Development of UROGRAFT: A Bladder Acellular Matrix-Based Composite for Advanced Cystoplasty, Highlighting the Role of Graft Shape and Composition

TL;DR

Researchers developed UROGRAFT, a new bladder graft material that could replace gastrointestinal segments in bladder augmentation surgeries.

Contribution

The novel UROGRAFT composite combines bladder acellular matrix with collagen and cellulose, optimized for biocompatibility and graft shape.

Findings

A Triton X-100 and SDS decellularization protocol effectively removed cells while preserving ECM structure.

Cross-linking with collagen and cellulose improved scaffold properties and reduced porosity.

Preclinical trials in pigs showed UROGRAFT is biocompatible, safe, and supports cell growth for potential tissue engineering.

Abstract

Urinary bladder augmentation with gastrointestinal segments,
despite
many complications, remains a gold standard treatment of low-capacity,
poorly compliant, or refractory overactive urinary bladder. In this
study, we developed the UROGRAFT, a new bladder acellular matrix–collagen–cellulose
(BAM–CC) composite for urinary bladder augmentation. The study
presents the step-by-step development process of UROGRAFT, including
the selection of an optimal decellularization protocol and cross-linking
method to ensure optimal biomaterial properties. Histological and
biochemical analyses demonstrated that the combined protocol of Triton
X-100 and sodium dodecyl sulfate (SDS) was the most effective, completely
removing cellular components while preserving the extracellular matrix
(ECM). DNA quantification confirmed a significant reduction in residual
genetic material, ensuring a low immunogenic profile. Scanning electron
microscopy (SEM) confirmed high porosity and well-preserved collagen
fibers. To reduce porosity and permeability, BAM was cross-linked
with collagen type I and dialdehyde carboxymethyl cellulose, optimizing
scaffold performance. Biocompatibility tests confirmed the absence
of toxicity, tissue reactions, acute systemic toxicity, and mutagenic
effects. Based on computational modeling, verified by implantation
trials, a unique three-armed graft shape resembling lily petals was
developed. A preclinical study in porcine models demonstrated that
UROGRAFT is highly biocompatible, well-tolerated, and safe for urinary
bladder augmentation. Composite BAM–CC scaffolds provide an
appropriate environment for adipose derived mesenchymal stromal cells
(AD-MSCs) growth; therefore, the UROGRAFT can be used in the future
as an acellular graft (biomedical device) or a cell-seeded tissue-engineered
product (combined ATMP-biomedical device). UROGRAFT developed in this
study is a promising new product with the potential to be used in
augmentation cystoplasty, offering a safe and effective alternative
to gastrointestinal segments.

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