*2.3.1 Matriderm*

The application of Matriderm involves a single stage procedure, which may be preferable to the staged reconstruction required for both Integra and BTM. The wound bed requires meticulous preparation and application of Matriderm. It can be challenging to use over large defects and is sheet split skin grafting rather than meshed is generally required and therefore requires available and good quality donor sites [5, 8].

### *2.3.2 Integra*

Integra requires a two-stage application, firstly the excision of the scar application of the dermal substitute. Then, once integrated, delamination and application of split skin grafting. Timing between the two procedures varies dependent upon integration. As burn resurfacing is an elective surgery the risk of infection with Integra is somewhat mitigated in comparison to its use in acute burn wound care. The functional and aesthetic outcome of Integra has been observed to be reliable [1–3, 5, 8].

#### *2.3.3 Biodegradable Temporising Matrix*

Similar to Integra BTM is a two-stage procedure. The patient can be managed in an outpatient setting until integration is completed. The risk of infection in an elective setting is minimal due to the synthetic nature of the product and the aesthetic and functional outcomes are comparable with the more established dermal substitutes [12, 16–18].

### **2.4 Future advances toward an ideal dermal substitute**

#### *2.4.1 Ideal skin substitute*

The ideal skin substitute does not yet exist. The following features have been proposed as desirable properties to consider in the development of novel skin substitutes [5, 6].


### *2.4.2 Scientific challenges and future advances*

Several scientific and regulatory challenges must be overcome in the development of the aspirational ideal skin substitute. Creating an anatomical and physiological substitute for normal skin is a challenge faced by burns and trauma patients that has involved tissue bioengineers, polymer chemists, cellular and molecular biologists, surgeons, nurses, and therapists. A critical challenge in skin substitute design has been replication or regeneration of basement membrane the undulating dermal-epidermal junction which it produces through a process of paracrine dialogue between fibroblasts and keratinocytes. This specialised junction is responsible for limiting shear by establishing a molecular bond that anchors the cellular epidermis to the extracellular matrix of the dermis [19, 20].

As such, epidermal-only substitutes may offer a clinical adjunct to expedite reepithelialisation in conjunction with other wound reconstruction strategies but are insufficient in replication of autologous skin graft due to their limited expansion rate, mechanical fragility on handling, tendency to blister in vivo and vulnerability to shear

#### *Role of Skin Substitutes in Burn Wound Reconstruction DOI: http://dx.doi.org/10.5772/intechopen.105179*

after application. Reconstructive strategies using novel composite epidermal-dermal constructs [21–23], although challenging to engineer, offer theoretically increased wound stability compared with combining separate dermal and epidermal substitutes which lack the critical component of a functional dermal-epidermal junction required for long term graft stability. A randomised comparison of an engineered skin substitute with autograft [22] (autologous keratinocytes and fibroblasts attached to a collagen-based scaffold) in 15 paediatric patients demonstrated reduced mortality and requirements for donor skin harvesting, for autografting of full- thickness burns of greater than 50% TBSA. A pre-clinical study of a fibrin-based human skin substitute [23] with epidermal and dermal components (fibroblasts cultured in fibrin gel with keratinocytes seeded on top) carried out on in vitro deep burn necrotic tissue showed similar outcomes compare with split-thickness skin graft, concluding that this could potentially represent a viable management option for deep burn injuries, without the need for autologous skin graft. The challenge of further clinical research efforts will be to evaluate and compare between the ever-growing variety of reconstructive strategies that have been made possible due to the wide array of skin substitute products now commercially available.

New frontiers of research are being forged through clinical translation of advanced tissue bio-engineering techniques combined with 3D printing technology [24–26] to produce novel bi-layered and even tri-layered constructs with hypodermis [25]. Positive clinical results obtained with autologous and allogeneic TESSs based on human adult skin cells and human mesenchymal stem cells regarding successful engraftment (60–90% in the majority of studies [24]) safety, re-epithelialization and wound healing rates, are promising. Takami et al. has developed a TESS composed of autologous cultured keratinocytes, fibroblasts, and cadaveric de-cellularised allogenic dermal matrix.

This skin substitute demonstrated at 96% graft survival rate in four patients with debrided full thickness burn wounds with no delayed graft loss [27]. Although many tissue engineered skin substitutes (TESS) remain at pre-clinical development stage, they offer hope that the ultimate goal of developing an ideal skin substitute is attainable through further clinical research efforts.
