Understanding Roles of Porcine Small Intestinal Submucosa in Urinary Bladder Regeneration: Identification of Variable Regenerative Characteristics of Small Intestinal Submucosa

Abstract

Neuropathic bladders are the result from damages to the central or peripheral nervous system, and ultimately may require surgical reconstruction to increase bladder volumes and to reduce the risk of damages to the kidneys. Surgical reconstruction through bladder augmentation has traditionally been practiced using a segment of the ileum, colon, or stomach from the patient through enterocystoplasty. However, the use of gastrointestinal segments can lead to serious adverse consequences. Porcine small intestinal submucosa (SIS), a xenogeneic, acellular, biocompatable, biodegradable, and collagen-based bioscaffold is best known to encourage bladder regeneration without ex vivo cell seeding before implantation in various experimental and preclinical animal models. Although it has been demonstrated that SIS supports bladder cell growth in vitro, and SIS-regenerated bladders are histologically and functionally indistinguishable from normal functional tissues, clinical utilization of SIS for bladder augmentation has been hampered by inconsistent preclinical results. Several variables in SIS, such as the age of pigs, the region of the small intestine, and method of sterilization, can have different physical properties, biochemical characteristics, inflammatory cell infiltration, and regenerative capacity due to cellular responses in vitro and in vivo. These parameters are particularly important for bladder regeneration due to its specific biological function in urine storage. Clinical application of SIS for surgical bladder reconstruction may require graft materials to be prepared from a specific region of the small intestine, or to be further formulated or processed to provide uniform physical and biochemical properties for consistent, complete, and functional bladder regeneration.

Topical Collagen-Based Biomaterials for Chronic Wounds: Rationale and Clinical Application

“…Further processing, including lyophilization and the method of terminal sterilization, can impact the material's strength and availability of functional bioactive molecules. 50 Nonetheless, the remaining matrix complexity far exceeds that of polymerized scaffold materials. The composition and ultrastructure of the ECM vary based on the source tissue and the methods used to decellularize the tissue.…”

“…49 this material based on the age of the animal and whether the material was obtained from the distal or proximal jejunum. 50 This may account for some of the variability in outcomes and provides some rationale for use of tissue from young or fetal sources. 57,58 Several commercially available ECM scaffolds are derived from fetal tissue, which is rich in glycosaminoglycans and Col III with less crosslinking.…”

Regenerative Medicine: Charting a New Course in Wound Healing

“…23 Matrix composition varies by tissue, but collagen is the most abundant component overall, and collagen-based matrices are used in clinical conditions varying from wound healing to urinary incontinence. [24][25][26][27] Other components of extracellular matrices such as proteoglycans and fibrin are also used in regenerative medicine either with or without collagen. Moreover, a variety of synthetic biomaterials are being developed to capitalize on the spatial and biomechanical cues of endogenous extracellular matrices during development.…”

Genitourinary System

“…PLGA coated with collagen or fibrin has shown biocompatibility and supported cell growth and differentiation. Other materials, such as SIS and silk, have been used as scaffolds for bladder tissue augmentation [44,45]. In one study, augmentation cystoplasty was performed in 10 pigs using acellular silk scaffolds.…”