1. Prevalence and prognosis of diabetic foot ulcers combined with renal diseases
39.3% of the diabetic foot patients will suffer from chronic renal diseases[6]. As the glomerular filtration rate (GFR) reduces, there will be a fold increase in nonhealing ulcers, major amputation, and mortality risk[6-8]. The massive proteinuria is not only a crucial risk factor causing nonhealing ulcers and amputation, but also an independent risk factor for cardiovascular events and death, as well as all-cause mortality[9-10]. Both the hemodialysis and peritoneal dialysis can increase the risk of DFU by more than four times among patients in the stage of uremia[11]. It averagely takes diabetic patients 7 months (2-40 months) to experience from hemodialysis to amputation[12]. Our department has received and cured 115 dialysis patients with DFU since 2017, with the limb salvage rate reaching 83.1%.
2. Formulation of therapeutic schemes
This report is concerned with an aged female, who, with multiple complications and combined diseases, has undergone the hemodialysis treatment for 3 years. Although the blood supply in both lower limbs seemed sufficient according to the ABI that was measured to be 0.6 on the left side and 0.7 on the right side, the results of X-ray, color dopplar ultrasound and CT angiography indicated that the patient had severe arterial calcification in her lower limbs. Therefore, the ABI was considered to be too “impractically high” to evaluate the degree of foot ischemia accurately. Under such circumstances, the endovascular drug-coated balloon dilatation was performed to improve the blood supply to the distal end of left lower limb.
Considering that the heel ulcer is located in the weight-bearing area, the sural neurouascular flap or free flap can be used to repair the wound so that the healed skin is extremely hard-wearing[13]. However, the patient in this case, with a large area of ulcer in the flap donor site on the back of her lower leg, was intolerant to the anesthesia implemented during the free flap operation, and the therapeutic effect could not be guaranteed. Therefore, the tissue-engineered skin containing an artificial dermal matrix was grafted for her. After treatment, the heel ulcer healed with good abrasive resistance, and the patient was able to walk under the help of a walking aid.
3. Mechanism of plantar ulcer repair with tissue-engineered skin
The artificial composite dermis prepared by Yanns et al.[14] using collagen matrix and medical silicone rubber membrane in 1982 was successfully used as a dermal regeneration template to repair the deep burn wound. In 2017, China researched and developed the first double-layer tissue-engineered skin, which achieved good results in various departments, such as Department of Burn, Department of Plastic Surgery, Department of Hand and Foot Surgery, etc[5]. Now, the tissue-engineered skin has been widely applied to deep burn, traumatic skin defect, chronic skin ulcer, wound repair after the tumor resection, and scar plastic surgery, with the therapeutic effect highly recognized by clinicians at home and abroad[15-16].
In domestic and foreign literature, the dermal substitute is also known as tissue-engineered skin, tissue-engineered skin matrix, artificial skin, and artificial dermis in accordance with different structures, materials, and preparation methods. But in essence, it is to induce the regeneration of dermis through a dermal stent template, thus substituting the defective dermal tissues and optimizing the appearance and function of healed wound.
In this report, the double-layer tissue-engineered skin was adopted. Thereinto, the upper layer was a semipermeable silicone rubber membrane used for medicine, which acted like the epidermis to control the evaporation of water and inhibit the invasion of microorganism; the lower layer, namely the spongy dermal stent layer constructed by collagen-chondroitin sulfate, had high biocompatibility and low immunogenicity[17-18], acting as a cell proliferation stent to promote the intrusive growth of vascular endothelial cells and fibroblasts (Fb) in the graft site, thus forming a composite constituted by stent, new capillaries, and cells. After the adequate vascularization for 2-3 weeks, the autologous split-thickness skin could be grafted[19]. Then, the dermal stent was gradually degraded and substituted by new dermal tissues.
Research at home and abroad shows that the tissue-engineered skin, which can promote and accelerate the wound healing of chronic ulcers[20-22], has been successfully used to treat diabetic, vascular and pressure ulcers. When the wound caused by chronic ulcers is repaired with tissue-engineered skin, the debridement must be repeated to avoid infection, and the graft cannot be performed until the wound is clean and the basal blood supply is sufficient. It may take two or more weeks to realize the adequate vascularization of tissue-engineered skin on the chronic ulcer wound, so the autologous skin shall be grafted according to the actual situation of vascularization.
In case of deep wound, the tissue-engineered skin can be overlaid repeatedly to thicken the new dermis, which is a method used in this case, in which the tissue-engineered skin was repeatedly grafted to the heel, and the wound healed before skin grafting. There are many clinical reports about the treatment of DFU using tissue-engineered skin[23-25], but the application to weight-bearing areas and dialysis patients with ischemic diabetic foot ulcers is not yet reported. (Table 1)
Table 1
Literature review of similar case reports on the treatment of diabetic foot ulcers
No.
|
TEXA Grade
|
Complication
|
Diseased Region
|
Application Method
|
Outcome
|
Healing Time
|
1
|
2B
|
Peripheral neuropathy
|
Heel
|
Sural neurouascular flap transposition under epidural anesthesia
|
Partly healed
|
4 weeks
|
2
|
2B
|
Peripheral neuropathy; hypertension
|
Heel
|
Sural neurouascular flap transposition under epidural anesthesia
|
Healed
|
6 weeks [51]
|
3
|
2A
|
Peripheral neuropathy; coronary heart disease
|
Non-weight-bearing area
|
Tissue-engineered skin
|
Healed
|
2 months
|
3
|
2A
|
Hypertension
|
Non-weight-bearing area
|
Tissue-engineered skin
|
Healed
|
2 months
|
4
|
2A
|
Peripheral neuropathy
|
Non-weight-bearing area
|
Tissue-engineered skin
|
Healed
|
3 months
|
5
|
4D
|
Peripheral neuropathy; peripheral vascular disease; retinopathy; state of dialysis for uremia; hypertension; coronary heart disease; anemia; hypoproteinemia; arteriosclerosis obliterans of upper limbs with gangrene
|
Planta pedis, heel, and back of the lower leg
|
PTA, negative pressure treatment, autologous split-thickness skin graft, and tissue-engineered skin
|
Healed
|
4 months
|