Chapter 65 CYSTOCELE REPAIR USING BIOLOGIC MATERIAL

A variety of surgical options are available to the reconstructive surgeon for treatment of anterior vaginal wall prolapse. The traditional surgical approach for cystocele repair is anterior colporrhaphy with plication of the pubocervical fascia. Despite an increased knowledge of pelvic anatomy and advances in surgical techniques, success is variable, and recurrence rates vary from 20% to 40%.¹ Recent literature has suggested that the interposition of graft material over the fascial defect to repair both central and lateral defects of the anterior vaginal wall may increase the success rate of surgery. The purpose of the graft is to allow for replacement or regeneration of fascia by providing a matrix into which in-growth of support tissue will occur.² A variety of graft materials are available for such pelvic floor reconstruction.

The properties of an ideal implant (graft material) were described by Cumberland ³ and Scales⁴ more than 50 years ago, and the principles remain true today. These characteristics include the proposal that the implant should be elastic or supple, should be easily tailored, and it should have good tensile strength. Additionally, the implant should cause minimal foreign body reaction and allow for good tissue incorporation and collagen in-growth while promoting permanent tissue repair. Finally, the graft must be tolerated in an infected environment and cause minimal wound complications.

To date, the graft that meets all of the above criteria remains elusive. Currently available grafts are most easily classified as biologic or synthetic. Biologic grafts can be further described as autologous, allograft (cadaveric fascia and dermis), or xenograft (e.g., porcine dermis, porcine small intestine submucosa). Synthetic grafts and some biologic biomaterials are discussed elsewhere in the text; this chapter discusses the use of dermal allografts and xenografts for the treatment of anterior vaginal wall prolapse.

BIOMATERIALS

The United States National Institutes of Health (NIH) defines a biomaterial as “any substance (other than a drug) or a combination of substances, synthetic or natural in origin, which can be used for any period of time, as a whole or a part of a system which treats, augments, or replaces any tissue, organ, or function of the body.”⁵ Currently, there are five types of biomaterials being used in the medical environment: polymers (i.e., in catheters), composites, metals and alloys, ceramics, and biologic materials.⁶ Each material offers unique capabilities and advantages based on its composition, its architecture, and whether it is biodegradable.

The concern over possible costly litigation resulted in a worldwide shortage of biomaterials in the mid-1990s. In response, the Biomaterials Access Assurance Act was passed by the U.S. Congress in July 1998 to provide some protection to manufacturers as well as encourage development of new materials.⁶ In the United States, the Food and Drug Administration (FDA) regulates medical devices, but not biomaterials, unless they are a component of a medical device. In Europe, any device or apparatus intended for human use is required to have a CE mark, indicating that safety and performance criteria have been met for a particular indication.⁷

Although most would agree that the ideal biomaterial should be reproducible, biocompatible, biodegradeable, and nontoxic, less is understood about the properties required to facilitate the colonization and integration of cells into a functional tissue.⁸ A principal factor in the success of a new material is its ability to perform with an appropriate host response in a specific application (i.e., its tissue biocompatibility). Tissue reactions to implanted materials vary widely, and the response determines to a great extent whether the material will be biocompatible.⁹

In the urologic and urogynecologic community, there are a broad range of uses for biomaterials. Biomaterials are used in artificial urinary sphincters, in testicular and penile prostheses, and as injectables for stress incontinence. Additionally, they can be used for the restoration of function or structure (i.e., grafts for Peyronie’s disease, bladder augmentation) and for reinforcement of the vaginal wall in prolapse/reconstructive procedures.⁷

The most commonly used natural materials available for prolapse repair include autograft (rectus fascia), allograft (cadaveric fascia,) and xenografts. Xenografts may be either nonabsorbable (i.e., Pelvicol) or absorbable collagen (small intestine submucosa [SIS]).

NONABSORBABLE PORCINE COLLAGEN

Pelvicol (C.R. Bard, Covington, GA) is the most frequently researched and implanted xenograft collagen. It was developed at the University of Dundee in the United Kingdom and was designed for permanent implantation in humans for use in pubovaginal slings, vaginal wall repair, cystoplasty, and phalloplasty.⁷ Pelvicol was licensed for use in Europe in 1998 and received approval from the U.S. FDA in 2000. When the tissue is used for applications outside urology and urogynecology, it is distributed under the name Permacol. Porcine collagen is 95% homologous to human collagen, and it appears to provide a strong, nonallergenic scaffold for human tissue growth.¹⁰

Pelvicol is derived from porcine dermis. A patented process removes all fats and cellular materials, including cells, cell components, and nucleic acids, through a series of organic and enzymatic extractions that leave the material without any DNA.^11,¹² The final stage of the processing involves stabilizing the matrix with an approved cross-linking agent to maintain strength and provide permanence. Gamma sterilization of the tissue ensures sterility.

Originally, the grafts were cross-linked with glutaraldehyde. However, this agent was associated with significant calcifications,¹³ so now diisocyanate, which has less graft mineralization, is used as the cross-linking agent.^10,¹⁴ Ultimately, this final product is a piece of fibrous, acellular, cross-linked porcine dermal collagen that is nonallergenic, is nontoxic, and does not elicit a foreign body response.¹⁵ Also, the resulting material conserves the original three-dimensional architecture of the collagen matrix with a small amount of elastin.¹²

The treated tissue is free of DNA remnants as well as foot and mouth disease,¹⁶ and the manufacturing process has been demonstrated to remove the viral and bacteriologic load from Pelvicol implants. Reoviruses are reduced by more than 12 logs and porcine parvoviruses by 6.7 logs, levels that are acceptable to both the FDA and the European United (EU) regulatory authorities.¹⁷ Once implanted in to human tissue, the implant has been shown to be a biocompatible, sterile, and strong biologic matrix that is permanently incorporated into the host tissue.¹⁵ The graft is available in several sizes depending on its clinical use.

There are other nonabsorbable xenograft collagens produced by other companies, but, as of this publication, human use of these grafts has not been reported. One such graft, Cytrix Soft Tissue Repair Matrix (TEI Biosciences, Boston, MA) is a bovine dermis that does not undergo cross-linking.¹⁸ Whether this difference in processing alters graft strength remains to be seen. In a rat model, Rosenblatt showed that this graft was populated by host fibroblasts and a supporting vasculature. Over 15 months, the implant collagen was remodeled and replaced by the host into collagen that repaired the iatrogenic muscle defect.¹⁸

Fate of the Graft: Porcine Collagen

Although rejection of porcine dermis has not been reported, case studies suggest an unpredictable tissue response once the graft is implanted. Cole identified a completely encapsulated porcine dermis sling during urethrolysis at 6 months after surgery. Grossly, the sling was intact, and histologically, it was acellular and did not show evidence of human tissue proliferation.¹⁹ Salomon and assocuates reported on 1 patient who underwent exploratory surgery 1 year after implantation of a transobturator Pelvicol graft for cystocele repair. At the time of surgery, there was no inflammation around the graft which was easily freed from surrounding tissues. Histologic evaluation showed colonization by fibroblasts and blood vessels with minimal inflammatory response.¹⁷

Gandhi and colleagues reviewed the tissue specimens of seven patients with a prior porcine dermal sling and found limited collagen remodeling and evidence of a foreign body–type reaction in patients with postoperative retention. In cases of recurrent stress incontinence, implants appeared to be completely replaced by dense fibroconnective tissue and moderate neovascularization without evidence of inflammation or graft remnants. The authors concluded that this variable tissue reaction raises questions of tolerability and efficacy and may contribute to unpredicitable clinical outcomes.²⁰

After implantation, there is a migration of cells, in-growth of tissue, neovascularization, and collagen formation in and around the graft. Although it is unclear what the ultimate biomechanical properties will be like once the graft is implanted, some researchers believe that this connective tissue surrounding the implant adds to its strength.²¹

On the other hand, Dora and coworkers demonstrated in a rat model that porcine dermis and porcine SIS show a marked decreased in tensile strength and stiffness after being implanted for 12 weeks on the abdominal rectus fascia.²² Whether this mechanical change is of clinical significance remains unknown. In still another animal study, Macleod and colleagues evaluated Permacol 20 weeks after implantation in the Sprague-Dawley rat. Although the graft maintained its thickness over the 20 weeks, there was a decrease in mean collagen density. These findings suggest an overall loss of collagen over the 20 weeks.⁹

Although it appears that there is not one specific factor that is paramount for porcine dermis graft success, attempts have been made to evaluate the integral pieces necessary for success. One belief is that the graft relies, to some degree, on its capacity to be colonized by host cells, and when recurrence occurs, it may be because of compromised native tissue and vascularity contributing to poor graft behavior.²³ In another evaluation of the tissue, Boon and coworkers implanted the graft subcutaneously in a rat model and found minimal fibroblast in-growth into cross-linked collagen. They suggested that cross-linked collagen may be considered for use in situations where neither incorporation nor dissolution of the biomaterial is desired.²⁴ Others have also seen a low inflammatory response to the Pelvicol.²¹ This “tolerance” may contribute to a more ordered deposition of collagen,²¹ perhaps allowing the graft to behave similar to autologous tissue.

With respect to vaginal examination after porcine dermis implantation, we are in agreement with the assessment by others that the Pelvicol implant is difficult to palpate postoperatively, whereas that is not always true with some mesh materials.² Additionally, there is minimal to no shrinkage of the material, a key factor in sexually active women and in those with preoperative vaginal stenosis.

Some authors have shown that perforating the porcine dermis improves the graft take and decreases wound infections by allowing for increased tissue in-growth and revascularization of the vaginal epithelilum overlying the graft. Tensile strength and suture pull-out strength were maintained in the perforated graft.²⁵