Acellular Dermal Matrices in Breast Implant Surgery: Defining the Problem and Proof of Concept

Private Practice, Seattle, WA, USA

^* 6100 219th Street SW, Suite 290, Mountlake Terrace, WA 98043.

E-mail address: drbaxter@drbaxter.com

Abstract

The use of acellular dermal matrices (ADMs) has become a useful adjunct to implant-based breast reconstruction and revision of the augmented breast. In both instances, the goal is replacement or reinforcement of thinned or missing tissues for implant support and control of the implant pocket. This article reviews the factors that contribute to periprosthetic tissue thinning, and the advantages and limitations of the use of ADMs for revision breast surgery and breast reconstruction. Proof of concept for the use of ADMs in the periprosthetic space is detailed from early clinical experience and histologic analysis documenting vascular ingrowth and cellular repopulation.

Keywords

• Acellular dermal matrix • Revision breast augmentation • Breast reconstruction • Implant capsule

Overview of breast augmentation and breast reconstruction

Breasts are important in disproportion to their specific functional role in reproduction. Why this should be so, and why the human is the only species in which breasts are permanently enlarged is a question for anthropologists and social scientists, but the evidence is clear. For example, patients who undergo mastectomy experience measurable benefits in quality of life and overall well-being after reconstruction. Among these benefits are improved feelings of sexuality ¹ and body image,² particularly in, but not limited to, younger women. A line of evidence is developing suggesting that patients who undergo mastectomy plus reconstruction fare better than patients who are treated with lumpectomy plus radiation in both quality of life and physical measures (arm edema, shoulder range of motion).³ This suggests that the characteristics of the breast, and not simply the presence of a breast mound, are important; a breast hardened by radiation treatment may not necessarily be a preferable option to a reconstructed breast, provided that the reconstruction can be done with minimal morbidity and aesthetically pleasing results. Trends in recent years toward early reconstruction with implants supported by ADMs indicate that a shift in approaches to breast cancer treatment is underway.

Patients who undergo breast augmentation similarly accrue tangible rewards in life.⁴ For these reasons, and others less easily discernible, cosmetic and reconstructive breast surgery occupies a central role in plastic surgery. The drive to build better breasts has fueled significant innovation in the 50 years since silicone breast implants were introduced. The number of breast augmentations and postmastectomy reconstructions have dramatically increased, with augmentation becoming the most popular cosmetic surgery operation in the United States in recent years⁵ and breast reconstruction moving up to the top 5 for reconstructive procedures. Concerns about complications focused initially on the implants and led to improved design such as the use of a barrier layer to minimize gel bleed, more cohesive silicone gels, and greater variety of profiles for better matching of implant dimensions to each patient’s anatomy. These improvements led to a more favorable attitude about breast implant safety.

Surgical analysis and planning have simultaneously advanced in sophistication, including tissue analysis,⁶ optimization of muscle coverage with the dual plane,⁷ and modifications.⁸ However, certain problems inherent to breast implant surgery are inevitably magnified with the increase in the numbers of women undergoing implant surgery and a larger pool of long-term implant recipients. Despite advances in implant technology and surgical techniques, as many as 1 in 4 patients who undergo augmentation will have a reoperation within 4 years.⁹ In patients who undergo reconstruction, reoperation rates are even higher, a point emphasized by the US Food and Drug Administration in a 2011 status update.¹⁰ Of particular note are rates of reoperation for revision surgery, estimated at more than 1 in 3.⁹ Revision often begets further revisions, pointing to the challenges of reoperative breast implant surgery and highlighting the inadequacy of traditional approaches. Although some would argue that problems of capsular contracture, implant malposition, visible rippling, animation deformity, and other issues are largely avoidable with proper technique and implant selection, the need for solutions to these problems remains. Given that changes in tissue-implant relationships can occur over a period of years, the need for revision surgery is unlikely to be reducible beyond a minimum that is yet to be determined.

The use of ADMs has become a useful option for many of these problems. Originally conceived as a dermal substitute for burn reconstruction, ADMs did not find early acceptance for that application, but began to be used for implantation for soft tissue augmentation or replacement in other clinical settings.¹¹ Volume persistence in the range of 80% to 85% at 22 months was reported for facial augmentation,¹² and static slings for correction of facial paralysis were noted to be stable even after radiation treatment.¹³ Success with lip augmentation,¹⁴ septal perforation repair,¹⁵ and periodontal surgery¹⁶ suggested a range of other possible uses. The concept of stable tissue support and/or enhancement could be extrapolated to applications in breast implant surgery.

Clinical experience with ADMS

With increasing exploratory use of ADMs in revision breast surgery, the indications for their use expanded (See cases in Boxes 1 through 4). The examples begin with early experience and progress to more recent examples of various clinical problems. Although they represent different applications, the underlying issues highlight the common denominator of inadequate soft tissue support.

Box 1 CASE 1: BREAST REVISION SURGERY AFTER BILATERAL MASTECTOMY

A 49-year-old woman presented after bilateral mastectomy for ductal carcinoma in situ and delayed reconstruction with an expander-implant sequence using saline implants. The expanders had been placed following satisfactory healing after mastectomies, using a dual-plane technique with muscle coverage superiorly and medially and pectoralis release inferiorly. The expansion phase was 6 weeks, reportedly without complications. A revision was done with capsulotomies and implant replacement several weeks after the expander-implant exchange. The patient’s concerns were visible rippling, asymmetry, wide intermammary space, and unnatural contours. Because of an athletic lifestyle and personal preferences, the patient refused muscle flap procedures.

Directed examination showed a tall thin woman with a body mass index (BMI) of 20.5 kg/m². The implants were asymmetrically positioned with inframammary fold malposition on the right side and an intermammary distance of 6 cm. Tissue coverage was thin, with a pinch test of 5 mm on the upper pole (CASE Fig.1A).

Given the patient’s concerns, options were limited. A lack of tissue for implant support and coverage was determined to be the underlying problem, a condition that may be termed periprosthetic atrophy. In this case, the problem was amplified by implants of inadequate diameter (the options for implant profiles were limited at that time, which was before the introduction of high-profile or low-profile shapes.) Fat grafting was considered but there was a lack of donor volume and, although coverage may have been improved, this would not have added support. The use of acellular matrices in the periprosthetic setting had not yet been documented. However, based on limited but successful personal experience with augmentation revisions using ADMs, it seemed to be a reasonable choice among few options.

In conjunction with implant exchange and capsule revisions including bilateral medial capsulotomies and a right inferolateral capsulorrhaphy, a series of thick AlloDerm^® grafts (Lifecell Corp., Branchburg, NJ, USA) was placed. The grafts were affixed with resorbable sutures, with 1 edge of the graft across the junction of the anterior and posterior capsule. The concept was to define the boundaries of the capsule, smooth the transition from chest wall into the breast mound, and improve coverage of the implant. Long-term results have been stable, with now more than 10 years of follow-up (see CASE Fig. 1B).

CASE Fig. 1 (A) Preoperative view of a patient after bilateral mastectomy and reconstruction with expanders and saline implants, and 1 revision. (B) One year after implant replacement and capsule revisions with acellular dermal grafts, and nipple reconstruction.

Box 2 CASE 2: BREAST ASYMMETRY AFTER SALINE IMPLANT TRANSAXILLARY AUGMENTATION

A 26-year-old woman presented with significant asymmetry after transaxillary augmentation with saline implants (left 225 mL, right 410 mL). Her concerns further included symmastia (medial fold malposition) and bottoming out (lower fold malposition) (CASE Fig. 2A). Analysis of the problem determined a complex tissue deficit consisting of both a severe chest wall deformity, pectus excavatum, and a thin, lax soft tissue envelope for the breast, with a pinch test of 5 mm over the central mound despite submuscular placement.

Given the multiple problems in combination, traditional options were again determined to be inadequate. A supportive tissue envelope needed to be created to prevent relapse of the right implant across the midline, but muscle flap procedures were deemed inappropriate and capsule flaps insubstantial. ADMs had proved useful for more routine cases of medial fold malposition and so the concept was extended to this more challenging situation.

To have the option of adjusting fill volumes with patient input, the revision was done in stages using expander implants (Spectrum, Mentor Corp., Santa Barbara, CA, USA) and a solid silicone block behind the right implant. In addition, extensive capsule revisions were done including a superiorly based rectus abdominis fascia flap and two 4 × 7 AlloDerm® sheets placed medially and inferiorly as onlay grafts on the right side forming a sling to the pectoralis muscle. Fill ports were removed with a final volume of 375 mL on each side. Results are shown at 1 year (see CASE Fig. 2B).

CASE Fig. 2 (A) This patient presented after transaxillary augmentation using saline implants; she now has asymmetry, and right medial and lower fold malposition, with underlying pectus excavatum and chest wall asymmetry. (B) One year after revisions including ADM grafts and adjustable expander implants.

Box 3 CASE 3: BREAST REVISION SURGERY AFTER SUBPECTORAL SALINE IMPLANTS

A 29-year-old fitness instructor presented for revision surgery after having subpectoral saline implants placed 7 years earlier. A year later, revision surgery had been done for malposition issues (details unknown). A deflation 3 years later prompted a replacement of both implants with 425-mL silicone gel high-profile implants. A capsulorrhaphy had been performed because of lower fold malposition with the first implants. The patient expressed concerns about severe rippling but was generally pleased with the size.

Directed examination showed a thin patient (BMI 21.7 kg/m²) and significant traction ripples over both beasts (CASE Fig. 3A, B). Implant coverage over the upper pole was estimated at less than 1 cm by pinch test. Base diameter was measured at 13 cm.

The surgical plan included replacement with moderate-profile implants (Allergan Style 15, 421 mL) and ADM grafting to all 4 quadrants (AlloDerm^® thick, 4 × 7 cm). This created an implant pocket separate from the skin envelope. Six-month follow-up confirmed stable correction (see CASE Fig. 3C, D). The larger pieces of porcine-derived ADM available now would likely be a better choice.

CASE Fig. 3 (A, B) Traction ripples in a patient with a history of saline implants, revision, then bilateral replacement with silicone gel–filled implants after a deflation. (C, D) Six months after 4-quadrant placement of ADM grafts.

Box 4 CASE 4: BREAST REVISION SURGERY AND AUGMENTATION AFTER SUBPECTORAL SALINE IMPLANTS

A 34-year-old gravida 3 woman presented 5 years after having subpectoral saline implants placed. Fill volume information was unknown but implants were reported to be 375 mL. The patient complained of rippling, a wide intermammary distance, animation deformity, lower fold malposition, and lateral malposition. She further requested an increase in implant size.

Examination confirmed these findings in a thin patient (BMI 20 kg/m²), with an intermammary distance of 4 cm and base diameter of 13 cm (CASE Fig. 4A). With flexion of the pectoral muscles, significant displacement of the implants with distortion of the breast shape was observed (see CASE Fig. 4B). Tissue coverage was estimated at 5 mm over the lower pole and lateral aspect.

At surgery, the pectoral muscle edge was mobilized from the anterior capsule (see CASE Fig. 4C). Cautious medial capsulotomies were done, along with an inferolateral capsulorrhaphy to create a pocket to accommodate a 450-mL high-profile implant with a base diameter of 12.4 cm. An elliptical ADM graft (Strattice^™ Contour 2, Lifecell Corporation, Branchburg, NJ, USA) was used with 1 side affixed to the pectoral muscle edge and to the pocket along the inframammary and lateral folds to support the capsulorrhaphy. This concept of pectoral extension addresses the animation deformity by directing the force of muscle contraction away from the scar capsule while also improving implant coverage. Results were stable at 9 months (see CASE Fig. 4D, E).

CASE Fig. 4 (A) Subpectoral saline implants with malposition, wide intermammary distance, and implant visibility. (B) Animation deformity shown with active muscle contraction. (C) Intraoperative view showing the anterior capsule dissected down to mobilize the pectoral muscle. The ADM will be sutured to the muscle along 1 edge, and the other to the inframammary fold. (D) Nine months after revision with Strattice^™ Contour 2 graft (Lifecell Corp., Branchburg, NJ, USA) using the reconstructive model of pectoral extension. (E) Postoperative muscle flexion view showing amelioration of animation deformity.

Results: histology and proof of concept

Because of concerns about the fate of ADM grafts in the periprosthetic environment, early use was conservative, limited to multiple small pieces rather than large ones. As a result, some cases had a partial improvement rather than a definitive repair, with patients requesting additional grafts. This outcome provided the opportunity to examine the grafts at intervals after initial placement. In every such case, a similar appearance was noted, with a glossy surface, complete volume retention (gross visual estimation), and bleeding when incised (Fig. 1A).

Fig. 1 (A) Gross appearance of a previously placed graft (appears as a white patch). (B) Hematoxylin-eosin stain of an onlay graft of ADM at 6 months, showing organized collagen and lack of inflammation. (C) CD34 stain for vascular endothelium documents vascular channels. (D) Vimentin stain shows active fibroblasts populating the graft.

Documentation of the histologic behavior of ADMs established a foundation for proof of concept for their use in the periprosthetic compartment.¹⁷ Biopsies at 6 months revealed organized collagen with intact vascular channels, active fibroblasts, and a lack of scarring and inflammation (see Fig. 1B–D). The first available product, AlloDerm^®, is derived from human donors and processed to minimize alteration of the extracellular matrix. The presence of an intact collagen scaffold along with matrix glycoproteins and cytokines are thought to be important factors in enabling cellular repopulation and long-term stability. The methods used to decellularize the matrix and/or sterilize it significantly alter the expression of growth factors as well as the ability of the matrix to support cell growth.¹⁸

ADMs seem to alter the nature of the capsule as well, a phenomenon that may be useful in dealing with capsular contracture (Fig. 2). A single cell layer membrane typically develops on the implant-facing surface over an ADM.

Fig. 2 Hematoxylin-eosin stain of a Strattice^™ porcine-derived ADM graft at the transition to native capsule. Note the single cell layer over the graft (left side).

Cellular repopulation of ADMs has been extensively documented and further characterized. Using a composite flap model based on the superficial inferior epigastric pedicle in the rat, Wong and colleagues ¹⁹ showed active host cell proliferation in the matrix as early as 7 days. In parallel with normal wound healing, endothelial migration continued for up to 14 days, by which time intact lymphatic channels were found as well. ADM sheets in the subcutaneous layer of the face are rapidly incorporated and maintain gross volume over a period of months.²⁰ Expander-implant reconstruction using ADMs provides an opportunity for evaluation of the graft at the time of expander-to-implant exchange. A predictable take with less inflammatory response compared with native submuscular capsule was reported in a series of 20 patients having staged reconstruction.²¹ Experience with this approach has now been well documented.^22,²³

Among the early concerns for ADMs in breast implant procedures was placement of a tissue-derived graft in a space with poor access to metabolic support, having a breast implant against one surface and capsule on the other. An autologous full-thickness skin graft in this environment would not be expected to be successful, given the metabolic demands of a cellular material. AlloDerm^® was originally developed for reconstruction of full-thickness burn wounds, in which circumstance the graft is placed with one surface on host tissue, with a dressing material on the outer surface. In the setting of the periprosthetic space, the hydrodynamics of the closed environment may even be theoretically advantageous. In an aseptic space with no risk of graft desiccation, circumstances may favor graft take.

It is now thought that acellular dermis occupies a middle ground, with no metabolic demands until cellular migration and vascular ingrowth occur. Immediately after implantation, it is neither living tissue nor prosthetic. In the absence of an inflammatory response, acellular dermis seems to be stable and metabolically inert, but, once integrated and transformed into living tissue, ongoing remodeling can take place as with native host tissues. In optimal conditions, there is minimal, if any, apparent loss of graft volume over time.

The degree to which an unaltered matrix is important for graft performance remains a topic of deliberation. If altered through collagen cross-linking or sterilization processes that damage collagen or matrix glycoproteins, grafts may provoke an inflammatory response leading to encapsulation or resorption. Many such products are available now, although data comparing them with clinical results are scant.

Discussion of ADMS in breast surgery

Few issues in plastic surgery have stimulated as much debate as the use of ADMs in breast implant surgery. Many of these issues are common to both aesthetic and reconstructive procedures. In both cases, reoperation rates for patients with breast implants have been of concern to surgeons, patients, and regulators alike. The need for early reoperative surgery is driven by several factors, a large one being simply a choice for a change in implant size rather than a complication per se, but a pattern becomes evident when considering the various contributors to implant problems leading to revision surgery: inadequate coverage and support. When these issues arise in the immediate postoperative period, they can be attributed in part to poor surgical planning or execution; in the long-term, there can be thinning of the tissues in response to the implant regardless of surgical planning and execution. This thinning of the tissues may be termed periprosthetic atrophy, but, in any case, the cause of the patient presenting with these conditions requires thoughtful analysis to obtain a lasting correction.

Tissue Deficit

The condition of periprosthetic atrophy represents a localized tissue deficit. In reconstructive cases with implants, the approach historically has been to attempt total muscle coverage, but this approach has been beset with difficulties. Elevation of the serratus anterior muscle can be associated with pain during the expansion phase, tight banding across the lower pole, and difficulty in controlling expansion vectors resulting in flattening and unnatural breast shape. Similar issues ensue from rectus abdominis elevation for lower pole support and coverage. The latissimus flap is a versatile workhorse option but is limited by potential donor site morbidity and scarring.

Inadequacy of the soft tissue envelope may be caused by several factors, either preexisting (the thin patient), surgical (mastectomy or reoperation), or a condition that develops gradually in response to implant-tissue interactions. In the thin patient, early results may be favorable but the tissues fail to provide support and coverage over time, and this may then progress to stretch deformity, traction rippling, or implant malposition. Options for definitive correction of these problems are limited because of the tissue deficit. With the concept of an internal bra, the use of ADMs addresses the problem by replacing a supportive framework.

Implant Dimensions

In some cases, implant dimensions exceed the compliance of the tissue envelope, the response being tissue thinning. For this reason, base diameter is a critical aspect of implant selection.²⁴ When implant diameter exceeds breast width, the anatomic boundaries must either be surgically violated, thereby hastening thinning, akin to the phenomenon of stress creep that is seen in other procedures in which tissues are placed on tension. Even without undue tissue stress, if the implant is too wide it must be radially constricted causing folding, which is manifest as ripples. Both factors contribute to long-term problems, but the former condition places direct pressure on the tissues as happens (albeit in a more controlled fashion) with tissue expansion. Once this has occurred, dimensional pocket reduction with capsulorrhaphy may be unsuccessful and does not address the issue of coverage.

Visible ripples may be seen even with an implant of appropriate dimensions. This rippling is most common laterally and inferiorly where there is typically no muscle coverage. The use of thin sheets of ADM for concealment of rippling in breast augmentation cases has been reported by Duncan.²⁵ Although these pieces are generally no more than a millimeter in thickness, control of the pocket dimensions and added support may be more helpful than coverage per se, particularly in the instance of traction ripples. Highly cohesive (form-stable) implants may be less prone to rippling but still require adequate coverage and support for optimal results.

Capsular Contracture

Another contributing factor is capsular contracture, the most frequent cause of implant reoperation surgery. If the severity of the contracture indicates a surgical approach, a capsulectomy is generally performed along with implant replacement and site change, which may further contribute to tissue thinning with potential loss of implant support. In this instance, the use of ADMs may serve a dual purpose of reinforcing the pocket while possibly reducing the risk of a recurrence.²⁶

Combination Implant Problems

A common theme is how implant problems often present in combination. With periprosthetic atrophy, there is rippling, loss of support leading to fold malposition, either lower (bottoming out), medial (symmastia), or lateral, in various combinations. Because the underlying problem of periprosthetic atrophy manifests in disparate ways, patients often present with multiple problems in combination. Case 1 represents what has become a classic example, with fold malposition, rippling, and unfavorable contours (see Box 1). Case 2 is a more extreme example but, again, the condition of tissue atrophy on a foundation of chest wall asymmetry translates into complex combination problems and an artificial appearance caused by poorly disguised implant contours (see Box 2). By addressing the common issues with the use of ADM matrices, complex problems can be reduced to a more manageable concept.

The fourth case presentation represents not only the combination of problems (malposition, implant visibility, animation deformity) but the contributions of many who have advanced the techniques and the improved ADM products available now (see Box 4). In particular, the reconstructive model in which an internal bra is fashioned with fixation along 1 edge to the inframammary fold and the other to the released pectoralis muscle, has been useful in both implant-based reconstruction²⁷ and revision surgery for augmentation-related problems. Using the larger pieces now available, a total muscle-ADM pocket is formed that creates a unified approach to the multiple problems that tend to present together.

Another observation is the contribution of previous revision surgery, as in the first 3 cases. Each surgical intervention induces a new cycle of scarring and tissue stress, and subsequent attempts become progressively more challenging. This observation is illustrated by the statistics on revision surgery, the biggest predictor of which is a prior revision. An understanding of the tissue response to implants over time, and the effects of secondary surgery, leads to an appreciation of the underlying problem of periprosthetic atrophy.

Reflecting on more than a decade of using ADMs in breast surgery, a few themes become evident:

• One is the importance of breast reconstruction and breast aesthetics in general. Despite a controversial history, demand for implant surgery has continued to escalate. Perhaps for lack of good solutions, certain problems with breast implants were largely ignored, even while implant design and surgical techniques improved.

• Another theme that emerges is a reassessment of approaches to postmastectomy reconstruction, and even our approach to breast cancer treatment. The great push of the late twentieth century toward lumpectomy and radiation as breast-conserving therapy may now be giving way to skin-sparing mastectomy and immediate direct-to-implant reconstruction aided by an ADM internal bra. Comparative resource allocation, psychosocial impact, and patient morbidity are all being reevaluated in the light of developments in the past 10 years.

Looking forward, a motif of unifying significance appears. The use of ADMs represents 1 facet of the emerging field of regenerative medicine, the ability to fulfill the basic goals in reconstructive surgery of replacing like with like using scaffolds that direct tissue growth in specific ways. For example, ADMs have been explored as a template for seeding with adipose-derived adult stem cells, with demonstration of early penetration, proliferation, and expression of differentiation markers.²⁸ Tissue engineering acquires a new dimension with ADMs, beyond the two-dimensional concept of skin replacement or implant support. This concept is shown experimentally with a wound-healing model comparing healing with fibroblast-seeded ADMs versus ADM alone in rats. The filling of the defect as measured by magnetic resonance tomography was greater on the fibroblast-seeded side and the wounds had significantly increased breaking strength.²⁹ The effect persisted even in the presence of preoperative or postoperative radiation.

Nevertheless, the breast implant periprosthetic space represents a particular challenge, in that a tough but supple tissue layer is needed for implant support and coverage, but provoking too strong a tissue reaction may result in capsular contracture. The successful record of ADMs in this application, even though possibly lowering the incidence of capsular contracture, offers hope for the possibilities of regenerative medicine across a range of clinical needs. Lessons learned from early experience and proof-of-concept studies will help guide future work.

References

1. A. Manganiello, L.A. Hoga, L.M. Reberte, et al. Sexuality and quality of life of breast cancer patients post mastectomy. Eur J Oncol Nurs. 2011;15(2):167-172.

2. H. Medina-Franco, M.N. Garcia-Alvarez, P. Rojas-Garcia, et al. Body image perception and quality of life in patients who underwent breast surgery. Am Surg. 2010;76(9):1000-1005.

3. R. Freita-Silvas, D.M. Conde, R. de Freitas-Júnior, et al. Comparison of quality of life, satisfaction with surgery and shoulder-arm morbidity in breast cancer survivors submitted to breast conserving therapy or mastectomy followed by immediate breast reconstruction. Clinics (Sao Paulo). 2010;65(8):781-787.

4. D.K. Murphy, M. Beckstrand, D.B. Sarwer. A prospective, multi-center study of psychosocial outcomes after augmentation with Natrelle silicone-filled breast implants. Ann Plast Surg. 2009;62(2):118-121.

5. National clearinghouse of plastic surgery statistics. 2010 plastic surgery statistics. Arlington Heights (IL): American Society of Plastic Surgeons; 2011.