# Decellularized Scaffolds for Skin Repair and Regeneration
## 2 Tissue Sources for Preparation of ECM-Based Biomaterials for Skin Repair
### Decellularized Mesothelioma
#### 2.2.1 Decellularized Intestine and Urinary Bladder  
One of the most studied decellularized matrices for a variety of biomedical and tissue-engineering applications derives from the intestine. The ileum, jejunum, and small intestinal submuc (SIS) are the sources of decellularized intestine scaffolds (Figure 1C) [26]. Porcine SIS is derived from the thin, translucent tunica submuc layer of the small intestine, which remains after removing the mucosal and muscular layers (Figure 2C). Once processed, SIS biomaterials constitute cross-linked 3D matrices consisting of constitutive proteins that are mostly collagen, with smaller amounts of carbohydrates and lipids [59]. This material supports the formation of a skin barrier 14 days after seeding with human keratinocytes, fibroblasts, and endothelial cells.  
The role of SIS in promoting wound closure has been extensively investigated [25]. Incubation with SIS inhibits matrix metalloproteinases, which are important contributors to wound chronicity and are abundantly expressed in chronic wounds [60; 61]. Moreover, SIS scaffolds contain transforming growth factor (GF)-\(\beta\), basic fibrobl GF, vascular endothelial GF, and epidermal GF, thus promoting angiogenesis, cell growth, and differentiation, and consequently tissue regeneration [26]. Advantageous properties of SIS scaffolds in healing wounds include their effective barrier function of the wound bed dehydration because of their low porosity, and their strength and flexibility even after a long-term storage in a lyophilized form [59].  
Oasis(r) Wound Matrix (Cook Biotech, Inc., West Lafayette, IN, USA) is a collagen scaffold derived from porcine intestine submuc cleared for marketing by the FDA for the management of partial and full-thickness wounds, including pressure, venous, diabetic, and chronic vascular ulcers, surgical wounds, and draining wounds. A clinical study revealed that in a cohort of patients carrying with chronic leg ulcer treated with SIS, complete wound closure was achieved in 55% cases. The use of SIS seemed to accelerate healing rates and to reduce the incidence of ulcer recurrence [62]. Decellularizedporcine urinary bladder matrix (UBM) also has been reported to be an alternative to complex surgical procedures involving flap-associated donor site morbidity to treat complex extremity wounds. Use of UBM seemed to be rather beneficial for the management of patients suffering from comorbidities such as obesity, diabetes mellitus, and cardiopulmonary compromise [27]. After UBM decellularization, the remaining components include collagen, fibronectin, laminin, GAGs, and GFs. The UBM is likely to act through induction of bioactive GFs that support angiogenesis and facilitate proliferation of connective tissues, and the intact basement membrane is conductive to epithelial and endothelial cell proliferation [63].  
Commercially available porcine UBM products include MicroMatrix(r) (Accell, Inc., Columbia, MD, USA) and Cytal(r) Wound Matrix (Accell, Inc., Columbia, MD, USA). Regarding the mechanism of action, a preclinical study showed rapid cell infiltration into the UBM after application, followed by a robust angiogenic response and new host tissue deposition [64]. Another study demonstrated induction of a different immune response as compared to classical wound healing, one that involves M2-phenotype macrophages related to tissue remodeling rather than the M1 macrophages that are associated with scar tissue formation [65].