Comparative outcomes of human acellular dermal matrices in breast reconstruction: a systematic review and meta-analysis framework

Abstract

Background

Acellular dermal matrices (ADMs) have become popularly used in implant-based breast reconstruction (IBBR) due to their potential to decrease the risk of implant complications such as capsular contracture and malposition. AlloDerm and DermACELL are two of the most commonly used human ADMs, each processed differently to enhance sterility and biocompatibility. Despite their widespread use, the comparative effectiveness and safety of these ADMs remain debatable among plastic surgeons, with conflicting evidence in the literature regarding their complication profiles. This systematic review and meta-analysis aims to evaluate the clinical outcomes associated with AlloDerm versus DermACELL in breast reconstruction.

Methods

This review will follow the methodological guidance of the Cochrane Handbook for Systematic Reviews of Interventions. The database search will be conducted using MEDLINE (PubMed), Scopus, Web of Science, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Clinicaltrials.org targeting studies from inception to search date. Studies will be screened using inclusion and exclusion criteria and data extracted into a spreadsheet. Screening, extraction, and risk-of-bias assessments will be performed independently by two reviewers and discrepancies resolved by a third independent reviewer. Primary outcomes include complication rates (e.g., capsular contracture, infection, implant malposition), patient-reported satisfaction (BREAST-Q), and drain time. Data analysis and meta-analysis will be performed using Microsoft Excel and Review Manager 5.4 software. Heterogeneity will be assessed using the I² statistic. A random-effects model will be applied in cases of significant heterogeneity followed by a sensitivity analysis. This review will be reported in accordance with the PRISMA 2020 checklist.

Discussion

With the increasing use of ADMs in IBBR, it is important that surgeons have adequate evidence available to assist operative decision-making. This meta-analysis will help surgeons determine whether one ADM is better than the other. This could potentially minimize the risk of patient complications, improve patient satisfaction, and decrease unnecessary hospital readmissions or reoperations due to avoidable complications, thereby decreasing healthcare costs.

Systematic review registration

PROSPERO CRD42024542928.

Introduction

Breast reconstruction following mastectomy plays an important role in restoring body image and improving quality of life in breast cancer patients. Acellular dermal matrices (ADMs) are popularly used in implant-based breast reconstruction (IBBR) to support the implant and decrease risks of malposition and capsular contracture [1, 2]. Among the most commonly used ADMs are AlloDerm and DermACELL, which are both human-derived ADMs but undergo different processing techniques.

AlloDerm undergoes a freeze-drying process, then sterilization with electron beam sterilization (SAL 10⁻³). Historically, AlloDerm required saturation in a sterile solution before use [3], but it now comes in a ready-to-use (RTU) formulation, enhancing its convenience during surgical procedures. On the other hand, DermACELL undergoes sterilization with low-dose gamma irradiation (SAL 10⁻⁶) and is processed using nondenaturing anionic detergent, three different antibiotics, and a recombinant endonuclease [3–5].

Thus, the fundamental difference between these products lies in their sterilization assurance levels following radiation; otherwise, these products are similar in size, shape, and claimed performance. This systematic review and meta-analysis aims to comprehensively compare the complication profiles and clinical outcomes of DermACELL and AlloDerm in breast reconstruction, guiding clinicians in making informed decisions about their use. The primary outcomes of interest will include complications such as Red Breast Syndrome, capsular contracture, implant failure, skin flap necrosis, wound dehiscence, delayed healing, explantation, infection, hematoma, seroma, drain time, and patient satisfaction (BREAST-Q).

Due to the conflicting evidence in the literature with studies reporting varying rates of complications between these two ADMs, a systematic review and meta-analysis will help in reaching definitive conclusions regarding these outcomes, optimizing patient care, and improving overall success rates of breast reconstruction surgeries in breast cancer survivors.

Methodology

This review has been registered with the International Prospective Register of Systematic Reviews (PROSPERO), part of the National Institute for Health Research (NIHR). Registration is as follows: PROSPERO 2024 CRD42024542928 [6] and the regulations of the preferred reporting items of systematic reviews and meta-analyses (PRISMA) will be followed [7]. This protocol followed the PRISMA-P guidelines for protocols [8] (Supplementary information) and will follow the Cochrane Handbook for Systematic Reviews of Interventions [9].

Literature search

A preliminary search strategy using the terms “(AlloDerm) AND (DermACELL)” was piloted in PubMed during protocol development to ensure the feasibility of a meta-analysis. A full, finalized search strategy using expanded free-text and MeSH terms will be applied and reported in the final systematic review in accordance with PRISMA guidelines. The formal search will be conducted with the following databases: MEDLINE (PubMed), Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.org. The Cochrane Database of Systematic Reviews will also be searched to identify relevant primary studies cited within existing similar systematic reviews that may not have been captured by our primary search strategy. The search timeframe will include all studies from inception to the search date. We will also screen the reference lists of included studies and relevant reviews. Additional gray literature sources, such as OpenGrey and conference abstracts, will be reviewed.

Study selection and data extraction

Studies will be screened according to PICO criteria (Table 1), inclusion and exclusion criteria (Table 2) by two independent reviewers, and discrepancies will be resolved by a third independent reviewer. Non-randomized (retrospective and prospective) studies and randomized controlled trials will be included. Titles and abstracts will be screened, followed by a full-text screening. Information from studies that pass initial and full-text screening will be extracted by two independent reviewers, and conflicts will be resolved by a third reviewer. Data will be extracted into a spreadsheet format. Outcome data will include Red Breast Syndrome, capsular contracture, implant failure, skin flap necrosis, wound dehiscence, delayed healing, explantation, infection, hematoma, seroma, drain time, and patient satisfaction (BREAST-Q). Outcomes on oncologic safety (e.g., cancer recurrence) will also be assessed. Demographic data will include age, body mass index, diabetes, smoking status, radiotherapy, chemotherapy, and follow-up time.

Table 1.

PICO criteri for study selection

Population	1) Patients with breast cancer undergoing IBBR with ADM placement
	2) ADM must be either AlloDerm or DermACELL
Intervention	IBBR with AlloDerm
Comparison	IBBR with DermACELL
Outcome	1) Surgical complications (Red Breast Syndrome, capsular contracture, implant failure, skin flap necrosis, wound dehiscence, delayed healing, explantation, infection, hematoma, seroma)
	2) Oncologic safety
	3) BREAST-Q Patient Satisfaction
	4) Drain time

Table 2.

Inclusion and exclusion criteria for study selection

Inclusion criteria	1) Observational or experimental studies (randomized controlled trials, prospective cohort studies, retrospective cohort studies, and non-randomized clinical) comparing AlloDerm and DermACELL in IBBR
	2) Studies reporting complication rates, oncologic safety, drain time, and BREAST-Q patient satisfaction outcomes for both arms
Exclusion criteria	1) Studies where both AlloDerm and DermACELL were not compared
	2) Animal studies, case reports, case series, reviews, letters to the editor, commentaries, and editorials
	3) Studies with insufficient data on complication rates or patient satisfaction
	4) Studies where patients were switched from one ADM to the other

Study quality

Study quality and risk of bias will be assessed using the Cochrane ROB 2 score for randomized control trials and ROBINS-I tool for non-randomized studies [10, 11]. Studies will be independently reviewed by two authors. Disagreements in risk-of-bias assessments will be resolved through discussion, and if necessary, adjudicated by a third reviewer. Any amendments to the protocol will be documented via updates on PROSPERO and reflected in the final systematic review manuscript.

Statistical analysis

Meta-analysis will be performed using Review Manager 5.4 software. Dichotomous data with outcomes comparing complication rates will be presented as risk ratios (RR) with their respective 95% confidence intervals (CI) using the Mantel–Haenszel method. Continuous data with outcomes on drain time and BREAST-Q patient satisfaction will be presented as mean differences (MD) with their respective CI using the inverse variance method. Heterogeneity will be assessed using I² statistics. A random-effects model will be used throughout. Sensitivity analyses will be based on heterogeneity (leave-one-out test to eliminate the study with the highest contribution to heterogeneity), study quality, and risk of bias. Forest plots will be created for two-arm studies. A 95% confidence interval will be used to assess statistical significance. If enough data are available, subgroup analyses on types of reconstruction (e.g., subpectoral or prepectoral), radiotherapy, chemotherapy, and different types of mastectomies will be performed to assess heterogeneity and eliminate potential confounding. Publication bias will be assessed using funnel plots and Egger’s test where an outcome has been reported by 10 or more studies [12].

The certainty of evidence for each outcome will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach [13]. This will consider study design, risk of bias, inconsistency, indirectness, imprecision, and publication bias. The results will be summarized ina summary of findings (SoF) table using GRADEpro software.

Discussion

The use of ADMs in IBBR has become increasingly common. This systematic review and meta-analysis will aim to compare the complication rates and patient-reported outcomes of AlloDerm and DermACELL, two widely used ADMs, with AlloDerm being the most widely used.

Complication rates

There are many studies comparing these two ADMs with no head-to-head meta-analysis reaching definitive conclusions to date. Pittman et al. [14] reported that DermACELL had a significantly lower incidence of “red breast syndrome” and fewer days before drain removal compared to AlloDerm RTU. Conversely, Greig et al. [15] and Swisher et al. [16] reported a higher incidence with DermACELL compared to AlloDerm. Johnson et al. [17] also found a significantly higher incidence of seroma formation in the AlloDerm group compared to DermACELL; in contrast, Stein et al. [18] found a slightly lower incidence in the AlloDerm arm.

Patient-reported outcomes

Stein et al. [18] conducted a randomized controlled trial comparing patient-reported (BREAST-Q) outcomes between AlloDerm and DermACELL. They found that while AlloDerm showed short-term advantages in patient satisfaction, there were no significant differences in long-term outcomes between the two ADMs. Similarly, Asaad et al. [19] reported no significant differences in patient-reported outcomes among AlloDerm, SurgiMend, and DermACELL.

Although conflicting, the current evidence suggests that while there may be some differences in short-term complications and patient-reported outcomes between AlloDerm and DermACELL, the long-term outcomes may be comparable. Nonetheless, definitive conclusions are yet to be made with the help of a head-to-head meta-analysis. The resulting data will be important for surgeons in making objective treatment decisions and informing future research on the topic.

Authors’ contributions

YT conceptualized and designed the study. GDSV, GG, JT, and SS assisted with the study design. All authors read and approved the manuscript prior to submission.

Funding

The authors have not received any financial support.

Data availability

Not applicable.

Declarations

Ethics approval and consent to participate

As this review analyzes papers that are already published and in the public domain, ethics approval is not required.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.