Comparison of therapeutic effects between artificial dermis combined with autologous split-thickness skin grafting and autologous intermediate-thickness skin grafting alone in severely burned patients: A prospective randomised study.

The purpose of this study was to evaluate the therapeutic effects of artificial dermis combined with autologous split-thickness skin grafting (STSG) compared with autologous intermediate-thickness skin grafting (ITSG) alone in severely burned patients. Fifty-six severely burned patients admitted to our hospital from December 2017 to January 2019 were enrolled and evenly grouped according to the random number table method [AD-STSG group: 28 patients, receiving the treatment of artificial dermis (AD) combined with autologous STSG; ITSG group: 28 patients, receiving autologous ITSG treatment alone]. The healing time and Vancouver Scar Scale (VSS) score of the donor area and graft area, survival rate and infection status of the autologous skin, psychological status (determined by Self-rating Anxiety Scale and Self-rating Depression Scale), and the activity of functional parts of all enrolled patients were included in the evaluation. General items of patients in AD-STSG group and ITSG group, including age, sex, and degree of burn, were all comparable. A significantly shortened healing time of donor skin in AD-STSG group was observed when compared with ITSG group (P < .05) while the recipient skin healed in the same tendency between the two groups. In addition, 21 days after the operation, AD-STSG group presented with significantly higher survival rate of graft skin than ITSG group (P < .05) while same infection status was observed in the two groups. Significantly lower VSS scores were found in AD-STSG group than that in ITSG group 3-, 6- and 10-months after operation (P < .05). Statistical difference regarding psychological status of patients from two groups was unobservable before operation while significantly lower Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores were found in AD-STSG group than that in ITSG group 3-, 6- and 10-months after operation (P < .05). Also, AD-STSG group presented improved mobility of functional part than that in ITSG group 10-months after operation without statistical difference (P = .051). Artificial dermis combined with autologous split-thickness skin grafting showed better therapeutic outcomes for the treatment of severely burned patients than autologous intermediate-thickness skin grafting in terms of graft healing time, scar formation, psychological recovery, and perhaps in functional reconstruction.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Burns are one of the most extensive forms of soft tissue injury. Pervasive physiological and psychological trauma are commonly seen in severe burns. Clinically, the availability of autologous skin (eg, the autologous skin was disposable, donor skin was difficult to heal if operated improperly, and re‐grafting occasionally happened, etc.) greatly affected the rebuild of the skin barrier of severely burned area. Also, contracture scar caused by autologous skin grafting could also restrain functional reconstruction of severely burned area. In addition, occasionally occurred repeated tension blisters and scar rupture in the donor or grafted area could result in chronic ulcer, which further restricted the recovery of severely burned patients. Those limitations of autologous skin grafting strongly alters the recovery of severely burned patients and substantially compromises their health and quality of life. In order to timely save burned patients' life and to reconstruct the function of burned area at conditions of insufficient autologous skin, the artificial dermis (AD), autologous microne skin, and granulosum skin were utilised to cover the wound area for skin barrier rebuilding. According to previously published literature, artificial dermis was constituted with two layers: the inner layer was made of cavernous artificial skin and the out layer was covered by silicon membrane. Artificial dermis was proved to be greatly beneficial in the clinic in treating chronic wound and bone leakage. , , However, reports on artificial dermis combined with autologous split‐thickness skin grafting (STSG) in treating severely burned patients were relatively rare. Thus, the current prospective research aimed to evaluate the clinical outcome of artificial dermis combined with STSG compared with autologous intermediate‐thickness skin grafting (STSG) treatment alone.

MATERIAL AND METHODS

General clinical data

A total of 56 severely burned patients admitted to our hospital from December 2017 to January 2019 were enrolled and evenly grouped according to the random number table method. Fifty‐six patients meeting the inclusion and exclusion criteria were randomly divided into study group and control group according to the ratio of 1:1. In the AD‐STSG group, 28 patients received the treatment of artificial dermis combined with ITSG. They were 22 to 45 years old, with an average age of 36.48 ± 3.47 years, and the male to female ratio was 1.15. The burned region of patients in this group was as follows: neck, 9 cases; popliteal, 6 cases; back, 6 cases; front ankle, 7 cases.

In the ITSG group, 28 patients received autologous ITSG treatment alone. They were 21 to 45 years old, with an average age of 36.38 ± 3.51 years, and the male to female ratio was 1.33. The burned region of patients in this group was as follows: neck, 8 cases; popliteal, 5 cases; back, 7 cases; front ankle, 8 cases. As presented in Table 1, general items of patients in AD‐STSG group and ITSG group, including age, sex, and degree of burn, were all comparable. All experimental procedures were approved by the Ethics Committee of our hospital (approval number: SFMU‐2019‐028) and were in accordance with the Helsinki Declaration.

TABLE 1

Demographic data

Item		AD‐STSG	ITSG	t/χ2	P
Gender (male/female ratio)		1.15	1.33	0.072	.788
Age		36.48 ± 3.47	36.38 ± 3.51	0.107	.915
Burned area (N, %)	Neck	9 (32.14)	8 (28.57)	0.084	.771
	Popliteal	6 (21.43)	5 (17.86)	0.113	.737
	Back	6 (21.43)	7 (25.00)	0.1	.752
	Front ankle	7 (25.00)	8 (28.57)	0.091	.763

Abbreviations: AD‐STSG, artificial dermis combined with autologous split‐thickness skin grafting; ITSG, intermediate‐thickness skin grafting.

Inclusion and exclusion criteria

Inclusion criteria: (a) integrated clinical data; (b) total burn area > 85% total body skin area (TBSA) with III degree burn area > 50% TBSA and scar area > 50% TBSA; (c) normally function in major organs including heart, lung, liver, and kidney; (d) patients were willing to participate in the current research with hand‐signed informed consent document. Burned surface area is calculated as a percentage of total body surface area by “rule of nines”.

Exclusion criteria: (a) diabetes mellitus; (b) patients who were unwilling to have scar formation on donor area; (c) accompanied with other skin diseases; (d) accompanied with severe infection on the wound area or systemically infection; (e) severe scar ulcer with bacterial infection; (f) moderate to severe malnutrition; (g) severe mental disorder; (h) patients who were unwilling to participate in the current research.

Surgical procedure

Patients of the two groups were all given health education and their psychological status were evaluated before and after the operation. In the meanwhile, psychological support was all given before, during, and after the operation. Areas with thick derma, namely, skins form lateral upper arm, thigh, side chest, back and head, were chosen as source of donor skin. Autologous split‐thickness skins (0.15‐0.20 mm thick) and intermediate thickness skin (0.30‐0.35 mm thick) were harvested by an electric dermatome. Status of effusion, angiogenesis, and granulation tissue grown were checked 7 days after the final operation and the survival status of grafted skin were checked 21 days after the operation.

In the ITSG group, patients underwent general anaesthetised and then the surgery area was sterilised by iodophor. Surgical strategies on functional area were designed based on the status of scar hyperplasia and contracture. Burned areas were completely debrided of scar area and excised to a viable area without hurting critical muscle and nerve tissues. After softening the phase I scar, thin‐intermediate thickness skin was sutured to the recipient bed with 3 to 0 nylon. Finally, the surgical areas were bound up with pressure.

In the AD‐STSG group, patients were anaesthetised and debrided in the same manner as that in ITSG group. At phase I operation, gentamycin saline rehydrated artificial dermis was then sutured to the recipient bed with 3 to 0 nylon, and surgical areas were bound up with pressure as well. The surgical areas were checked for status of effusion, angiogenesis, and granulation tissue grown under polyester fibre membrane 7 days after operation under. After the granulation tissue grown fully under the polyester fibre membrane, which usually takes 12 to 21 days, a phase II operation were performed. The polyester fibre membrane was removed, and granulation tissues were flushed with gentamycin saline. Autologous split‐thickness skins were sutured to the recipient bed with 3 to 0 nylon surgical areas were bound up with pressure.

Observational indicators

Healing time of donor or recipient skin: the time token from skin harvest or skin graft to complete skin healed.

Scar formation : scar formation status was calculated according to Vancouver scar scale (VSS) score. The total score of VSS was 15.0 and the higher score represented higher scar formation. Scar formation status of donor and recipient areas were calculated 3‐, 6‐, 10‐months after final operation.

Survival status of grafted skin: the survival rate of graft skin was calculated (survival area of grafted skin / total area of grafted skin×100%) and presented as percentage.

Infection status: the criteria of infection was listed as following: (a) bacterial culture of wounded area shows positive; (b) a clear red swelling and secretions of inflammation were observed around wounded area; (c) low (<36°C) or high (>38°C) body temperature caused by infection was observed. The infection rates were calculated (number infected patients/ total number of patients×100%) and presented as percentage.

Psychological status: the psychological status of patients were determined by self‐rating anxiety scale (SAS) and self‐rating depression scale (SDS) before and 3‐, 6‐, 10‐months after the final operation. Both SAS and SDS had a total score of 80 points. For patients who scored less than 50 was regarded as normal, scored 50 to 59 were taken as slight anxiety or depression, scored 60–69 were taken as moderate anxiety or depression and those scored more than 70 were taken as severe anxiety or depression.

Activity recovery rate of functional parts (neck, back, popliteal, ankle) : 10 months after autologous skin grafting, the activity recovery of functional parts was determined, and the results were presented as a rate of normal activity status of functional parts. Patients with more than 70% functional recovery to normal level were taken as excellent recovery, 40% to 70% functional recovery were taken as good, and less than 40% were taken as poor. The activity recovery rate was calculated [(number of excellent + good patients)/ total number of patients×100%] and presented as percentage.

Statistical analysis

Data were analysed by SPSS 23.0 software. Measurement data were presented as mean ± SD. An analysis of variance (ANOVA) method was applied for general repeated measurement data comparison. An independent sample t test was used for statistical analysis between two groups. The categorical data were presented as percentage and were compared by Chi‐square test. P < .05 was considered statistically significant.

RESULTS

Healing time of donor and recipient skin

The healing time of donor and recipient skin was presented in Table 2. Significantly shortened healing time (generally up to more than 4 days shorter) of graft skin in AD‐STSG group was observed when compared with ITSG group (P < .05). However, there was no statistically significant difference in healing time of the donor area between two groups (P > .05).

TABLE 2

Healing time of donor and recipient skin

Item	AD‐STSG	ITSG	t	P
N	28	28
Healing time of recipient skin	12.31 ± 1.02	12.76 ± 1.01	−1.659	.103
Healing time of donor skin	11.19 ± 0.76	15.32 ± 0.41	−25.307	<.001

Abbreviations: AD‐STSG, artificial dermis combined with autologous split‐thickness skin grafting; ITSG, intermediate‐thickness skin grafting.

Survival rate of grafted skin and infection status of patients

As presented in Table 3, the AD‐STSG group had significantly higher survival rate of grafted skin than the ITSG group (P < .05), and there was no statistically significant difference in the infection rate between two groups (P > .05).

TABLE 3

Survival rate of grafted skin and infection status of patients

Item	AD‐STSG	ITSG	t/χ2	P
N	28	28
Survival rate of grafted skin	(95.011 ± 3.001) %	(93.002 ± 2.002) %	2.935	.005
Infection rate	2 (7.14%)	1 (3.57%)	0.352	.553

Abbreviations: AD‐STSG, artificial dermis combined with autologous split‐thickness skin grafting; ITSG, intermediate‐thickness skin grafting.

Scar formation status of donor and recipient areas

After 3‐, 6‐, 10‐months of the final operation, scar formation status of donor and recipient areas were carefully evaluated using VSS. Lower VSS scores of donor or recipient areas were observed in AD‐STSG group when compared with the ITSG group 3‐, 6‐, 10‐months after the final operation (P < .05) (as shown in Table 4).

TABLE 4

Scar formation status of donor and recipient areas

Item		AD‐STSG	ITSG	t	P
VSS score of donor skin (months after operation)	3‐months	7.13 ± 0.98	13.46 ± 2.02	−14.919	<.001
	6‐months	7.26 ± 1.04	13.67 ± 2.18	−14.043	<.001
	10‐months	7.39 ± 0.97	13.78 ± 2.01	−15.15	<.001
VSS score of recipient skin (months after operation)	3‐months	3.62 ± 1.18	5.09 ± 0.65	−5.774	<.001
	6‐months	4.92 ± 1.18	7.01 ± 1.31	−6.273	<.001
	10‐months	5.24 ± 0.76	8.56 ± 0.97	−14.256	<.001

Abbreviations: AD‐STSG, artificial dermis combined with autologous split‐thickness skin grafting; ITSG, intermediate‐thickness skin grafting; VSS, Vancouver scar scale.

Psychological status of patients before and after the operation

According to data measured by SAS and SDS, patients of both groups all presented comparable severe anxiety and depression before operation. After 3‐, 6‐, 10‐months of the final operation, patients of both groups had improved psychological status when compared with than before operation (P < .05). Especially, patients in the AD‐STSG group had significantly lower SAS and SDS scores than those of patients in the ITSG group in all indicated time points after operation (P < .05, as shown in Table 5).

TABLE 5

Psychological status of patients before and after the operation

Item		AD‐STSG	ITSG	t	P
SAS score (months before and after operation)	Before	72.91 ± 2.38	72.89 ± 2.41	0.031	.975
	3‐months	53.02 ± 2.12 a	63.03 ± 3.02 a	−14.355	<.001
	6‐months	44.83 ± 2.07 a	61.98 ± 2.87 a	−25.654	<.001
	10‐months	40.98 ± 1.98 a	58.98 ± 1.76 a	−35.954	<.001
SDS score (months before and after operation)	Before	73.01 ± 3.02	72.95 ± 2.98	0.076	.94
	3‐months	54.09 ± 2.39 a	64.01 ± 2.46 a	−15.304	<.001
	6‐months	47.01 ± 2.19 a	60.99 ± 2.38 a	−22.872	<.001
	10‐months	41.52 ± 1.87 a	57.87 ± 1.93 a	−32.194	<.001

Abbreviations: AD‐STSG, artificial dermis combined with autologous split‐thickness skin grafting; ITSG, intermediate‐thickness skin grafting; SAS, self‐rating anxiety scale; SDS, self‐rating depression scale.

P < .05, compared with before operation.

Activity recovery rate of functional parts

As shown in Table 6, both operation methods promoted activity recovery rate of functional parts (P > .05). Patients in the AD‐STSG group had better activity recovery rate of functional parts than that of patients in the ITSG group with a statistical result of P = .051.

TABLE 6

Activity recovery rate of functional parts

Item	AD‐STSG	ITSG	χ2	P
N	28	28
Excellent	8 (28.57)	6 (21.43)
Good	19 (67.86)	15 (53.57)
Poor	1 (3.57)	7 (25.00)
Recovery rate	27 (96.43)	21 (75.00)	5.25	.051

Abbreviations: AD‐STSG, artificial dermis combined with autologous split‐thickness skin grafting; ITSG, intermediate‐thickness skin grafting.

DISCUSSION

Burns, commonly induced by skin exposure to boiled water or oil, frame, high temperature gas, and light, can cause damages to skin, mucosal, and even to inner tissues or organs like muscle, bone joints, and so forth. Especially, severe burns, implied as area of degree III burned area > 20% TBSA or total burned area > 50% TBSA, is one of the most complicated frequent surgical diseases. Complications of severe burn like infection, shock, and multiple organ failure can all be fatal, infections are the leading cause of death in patients with severe burns because of the lack of most skin barriers. Autologous skin grafting is widely used in the clinic to rebuild skin barriers. However, as availability of autologous skin is quite limited, effectively utilising the limited skin source for severe burn has always been a critical clinical research topic. Massive biomaterials were proved to be useful in the experimental setting while little was translated into the clinical use because of all kind of shortages such as the cost is too high or the biomaterials used in the experimental setting is hard to obtain in the clinic.

Artificial dermis is composed of cavernous collagen inner layer and silicon membrane constituted out layer, and is artificially designed to mimic the structure of human dermis in order to promote the migration and growth of fibroblasts so that the vascularization of dermal tissue can happen. Once fibroblasts migration and vascularization occurred in the inner layer of artificial dermis, a well formatted dermis tissue came into shape. This design will be helpful to the implantation of split‐thickness skin and reduce the scar formation. By utilising such advantages of artificial dermis, many kinds of skin damage can be effectively repaired, especially for severe burns that requires massive skin grafting. Liu et al demonstrated that AD‐STSG showed promising results in children of burned limbs and in adults with degree IV burn of distal limb. , As proved in this study, accelerated healing time of recipient skin and higher survival rate of grafted skin were observed in severely burned patients with AD‐STSG treatment, suggesting the potential critical clinical value of AD‐STSG. In this study, two patients had infections, which may be caused by long time course of AD‐STSG treatment with a secondary debride and by difficulties in completely clear the red swelling and secretions of inflammation under the polyester. Also, collagens at body temperature were perfect culture media for bacteria growth, which potentially increased the risk of infection.

Scar formation is a side product of excessive repair to counteracting with burn‐induced skin damage. Because the specific mechanism of scar formation remains largely exclusive, current interventions on scar formation prevention and modification still cannot reach satisfactory effects in the clinic. Commonly used drug injection or laser compression therapy helps little in preventing scarring at joints. As formatted scar negatively affects the functional reconstruction, restrain scar formation has always been a hot issue in burn treatment. Current burn treatment therapies take full or intermediate thickness skin as donor for skin grafting. Source of full thickness skin in severely burned patients are extremely limited while intermediate‐thickness skin grafting could result in skin contracture at later phase of recovery.

AD‐STSG treatment could be a promising therapy for scar control and prevention. As demonstrated by Banjerd et al., artificial dermis treatment resulted in satisfactory effects in scar modification of burn area. Our results proved that AD‐STSG treatment resulted in lower VSS score in donor and recipient skin 3‐, 6‐, 10‐months after the final operation, which further suggested that AD‐STSG is beneficial in scar prevention and control for severely burned patients. Artificial dermis induced dermis liked structure together with autologous split‐thickness skin could act like full thickness skin. In addition, the thickness of split‐thickness skin was 0.15 to 0.20 mm. Those two reasons contribute to less scar formation and lower the requirement of donor area, which provided good news to severely burned patients with insufficient autologous skin.

Severe burn treatment was always time‐consuming with high mortality rate. Cured patients were often left with severe scar, malformation, and deformity, which long‐lastingly affect their social life and mental health. Thus, it is of great importance to provide psychological support during and after burn treatment. In the current study, all patients developed severe anxiety and depression before operation. All patients had lightened anxiety and depression status after operation and continues psychological counselling. More importantly, patients with AD‐STSG treatment has less anxiety and depression status than those of patients with ITSG treatment alone, which might be another reflection that AD‐STSG treatment could resulted in promising clinical outcome.

According to our results, both AD‐STSG and ITSG treatment could all resulted in activity recovery rate of functional parts while an improved activity recovery rate of functional parts was found in AD‐STSG treated patients when compared with ITSG treatment with a P value close to statistical difference (P = .051). This may be a consequence of enhanced blood supply achieved by utilising artificial dermis so that grafted skins survival better with less scar formation. The advantages of using artificial dermis in clinic included: (a) cost‐effective with low risk of infection; (b) good biocompatibility so that the risk of immune rejection was low; (c) smaller damage to donor skin; (d) ideal mechanical performance of the polyester membrane so that the integrity of tissues of lower layer could be effectively protected. The main disadvantage of artificial dermis was that it had two‐phase operation procedures, which could result in prolonged hospitalisation and increased surgical risk.

Several limitations existed in our current study. First, this research was a single‐centre study, which may not be representative enough. Second, the cases of severe burn were form different region while the comparation includes all cases as one group. Third, the number of cases included in the current study should also be enlarged in further studies. Fourth, the follow up period of patients involved was relatively short, long term outcome of such treatment method could also be considered in future studies.

CONCLUSION

In this study, significantly better therapeutic outcomes were obtained from artificial dermis combined with autologous split‐thickness skins grafting compared with autologous intermediate‐thickness skin grafting alone in severe burn treatment. Based on our results, it is highly recommended utilising artificial dermis combined with autologous split‐thickness skins grafting for severe burn treatment in the clinic.