Acellular dermal matrices (ADMs) are being used for soft tissue augmentation with increasing frequency across surgical specialties.1,2 These products are produced from human cadaveric donors and undergo a proprietary process of cleaning, rinsing, and decellularizing, which results in significant removal of cellular debris, including DNA, RNA, proteins, and antigens. The final product is a 3-dimensional, collagen-rich, biocompatible, non-cytotoxic matrix that retains its original biomechanical properties.3 The graft is then ready for implantation into the recipient patient, where it is subsequently revascularized and the cell population is replaced as early as 8 weeks after placement.4
The increased use of ADMs has been particularly apparent in the setting of implant-based breast reconstruction, where matrices are used to supplement the thickness of the mastectomy skin flaps and ensure adequate soft tissue coverage of implants.5,6 However, long-term review of these devices has indicated that there is a strong correlation between seroma formation and the use of ADM.7–9 Because allograft integration and neovascularization is dependent on having direct opposition between the ADM and a vascular bed, the presence of seromas can inhibit the area of the graft that is in contact with the native tissue.10
To combat this challenge, most ADM products are available in a variety of meshed or perforated forms, which not only increases the surface area of the product but allows for active fluid egress, thus increasing the ability of the matrices to integrate into the surrounding native tissues.11 Because of the lack of consistency between manufacture designs for meshing or perforation, we set out to determine the fluid egress properties and the increase in surface area resulting from each of the common cut patterns.
This study analyzed the fluid egress and surface area for 3 different commonly encountered commercially available ADM cut patterns: 1 meshed design and 2 distinct perforation designs. Mesh Pattern #1 was designed with 1:1 meshed cuts each measuring 1.5 mm in length (Fig. 1). Perforation Pattern #1 was designed with 3-mm diameter perforations at a density of 0.128 perforations per cm2 (Fig. 2). Perforated Pattern #2 was designed with 3-mm diameter perforations at a density of 0.25 perforations per cm2 (Fig. 3).
Six full-thickness ADM tissues from 3 different donors were processed (AlloMend, AlloSource, Centennial, Colo.). From each donor, 2 samples were prepared with Mesh Pattern #1, 2 with Perforation Pattern #1, and 2 with Perforation Pattern #2. Thus, the study utilized a total of 18 samples, with 6 of each cut pattern. A sample thickness of each sheet of product was measured to the nearest hundredth of a millimeter in 5 locations with a caliper and recorded to account for a possible variation between donors and tissue source locations.
Determining Fluid Egress
A testing device was designed to measure the fluid egress properties of the 18 total tissue samples. Each ADM sample was placed between 2 pipe flanges with a valve below and clear pipe above (Fig. 4). The pipe was filled with fetal bovine serum (FBS). The valve was opened, allowing fluid to flow through the sample (Fig. 5). A camera recorded the amount of time (in seconds) required for the FBS to pass between 2 marked lines on the pipe (distance: 21.6 cm) (Fig. 5). Each sample was run in triplicate.
Average egress times, SDs, and 95% confidence intervals were calculated for each of the cut patterns. MiniTab 17 (MiniTab, LLC., State College, Penn.) was used to calculate a one-way ANOVA to determine if there was a significant difference in egress properties across the 3 patterns and a general linear model ANOVA was used to determine if variation in the tissue donor or graft thickness had a significant impact on the results. P < 0.05 was used to determine statistical significance. Specific mathematical equations are included below.
Determining Surface Area
Meshing or perforating ADM tissue can change its surface area due to the additional area inside the pores or mesh. However, unlike meshing, perforation also removes a portion of surface area to create the holes. The surface area of these modified ADM samples is calculated based on the length, width, and thickness of the graft, and also must account for the mesh length or the perforation diameter and frequency. SolidWorks was used to visualize each of the 3 cut patterns.
The surface area of a perforated ADM graft is reduced when holes are stamped into the product, but simultaneously, the surface area is increased by the addition of new walls inside the hole. Therefore, the surface area of a perforated graft can be calculated as follows:
(*“Original Area” refers to the surface area (length × width) of the unperforated graft.). Unlike the perforating process, meshing does not remove any material from the graft. Instead, small lines are cut into the tissue and, as the graft is stretched, each line becomes a small pore. Thus, the surface area of a meshed graft is equal to the entire surface area of the top of the graft plus the area inside the pores. The total surface area of a meshed tissue is calculated as follows:
The percent increase in surface area from either perforating or meshing is:
Analyzing Fluid Egress
There was a significant difference in egress properties across the three cut patterns (P = 0.000) (Fig. 6). The average egress time of Mesh Pattern #1 ADM was 1.974 seconds (SD 1.157 seconds). The average egress time of Perforation #2 pattern ADM was 6.504 seconds (SD 1.273 seconds) and of the Perforation Pattern #1 ADM was 10.369 seconds (SD 1.598 seconds) (Table 1). Note that the time required for the FBS to pass through the testing device is inversely proportional to the volumetric flow rate through the graft (ie, a lower time indicates a higher volumetric flow rate).
Table 1. -
Timing of Fluid Egress, SD, and Confidence Interval for Each Perforation Pattern
||Average Time (s)
||95% Confidence Interval
Neither donor (P = 0.249) nor graft thickness (P = 0.914) had a significant impact on the results. Thus, the meshed ADM tissue had an average volumetric flow rate of approximately 5.3 times that of the Perforated Pattern #1 tissue and approximately 3.3 times the flow rate of the Perforated Pattern #2 tissue.
Analyzing Surface Area
The surface area calculations for each type of cut pattern are noted below. The tissue thickness was assumed to be 1 mm for the purpose of this analysis.
In a 16 × 20 cm graft, there are 10,400 mesh lines, each mesh line measuring 1.5 mm in length. The calculation for the surface area of a meshed tissue is as follows:
Thus, meshing in a 1:1 pattern nearly doubles the surface area of the graft.
In a 16 × 20cm graft, the area of a perforated surface is calculated as follows:
Perforation pattern #1 is calculated as follows:
Perforation pattern #2 is calculated as follows:
Therefore, perforation at either of these 2 densities yields less than a 1% increase in the total surface area of the ADM tissue.
Acellular dermal matrices have found routine use in implant-based breast reconstruction. Like any graft, for ADM to become revascularized, it must be in contact with a well-vascularized bed of tissue. Thus, it is generally accepted that creating holes in the ADM can facilitate fluid egress across the membrane. This not only prevents fluid from separating the ADM off the recipient tissue, but also increases the surface area of contact with the recipient bed. However, many of the commercially available products have variable patterns of perforations. To our knowledge, our study is the first to directly compare clinically applicable properties between different ADM perforation patterns. By comparing a variety of perforation patterns, ranging from simple punch-shape perforations to a full 1:1 mesh pattern, we were able to demonstrate that meshing significantly increases egress of fluid across the membrane and surface area available to contact the recipient bed of tissue.
In a recent study, Lotan and colleagues compared meshed versus non-meshed biologic material in the setting of breast reconstruction.11 They demonstrated reduced rates of postoperative seroma, hematoma, and infection, and decreased time to drain removal. Our dry laboratory data corroborate these clinical findings. For example, we found that the meshed ADM allowed for an almost 3-fold increase in the rate of egress of fluid across the material. This may explain the decreased seroma rates observed in the above study, as a configuration that prevents the sequestration of fluid may easily prevent clinically relevant fluid collections. Furthermore, an increased surface area of contact, as demonstrated in our study, may also contribute to an accelerated rate of incorporation and vascularization of the material into the mastectomy pocket. This would clearly also contribute to decreased fluid production and resultant seroma occurrences.
Additionally, we routinely encounter the meshed ADM several weeks after expansion is complete and the permanent implant is being placed in the clinical setting (Fig. 7). This allows us to subjectively evaluate the degree of incorporation of the ADM we use. At these procedures, the meshed ADM is generally well-incorporated into the overlying mastectomy skin and underlying muscle tissue as evidenced by the ingrowth of the patient’s own tissue into the interstices of the mesh. It is also interesting to note that the mesh appears to expand the most over the highest projecting parts of the expander and remains minimally stretched over the flatter parts such as the posterior aspect that is against the chest wall. Future studies are in progress to determine a methodology to objectively measure the degree of incorporation of ADM meshing patterns in vivo and the resulting differences in complication rates.
In this study, we selected various perforation and mesh patterns that closely resemble those that are available on commercially available products that are commonly used for breast reconstruction. Our dry-laboratory data indicate that a 1:1 mesh pattern significantly increases both fluid egress across the material and surface area available for direct contact with the recipient bed of tissue. It is likely that an increased mesh ratio, such as 2:1 or 3:1, would further increase these measured outcomes. However, more aggressive mesh ratios produce larger open spaces that are devoid of matrix. Because the purpose of using ADM in breast reconstruction is to provide soft tissue augmentation to reinforce the otherwise thin, and often deficient, soft tissue coverage of the implant and its associated pocket, increasing the mesh ratio beyond the 1:1 ratio is not recommended.
Another very important property of any material that might be used for soft tissue augmentation in breast reconstruction is its ability to stretch with tissue expansion or when placed over a spherical implant. Although it is expected that meshing would improve the ability of any material to stretch over an irregular surface, it is not an endpoint evaluated here.
Future studies aimed at assessing this property might add further evidence to determine the ideal biologic material for soft tissue augmentation in breast reconstruction.
This quantitative comparison revealed that meshing ADM tissue significantly improves fluid egress properties and substantially increases the surface area compared with ADM tissue perforated at levels (or beyond those) typically available on the market. Meshing increases fluid flow out of the surgical site, enhances conformability, and increases the surface area of the graft.
1. Kim JYS, Mlodinow AS. What’s new in acellular dermal matrix and soft-tissue support for prosthetic breast reconstruction. Plast Reconstr Surg. 2017; 1405S Advances in Breast Reconstruction30S
2. Bertasi G, Cole W, Samsell B, et al. Biological incorporation of human acellular dermal matrix used in Achilles tendon repair. Cell Tissue Bank. 2017; 18:403–411
3. Nilsen TJ, Dasgupta A, Huang YC, et al. Do processing methods make a difference in acellular dermal matrix properties? Aesthet Surg J. 2016; 36suppl 2S7–S22
4. Garcia O Jr, Scott JR. Analysis of acellular dermal matrix integration and revascularization following tissue expander breast reconstruction in a clinically relevant large-animal model. Plast Reconstr Surg. 2013; 131:741e–751e
5. Sobti N, Ji E, Brown RL, et al. Evaluation of acellular dermal matrix efficacy in prosthesis-based breast reconstruction. Plast Reconstr Surg. 2018; 141:541–549
6. Spear SL, Seruya M, Clemens MW, et al. Acellular dermal matrix for the treatment and prevention of implant-associated breast deformities. Plast Surg Nurs. 2017; 37:76–87
7. Ganske I, Verma K, Rosen H, et al. Minimizing complications with the use of acellular dermal matrix for immediate implant-based breast reconstruction. Ann Plast Surg. 2013; 71:464–470
8. Lee KT, Mun GH. Updated evidence of acellular dermal matrix use for implant-based breast reconstruction: a meta-analysis. Ann Surg Oncol. 2016; 23:600–610
9. Israeli R. Complications of acellular dermal matrices in breast surgery. Plast Reconstr Surg. 2012; 1305 suppl 2159S–172S
10. Fosnot J, Kovach SJ III, Serletti JM. Acellular dermal matrix: general principles for the plastic surgeon. Aesthet Surg J. 2011; 317 Suppl5S–12S
11. Maisel Lotan A, Ben Yehuda D, Allweis TM, et al. Comparative study of meshed and nonmeshed acellular dermal matrix in immediate breast reconstruction. Plast Reconstr Surg. 2019; 144:1045–1053