A Novel Wound Therapy Modality: Autologous Wound Edge Dotted Full-Thickness Skin Grafting Improving Diabetic Foot Ulcer Healing

Figures & data

Figure 1 The flowchart of the study design and patient recruitment.

Figure 2 The clinical course of Negative Pressure Wound Therapy (NPWT) for DLEUs. (A) The cleaning and assessment of the wound. (B) The schematic representation of the NPWT initiation. (C) The schematic representation of the process of NPWT. (D) The schematic and device diagram of NPWT.

Figure 3 The dynamic process of platelet-rich plasma (PRP) treatment. (A) The cleaning and assessment of the wound. (B) The schematic representation of the PRP treatment. (C) The schematic representation of the wound closure process. (D) The wound was completely closure.

Figure 4 Skin extractor for the autologous wound edge dotted full-thickness skin grafting.

Figure 5 The dynamic process of the skin graft treatment. (A) The cleaning and assessment of the wound, and skin pieces were directly taken from the edge of the wound with the skin sampler and were spread relatively evenly on the wound surface. (B) The schematic representation of the negative pressure closed drainage of the wound. (C) The schematic representation of the wound healing process. (D) The schematic representation of the complete wound closure.

Table 1 Comparison of Baseline Clinical Characteristics Among the Three Groups

Characteristics	CWT Group (n = 23)	PRP Group (n = 20)	Graft Group (n = 20)	P value
Ulcer area before treatment (cm²)	11.70 (7.03, 24.68)	30.19 (18.24, 49.26)	27.59 (15.52, 45.54)	0.001*
Age (years)	59.39 ± 7.60	60.64 ± 10.33	60.60 ± 19.65	0.886
Gender (n, %)				0.802
Female	8 (34.8%)	8 (40.0%)	6 (30.0%)
Male	15 (65.2%)	12 (60.0%)	14 (70.0%)
BMI (kg/m²)	22.59 (22.03, 25.95)	22.33 (19.79, 24.46)	22.08 (20.87, 24.25)	0.354
Duration of diabetes (years)	9.00 (3.00, 10.00)	8.13 (4.36, 11.81)	5.00 (4.00, 7.75)	0.198
Hemoglobin (g/L)	99.00 (88.00, 118.00)	117.49 (100.74, 124.60)	108.50 (89.47, 133.00)	0.145
Albumin (g/L)	33.36 ± 5.44	32.40 ± 6.44	32.15 ± 5.07	0.759
HbA1c (%)	8.70 (7.70, 12.00)	8.38 (7.04, 9.70)	8.10 (6.25, 12.25)	0.524
eGFR (mL/min·1.73m²)	63.56 ± 32.20	67.22 ± 26.23	73.24 ± 33.21	0.589
TC (mmol/L)	3.61 (3.19, 4.53)	3.69 (2.98, 4.57)	3.48 (3.21, 4.38)	0.990
TG (mmol/L)	1.06 (0.82, 1.58)	1.40 (1.11, 1.67)	1.24 (0.91, 2.53)	0.209
HDL-C (mmol/L)	0.88 ± 0.25	0.86 ± 0.28	0.88 ± 0.36	0.964
LDL-C (mmol/L)	2.45 ± 0.84	2.59 ± 0.77	2.31 ± 0.81	0.531
ABI	0.81 ± 0.27	0.85 ± 0.30	0.92 ± 0.32	0.489
TcPO2 (mmHg)	39.46 ± 11.01	38.94 ± 11.96	39.64 ± 8.82	0.977
History of smoking (n, %)				0.934
No	16 (69.6%)	13 (65.0%)	13 (65.0%)
Yes	7 (30.4%)	7 (35.0%)	7 (35.0%)
History of alcoholism (n, %)				0.387
No	21 (91.3%)	17 (85.0%)	15 (75.0%)
Yes	2 (8.7%)	3 (15.0%)	5 (25.0%)
History of hypertension (n, %)				0.278
No	10 (43.5%)	6 (30.0%)	11 (55.0%)
Yes	13 (56.5%)	14 (70.0%)	9 (45.0%)
History of dyslipidemia (n, %)				0.587
No	15 (65.2%)	10 (50.0%)	11 (55.0%)
Yes	8 (34.8%)	10 (50.0%)	9 (45.0%)
History of ischemic heart disease (n, %)				1.000
No	21 (91.3%)	18 (90.0%)	18 (90.0%)
Yes	2 (8.7%)	2 (10.0%)	2 (10.0%)
History of foot ulcer (n, %)				0.403
No	19 (82.6%)	13 (65.0%)	14 (70.0%)
Yes	4 (17.4%)	7 (35.0%)	6 (30.0%)
History of minor amputations (n, %)				0.127
No	13 (56.5%)	17 (85.0%)	14 (70.0%)
Yes	10 (43.5%)	3 (15.0%)	6 (30.0%)
Peripheral neuropathy (n, %)				0.561
No	6 (26.1%)	4 (20.0%)	7 (35.0%)
Yes	17 (73.9%)	16 (80.0%)	13 (65.0%)
Diabetic retinopathy (n, %)				0.077
No	9 (39.1%)	5 (25.0%)	12 (60.0%)
Yes	14 (60.9%)	15 (75.0%)	8 (40.0%)
Lower extremity venous insufficiency (n, %)				0.345
No	21 (91.3%)	16 (80.0%)	15 (75.0%)
Yes	2 (8.7%)	4 (20.0%)	5 (25.0%)
Wound secretion culture (n, %)				1.000
No	19 (82.6%)	17 (85.0%)	16 (80.0%)
Yes	4 (17.4%)	3 (15.0%)	4 (20.0%)
UTDWC (n, %)				0.744
1–3B	15 (65.2%)	13 (65.0%)	11 (55.0%)
1–3D	4 (34.8%)	7 (35.0%)	9 (45.0%)

Notes: continuous variables are shown as mean ± standard deviation (SD) or Median (Inter Quartile Range), and analyzed by one-way ANOVA or Kruskal–Wallis test. Categorical variables are shown as percentage (%) and analyzed by Chi-Square test or Fisher’s Exact test. *P < 0.05.

Abbreviations: CWT, conventional wound therapeutic; PRP, platelet-rich plasma; BMI, body mass index; HbA₁c, glycosylated hemoglobin; eGFR, estimated glomerular filtration rate; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; ABI, ankle-brachial index; TcPO₂, transcutaneous oxygen measurement; UTDWC, the University of Texas Diabetic Wound Classification.

Table 2 Cox Regression Analyses for the Predictive Factor of Diabetic Foot Ulcers Healing

Variables	Univariate Analysis			Multivariate Analysis
	HR	95% CI	P values	HR	95% CI	P values
Groups
CWT group	1			1
PRP group	2.373	1.047–5.378	0.038*	3.075	1.320–7.161	0.009*
Graft group	2.733	1.195–6252	0.017*	3.214	1.300–7.945	0.011*
Gender
Female	1
Male	0.952	0.484–1.871	0.887
Age	1.001	0.968–1.035	0.943
ABI	8.833	2.424–32.179	0.001*	9.917	2.675–36.760	0.001*
TcPO2	1.031	0.999–1.064	0.059	1.040	1.005–1.076	0.023*

Note: *P < 0.05.

Abbreviations: CWT, conventional wound therapeutic; PRP, platelet-rich plasma; HR, hazard ratio; CI, confidence interval; ABI, ankle-brachial index; TcPO₂, transcutaneous oxygen measurement.

Table 3 Univariate and Multivariate Cox Regression Analysis for ABI- and TcPO₂-Stratified Analyses

Stratified Variables	Univariate Analysis			Multivariate Analysis
	HR	95% CI	P value	HR	95% CI	P value
TcPO2>40 mmHg*
CWT group	1			1
PRP group	0.662	0.225–1.948	0.454	1.554	0.457–5.286	0.481
Graft group	5.063	2.016–12.711	0.001	15.805	4.414–56.594	0.000
ABI > 0.9**
CWT group	1			1
PRP group	3.497	1.272–9.612	0.015	5.029	1.743–14.509	0.003
Graft group	3.009	1.082–8.364	0.035	3.748	1.210–11.607	0.022

Notes: *Multivariate analysis adjusted with Gender, age, ABI. **Multivariate analysis adjusted with Gender, age, TcPO₂. The reference group was CWT group.

Abbreviations: CWT, conventional wound therapeutic; PRP, platelet-rich plasma; HR, hazard ratio; CI, confidence interval.

Figure 6 Kaplan-Meier curves of the cumulative incidence of unhealing wound among each group.

Table 4 The Comparison of the Wound Healing Speed Among Three Groups

Time (Weeks)	CWT Group (n = 23)	PRP Group (n = 20)	Graft Group (n = 20)
2 weeks (%)	15.43 (10.89, 30.92)	28.96 (10.77, 49.96)	22.11 (15.31, 32.94)
4 weeks (%)	34.75 (26.88, 42.65) ^▲	38.24 (30.31, 61.32)	74.40 (67.71, 86.52) *^#▲
8 weeks (%)	59.25 (53.29, 69.49) ^▲■	67.92 (58.17, 77.96) ^▲■	91.09 (86.95, 100.00) *^#▲■
12 weeks (%)	84.56 (68.11, 100.00) ^▲■●	100.00 (83.08, 100.00) ^▲■●	100.00 (95.05, 100.00) *^▲■

Notes: *Compared to the CWT group, P<0.05; ^#Compared to the PRP group, P<0.05. ^▲Compared to the 2 weeks, P<0.01; ^■Compared to the 4 weeks, P<0.01; ^●Compared to the 8 weeks, P<0.01.

Abbreviations: CWT, conventional wound therapeutic; PRP, platelet-rich plasma.

Table 5 Comparison of Healing Time and Total Treatment Costs Among Three Groups

	CWT Group	PRP Group	Graft Group
Healing time (days)	75.00 (68.25, 78.50)	64.50 (54.75, 67.25) *	49.00 (21.00, 62.00) *
Treatment cost ($)	657.00 (255.50, 919.80)	583.60 (523.38, 721.75)	394.20 (306.60, 515.49)^#

Notes: *Compared to the CWT group, P<0.01; ^#Compared to the PRP group, P<0.01.

Data Sharing Statement

The original raw data used in this study is available from the corresponding author and can be provided upon reasonable request.