Effect of Immediate Implant-Based Breast Reconstruction After Mastectomy With and Without Acellular Dermal Matrix Among Women With Breast Cancer: A Randomized Clinical Trial.

Importance: The use of acellular dermal matrix (ADM) in implant-based breast reconstructions (IBBRs) is established practice. Existing evidence validating ADMs proposed advantages, including improved cosmetics and more single-stage IBBRs, is lacking. Objective: To evaluate whether IBBR with ADM results in fewer reoperations and increased health-related quality of life (HRQoL) compared with conventional IBBR without ADM. Design, Setting, and Participants: This was an open-label, multicenter, randomized clinical trial of women with primary breast cancer who planned for mastectomy and immediate IBBR, with a 2-year follow-up for all participants. Participants were enrolled at 5 breast cancer units in Sweden and the United Kingdom between 2014 and May 2017. Exclusion criteria included previous radiotherapy and neo-adjuvant chemotherapy. Data were analyzed until August 2017. Interventions: Participants were allocated to immediate IBBR with or without ADM. Main Outcomes and Measures: The primary trial end point was number of reoperations at 2 years. HRQoL, a secondary end point, was measured as patient-reported outcome measures using 3 instruments from the European Organization for Research and Treatment of Cancer Quality of life Questionnaire. Results: From start of enrollment on April 24, 2014, to close of trial on May 10, 2017, a total of 135 women were enrolled (mean [SD] age, 50.4 [9.5] years); 64 were assigned to have an IBBR procedure with ADM and 65 to the control group who had IBBR without ADM. There was no statistically significant difference between groups for the primary outcome. Of 129 patients analyzed at 2-year follow-up, 44 of 64 (69%) had at least 1 surgical event in the ADM group vs 43 of 65 (66%) in the control group. In the ADM group, 31 patients (48%) had at least 1 reoperation on the ipsilateral side vs 35 (54%) in the control group. The overall number of reoperations on the ipsilateral side were 42 and 43 respectively. Within the follow-up time of 24 months, 9 patients (14%) in the ADM group had the implant removed compared with 7 (11%) in the control group. We found no significant mean differences in postoperative patient-reported HRQoL domains, including perception of body image (mean difference, 3; 99% CI, -11 to 17; P = .57) and satisfaction with cosmetic outcome (mean difference, 8; 99% CI, -6 to 20; P = .11). Conclusions and Relevance: Immediate IBBR with ADM did not yield fewer reoperations compared with conventional IBBR without ADM, nor was IBBR with ADM superior in terms of HRQoL or patient-reported cosmetic outcomes. Patients treated for breast cancer contemplating ADM-supported IBBR should be informed about the lack of evidence validating ADM's suggested benefits. Trial Registration: ClinicalTrials.gov Identifier: NCT02061527.

Ready-to-Use Micronized Human Acellular Dermal Matrix to Accelerate Wound Healing in Diabetic Foot Ulcers: A Prospective Randomized Pilot Study.

OBJECTIVE: To examine and report clinical outcomes of a ready-to-use micronized dermal matrix for diabetic foot ulcers (DFUs) and compare it to treatment with conventional negative-pressure wound therapy (NPWT) only. METHODS: The researchers randomly allocated 30 DFUs Wagner grade 2 or higher from 30 adult patients into two groups. The control group (n = 15) was treated with conventional NPWT, and the experimental group (n = 15) was treated with micronized dermal matrix and NPWT. The researchers evaluated the following outcomes: granulation tissue formation, proportion of patients with closed or granulated wounds at 42 and 120 days, achievement of complete wound healing in the 6 months of follow-up, and intervals from enrollment to final surgical procedures. RESULTS: All 15 wounds treated with the micronized matrix showed healthy granulation tissue without noticeable complications during follow-up. At 42 days, 46.7% of wounds in the experimental group had closed compared with 28.6% in the conventional NPWT group (P = .007). At 120 days, 86.7% of the experimental group had completely closed wounds, compared with 57.1% in the conventional therapy group (P = .040). During the 6-month follow-up period, 93.3% of the experimental group achieved complete wound healing compared with 85.7% of the conventional therapy group (P = .468). CONCLUSIONS: The healing outcomes for DFUs in the experimental group were superior when micronized matrix treatment was combined with NPWT.

Comparison of xenogeneic acellular dermal matrix and skin grafts in reconstruction of postoperative defects of hypopharyngeal cancer: A retrospective cohort study.

Successful reconstruction after tumor resection facilitates rapid recovery and retention of good quality of life, and this is important for a successful operation. This study aimed to analyze and compare the application and efficacy of xenogeneic acellular dermal matrix (xeno-ADM) and abdominal skin graft in hypopharynx reconstruction.This is a retrospective cohort study that included 25 patients with posterior hypopharyngeal wall cancer who underwent partial hypopharyngectomy with laryngeal preservation. The patients were divided into 2 groups according to the repair materials used. Eleven patients were treated with xeno-ADM, and 14 patients with abdominal skin grafts for repairing hypopharyngeal mucosal defects. The intraoperative data, postoperative recovery time of eating function, graft contraction, infection and pharyngeal fistula rate, and 1-year survival rate of the 2 groups were analyzed and compared.Compared with skin grafts group (23.1 ±â€Š5.8 days), the recovery time of eating function in xeno-ADM group was shorter (17.3 ±â€Š6.4 days), (P = .026). Also the number of postoperative hospitalization days were less in the xeno-ADM group (18.5 ±â€Š6.7 days) than in the skin grafts group (24.1 ±â€Š5.6 days) (P = .035). Besides, no significant differences were observed in other comparisons between the 2 groups. Also no obvious rejection and severe graft contraction were observed in both the groups. All patients were successfully decannulated.Both xeno-ADM and abdominal skin grafts demonstrated good effects in the reconstruction of hypopharynx, but the recovery time of eating function in patients with xeno-ADM was faster, which may be due to rapid epithelialization. In addition, it avoids trauma of donor sites.

Regulation of decellularized matrix mediated immune response.

The substantially growing gap between suitable donors and patients waiting for new organ transplantation has compelled tissue engineers to look for suitable patient-specific alternatives. Lately, a decellularized extracellular matrix (dECM), obtained primarily from either discarded human tissues/organs or other species, has shown great promise in the constrained availability of high-quality donor tissues. In this review, we have addressed critical gaps and often-ignored aspects of understanding the innate and adaptive immune response to the dECM. Firstly, although most of the studies claim preservation of the ECM ultrastructure, almost all methods employed for decellularization would inevitably cause a certain degree of disruption to the ECM ultrastructure and modulation in secondary conformations, which may elicit a distinct immunogenic response. Secondly, it is still a major challenge to find ways to conserve the native biochemical, structural and biomechanical cues by making a judicious decision regarding the choice of decellularization agents/techniques. We have critically analyzed various decellularization protocols and tried to find answers on various aspects such as whether the secondary structural conformation of dECM proteins would be preserved after decellularization. Thirdly, to keep the dECM ultrastructure as close to the native ECM we have raised the question "How good is good enough?" Even residual cellular antigens or nucleic acid fragments may elicit antigenicity leading to a low-grade immune response. A combinative knowledge of macrophage plasticity in the decellularized tissue and limits of decellularization will help achieve the native ultrastructure. Lastly, we have shifted our focus on the scientific basis of the presently accepted criteria for decellularization, and the effect on immune response concerning the interaction between the decellularized extracellular matrix and macrophages with the subsequent influence of T-cell activation. Amalgamating suitable decellularization approaches, sufficient knowledge of macrophage plasticity and elucidation of molecular pathways together will help fabricate functional immune informed decellularized tissues in vitro that will have substantial implications for efficient clinical translation and prediction for in vivo reprogramming and tissue regeneration.

Evaluation of a novel breast reconstruction technique using the Braxon® acellular dermal matrix: a new muscle-sparing breast reconstruction.

BACKGROUND: Implant-based breast reconstruction is becoming increasingly popular because of the widespread adoption of acellular dermal matrix (ADM), which allows surgeons to obtain good aesthetic results with fewer operations. To develop more conservative surgical techniques, a retrospective, three-centre, proof-of-concept study was performed to study the effectiveness of a new, immediate, muscle-sparing breast reconstruction technique using the patented Braxon® ADM, which enables subcutaneous positioning of the breast implant without detaching the pectoralis major. METHODS: Ethics committee of the study coordinating centre approved medical record review on 19 women who underwent muscle-sparing breast reconstruction between November 2012 and January 2014. The first 10 implants were performed using 0.9-mm-thick porcine ADM, with preservatives. In the subsequent 15 implants, the product was changed to 0.6-mm-thick porcine dry ADM, without preservatives. RESULTS: Nineteen patients (25 implants) received six bilateral and 13 unilateral muscle-sparing breast reconstructions. For the first type of ADM used (0.9-mm-thick with preservatives), the rate of implant loss was 12% (n = 3) because of seroma (8%, n = 2) and infection (4%, n = 1). Minor complications, such as seroma (8%, n = 2), occurred when using the 0.6-mm-thick Braxon® ADM and were treated by aspiration. Symmetrical and natural breasts with good shape, ptosis and softness to the touch were obtained. None of the patients reported experiencing pain. CONCLUSIONS: The preliminary results are encouraging from aesthetic and clinical viewpoints. Further studies are planned to evaluate long-term results.

The Preparation of Acellular Dermal Matrices by Freeze-Thawing and Ultrasonication Process and the Evaluation of Its Antigenicity.

Antigenicity is the biggest obstacle of xenogeneic acellular dermal matrices (ADM) as dermal scaffold in treatment of large-area skin defect. We prepared ADM by repeated freezing and thawing and ultrasonic process, and then injected the ADM homogenate and degradation product into porcine skin to evaluate the effectiveness of the decellularized method and the antigenicity of porcine ADM. In this work, chinese miniature pigs (n = 10) were sensitized by subcutaneous injection with human ADM degradation products on days 0, 7, and 14. After 21 days, their abdominal skin was divided into five regions for intradermal injection of porcine ADM homogenate (PADM), PADM degradation products, human ADM homogenate (HADM), HADM degradation products, and physiological saline (negative control). Positive controls (n = 2) were processed with fresh human skin homogenate by the same method. The skin manifestations in related areas were observed at 24 and 48 h and then the skin was subjected to histopathological and immunohistochemical analysis. The results showed that skin erythema and hydroderma were not observed in all groups but in positive control group. The histopathological and immunohistochemical results confirmed that no inflammatory cell infiltration, irregular extracellular matrix, IL-2, and IFN-γ expression were observed in all four test groups. Our results suggest that the combination with repeated freeze-thawing and ultrasonication can be an effective method to prepare ADM, which has great potential in clinical application.

Impact and outcome of human acellular dermal matrix size for immediate and two-stage breast reconstruction.

BACKGROUND: Following mastectomy, patients may choose to have breast reconstruction with autologous tissue or implants. Human acellular dermal matrix has been described as a tissue supplement where the implant is covered, without requiring further muscle elevation or dissection. The authors evaluated the impact of different matrix sizes. METHODS: Fifty-two patients (average age, 48.5 years) and 88 operated breasts were evaluated. The cohort was divided into two, depending on matrix size. In group A, a small matrix with a surface area of 48 or 96 cm was used. In group B, a larger matrix with either 128 or 160 cm was used. Intraoperative fill volumes, expansion procedure, and complications were analyzed. RESULTS: Size difference was significant (69.2 versus 135.5 cm). The calculated mean initial filling volume-to-excised pathology tissue weight ratio and the initial filling-to-final implant volume ratio were significant. Average number of fills to reach final expansion volume was 62.3 percent, or 4.7 times lower in group B. Seven complications were reported without any statistical difference between groups. CONCLUSIONS: This study suggests that using a larger human acellular dermal matrix in breast reconstruction offers a potential to increase the initial expander fill volume-to-breast pathology weight ratio and initial expander fill volume-to-final implant volume ratio. Larger matrices can reduce the number of subsequent expansions and may even decrease the risk of postoperative complications. This study also revealed that using a larger matrix is a safe method that does not increase complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.