Wei-Dong Zhu

Evaluation of the biocompatibility and mechanical properties of naturally derived and synthetic scaffolds for urethral reconstruction

The aim of this study was to evaluate the mechanical properties and biocompatibility of biomaterials, including bladder submucosa (BAMG), small intestinal submucosa (SIS), acellular corpus spongiosum matrix (ACSM), and polyglycolic acid (PGA), to identify the optimal scaffold for urethral tissue engineering. Tensile mechanical testing was conducted to evaluate mechanical properties of each scaffold. Rabbit corporal smooth muscle cells were cultured with the extracts of biomaterials and mitochondrial metabolic activity assay was used to determine the cytotoxicity of scaffold. The pore sizes of each scaffold were measured. Additionally, smooth muscle cells were seeded on biomaterials. Cell infiltration was evaluated. Mechanical evaluation showed that Young modulus, stress at break in ACSM were prior to those in other biomaterials (p < 0.05). MTT assay confirmed that all scaffolds supported normal cellular mitochondrial metabolic without inducing cytotoxic events. SEM demonstrated that PGA has the largest pore size (>200 microm). The ACSM has different pore sizes in urethral (<5 microm) and cavernosal surfaces (>10 microm). Widespread distribution of cells could be observed in PGA 14 days after seeding. Multilayer cellular coverage developed in BAMG and urethral surface of ACSM without any sign of cellular invasion. Moderated cellular penetration could be found in SIS and cavernosal surface of ACSM. Although each scaffold demonstrated suitable mechanical properties, which is similar to normal urethra, ACSM showed better response in some parameters than those in other biomaterials. It suggested that this scaffold may be an alternative for urethral reconstruction in the future. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

Tissue performance of bladder following stretched electrospun silk fibroin matrix and bladder acellular matrix implantation in a rabbit model

The goal of this study was to investigate the tissue performance of bladder following stretched electrospun silk fibroin matrix (SESFM) implantation compared with bladder acellular matrix (BAM). We compared SESFM with BAM based on porosity and pore size. Scaffolds were separately transplanted into opposite walls of the bladder of 30 rabbits after stripping the bladder mucosa and smooth muscle (1.5 × 2.0 cm(2)). Gross anatomical observation, histological analysis and muscle contractility studies were performed at 2, 4, and 8 weeks post-op. SESFM has higher porosity and larger pore size compared with BAM (p < 0.05). At 2 weeks, the presence of vesical calculus was evident in 7/10 rabbits. Histological analysis showed that SESFM and BAM promoted similar degree of urothelium regeneration (p > 0.05). However, SESFM promoted a higher degree of smooth muscle and vessel regeneration compared to BAM (p < 0.05). In addition, muscle strips supported by SESFM displayed higher contractile responses to carbachol, KCl, and phenylephrine compared with BAM. At 8 weeks, both matrices elicited similar mild acute and chronic inflammatory reactions. Our results demonstrated that SESFM has greater ability to promote bladder tissue regeneration with structural and functional properties compared to BAM, and with similar biocompatibility.

Urethral reconstruction with a 3D porous bacterial cellulose scaffold seeded with lingual keratinocytes in a rabbit model.

The goal of this study was to evaluate the effects of urethral reconstruction with a three-dimensional (3D) porous bacterial cellulose (BC) scaffold seeded with lingual keratinocytes in a rabbit model. A novel 3D porous BC scaffold was prepared by gelatin sponge interfering in the BC fermentation process. Rabbit lingual keratinocytes were isolated, expanded, and seeded onto 3D porous BC. BC alone (group 1, N  =  10), 3D porous BC alone (group 2, N  =  10), and 3D porous BC seeded with lingual keratinocytes (group 3, N  =  10) were used to repair rabbit ventral urethral defects (2.0   ×   0.8 cm). Scanning electron microscopy revealed that BC consisted of a compact laminate while 3D porous BC was composed of a porous sheet buttressed by a dense outer layer. The average pore diameter and porosity of the 3D porous BC were 4.23   ±   1.14 μm and 67.00   ±   6.80%, respectively. At 3 months postoperatively, macroscopic examinations and retrograde urethrograms of urethras revealed that all urethras maintained wide calibers in group 3. Strictures were found in all rabbits in groups 1 and 2. Histologically, at 1 month postoperatively, intact epithelium occurred in group 3, and discontinued epithelium was found in groups 1 and 2. However, groups 2 and 3 exhibited similar epithelial regeneration, which was superior to that of group 1 at 3 months (p  <  0.05). Comparisons of smooth muscle content and endothelia density among the three groups revealed a significant increase at each time point (p  <  0.05). Our results demonstrated that 3D porous BC seeded with lingual keratinocytes enhanced urethral tissue regeneration. 3D porous BC could potentially be used as an optimized scaffold for urethral reconstruction.

Reconstruction of Penile Urethra With the 3-Dimensional Porous Bladder Acellular Matrix in a Rabbit Model

OBJECTIVE To evaluate the effect of reconstruction of penile urethra with the 3-dimensional (3-D) porous bladder acellular matrix (BAM) in a rabbit model. MATERIALS AND METHODS In 30 male rabbits, a ventral urethral mucosal defect (1.5 × 0.8 cm) was created. Substitution urethroplasty was performed with 5% peracetic acid (PAA)-treated BAM (3-D porous BAM; 15 rabbits, PAA-treated BAM group) and non-PAA-treated BAM (15 rabbits; non-PAA-treated BAM group) in an onlay fashion. At 1, 2, and 3 months after surgery (5 rabbits at each time point) in the 2 groups, retrograde urethrogram and histologic analysis were performed to evaluate the outcomes of urethroplasty. RESULTS In the PAA-treated BAM group, 13 rabbits maintained a wide urethral caliber without a fistula or stricture. In contrast, 10 rabbits kept a wide caliber in the non-PAA-treated BAM group. Histologically, at 1, 2, and 3 months after the surgery, the speed of urothelium regeneration in the PAA-treated BAM group was faster than that in the non-PAA-treated BAM group. The smooth muscle-to-collagen ratio and the content of smooth muscle in the PAA-treated BAM group were significantly higher than that in the non-PAA-treated BAM group at each time point (P <.05). The endothelium density between the non-PAA-treated BAM and the PAA-treated BAM groups revealed a significant increase at all 3 time points (P <.05). CONCLUSION Our results confirmed that PAA-treated BAM urethroplasty enhanced urothelium, smooth muscle regeneration and neovascularization compared with those of the non-PAA-treated BAM. The 3-D porous BAM as an optimized biological scaffold may be used for cell-based tubular and long-segmental urethral reconstruction in the future.

Two Micrometer Continuous-Wave Thulium Laser Treating Primary Non-Muscle-Invasive Bladder Cancer: Is It Feasible? A Randomized Prospective Study

BACKGROUND AND OBJECTIVE Until now, various laser types have been used in the treatment of bladder cancer. The purpose of this study is to evaluate the feasibility and effectiveness of 2 μm continuous-wave (CW) thulium laser in treating primary non-muscle-invasive bladder cancer (NMIBC). METHODS A comparative (randomized prospective) interventional study was conducted in our center. A total of 400 patients with Ta or T1 bladder cancer were enrolled and randomized to transurethral resection of bladder tumor (TURBT) or laser vaporesection (LVRBT). Patients in the TURBT group received standard transurethral resection with a bipolar electrocautery system, while those in the LVRBT group received transurethral vaporesction with a 2 μm CW thulium laser. All patients received intravesical irrigation with sterile water for at least 12 h immediately after the procedure. The end-points of this study were tumor recurrence and/or progression, or the completion of 36 months of follow-up (10 cystoscopies) with no recurrence. RESULTS A total of 292 patients were included in our analysis, of whom 143 received TURBT and 149 received LVRBT. During 36 months of follow-up, 129 cases (44.2%) had recurrence: 61 (42.7%) in the TURBT group and 68 (45.6%) in the LVRBT group (p = 0.608). Tumor progression was found in 19 patients (6.5%): 11 in the TURBT (7.7%) and 8 (5.4%) in the LVRBT group (p = 0.421). Median tumor-free survival was 25.2 months (25.46 in the TURBT group vs. 24.9 in the LVRBT group, p = 0.729). Overall recurrence rate was 14.7%, 42.1%, and 62.5% in the low, intermediate low, and intermediate high risk subgroups, respectively. Operation time was significantly lower in the TURBT than in the LVRBT group (28.43 vs. 31.5 min, p = 0.044). CONCLUSIONS Use of a 2 μm CW thulium laser is feasible and effective in treating primary NMIBC. With a cystoscopic biopsy of the bladder muscle, 2 μm CW thulium laser could retrieve sufficient diagnostic and prognostic specimens.