Clinical application of a double-modified sulfated bacterial cellulose scaffold material loaded with FGFR2-modified adipose-derived stem cells in urethral reconstruction

Abstract

Background Urethral stricture and reconstruction are one of the thorny difficult problems in the field of urology. The continuous development of tissue engineering and biomaterials has given new therapeutic thinking to this problem. Bacterial cellulose (BC) is an excellent biomaterial due to its accessibility and strong plasticity. Moreover, adipose-derived stem cells (ADSCs) could enhance their wound healing ability through directional modification. Methods First, we used physical drilling and sulfonation in this study to make BC more conducive to cell attachment and degradation. We tested the relevant mechanical properties of these materials. After that, we attached Fibroblast Growth Factor Receptor 2 (FGFR2)-modified ADSCs to the material to construct a urethra for tissue engineering. Afterward, we verified this finding in the male New Zealand rabbit model and carried out immunohistochemical and imaging examinations 1 and 3 months after the operation. At the same time, we detected the potential biological function of FGFR2 by bioinformatics and a cytokine chip. Results The results show that the composite has excellent repairability and that this ability is correlated with angiogenesis. The new composite in this study provides new insight and therapeutic methods for urethral reconstruction. The preliminary mechanism showed that FGFR2 could promote angiogenesis and tissue repair by promoting the secretion of Vascular Endothelial Growth Factor A (VEGFA) from ADSCs. Conclusions Double-modified sulfonated bacterial cellulose scaffolds combined with FGFR2-modified ADSCs provide new sight and treatments for patients with urethral strictures.

Decellularization of the human urethra for tissue engineering applications

“…for urethral TE were extensively studied in preclinical and clinical trials. [15][16][17][18] Besides that, one of the most promising tissue and organ regeneration methods is decellularization, in which the ECM is isolated from the native tissues to create a natural structure. The ECM -which ideally retains its complex composition, vascular networks, tissuespecific architecture, and biochemical and biomechanical properties -can then be repopulated with cells to form a functional tissue or organ.…”

Adipose-Derived Mesenchymal Stromal Cells in Basic Research and Clinical Applications

“…Cell modification through increased expression of the FGF receptor in another study led to the stimulation of angiogenesis, wound healing, and cell proliferation. In this study, a combination of engineered cells and bacterial cellulose scaffolds enabled the reconstruction of the urethra in an animal model [ 111 ].…”

Cell-Based Therapy for Urethral Regeneration: A Narrative Review and Future Perspectives

“…Therefore, targeted modification of ADSCs to overexpress FGFR2 may contribute to their secretory function and reparative effects. Zhu et al [ 73 ] constructed a composite scaffold of ADSCs overexpressing FGFR2 ( Figure 1 a). The ADSC modification promoted the secretion of angiogenic factors and enhanced their proliferation and migration abilities, which promoted tissue angiogenesis and regeneration, resulting in excellent reparative effects in a rabbit urethral injury model.…”