A single-stage bilayered skin reconstruction using Glyaderm® as an acellular dermal regeneration template results in improved scar quality: an intra-individual randomized controlled trial

Abstract

Background: Absence of almost the entire reticular dermal layer is inherent to the use of autologous split-thickness skin grafting (STSG) to close full-thickness wounds, often resulting in hypertrophic scars and contractures. Many dermal substitutes have been developed, but unfortunately most have varying results in terms of cosmetic and/or functional improvement as well as patient satisfaction, in addition to high costs. Bilayered skin reconstruction using the human-derived glycerolized acellular dermis (Glyaderm®) has been reported to result in significantly improved scar quality using a two-step procedure. Unlike the necessary two-step procedure for most commercially available dermal substitutes, in this study we aimed to investigate the use of Glyaderm® in a more cost-effective single-stage engrafting. This is a method which, if autografts are available, is preferred by the majority of surgeons given the reduction in costs, hospitalization time and infection rate.

Methods: A prospective, randomized, controlled, intra-individual, single-blinded study was performed, investigating the simultaneous application of Glyaderm® and STSG vs. STSG alone in full-thickness burns or comparable deep skin defects. During the acute phase, bacterial load, graft take and time to wound closure were assessed and were the primary outcomes. Aesthetic and functional results (secondary outcomes) were evaluated at 3, 6, 9 and 12 months follow-up using subjective and objective scar measurement tools. Biopsies for histological analysis were taken at 3 and 12 months.

Results: A total of 66 patients representing 82 wound comparisons were included. Graft take (>95%), pain management and healing time were comparable in both groups. At 1 year follow-up, the overall Patient and Observer Scar Assessment Scale assessed by the patient was significantly in favour of sites where Glyaderm® was used. Not infrequently, patients attributed this difference to improved skin sensation. Histological analysis showed the presence of a well-formed neodermis, with donor elastin present for up to 12 months.

Conclusions: A single-stage bilayered reconstruction with Glyaderm® and STSG results in optimal graft take without loss of Glyaderm® nor the overlaying autografts due to infection. The presence of elastin in the neodermis was demonstrated during long-term follow-up in all but one patient, which is a crucial factor contributing to the significantly improved overall scar quality as evaluated by the blinded patients.

Trial registration: The trial was registered on clinicaltrials.gov and received the following registration code: NCT01033604.

Keywords: Burn; Dermal regeneration template; Dermal substitute; Elastin; Glyaderm®; Scar; Skin.

Conflict of interest statement

None declared.

© The Author(s) 2023. Published by Oxford University Press.

Figures

Figure 1

Artistic illustration of the immediate simultaneous bilayered skin reconstruction using Glyaderm® as a dermal substitute on a full-thickness skin defect. (a) Defect with epidermal and dermal component involved. (b.1) Single-layer reconstruction by autografting without placement of a dermal substitute. (b.2) Simultaneous bilayered reconstruction using Glyaderm® and autografts. Subsequent vascularization of the dermal substitute. (c.1) Spatial orientation of the fibres is crude and parallel. Scar shows more contracture and hypertrophy compared to the bilayered skin reconstruction. (c.2) Spatial orientation of the fibres is similar to the natural basket-weave pattern due to Glyaderm® acting as a guide for infiltrating cells. As a result, the scar shows less contracture and hypertrophy compared to autograft alone

Figure 2

Study flowchart

Figure 3

Example case 1. (a) A patient admitted with a scald burn (frying oil). (b) Burn depth assessment by means of laser Doppler imaging (LDI) on the third day post-burn. LDI blue colour indicates a full-thickness burn. (c) Four days after allograft application. (d) After removal of allografts and prior to application of Glyaderm® and/or autografting

Figure 4

Example case 1. (a) Application and fixation of Glyaderm® on the most proximal half of the upper leg. Control and intervention sites are situated left and right of the black line respectively. Arrow indicates Glyaderm® which can be seen as a thin glistening layer. (b) Autograft application and coverage with Surfasoft®. (c) Removal of Surfasoft® on the sixth day post-autografting. (d) Complete wound closure 3 weeks post-autografting

Figure 5

Example case 1. (a) Three months after wound closure. (b) Six months after wound closure. (c) Nine months after wound closure. (d) Twelve months after wound closure, the site that received Glyaderm® is more supple, has less contracture and the colour is more normalized compared to the control. Control and intervention sites are situated left and right of the black line respectively.

Figure 6

Consort study flowchart of intra-individual study design. Pts patients, RFF radial forearm flap donor site, ALT anterolateral thigh flap donor site, FTD full-thickness skin defects, STSG split-thickness skin graft

Figure 7

Example case 2. (a) Patient admitted with a full-thickness skin defect after a car accident (friction trauma); prior to debridement. (b) Left shoulder post-debridement (target wound 1); subsequently, allografts were applied. (c) Right shoulder post-debridement (target wound 2); subsequently, allografts were applied. (d) Four days after allograft application

Figure 8

Example case 2. (a) Control site (left shoulder) after allograft removal and prior to autografting. (b) Intervention site (right shoulder) after allograft removal and prior to Glyaderm® application and autografting. (c) Application of Glyaderm® on the right shoulder; arrow indicates Glyaderm®. (d) Autografting of both sites(left shoulder control site / right shoulder intervention site) and coverage with Surfasoft®

Figure 9

Example case 2. (a) Removal of Surfasoft® 6 days post-autografting: left shoulder control; right shoulder intervention. (b) Complete wound closure, 3 weeks post-autografting, (c) 6 months after wound closure and (d) 12 months after wound closure; the site that received Glyaderm® is more supple, has a smoother surface, less hypopigmentation and a more normalized sensation according to the patient

Figure 10

Example case 3. (a) Left upper arm after radial forearm flap harvest. (b) Dorsal side of the upper arm received Glyaderm®. (c) Dorsal side after autograft application onto Glyaderm®. (d) Ventral side of left upper arm is covered with autografts only. Dorsal and ventral sides are separated with a black line. A black arrow indicates the side that received Glyaderm®. On the upper side of the black line, the control site is situated (venral side of the left upper arm). On the lower side of the black line, the intervention site is situated (dorsal side of the left upper arm)

Figure 11

Example case 3. (a) Control site 1 week after autografting. (b) Glyaderm®-treated site 1 week after autografting. (c) Control site 2 weeks after autografting. Black line indicates transition zone. (d) Glyaderm®-treated site 2 weeks after autografting. Dorsal and ventral sides are separated with a black line. On the upper side of the black line, the control site is situated (ventral side of the left upper arm). On the lower side of the black line, the intervention site is situated (dorsal side of the left upper arm)

Figure 12

Example case 3. (a) Control site 6 months after wound closure. (b) Glyaderm®-treated site 6 months after wound closure. (c) Control site 12 months after wound closure. Black line indicates transition zone. (d) Glyaderm®-treated site 12 months after wound closure. Glyaderm®-treated sites shows less contracture, a smoother appearance and a more favourable colour distribution. Dorsal and ventral sides are separated with a black line. On the upper side of the black line, the control site is situated (ventral side of the left upper arm). On the lower side of the black line, the intervention site is situated (dorsal side of the left upper arm)

Figure 13

POSAS patient. Overall opinion as subjectively attributed by blinded patients using the POSAS at different time intervals during the follow-up period of 1 year after wound closure for both treatments; * significant difference, ** strong significant difference. POSAS Patient and Observer Scar Assessment Scale

Figure 14

Light microscopy of histological slices. (a) Hematoxylin and eosin (H&E) histological slice of control site at 3 months follow-up. (b) H&E histological slice of intervention site at 3 months follow-up. (c) Alpha-smooth muscle actin staining of histological slice of the intervention group at 3 months follow-up. Arrows indicate vascular structures in the papillar and reticular dermis indicating a well-vascularized neo-dermis. (d) H&E histological slice of control site at 12 months follow-up. (e) H&E histological slice of intervention site at 12 months follow-up. (f) Elastica Von Giesson staining visualizing the presence of donor elastin fibres at 12 months follow-up; autograft and Glyaderm® are indicated. Single arrows indicate some example donor elastin fibres in the deep dermis. The elastic fibres are coloured blue due to the staining procedure. Scale bars of 100 μm are indicated in the right lower corner of each individual image