The Challenge of Stress Incontinence and Pelvic Organ Prolapse

Revisiting Biologic Mesh Materials

William D'Angelo; Jenna Dziki; Stephen F. Badylak

Disclosures

Curr Opin Urol. 2019;29(4):437-442. 

In This Article

Biologic Meshes for Pelvic Organ Prolapse/Stress Urinary Incontinence Repair in Human Clinical Trials

Biologic meshes composed of mammalian extracellular matrix (ECM) or ECM-derived products have been used in a wide variety of clinical applications.[19] ECM provides mechanical and biochemical cues that influence cell behavior, and when applied to an injury site, ECM-based biomaterials have been shown to promote functional tissue restoration through recruitment of host stem/progenitor cells and stimulation of an immune cell phenotypic switch from a pro-inflammatory state to a pro-remodeling state.[19] On the basis of their ability to integrate with host tissues, biologic meshes composed of extracellular matrix have been proposed as an alternative to synthetic materials for surgical repair of SUI/POP, and several recent reports have investigated their performance in both preclinical animal models and in clinical studies.

Common source tissues used for ECM-based meshes include cadaveric human dermis, porcine or bovine dermis and porcine urinary bladder matrix (UBM) and small intestinal submucosa (SIS),[20] all of which have been evaluated for safety and efficacy in human clinical studies. For example, a clinical cohort study of 17 patients with POP, including 5 with concomitant SUI, in which they evaluated the use of a porcine SIS patch (Biodesign, Cook Medical; Bloomington, IN, USA) for pelvic floor repair showed no recurrence of symptoms in women with both POP and SUI, and only one patient experienced recurrent stage II prolapse.[21] A similar study evaluated 24 women with POP repaired with Pelvicol (CR Bard; Murray Hill, NJ, USA), a chemically crosslinked porcine dermal acellular xenograft, and showed a failure rate of 7.4%, with no mesh-related complications.[22] A study in which 20 patients with surgical repair of rectal prolapse using a porcine UBM surgical mesh (Matri-Stem Surgical Matrix PSMX, ACell; Columbia, MD) with 3-year follow-up showed only one patient with mild recurrence, and no recorded significant mesh-related complications.[23] Juma et al. evaluated the use of solvent-dehydrated cadaveric dermal allograft (Axis, Coloplast; Fredensborg Municipality, Denmark) for cystocele repair in 184 women. Results showed that 19% of patients had significant recurrence of POP, 10% required repeat surgery, and less than 1% experienced adverse effects (i.e. erosion, dyspareunia, transient hydronephrosis); thus efficacy was similar to other mesh materials, but with fewer adverse effects.[24]

These three clinical examples highlight the positive outcomes associated with a variety of ECM-based mesh materials derived from different source tissues and utilizing different processing methods as a concomitant reinforcement to primary POP repair. Recent studies have extended these findings through direct comparison of outcomes in pelvic floor surgical repair between ECM-based surgical meshes versus polypropylene meshes. For example, Seitz et al. compared outcomes, including physical examination and POP Quantification (POP-Q) scoring and responses to discomfort and surgical satisfaction questionnaires, in 274 women 1 year after surgery using either polypropylene mesh (Uphold, Boston Scientific; Natick, MA, USA; n = 231) or cadaveric human dermis allograft (either Axis, Coloplast, or Repliform, Boston Scientific; n = 43). In this case, dermis allograft implantation was associated with a higher incidence of recurrence and reoperation, and polypropylene implantation was associated with a 5.3% incidence of exposure, a complication not evident in the dermis group.[25] Similarly, Balzarro et al. assessed outcomes of 109 women treated with either primary repair, a porcine acellular dermal collagen xenograft (Pelvisoft, Bard), or polypropylene mesh (Prolene, Ethicon; Somerville, NJ), with a mean follow-up time of approximately 5 years. In contrast to Seitz' study, Balzarro found that all treatments performed similarly in terms of mitigating worsening or recurrent prolapse, but more adverse effects were reported with the polypropylene mesh.[26] It is important to note the widely variable criteria of reporting outcomes and outcome measures in synthetic mesh procedures for POP makes it difficult to combine or compare results in systematic reviews.[27] In addition, many of the published studies use small sample sizes, do not differentiate between first and repeat surgeries, have no randomized control groups, and are not always blinded.[28] The authors of the PROSPECT (PROlapse Surgery: Pragmatic Evaluation and randomised Controlled Trials) study published in 2017, therefore, sought to rigorously and comprehensively measure outcomes in the first 24 months after surgical repair of prolapse using no mesh (primary repair), polypropylene mesh, or biologic mesh (either porcine acellular dermal collagen, porcine SIS, or bovine dermal ECM). The study involved 1352 patients and 65 surgeons at 35 sites and was limited to patients receiving their first prolapse repair surgery. Additionally, surgeons chose which mesh was used based on experience and preference to avoid problems arising from unfamiliarity with the material. Assessment of outcomes was based both on physical examination and scoring using a validated POP-quantification scoring system and patient-reported symptoms. Results showed that augmentation with any mesh (either synthetic or biologic) did not significantly improve outcomes at 2 years relative to standard (primary) repair, though the use of meshes did result in some adverse effects.[28] These results suggest that surgical mesh materials provide no benefit in the majority of cases, although the authors noted that 80% of patients still had at least one prolapse symptom in the 2 years following surgery.

Taken together, such clinical studies emphasize the unmet need for better treatment options for POP and mitigating surgical complications. Though the use of biologic mesh materials in some cases may promote better outcomes than their synthetic counterparts, factors including source tissue utilized, manufacturing and processing methods, preclinical evaluation criteria, and clinical study design and execution undoubtedly can significantly affect clinical outcomes.

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