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

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.