelialisation within four weeks [236]. Interestingly, Zhang et al, developed a skin model with sweat glands and hair follicles.…”

Preparation and Use of Decellularized Extracellular Matrix for Tissue Engineering

“…In two separate cases where dECM was used to repair damaged urethras, the grafts appeared to form natural urethral mucosa [ 365 ]. Kesavan R et al (2021) used minimally manipulated dECM from autologous homologous adipose tissue to 3D print a wound patch, and all of the patients in the treatment group showed complete wound closure and epithelization within four weeks, whereas patients in the control group who received the standard wound care showed delayed wound healing (~50% at 12 weeks) [ 366 ]. Using dECM from the bladder and small intestine has been shown to work well for treating some mucosal tissues.…”