Preliminary outcomes and transcriptomic analysis of xenogeneic human-derived acellular dermal matrix patches for complex ureteral stricture reconstruction in a porcine model

Introduction

Ureteral stricture, defined as a pathological narrowing of the ureteral lumen, significantly impairs urinary drainage and may lead to progressive renal deterioration (1). The etiology is multifactorial, with iatrogenic injury being the most prevalent cause, particularly given the widespread adoption of endourological interventions such as ureteroscopic laser lithotripsy (2). Additional etiologies include congenital ureteral abnormalities, calculus-induced trauma, radiation-induced fibrosis following abdominal or pelvic malignancies, gynecological or obstetric surgical injuries, retroperitoneal fibrosis, and chronic infections (3). Regardless of anatomical location, persistent luminal narrowing elevates intraluminal pressure, leading to progressive hydronephrosis and gradual deterioration of ipsilateral renal function. Without timely intervention, severe ureteral obstruction culminates in irreversible renal damage or complete loss of renal function (4,5). Current therapeutic strategies encompass endoscopic management with long-term indwelling of ureteral stents, reconstructive surgery, and, in extreme scenarios, renal transplantation (4). Among these modalities, reconstructive ureteral surgery is widely regarded as the most definitive treatment (4,6).

Common reconstructive techniques include pyeloureteroplasty, ureteroureterostomy, buccal mucosa graft ureteroplasty, and ileal ureter substitution. However, managing complex strictures involving the upper or middle ureter, particularly those exceeding 2.0 cm, remains challenging (6). For segmental defects of this length, direct end-to-end anastomosis may cause excessive anastomotic tension and increase the risk of postoperative restenosis and urinary leakage (7). Current alternatives usually depend on autologous tissues such as buccal mucosa, appendix, or intestinal segments (7). While autologous grafts demonstrate excellent biocompatibility and low immunogenicity (8), their harvesting inherently introduces additional surgical trauma. Donor-site complications, particularly in buccal mucosa procurement, include oral discomfort, numbness, restricted mouth opening, and feeding difficulties, which impair postoperative recovery and patients’ quality of life (8). These clinical limitations highlight the need for off-the-shelf graft materials that provide adequate mechanical support and biological compatibility while eliminating donor-site morbidity (9).

Acellular dermal matrix (ADM) represents an alternative biomaterial. Derived from human or animal dermis through decellularization, ADM retains the native three-dimensional collagen framework, elastic fibers, proteoglycans, and glycosaminoglycans while markedly reducing its immunogenicity (10). Broadly utilized in plastic and reconstructive surgery, burn treatment, and wound repair, ADM has shown favorable outcomes regarding tissue integration, neovascularization, and structural support (11). Recently, its use in urology has expanded to include urethral reconstruction, hypospadias repair, and penile reconstructive procedures. Nevertheless, the feasibility of ADM, particularly human-derived ADM (ADM-H) used as a xenogeneic scaffold in a porcine model, remains insufficiently investigated for complex ureteral reconstruction (12,13). The ureter is structurally and functionally more complex than the urethra, relying on coordinated smooth muscle peristalsis to maintain continuous antegrade urine transport (14). Therefore, careful evaluation of whether low-immunogenicity xenogeneic ADM-H matrices can serve as potential ureteral substitutes is needed to expand reconstructive options.

We hypothesized that an ADM-H patch could act as an extracellular matrix scaffold that may support host-cell migration, urothelial coverage, and smooth muscle remodeling after ureteral reconstruction. In this pilot study, ADM-H was used as a xenogeneic tubular scaffold to reconstruct segmental ureteral defects in a porcine model. The study was designed as a preliminary proof-of-concept experiment to assess surgical feasibility, early structural integrity, and early regenerative changes, rather than to establish definitive efficacy. Histological and transcriptomic analyses were performed to explore mechanisms associated with epithelial regeneration and smooth muscle remodeling in the reconstructed ureter. We present this article in accordance with the ARRIVE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0501/rc).

Methods

ADM-H preparation

ADM-H was employed as the experimental scaffold material (Xin Kang Chen Biotechnology Co., Ltd., Beijing, China). The ADM-H material was processed through standardized decellularization procedures to completely remove cellular components while preserving the native extracellular matrix architecture. The primary components include type I collagen with a small proportion of type III collagen, elastic fibers, proteoglycans, and glycosaminoglycans. Prior to implantation, ADM-H sheets were thoroughly rinsed with sterile 0.9% saline solution to remove residual preservatives and to rehydrate the matrix. The primary mechanical parameters of ADM-H are summarized in Table S1.

Animal model and surgical procedure

Experimental animals

Three 6-month-old female Bama miniature pigs weighing 35–40 kg were used. All animals were housed under standard laboratory conditions with free access to food and water. Animals were housed individually in pens (1.5 m × 2.0 m) with controlled temperature (22±2 ℃), humidity (50%±10%), and a 12 h light/dark cycle. Environmental enrichment included sterilized chew toys and daily human interaction. Bedding was changed every three days. Each animal served as its own internal healthy reference: one ureter was designated as the experimental side for stricture modeling and reconstruction, while the contralateral ureter was left untreated. The contralateral ureter was used for anatomical and histological reference only and was not considered an active surgical control. This study was approved by the Laboratory Animal Ethics Committee of Yangling Zhongyou Life Science Co., Ltd. (approval No. YLZY-IACUC-2025-CGSC-0035). All animal experiments were conducted following institutional and national guidelines for the care and use of laboratory animals (Figure S1).

Surgical procedure

One month prior to reconstruction surgery, baseline ureteroscopy was performed bilaterally to assess the native ureteral lumen and exclude pre-existing pathology. Following this evaluation, the experimental pigs underwent thulium laser ablation of the ureteral wall to create a model of ureteral strictures. The laser output was set at 2 J, repetition frequency 10 Hz, and power 20 W. Two weeks post-ablation, ureteroscopy and antegrade urography were conducted to evaluate the severity of ureteral strictures. Following model verification, animals underwent a 2-week recovery period prior to reconstruction surgery. General anesthesia was maintained with isoflurane inhalation throughout surgery. After anesthetic induction, surgery was performed through a midline incision under sterile conditions. The surgical-side ureter was carefully exposed. Because the length and extent of complete obliterative narrowing induced by thulium laser cauterization cannot be fully controlled, we adopted a standardized 2-cm transection criterion during reconstruction. The visually and endoscopically confirmed obstructed stenotic segment, together with adjacent scarred tissue within an approximately 2-cm segment, was resected to create a reproducible segmental defect. This design matched the purpose of this preliminary study, namely to evaluate whether ADM-H could serve as a potential substitute for autologous graft material in ureteral reconstruction rather than to compare ADM-H with primary end-to-end anastomosis. Dissection was performed to preserve the periureteral vascular supply. Under sterile conditions, the ADM-H material was trimmed into square patches measuring approximately 2.5 cm × 1.5 cm. The trimmed ADM-H patch was then rolled longitudinally into a tubular construct with an internal diameter of approximately 5 mm, approximating the caliber of the native porcine ureter. The rolled ADM-H scaffold was interposed between the proximal and distal ureteral ends. Before initiating the end-to-end suture, a double-J stent was placed in the reconstructed ureter and left in place for 4 weeks. Subsequently, a tension-free end-to-end anastomosis was performed using 2-0 Vicryl absorbable sutures. Care was taken to ensure correct mucosal alignment at both anastomotic ends while maintaining luminal continuity. Upon completion of the anastomosis, standard layered abdominal closure was performed (Figure S1).

Postoperative care, monitoring, and euthanasia

Postoperative analgesia consisted of intramuscular buprenorphine (0.05 mg/kg every 12 h for 48 h). Wound infection was prevented by topical povidone‑iodine and systemic ceftiofur (5 mg/kg IM, once daily for 5 days). The animals received standard postoperative monitoring. No unexpected adverse events (e.g., severe bleeding, graft rejection, fistula, or death) occurred. Transient mild hematuria was observed in all animals for 2 days post‑surgery, which resolved spontaneously. All three experimental pigs survived the observation period without exhibiting any abnormal behaviors or febrile episodes. Humane endpoints were defined as: (I) inability to stand or access food/water for >24 h; (II) weight loss >20% of baseline; (III) severe hydronephrosis with ruptured renal pelvis confirmed by ultrasound; (IV) persistent fever >40.5 ℃ despite treatment. None of these endpoints were reached during the study. At 45 days post‑reconstruction, antegrade urography and ureteroscopy were repeated. Under deep anesthesia, animals were humanely euthanized by intravenous administration of an anesthetic overdose. The reconstructed ureters, the contralateral control ureters, and the bilateral kidneys were harvested for analysis.

Imaging and endoscopic evaluation

Intravenous urography was conducted on the day of laser modeling and on day 45 postoperatively. Radiographic images were acquired following contrast agent injection to evaluate transit of contrast medium through the reconstructed ureteral segment into the bladder. In addition, ureteroscopy was performed before ureteral stenosis (US) modeling, two weeks after modeling, and on day 45 post-ureteroplasty. The ureteroscope was advanced transurethrally for direct visualization of the reconstructed segment. Clinical parameters were recorded, including ureteral patency, luminal surface morphology, presence of stenosis or adhesions, and overall morphology.

Macroscopic evaluation and histological analysis

At day 45, the bilateral ureters and kidneys were harvested and photographed. The gross morphology, diameter, and color of the reconstructed and control ureters were documented. The kidneys were bisected longitudinally to evaluate renal pelvic dilation. For histological analysis, ureteral segments including 2 mm of contralateral normal tissue, stenosis tissue, and reconstructed tissue were fixed in 4% neutral buffered formalin for 24 hours. The samples were dehydrated, embedded in paraffin, and sectioned at a thickness of 4 µm. Hematoxylin and eosin (H&E) staining was performed to evaluate urothelial thickness, inflammatory cell infiltration, granulation tissue formation, and general tissue architecture. Masson’s trichrome staining was performed to assess collagen deposition and smooth muscle regeneration. All histological slides were evaluated independently by two experienced pathologists in a blinded manner.

RNA extraction and sequencing

Fresh tissue (approximately 50 mg) was homogenized in TRIzol reagent, and total RNA was extracted following the manufacturer’s protocols. RNA quality was rigorously assessed via a NanoDrop 2000 spectrophotometer to determine concentration and purity, and an Agilent 2100 Bioanalyzer to ensure an RNA Integrity Number (RIN) of at least 7.5. For library construction, Poly(A) mRNA enrichment was performed using the NEBNext Poly(A) Magnetic Isolation Module. Strand-specific libraries were prepared using the NEBNext Ultra II RNA Library Prep Kit. Paired-end 150 bp sequencing on the Illumina NovaSeq 6000 platform generated approximately 6 Gb of raw data per sample. Bioinformatics analysis was conducted by first utilizing fastp (v0.20.1) to trim adapters and filter low-quality reads. The clean reads were then aligned to the Sus scrofa reference genome (Ensembl Sscrofa11.1) using HISAT2 (v2.2.1). FeatureCounts (v2.0.3) was used to quantify gene expression, and transcripts per million (TPM) values enabled accurate between-sample comparisons. DESeq2 (v1.40) identified differentially expressed genes based on thresholds of |log₂ fold change| >1 and a false discovery rate (FDR) <0.05. Finally, clusterProfiler (v4.8) was utilized to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses (adjusted P<0.05).

Statistical analysis

Given the pilot nature of this study and the limited sample size (n=3 per group), continuous variables are summarized descriptively and expressed as the mean ± standard deviation. For the quantitative imaging and histomorphometric comparisons, overall group differences were assessed using one-way analysis of variance, followed by exploratory two-sided Welch t-tests for pairwise comparisons without adjustment for multiple testing. Individual data points are shown to demonstrate the data distribution. All analyses were performed using R (version 4.5.1; R Foundation for Statistical Computing, Vienna, Austria). P values are reported for reference and should be interpreted cautiously because of the limited sample size and exploratory design.

Protocol registration

A study protocol describing the research question, key design features (including the stricture model, reconstruction procedure, and analysis plan) was prepared prior to the study. This protocol was not registered in a publicly accessible database because the study was a pilot, proof‑of‑concept investigation.

Results

Early imaging and endoscopic findings indicate ureteral patency after ADM-H reconstruction

Serial contrast urography showed the baseline ureter before modeling (Figure 1A), hydronephrosis and ureteral stenosis 2 weeks after thulium laser modeling (Figure 1B), and partial improvement at day 45 after ADM-H reconstruction (Figure 1C); the corresponding ureteral-width measurements are shown in Figure 1D-1F. Preoperative endoscopy revealed a normal ureter with red-colored mucosa, adequate width, and blood supply (Figure 1G). Two weeks post-thulium laser modeling, the stenotic ureter exhibited pallid mucosa, preventing guidewire advancement (Figure 1H). At day 45 after ADM-H ureteroplasty, the reconstructed segment showed a patent lumen with no obvious stenosis or diverticulum (Figure 1I). Macroscopic examination at day 45 suggested graft-host integration, with a smooth luminal surface and no visible scarring or calculus formation. The excised stenotic segment exhibited marked thickening (Figure 1J). Marked hydroureter was observed proximal to the reconstructed segment (Figure 1K). Direct measurement of the reconstructed ureteral external diameter is shown in Figure 1L. The bilateral urinary system specimen showed no significant renal atrophy, although mild dilation of the surgical-side renal pelvis was observed (Figure 1M). The reconstructed ureter had an external diameter of 12.7±1.4 mm, compared with 5.2±0.3 mm for the contralateral healthy ureter (Figure 1N,1O).

Figure 1 Comprehensive imaging assessment and acquisition of gross specimens. (A) Preoperative ureteral contrast imaging. (B) Demonstrates hydronephrosis and ureteral stenosis 2 weeks after thulium laser stenosis modeling. (C) Improvement of hydronephrosis and ureteral stenosis on day 45 after complex ureteral reconstruction using the ADM-H patch as a xenogeneic scaffold. (D) The width of the normal ureter in contrast imaging without intervention. (E) Demonstrates ureteral width on contrast imaging 2 weeks after thulium laser stenosis modeling. (F) Improvement of hydronephrosis and hydroureter on day 45 after complex ureteral reconstruction using the ADM-H patch as a xenogeneic scaffold. (G) The patency of the preoperative normal ureter observed via ureteroscopy. (H) After 2 weeks of thulium laser stenosis modeling, the ureteral occlusion site cannot be passed through by a ureteral guidewire, indicating complete occlusion. (I) Ureteroscopy performed after complex ureteral reconstruction using the ADM-H patch as a xenogeneic scaffold reveals patency at the original occlusion site. (J) The dissected stenotic segment of the successfully modeled ureter obtained during the procedure. (K) Specimen of the affected kidney and ureter obtained on day 45 post-ADM-H patch ureteroplasty. (L) External diameter of the reconstructed ureter. (M) Urinary system specimen on day 45 postoperatively: the kidney on the stenosis side is slightly enlarged, while the reconstructed ureter is thickened. (N) Width of the reconstructed ureteral segment. (O) Width of the healthy-side control ureter. ADM-H, human-derived acellular dermal matrix.

ADM-H scaffold maintains structural integrity and supports early-stage ureteral reconstruction

H&E and Masson’s trichrome staining were performed on healthy [normal control (NC)], stenosed (US), and reconstructed (ADM) ureters (Figure 2). H&E staining showed severe luminal narrowing in the US group and a wider lumen in the ADM group (Figure 2, A1,A2). Masson’s trichrome staining showed less extensive collagen-rich fibrosis in the ADM group than in the US group (Figure 2, B1,B2). Higher-magnification images show the mucosal epithelium (Figure 2, A3,B3), lamina propria and neovascularization (Figure 2, A4,B4), muscular layer (Figure 2, A5,B5), and adventitial layer (Figure 2, A6,B6).

Figure 2 Gross pathological and morphological evaluation. (A1) Low-magnification H&E-stained sections of the normal control (NC), ureteral stenosis (US), and reconstructed (ADM) ureters (scale bar, 2.5 mm). Compared with the patent lumen of the normal contralateral ureter without stenosis, the US lumen was markedly narrowed or occluded; the reconstructed ADM lumen was wider than the US lumen. (A2–A6) Higher-magnification H&E-stained images (scale bar, 250 µm) showing the ureteral wall (A2), mucosal epithelium (A3), lamina propria (A4), muscular layer (A5), and adventitial layer (A6). Arrows in A4 indicate neovascularization. (B1) Low-magnification Masson’s trichrome-stained sections of the NC, US, and ADM ureters (scale bar, 2.5 mm). The US group showed more extensive collagen-rich fibrosis than the NC and ADM groups. (B2–B6) Higher-magnification Masson’s trichrome-stained images (scale bar, 250 µm) showing the ureteral wall (B2), mucosal epithelium (B3), lamina propria (B4), muscular layer (B5), and adventitial layer (B6). Arrows in B4 indicate neovascularization. ADM, acellular dermal matrix; ADM-H, human-derived acellular dermal matrix; H&E, hematoxylin and eosin; NC, normal control; US, ureteral stenosis.

ADM-H ureteroplasty shows early recanalization and ureteral regenerative changes

By day 45, H&E staining revealed a continuous urothelial lining with a thickness of 82.5±8.51 µm. Masson’s trichrome staining showed newly formed smooth muscle bundles aligned parallel to the luminal axis, suggesting early structural remodeling. The regenerated muscle layer was thicker than that of the healthy ureter in this pilot sample; however, these histological findings do not by themselves confirm complete functional recovery of ureteral peristalsis (14-19). Quantitative analyses showed that the luminal radius was smaller in the US group than in the ADM and NC groups (Figure 3A). Smooth muscle layer thickness was greatest in the ADM group, followed by the US and NC groups (Figure 3B). Epithelial thickness was greater in the US group than in the NC group, whereas comparisons involving the ADM group were not significant (Figure 3C). Contrast-measured ureteral width was greatest in the US group, followed by the ADM and NC groups (Figure 3D).

Figure 3 Quantitative imaging and histomorphometric analyses. (A) Average luminal radius measured on H&E-stained sections. The ADM and NC groups were comparable, whereas the US group had a smaller luminal radius than both groups. (B) Smooth muscle layer thickness measured on histological sections. In this pilot sample, the ADM group had the greatest thickness, followed by the US and NC groups. (C) Epithelial cell layer thickness measured on H&E-stained sections. The ADM and NC groups were comparable; the US group had greater epithelial thickness than the NC group, whereas comparisons involving the ADM group were not significant. (D) Ureteral width measured on contrast urography. The US group had the greatest width, followed by the ADM and NC groups. Individual dots represent animals (n=3 per group); boxes show the median and interquartile range, and whiskers extend to 1.5 times the interquartile range. Overall group differences were assessed using one-way ANOVA; exploratory pairwise comparisons used two-sided Welch t-tests without adjustment for multiple testing. *, P<0.05; **, P<0.01; ****, P<0.0001; ns, not significant. ADM, acellular dermal matrix; H&E, hematoxylin and eosin; NC, normal control; US, ureteral stenosis.

RNA sequencing reveals coordinated epithelial, muscular, and extracellular matrix remodeling

RNA sequencing comparing US and control groups identified 1,114 upregulated and 560 downregulated genes. Volcano plots highlighted inflammation/fibrosis-related genes including NR4A3, ETS1, and CCN1. KEGG analysis showed enrichment of TNF, MAPK, NF-kappaB, and IL-17 signaling pathways in the US group.

At day 45, RNA sequencing of ADM-H reconstructed tissues vs. healthy controls showed distinct separation by principal component analysis. TNS4, ALK, OVOL1, and LMNA were upregulated, while immune markers TASL and CD84 were downregulated. GO enrichment showed enriched processes including cellular proliferation and cell adhesion. KEGG analysis revealed enrichment of cell adhesion molecules, PI3K-Akt, FoxO signaling, and cell cycle pathways (20-25) (Figure 4).

Figure 4 Transcriptomic profiling and pathway enrichment analysis. (A) PCA illustrating clustering and transcriptomic signatures between the ADM group and NC group. (B) Volcano plot identifying upregulated and downregulated DEGs. (C) Heatmap highlighting the expression patterns of the top DEGs. (D) Enrichment of biological processes associated with cell regeneration and tissue remodeling. (E) KEGG pathway scatter plot showing enrichment in cell adhesion molecules, primary immunodeficiency, and the FoxO signaling pathway, as indicated by Rich factor and gene counts. (F) PCA illustrating distinct clustering and transcriptomic signatures between the US group and NC group. (G) Volcano plot identifying upregulated and downregulated DEGs. (H) Heatmap highlighting the expression patterns of the top DEGs. (I) Enrichment of biological processes associated with inflammatory responses and fibrosis. (J) KEGG pathway scatter plot showing enrichment in TNF signaling, NF-kappaB signaling, IL-17 signaling, and Th1/Th2/Th17 cell differentiation. ADM, acellular dermal matrix; DEG, differentially expressed gene; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; NC, normal control; PCA, principal component analysis; TNF, tumor necrosis factor; US, ureteral stenosis.

Discussion

This study explored the feasibility of using ADM-H as a xenogeneic scaffold for reconstruction of complex ureteral strictures in a porcine model. Using imaging, endoscopic evaluation, histological analysis, and transcriptomic profiling, we observed that ADM-H-based reconstruction maintained early ureteral patency, supported urothelial regeneration, and was associated with neovascularization. The experimental design should be interpreted in the context of segmental reconstruction. After thulium laser-induced obliterative stricture formation, the exact length of the closed stenotic segment was not fully controllable; therefore, we used a standardized 2-cm resection to create a reproducible segmental defect. Direct end-to-end anastomosis across this defect would not model the clinical scenario in which tissue substitution is required and could introduce excessive anastomotic tension. Accordingly, ADM-H was evaluated as a potential substitute for autologous grafts in ureteral reconstruction, rather than as an alternative to tension-free primary anastomosis when primary repair is feasible. A primary advantage of ADM-H is its capacity to provide immediate mechanical support—a property that has driven its broad utilization in herniorrhaphy and cutaneous defect reconstruction (7). This structural integrity is particularly critical during the early postoperative period, when the reconstructed segment is most susceptible to collapse, urinary leakage, and fibrotic contracture. In our porcine model, the rolled ADM-H scaffold maintained luminal patency throughout the study, as confirmed by antegrade urography and ureteroscopic evaluation. Although mild dilation of the reconstructed ureter and renal pelvis was observed, no severe hydronephrosis or catastrophic complications such as graft rejection or complete obstruction were detected. Imaging assessments indicated a reduced flow rate of the contrast agent, suggesting that ureteral peristaltic function had not fully recovered. This incomplete functional recovery, combined with the inflammatory process following the indwelling double-J stent, likely contributed to the mild hydronephrosis observed on the surgical side. In the present short-term study, these findings suggest adequate early drainage but do not establish complete functional recovery.

Beyond mechanical support, ADM may function as a dynamic extracellular matrix scaffold that facilitates host-cell migration, adhesion, and proliferation. Histological analyses revealed that ADM-H provided a good platform for urothelial regeneration. Although the regenerated urothelium was thinner than that of the native ureter, it exhibited an organized cellular arrangement and continuity across the graft segment. Prompt re-epithelialization is important to prevent urinary extravasation, limit chronic inflammation, and mitigate subsequent fibrotic remodeling. In addition, our histological samples demonstrated the formation of a smooth muscle layer by day 45, indicating ureteral smooth muscle regeneration and/or compensatory hyperplasia. Coordinated regeneration of urothelium and smooth muscle may be necessary for restoring long-term functional integrity and peristaltic urine transport, but this cannot be confirmed from the present short-term histological data alone.

Transcriptomic profiling and pathway analyses provided exploratory insights into molecular processes associated with tissue remodeling. RNA sequencing revealed the upregulation of TNS4, ALK, and OVOL1, which are implicated in epithelial dynamics and differentiation, alongside the upregulation of LMNA, suggesting smooth muscle phenotypic modulation. Simultaneously, the downregulation of immune markers TASL and CD84 indicated a progression toward immune homeostasis (24,25). Adequate vascularization is essential for tissue regeneration, and increased microvessel density within the scaffold was consistent with neovascularization. KEGG analysis revealed the enrichment of cell survival-related pathways, including PI3K-Akt and FoxO signaling, which are mediators of epithelial regeneration, vascular stabilization, and tissue integration. The coexistence of inflammatory pathway enrichment with histological preservation suggests that controlled immune signaling supported constructive remodeling rather than rejection. A balanced inflammatory response is essential for recruiting endothelial progenitor cells and promoting neovascularization, indicating that ADM-H creates a microenvironment that supports tissue integration. Because radiographic and histological findings were obtained during a short observation window, cellular proliferation should be interpreted as early remodeling rather than definitive evidence of mature functional regeneration. As previous studies have reported, the prolonged indwelling of double-J ureteral stents independently induces chronic inflammatory responses (26); nevertheless, the reconstructed ureters maintained their luminal patency and demonstrated progressive, highly organized structural regeneration. Therefore, these transcriptomic findings should be considered associative and hypothesis-generating.

The findings of this study may have several implications for future research. First, ADM-H could be explored as a candidate alternative to autologous tissue grafts for complex ureteral strictures, particularly in situations where buccal mucosa harvesting or intestinal substitution is undesirable. Second, the rolled ADM-H configuration used in this study provides a reproducible surgical approach that approximates native ureteral anatomy and may be adaptable to minimally invasive or robotic-assisted reconstructive procedures (27,28). In addition, ADM-H has an established safety record in other surgical fields, which may support further translational evaluation in urological reconstruction (7,12,29).

Despite these early results, this pilot study has several critical limitations. The small sample size (n=3) limits statistical power and generalizability. Crucially, the 45-day follow-up represents a very early observation window. Because the double-J stents were maintained for four weeks postoperatively, the stent-free observation period was only approximately 17 days. Given that clinically significant ureteral strictures and fibrotic remodeling typically manifest months after stent removal, long-term durability, late stricture recurrence, and functional recovery of the ADM-H graft remain unknown. In addition, the absence of an active surgical control group precludes direct efficacy comparisons against current standard clinical approaches such as buccal mucosa graft ureteroplasty, intestinal substitution, autologous tissue grafts, or other biomaterials. Functional assessment relied on imaging and histology without detailed urodynamic or electrophysiological validation, and transcriptomics provided associative rather than causal data. Addressing these gaps will require more rigorous study designs. Subsequent larger-scale, multi-cohort animal experiments should extend stent-free follow-up to 3–6 months, include appropriate positive surgical controls, and adopt more detailed imaging assessments, such as dynamic fluoroscopy and serial measurement of renal pelvis and ureteral dilation. Future studies should also integrate urodynamics and peristaltic electrophysiological testing to evaluate functional recovery more directly. Finally, protein-level validation of the transcriptomic findings and further optimization of the scaffold structure will be important steps toward eventual clinical translation.

Conclusions

This pilot study provides preliminary evidence supporting the technical feasibility of ADM-H for complex ureteral stricture reconstruction in a porcine model. The rolled tubular scaffold maintained early luminal patency and was associated with urothelial coverage, smooth muscle remodeling, and neovascularization during the short observation period. ADM-H may reduce donor-site morbidity by avoiding autologous graft harvest, but its comparative efficacy and long-term functional durability remain to be established. Larger controlled studies with extended stent-free follow-up and functional assessment are needed to optimize scaffold design and evaluate long-term outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the ARRIVE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0501/rc

Data Sharing Statement: Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0501/dss

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0501/prf

Funding: This work was supported by the Research Project of Chongqing Science and Technology Bureau (grant No. CSTB2022NSCQ-MSX0799); the Funding for the Project of Cultivation of High-End Medical Talents in Chongqing for Middle-aged and Young (grant No. 02972018GDRC001); the Key Research Project of Chongqing Municipal Education Commission (grant No. KJZD-K202400405); the Research Project of The First Affiliated Hospital of Chongqing Medical University (grant No. HLZD2024-02); and the Key Discipline Construction Project of Nursing Science, Chongqing Medical University.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0501/coif). All authors report that this study was supported by the Research Project of Chongqing Science and Technology Bureau (grant No. CSTB2022NSCQ-MSX0799); the Funding for the Project of Cultivation of High-End Medical Talents in Chongqing for Middle-aged and Young (grant No. 02972018GDRC001); the Key Research Project of Chongqing Municipal Education Commission (grant No. KJZD-K202400405); the Research Project of The First Affiliated Hospital of Chongqing Medical University (grant No. HLZD2024-02); and the Key Discipline Construction Project of Nursing Science, Chongqing Medical University. All supports were paid to the authors’ institution. ADM-H was not provided free of charge or subsidized by a company. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was approved by the Laboratory Animal Ethics Committee of Yangling Zhongyou Life Science Co., Ltd. (approval No. YLZY-IACUC-2025-CGSC-0035). All animal experiments were conducted following institutional and national guidelines for the care and use of laboratory animals.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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