With increasing frequency, surgeons are electing to use acellular dermis to assist with tissue expander or implant-based primary breast reconstruction. [1, 2] In 2014, of the 102,215 breast reconstructions performed in the United States, 74,694 (73%) used a tissue expander and implant.  Several authors have reported favorable outcome studies using acellular dermis, and rapid early expansion has led to improved cosmetic outcomes. [1, 4, 5, 6]
Acellular dermal matrix (ADM) has been used as a soft tissue replacement since its introduction in 1994.  ADMs are soft tissue matrix grafts created by a process that results in decellularization but leaves the extracellular matrix intact. This matrix provides a scaffold upon and within which the patient’s own cells can repopulate and revascularize the implanted tissue. Its utility has been demonstrated in various reconstructive techniques, particularly in burn, abdominal wall, and breast reconstruction. [7, 8, 9]
Currently, several ADMs are available for use by reconstructive surgeons, including human-derived fully hydrated FlexHD® (Ethicon, Somerville, NJ); freeze-dried AlloDerm® (LifeCell, Branchburg, NJ), Neoform™ (Mentor, Santa Barbara, CA), and DermaMatrix™ (Synthes, West Chester, PA); and porcine-derived Permacol™ (Covidien, Boulder, CO) and Strattice® (LifeCell).
The introduction of ADM has provided surgeons with alternative means of obtaining sufficient vascularized soft tissue to cover the implant, thereby alleviating some complications. Breuing first reported the use of human acellular dermis in implant-based breast reconstruction in 2005.  Not long after, Bindingnavele reported acellular dermis–assisted tissue expander-based reconstruction. 
Several authors, including Salzberg  and Spear,  reported outcomes in the following years, citing increased fill volumes and improved aesthetic outcomes. In 2008, Preminger reported the first comparative study that analyzed intraoperative fill volume differences between ADM and non-ADM cohorts.  This provided the impetus for several other comparative studies, such as the comparison of ADM technique with submuscular coverage by Sbitany et al. 
In 2009, Nahabedian explored the use of acellular dermis in the context of postoperative irradiation.  This study addressed the increasingly widespread sentiment that acellular dermis affected complication rates in patients receiving postoperative radiation therapy and led other authors, such as Rawlani et al, to explore these effects further.  Larger studies, such as that of Chun et al,  published regression analyses of several surgical factors and their influences on complication rates.
Any woman who is a candidate for tissue expander or implant-based reconstruction is a potential candidate for the use of acellular dermis and should be informed of the option. Indications for expander-implant reconstruction have been described elsewhere. See Breast Reconstruction, Expander-Implant for more information.
The significant anatomy of the ADM-assisted expander-implant technique involves the anatomic borders of the breast mound, the associated blood supply, and the nerve supply. See Breast Anatomy for more information.
The breast mound is bordered superiorly by the second rib, inferiorly by the inframammary fold, medially by the sternum, and laterally by the midaxillary line. The blood supply to the breast is supplied by the internal mammary artery (a branch of the subclavian artery) on the left and the brachiocephalic artery on the right. The primary innervation to the nipple-areola complex is provided by the lateral branch of the fourth intercostal nerve.
The pectoralis major originates from the cartilage of the true ribs, starting at the anterior surface of the clavicle and running down the lateral half of the sternum to approximately the sixth or seventh rib. The fibers end laterally at a flat tendon and insert at the lateral lip of the intertubercular groove of the humerus. This muscle is dually innervated by the medial and lateral pectoral nerves, arising from the brachial plexus.
The serratus anterior originates medially from the upper eighth and ninth ribs and inserts at the costal medial margin of the scapula. It is innervated by the long thoracic nerve, which runs inferiorly along the surface of the muscle. Because this nerve is highly exposed, particular care should be taken during reconstructive procedures, especially if an axillary dissection was performed during mastectomy.
The purpose of using acellular dermis in expander-implant reconstructions is to improve on or maintain the essential components of breast aesthetics, including the inframammary fold, ptosis, and projection.
The inframammary fold is the inferior landmark of the breast. It is often altered during mastectomy and is a key component in achieving symmetry with the contralateral breast. Ptosis refers to drooping or overlapping skin in the lower pole that extends over the inframammary fold. Ptosis of the breast is caused by the effects of gravity on the breast tissue over time and is usually difficult to replicate with implants.
Finally, projection refers to the fullness of the breast, as measured by the distance from the chest wall to the most anterior point, usually the nipple. Initially, in the setting of tissue expanders, projection is less than was present with the original breast mound. The original projection may be restored with expansion, especially if the nipple is spared at the time of mastectomy.
The inferior border of the matrix is used to recreate the inframammary fold. The superior border is attached to the disinserted pectoralis major to create a complete subpectoral, subgraft pocket for expander placement. The acellular dermal sling provides numerous potential benefits. Complete implant coverage reduces the risk of implant exposure, extrusion, visibility, and palpability. [1, 5, 6] Tethering of the pectoralis major prevents the implant from migrating and creating an unnatural breast stepoff or fold effacement. [1, 5, 6]
The apparent resistance of acellular dermis to capsular contracture also reduces the chances of implant displacement.  Ultimately, better control of implant position allows greater lower-pole projection, improved inframammary fold definition, and increased potential for natural-looking ptosis. [1, 4, 5, 6]
Furthermore, it is generally felt that by producing a large pectoralis-dermal pocket, acellular dermis permits greater intraoperative tissue expander fill volumes, leading to fewer postoperative expansions and a subsequent acceleration of the expansion process. [1, 2, 12] However, this sentiment is not completely unanimous. 
Outcomes have been reported in pelvic, abdominal, and chest wall reconstructions  ; dural repair  ; hand surgery;  urethral reconstruction;  burn surgery  ; and gingival graft procedures  . Few authors have argued against the overall safety of acellular dermis–based reconstruction. Most studies have reported improved aesthetic outcomes and acceptable complication rates. [2, 18, 19]
In the literature, comparisons of ADM–assisted reconstruction with traditional expander reconstruction generally do not show statistically relevant differences in overall complication rates. The overall complication rates for reconstructions using ADM range from 3.2% to 48.7%. [12, 13, 20, 19]
In a study of 269 ADM-assisted breast reconstructions, Chun et al reported the following complication profile for ADM: 8.9% rate of infection, 23.4% rate of necrosis, 14.1% rate of seroma, and 2.2% rate of hematoma.  The investigators also found that ADM-assisted breast reconstructions were associated with higher rates of postoperative seroma and infection than complete submuscular breast reconstruction were.
In a study of 153 breast reconstructions, Antony et al reported an overall complication rate of 23.6%, with rates of 7.2% for seroma, 2.0% for hematoma, 3.9% for cellulitis, 4.6% for flap necrosis, and 3.3% for infection.  In a study of 121 breast reconstructions, Rawlani reported an overall complication rate of 16.5%, with rates of 7.4% for infection, 1.7% for seroma, and 6.6% for flap necrosis. 
Unfortunately, few studies have compared and stratified differences in outcomes with respect to type of acellular dermis, body mass index (BMI), radiation exposure, or intraoperative expander fill. Becker et al reported an overall complication rate of 4%.  Losken reported only 1 complication of native skin necrosis in a study of 31 breasts.  Because of differences in the processing and sterilization of the various ADMs, there is a possibility of alterations in collagen and protein structure that may ultimately affect revascularization and recellularization.
Rawlani et al reported an overall complication rate of 30.7% in women who received adjunct breast irradiation, compared with 13.7% in nonirradiated breasts.  They also noted that outcomes and complication rates with prehydrated ADM were generally comparable to those with freeze-dried ADM.
A study by Winocour et al indicated that in patients who undergo immediate tissue expander breast reconstruction, the 30-day surgical site infection rate is higher when ADM is used. The study reported that the national rate of surgical site infections in such operations is 4.5% when ADM is used, compared with 3.2% in non-ADM cases, with the investigators finding that at their own institution, these rates were 2.1% and 1.6%, respectively. 
Breuing et al  noted that despite a higher rate of complications, ADM-assisted tissue expander reconstructions seemed to resist radiation effects better than standard tissue expander reconstructions did—a phenomenon that has been observed by a number of authors and is currently being explored in the literature. 
Patient Education/Informed Consent
Patients should be informed of the screening processes for using acellular dermal matrix (ADM) so that they can better understand the minimal possibility of disease transmission. Generally, patients with moderate-sized to large breasts benefit most from the use of acellular dermis because release of the pectoralis allows better use of the excess skin. However, the ultimate decision whether to use acellular dermis should be made intraoperatively.
Well-vascularized mastectomy flaps are needed to avoid mastectomy flap necrosis. Lanier et al reported that patients with larger breasts had a higher overall complication rate than those with smaller breasts, although the differences did not reach statistical significance.  They hypothesized that larger mastectomy flaps are potentially at higher risk for ischemia, which can lead to delayed incorporation of acellular dermis and thus to increased complication rates. 
In addition, patients who may be undergoing postoperative radiation therapy, which can lead to complications, should be given the option to choose delayed autogenous reconstruction with a latissimus dorsi myocutaneous flap or reconstruction with a transverse rectus abdominis muscle (TRAM) flap. However, some studies have reported favorable outcomes and reduced complications with the acellular dermis technique in the setting of postoperative irradiation. [11, 23]
Arguably, ADM-assisted breast reconstructions yield results that are cosmetically superior—and more reproducibly so—to those achieved with traditional expander-based techniques. This is because of improvements in important functional variables (eg, intraoperative fill volumes), total postoperative clinic visits for filling, and control of expander-implant positioning. [1, 10, 12]
Several technical considerations should be taken into account in planning the procedure. The acellular dermis used must be the proper size—that is, it should be just large enough to cover the inferior pole of tissue expander or implant, providing complete coverage when sutured to the pectoralis. Excess acellular dermis creates the potential for graft inversion, which can become a nidus for chronic inflammation and giant cell foreign body reactions. 
In addition, ADMs that exhibit polarity must be properly inserted, with the dermal (porous) surface opposing the soft tissue and the epidermal (smooth) surface facing the tissue expander or implant. Failure to orient the dermis properly can lead to inflammatory processes that may mimic cellulitis. 
It is important to distinguish between traditional expander infections and the noninfectious erythema associated with the incorrect use of acellular dermis in the reconstruction. The latter is characterized by early erythema over the lower pole of the breast (superimposed over the anatomic extent of the acellular dermis) without systemic signs of infection and without any radiographic evidence of seroma or abscess. The etiology of this erythema has not been completely elucidated, but it may be a host inflammatory response to the acellular dermis itself.
Ideally, mastectomy flaps should be healthy enough to revascularize and integrate the acellular dermal graft. However, if the mastectomy flaps are relatively avascular or if the graft has a mechanical or physiologic impediment, the graft may fail to revascularize, and this failure may lead to an inflammatory reaction. An example of mechanical prevention of revascularization is the presence of fluid between the mastectomy flaps.
Alternatively, as noted (see above), inversion of the polarity of the graft can lead to physiologic retardation of the revascularization process because revascularization occurs from the mastectomy flap, and the epidermal surface has relatively poor porosity relative to the dermal surface. 
The same phenomenon even be seen even when thicker acellular dermal grafts are used. Revascularization may be further challenged by the deeper penetration required, and prolonged integration attempts may themselves stimulate a host inflammatory response. A more chronic form of this inflammatory process can be seen with occasional inversion or with the formation of granulomas around the folded acellular dermis. 
Nahabedian further discussed the importance of differentiating between mechanical and infectious complications.  The interventions required for a true primary infection are not the same as those required for a secondary mechanical complication, and the 2 conditions differ significantly with respect to complication rates and outcomes. These distinctions become significant because of the potential controversy regarding increased infection and seroma rates when acellular dermis is used in breast reconstructions.
Chun et al noted that the desire to increase intraoperative volume or to perform single-stage reconstructions using acellular dermis leads to a tendency to retain and use more native breast skin, thereby giving rise to increased seroma and infection rates.  They pointed out that acellular dermis does not protect against standard postoperative risks and recommended that surgical treatment be adjusted accordingly.
Chun et al also stated that the increased seroma rate may be related to proper drain placement when using acellular dermis.  Careful drain placement in both subcutaneous and subacellular dermal planes, along with longer postoperative drain time, should be used to minimize postoperative risk of seroma. 
Finally, the effects of radiation on breast reconstructions merit discussion. Generally, rates of radiation-effect complications, particularly capsular contracture, are lower in ADM-assisted reconstructions than in traditional tissue expander reconstructions. [11, 23] The protective effects have been reproduced and quantified in various mammalian studies. 
Although these initial results are by no means conclusive, establishing a significant expander volume early may be of benefit, providing a “stretch effect.” The incidence of capsular contracture may also be reduced as a result of a physiological “barrier effect” exerted by the acellular dermis, perhaps in combination with the aforementioned stretch effect. To date, no definitive explanation has been adduced to account for these behaviors, but future studies will help confirm these phenomena and elucidate the underlying physiologic processes.
Approach Considerations The acellular dermis matrix (ADM)-assisted expander-implant technique involves the use of tissue expanders or implants. In this technique, the surgeon disinserts the pectoralis major and shapes the lower pole of the breast, essentially using the acellular dermis as a sling. This allows increased control over expander placement, leading to better inframammary fold definition and, ultimately, a more natural soft tissue shape. [1, 4, 5, 6]
In addition, the use of acellular dermis creates a larger implant pocket, allowing greater intraoperative tissue expander fill volumes and an accelerated expansion process. [1, 2] After expansion, either expanders are exchanged for a permanent implant or they are removed and the breast is reconstructed with an autologous flap. Given sufficiently large mastectomy flaps, single-stage, direct-to-implant reconstructions have also been reported. [4, 5]
Breast Reconstruction with Acellular Matrix
Preoperative planning is completed as is normal for an expander-implant based reconstruction. Critical breast landmarks are identified, and evaluation of original breast ptosis, projection, and inframammary fold is documented. The size of the tissue expander is determined in the usual manner. The breast is marked to define the inframammary fold and the modified skin-sparing periareolar incision lines.
Placement of incision
Skin preservation is a key element of the mastectomy because a larger skin flap allows greater intraoperative expansion. The vertical component of the incision is the critical component in this regard, and minimizing that component will maximize skin flap size. Specifically, the incision pattern should be directed obliquely (“keyhole” incision) to give the breast surgeon access to all quadrants of the breast (the same surface area of exposure) while minimizing the vertical component of the incision. 
For a nipple-sparing mastectomy, the incisions should be directed in a lateral approach that avoids the actual areolar border. The reason is that the periareolar nipple-sparing approach has a higher rate of nipple necrosis and should generally be avoided. Inframammary incisions have been used on the grounds that they are less cosmetically conspicuous, but they are generally problematic on larger-breasted women because they provide only limited access to all of the breast tissue.
Preparation of acellular dermis
Once the assessment of skin excess and flap thickness is made intraoperatively and the decision is made to use ADM, the matrix should be prepared. If the acellular dermis is prehydrated, it can be rinsed in antibiotic solution; if it is freeze-dried, the hydration sequence can be initiated as indicated by the manufacturer.
Disinsertion of pectoralis and placement of acellular dermis
The pectoralis major is first disinserted at the inferior origin along the inframammary fold, then separated from the rectus and serratus fascia (see the first image below). A thick 6 × 16 cm piece of acellular dermis is sutured to the ensuing inferior defect in the pectoralis major (see the second image below).
The lateral aspect of the ADM is then secured to the serratus fascia in a similar fashion. The supralateral aspect of the cavity is secured by attaching the lateral border of the pectoralis major to the serratus (see the image below). Care must be taken in suturing the ADM to the fascia and muscle: folds or inversions of the ADM can create granulomas. [12, 24] Additionally, placement of the ADM should be arranged as to maintain or recreate the inframammary fold. A tissue expander or implant is then placed in the submuscular and subgraft space and secured.
Completion and closure
The muscle and graft interface is then closed. Drains are placed in the inferior space between the mastectomy flap and the graft, as well as in the axillary and superior subcutaneous planes (see the images below). 
Antibiotic irrigation is employed to rinse the operative pocket and the implants throughout the procedure. After complete coverage of the expander or implant has been accomplished, the expanders are carefully inflated according to the degree of skin excess, which ultimately determined by the surgeon. In non–nipple-sparing cases, limiting expansion to a maximum of two thirds of the expected final volume may minimize the possibility of mastectomy flap necrosis. [1, 12]
Postoperatively, the drains should remain in place until the output is less than 30 mL in 24 hours; this typically takes 7-10 days. Routine postoperative antibiotic prophylaxis should be given.
For patients with tissue expanders, serial expansions should be initiated after the incision has healed, which is typically 2-3 weeks after the operation. The volumes of serial tissue expansions and the intervals between them are determined by the surgeon on a per-patient basis. Patient discomfort and tissue tightness are the primary concerns taken into consideration.
Stage II reconstruction (if necessary)
After completion of adjuvant therapy and tissue expansion, stage II reconstruction with tissue expander–to-implant exchange can be performed if necessary. Procedures for contralateral symmetry are performed if the need becomes apparent or if they were previously planned but not performed during stage I. Preoperative and postoperative photos of a 2-stage expander-to-implant reconstruction and a single-stage direct-to-implant reconstruction are shown below.