Development and in vitro investigation of a biodegradable mesh for the treatment of stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The use of polypropylene (PP) mesh for stress urinary incontinence (SUI) surgery has declined because of safety concerns. The aim of this study is to evaluate a biodegradable polycaprolactone (PCL) mesh and a PCL composite mesh tissue engineered with human uterine fibroblasts (HUFs) for SUI surgery by comparing mechanical properties and in vitro biocompatibility to commercially available PP and porcine dermis (PD). METHODS: The mechanical properties of four scaffold materials were evaluated: PCL, PCL-collagen-hyaluronic acid composite, acellular porcine dermal collagen (PD) (Pelvicol™) and polypropylene (Gynecare TVT™ Exact®). HUFs were seeded on separate scaffolds. After 7 and 14 days scaffolds were assessed for metabolic activity and cell proliferation using Alamar Blue, Live/Dead and PicoGreen assays. Soluble collagen production was evaluated using a Sircol assay. RESULTS: PCL and the composite scaffold reached ultimate tensile strength (UTS) values closest to healthy pelvic floor tissue (PCL = 1.19 MPa; composite = 1.13 MPa; pelvic floor = 0.79 MPa; Lei et al. Int Urogynecol J Pelvic Floor Dysfunct. 18(6):603-7, 2007). Cells on PCL showed significantly greater cell viability than PP at day 7 (p < 0.0001). At D14 the composite scaffold showed significantly greater cell viability than PP (p = 0.0006). PCL was the best performing scaffold for soluble collagen production at day 14 (106.1 µg versus 13.04 µg for PP, p = 0.0173). CONCLUSIONS: We have designed a biodegradable PCL mesh and a composite mesh which demonstrate better biocompatibility than PP and mechanical properties closer to that of healthy pelvic floor tissue. This in vitro study provides promising evidence that these two implants should be evaluated in animal and human trials.

Production and Preparation of Porcine Urinary Bladder Matrix (UBM) for Urinary Bladder Tissue-Engineering Purposes.

Surgical repair for the end stage bladder disease utilises vascularised, autogenous and mucus-secreting gastrointestinal tissue to replace the diseased organ or to augment inadequate bladder tissue. Post-operatively, the compliance of the bowel is often enough to restore the basic shape, structure and function of the urinary bladder; however, lifelong post-operative complications are common. Comorbidities that result from interposition of intestinal tissue are metabolic and/or neuromechanical, and their incidence approaches 100%. The debilitating comorbidities and complications associated with such urological procedures may be mitigated by the availability of alternative, tissue-engineered, animal-derived extracellular matrix (ECM) scaffolds such as porcine urinary bladder matrix (UBM). Porcine UBM is a decellularized biocompatible, biodegradable biomaterial derived from the porcine urinary bladder. This chapter aims to describe the production and preparation techniques for porcine UBM for urinary bladder regenerative purposes.

Biomaterials and Regenerative Medicine in Urology.

Autologous gastrointestinal tissue is the gold standard biomaterial for urinary tract reconstruction despite its long-term neuromechanical and metabolic complications. Regenerative biomaterials have been proposed as alternatives; however many are limited by a poor host derived regenerative response and deficient supportive elements for effective tissue regeneration in vivo. Urological biomaterials are sub-classified into xenogenic extracellular matrices (ECMs) or synthetic polymers. ECMs are decellularised, biocompatible, biodegradable biomaterials derived from animal organs. Synthetic polymers vary in chemical composition but may have the benefit of being reliably reproducible from a manufacturing perspective. Urological biomaterials can be 'seeded' with regenerative stem cells in vitro to create composite biomaterials for grafting in vivo. Mesenchymal stem cells are advantageous for regenerative purposes as they self-renew, have long-term viability and possess multilineage differentiation potential. Currently, tissue-engineered biomaterials are developing rapidly in regenerative urology with many important clinical milestones achieved. To truly translate from bench to bedside, regenerative biomaterials need to provide better clinical outcomes than current urological tissue replacement strategies.

Evaluation of endoscopic laser excision of polypropylene mesh/sutures following anti-incontinence procedures.

PURPOSE: We reviewed our experience with and outcome of the largest series to our knowledge of patients who underwent endoscopic laser excision of eroded polypropylene mesh or sutures as a complication of previous anti-incontinence procedures. MATERIALS AND METHODS: A total of 12 female patients underwent endoscopic laser excision of suture/mesh erosions at 1 center during a 10-year period. Primary outcome variables were the requirement of additional endoscopic or open surgery to remove mesh/sutures. Secondary outcome variables were persistence of urinary symptoms, postoperative complications, continence status and requirement of additional anti-incontinence procedures. RESULTS: The mean interval from previous surgery to erosion was 59 months (range 7 to 144) and the duration of presenting symptoms ranged from 3 to 84 months (mean 19). Ten patients underwent endoscopic excision of the mesh/suture with the holmium:YAG laser and 2 underwent excision with the thulium laser. Mean operative duration was 19 minutes (range 10 to 25) and followup was 65.5 months (range 6 to 134). Postoperatively 6 patients remain asymptomatic and 2 required a rectus fascial sling for recurrent stress urinary incontinence. Four patients underwent a second endoscopic excision due to minor persistence of erosion. Only 1 patient ultimately required open cystotomy to remove the eroded biomaterial. No intraoperative complications were recorded and all patients are currently asymptomatic. CONCLUSIONS: Endoscopic laser excision is an acceptable first line approach for the management of eroded biomaterials due to its high long-term success rate and minimally invasive nature.

Biodegradable materials for surgical management of stress urinary incontinence: A narrative review.

Stress urinary incontinence (SUI) was managed with techniques such as colposuspension, autologous fascia sling and urethral bulking agents. The introduction of the mid-urethral polypropylene (PP) sling in the 1990s led to a significant and rapid global change in SUI surgery. The synthetic non-degradable PP sling had superior results to traditional SUI procedures but its use has now declined due to significant complications such as pain and mesh erosion. These complications are attributed to its poor biocompatibility and integration into vaginal tissues. The efficacy of PP was extrapolated from studies on abdominal wall repair and it is now clear that integration of implanted materials in the pelvic floor differs from the abdominal wall. With PP prohibited in some jurisdictions, female patients with SUI have few management options. In the present review we summarise recent advances in SUI surgery and evaluate potential alternatives to PP slings with a particular focus on degradable materials. Allograft and xenograft materials demonstrate good biocompatibility but have yielded suboptimal cure rates. Tissue engineered synthetic degradable materials outperform unmodified synthetic degradable materials in terms of biomechanics and cell support. Synthetic tissue engineered degradable materials show promising results from in vitro studies and future research should focus on animal and human trials in this field.

Xenogenic extracellular matrices as potential biomaterials for interposition grafting in urological surgery.

PURPOSE: The field of tissue engineering focuses on developing strategies for reconstructing injured, diseased, and congenitally absent tissues and organs. During the last decade urologists have benefited from remodeling and regenerative properties of bioscaffolds derived from xenogenic extracellular matrices. We comprehensively reviewed the current literature on structural and functional characteristics of xenogenic extracellular matrix grafting since it was first described in urological surgery. We also reviewed the clinical limitations, and assessed the potential for safe and effective urological application of extracellular matrix grafting in place of autogenous tissue. MATERIALS AND METHODS: We performed literature searches for English language publications using the PubMed® and MEDLINE® databases. Keywords included "xenogenic," "extracellular matrix" and "genitourinary tract applications." A total of 112 articles were scrutinized, of which 50 were suitable for review based on clinical relevance and importance of content. RESULTS: Since the mid 1990s xenogenic extracellular matrices have been used to successfully treat a number of pathological conditions that affect the upper and lower genitourinary tract. They are typically prepared from porcine organs such as small intestine and bladder. These organs are harvested and subjected to decellularization and sterilization techniques before surgical implantation. Bioinductive growth factors that are retained during the preparation process induce constructive tissue remodeling as the extracellular matrix is simultaneously degraded and excreted. However, recent documented concerns over durability, decreased mechanical strength and residual porcine DNA after preparation techniques have temporarily hampered the potential of extracellular matrices as a reliable replacement for genitourinary tract structures. CONCLUSIONS: Extracellular matrices are a useful alternative for successfully treating a number of urological conditions that affect the genitourinary tract. However, clinical concerns regarding mechanical limitations and biosafety need to be addressed before their long-term role in reconstructive urological surgery can be clearly established.

Urinary Bladder vs Gastrointestinal Tissue: A Comparative Study of Their Biomechanical Properties for Urinary Tract Reconstruction.

OBJECTIVE: To evaluate the mechanical properties of gastrointestinal (GI) tissue segments and to compare them with the urinary bladder for urinary tract reconstruction. METHODS: Urinary bladders and GI tissue segments were sourced from porcine models (n = 6, 7 months old [5 male; 1 female]). Uniaxial planar tension tests were performed on bladder tissue, and Cauchy stress-stretch ratio responses were compared with stomach, jejunum, ileum, and colonic GI tissue. RESULTS: The biomechanical properties of the bladder differed significantly from jejunum, ileum, and colonic GI tissue. Young modulus (kPa-measure of stiffness) of the GI tissue segments was on average 3.07-fold (±0.21 standard error) higher than bladder tissue (P < .01), and the strain at Cauchy stress of 50 kPa for bladder tissues was on average 2.27-fold (±0.20) higher than GI tissues. There were no significant differences between the averaged stretch ratio and Young modulus of the horizontal and vertical directions of bladder tissue (315.05 ± 49.64 kPa and 283.62 ± 57.04, respectively, P = .42). However, stomach tissues were 1.09- (±0.17) and 0.85- (±0.03) fold greater than bladder tissues for Young modulus and strain at 50 kPa, respectively. CONCLUSION: An ideal urinary bladder replacement biomaterial should demonstrate mechanical equivalence to native tissue. Our findings demonstrate that GI tissue does not meet these mechanical requirements. Knowledge on the biomechanical properties of bladder and GI tissue may improve development opportunities for more suitable urologic reconstructive biomaterials.

The effects of stent interaction on porcine urinary bladder matrix employed as stent-graft materials.

Deployment of stent-grafts, derived from synthetic biomaterials, is an established minimally invasive approach for effectively treating abdominal aortic aneurysms (AAAs). However, a notable disadvantage associated with this surgical technique is migration of the deployed stent-graft due to poor biocompatibility and inadequate integration in vivo. Recently, tissue-engineered extracellular matrices (ECMs) have shown early promise as integrating stabilisation collars in this setting due to their ability to induce a constructive tissue remodelling response after in vivo implantation. In the present study the effects of stent loading on an ECM׳s mechanical properties were investigated by characterising the compression and loading effects of endovascular stents on porcine urinary bladder matrix (UBM) scaffolds. Results demonstrated that the maximum stress was induced when the stent force was 8-times higher than a standard commercially available stent-graft and this represented about 20% of the failure strength of the UBM material. In addition, the influence of stent shape was also investigated. Findings demonstrated that the stress induced was higher for circular stents at low forces and a higher stress was induced on square stents when increased force was applied. Our findings demonstrate that porcine UBM possesses sufficient mechanical strength to withstand the compression and loading effects of commercially available stent-grafts in the setting of endovascular aneurysm repair.

Development of a rotational cell-seeding system for tubularized extracellular matrix (ECM) scaffolds in vascular surgery.

Tubularized porcine extracellular matrices (ECMs) are under investigation as adjuvant scaffolds for endovascular aneurismal repair (EVAR). Limitations with tubularized ECMs in this setting include difficulties in achieving a confluent endothelium on the scaffold's luminal surface prior to in vivo implantation. In this in vitro study a rotational "cell-seeding rig" (RCR) was constructed to assess the potential for endothelialization of tubular ECM constructs. Human aortic endothelial cells (HAECs) were cultured onto the luminal surfaces of tubular porcine urinary bladder matrix (UBM) scaffolds and rotated in the RCR at experimental rotational speeds. Results showed that endothelial attachment occurred at a rotation speed of six revolutions per hour. HAECs continued to proliferate after the initial attachment period of 24 h and formed a confluent endothelial monolayer after 14 days of growth. Our results demonstrate that RCRs facilitate attachment of HAECs in vitro at a speed of six revolutions per hour. The endothelialization technique presented in the current study may be important for advancing tissue-engineering approaches to address some of the current limitations in endovascular treatments of abdominal aortic aneurysms.