# Decellularized Scaffolds for Skin Repair and Regeneration
## 2 Tissue Sources for Preparation of ECM-Based Biomaterials for Skin Repair
### Acellular Dermal Matrix (ADM)
#### 2.1.5 Animal-Derived ADMs  
Grafts from xenogeneic dermal substitutes are often applied to extensive skin defects caused by severe burns. Although human ADMs and engineered human skin matrices have shown satisfactory effects in the treatment of extended second- and/or third-degree burns when xenogeneic ADMs lack histocompatibility, human ADMs are so expensive that their use is often impossible in these indications. The necessity of novel cost-effective dermal substitutes with equivalent efficiency has led to the search for alternative solutions [45]. The critical barrier to xenogeneic scaffolds in translational application is the recipient immune response to the antigenic components of the xenogeneic tissue [46]. Despite initial speculation, the decellularization process is insufficient to eliminate antigens from xenogeneic tissues because both cells and the ECM components themselves can elicit the host immune response. In addition, the remaining cell debris can be immunogenic [47]. Some strategies to achieve removal of specific antigens from xenogeneic scaffolds are being developed and are presented later in this review. These include enzymatic removal of known xenoantigens, such as \(\alpha\)-gal epitopes, stepwise solubilization-based antigen removal, or a combination of these approaches [47]. Although the animal skin can be extremely adherent and occasionally incorporated into the wound, xenografts are not yet considered true grafts or transplants. Xenografts do not vascularize, but they can still be beneficial to wound management by reducing the pain in partial-thickness injuries and improving healing rates. Such ADMs are being used for exfoliative skin disorders [48]. An extensive list of animal-derived ADM products is currently available, most of which achieve success in clinical use. Since the 1960s, pigs have served as the primary donors for xenografts in the United States, by virtue of their relative affordability and histological structural similarities to the human skin [48]. Several reports have attested to the benefits of using porcine skin in the treatment of extensive wounds. These advantages include reduced healing rates for partial-thickness wounds and granulating wounds and reduced pain with placement over burns [48]. Currently available acellular porcine dermal matrices include Permacol(tm) (Tissue Sciences Laboratories), Strattice(tm) (LifeCell Corp.), CollamendTM (Bard), Xenoderm (mbp), and XenMatrixTM (Davol, Inc.) [31]. According to the UnitedHealthCare(r) Medicare Advantage Policy Guideline for 2020, porcine skin dressings have been suggested as possibly necessary as an occlusive dressing for burns, donor sites of a homograft, and decubiti and other ulcers [49]. Permacol(tm) is composed of porcine dermal collagen that is subjected to crosslinking, which is suggested to improve tensile strength. Strattice(tm) is a non-crosslinked porcine-derived ADM in pliable and firm versions, which can be stored at room temperature and is available fully hydrated. Materials from different sources and processing exhibit different biochemical and mechanical properties and host responses upon implantation [50]. Therefore, suitable dressing material must be used based on the wound type. PriMatrix(TEI Biosciences) is an ADM processed from fetal bovine skin. It was cleared for marketing by the FDA for partial- and full-thickness wounds, for diabetic, pressure, and venous stasis ulcers, and for surgical wounds [51]. This fetal bovine collagen scaffold is processed to remove all lipids, carbohydrates, and non-collagenous proteins, leaving primarily intact fetal dermal collagen fibers with a great proportion of fibrillar collagen III [52]. This PriMatrixTM collagen III rich substrate is associated with healing in developing tissues, whereas the unique structural matrix of fetal tissues has been identified as a contributing factor in scarless wound healing [50]. SurgiMend(tm) PRS (TEI Biosciences) is another ADM processed from fetal bovine dermis. An acellular fish dermis has also been FDA approved.