Background:Over recent decades, scientists and surgeons have collaborated to develop various bioengineered and synthetic products as an alternative to skin grafts. Despite the numerous articles and reviews written about dermal skin substitutes, there is no general consensus.Methods:This article reviews dermal skin scaffolds used in clinical applications and experimental settings. For scaffold evaluation, we focused on clinical and/or histological results, and conclusions are listed. Explanations for general trends were sought based on existing knowledge about tissue engineering principles and wound healing mechanisms.Results:Decellularized dermis seems to remain the best option with no other acellular scaffold being clinically proven to gain better results yet. In general, chemically cross-linked products were seen to be less effective in skin tissue engineering. Biocompatibility could be enhanced by preseeding substitutes with fibroblasts to allow some natural scaffold remodeling before product application.Conclusions:Skin substitutes are a useful tool in plastic and reconstructive surgery practices as an alternative to skin grafts. In the choice of substitute, the general plastic surgery principle of replacing like tissue with like tissue seems to be still standing, and products most resembling the natural dermal extracellular matrix should be preferred.

We have previously described a mouse adipose tissue engineering model using a silicon chamber enclosing the superficial epigastric pedicle in a Matrigel based environment. We have shown that when Zymosan, a sterile inflammatory agent, is added to the chamber, angiogenesis and adipogenesis are significantly improved. As Zymosan interacts with toll-like receptors on macrophages, the role of macrophages in new tissue development in the tissue engineering chamber was assessed. Morphological and histological results showed that macrophages were presenting in high numbers at 2 weeks but had decreased significantly by 4 and 6 weeks in the chamber. Numerous immature new blood vessels had formed by 2 weeks, becoming more mature at 4 and 6 weeks. Immature adipocytes were visualized at 4 weeks and mature cells, at 6 weeks. To investigate the functional role of macrophages in the tissue engineering process, we knocked out the local macrophage population by inserting Clodronate liposomes in this chamber. This study shows for the first time that when macrophages are depleted, there is minimal new vascular and adipose tissue development. We propose a new theory for tissue engineering in which macrophages play a central role in both neovascularisation and adipogenesis.

In the authors' model, most of the implanted tissue died, but unresorbed dead fat accounted substantially for the long-term, reduced volume. A layer of host-derived, regenerated adipose tissue was present at the periphery. This regeneration may be driven by the presence of dying fat, and it was enhanced by addition of the authors' adipogenic adjuncts. Future research should perhaps focus not only on improving graft survival but also on enhancing the adipogenic environment conducive to fat regeneration.