Augmenting Breast Implant Research: Accessible Methods for Fabricating Miniature Smooth and Textured Breast Implants in a Laboratory Setting.

BACKGROUND: Because of the association of textured breast implants with breast implant-associated anaplastic large cell lymphoma, anatomically shaped breast implants, which rely on a textured surface to maintain rotational stability, have been recalled from the market. The dearth of anatomically shaped implants on the market reflects a need for novel breast implant technology, which has been traditionally developed by commercial breast implant manufacturers due to the complexities of implant manufacturing. To increase the accessibility of preclinical breast implant research, miniature breast implants made from polydimethylsiloxane were designed and fabricated for high throughput and low-cost prototyping and in vivo testing of both smooth and textured implants in a laboratory setting. METHODS: Two-piece negative molds measuring 2 × 1 cm were constructed in Fusion360 and 3D printed in Polysmooth filament. Textured molds were painted with a mixture of an epoxy and fine sugar or granular salt to create textured surfaces, while molds for smooth implants were smoothed using ethanol spray. Molds were injected with polydimethylsiloxane and cured for 12 hours at 37°C. The surface topography of laboratory-made implants and commercial textured and smooth implant shells was analyzed using scanning electron microscopy and implants were evaluated in vivo in an immunocompetent rodent model. RESULTS: Implants retained the original dome shape of the 3D-printed molds. Qualitative assessment of scanning electron microscopy images demonstrated similar surface topography between laboratory-made and commercial smooth and textured implants. There was no statistical difference in the diameter or density of the surface indentations of the Allergan's textured implant compared with laboratory-made textured implants ( P > 0.05). Finally, the surface topography and thickness of laboratory-made implant capsules were similar to previously published data using industry made miniature silicone devices implanted in rats. CONCLUSIONS: This study demonstrates a low-cost, highly customizable approach to fabricate miniature smooth and textured breast implant prototypes for in vivo studies. The accessibility of this implant fabrication strategy allows nonindustry investigators to develop novel implant designs more rapidly for preclinical investigation.

Charting the Effect of the Universal Offer Date on Plastic Surgery Residency Matches.

In 2019, the plastic surgery residency match changed their method for inviting students to interview. Instead of offering interview invitations and scheduling interviews on a first come, first served basis, all plastic surgery residency programs sent out secured interview spots on the same day. This universal offer date was intended to remove student worry that surrounded not scheduling an interview fast enough, as well as cause students to more carefully select which interview invitations to accept, increasing the likelihood that residency programs could interview only those students most interested in matching at their institutions. The effect of universal offer date was studied through analysis of available National Residency Match Program data, with a focus on the mean number of contiguous programs students ranked to match, as well as the mean number of applicants who residency programs ranked to fill each available position. Historical trends in plastic surgery match, trends in the match in other competitive surgical subspecialties, and applicant qualifications were also analyzed. In breaking with the general trend among all surgical subspecialties toward ranking more applicants per residency position, in 2020, fewer plastic surgery applicants were ranked by residency programs per available position, suggesting a more effective interview process and match. Matched applicant qualifications remained excellent across the period studied.

Prepectoral Breast Reconstruction Without the Use of Acellular Dermal Matrix: A 3-Year Review.

INTRODUCTION: Acellular dermal matrix (ADM) is frequently used during prepectoral tissue expander-based breast reconstruction. However, there has been a paucity of literature describing the experience of prepectoral reconstruction without the accompanying use of ADM. We seek to highlight our institutional experience with immediate prepectoral tissue expander placement without the use of ADM in breast reconstruction. METHODS: A retrospective, single-institution review of patient records was performed to identify all patients who underwent either skin sparing or nipple-sparing mastectomy with immediate tissue expander placement without the use of ADM. Demographics including age, body mass index, comorbidities, history of smoking or steroid use, perioperative radiation or chemotherapy, intraoperative details, and complication profiles during the tissue expander stage were retrospectively collected and analyzed. At the time of tissue expander placement, all mastectomy flaps were evaluated clinically and with indocyanine green laser angiography. Postoperative outcomes were tracked. RESULTS: Between 2017 and 2020, 63 patients (for a total of 108 breasts) underwent either skin sparing (16%) or nipple-sparing mastectomy (84%) with immediate prepectoral tissue expander without ADM placement. Fourteen percent of breasts developed postoperative cellulitis, 19% of breasts developed skin compromise, and 5% required a postoperative revisional procedure that did not result in immediate expander explant. There was a 13% (n = 14 breasts) explant rate occurring at a mean time of 74 days. Of those breasts that developed skin compromise, 45% went on to require eventual explant. Patients in the study were followed for an average of 6.3 months. CONCLUSIONS: Immediate prepectoral breast reconstruction using tissue expanders without ADM offers a viable alternative to established reconstructive paradigms. The major complication rate for prepectoral reconstruction without the use of ADM (17%) was found to be comparable with our historical subpectoral tissue expander reconstruction with ADM use. Tissue expander explant rates were also comparable between the prepectoral without ADM (13%) and the subpectoral with ADM cohorts. These preliminary data suggest that immediate breast reconstruction with tissue expander placement without accompanying ADM is viable alternative in the breast reconstructive algorithm.

Polycationic Nanofibers for Nucleic Acid Scavenging.

Dying cells release nucleic acids (NA) and NA-containing complexes that activate inflammatory pathways of immune cells. Sustained activation of these pathways contributes to chronic inflammation frequently encountered in autoimmune and inflammatory diseases. In this study, grafting of cationic polymers onto a nanofibrous mesh enabled local scavenging of negatively charged pro-inflammatory molecules in the extracellular space. Nucleic acid scavenging nanofibers (NASFs) formed from poly(styrene-alt-maleic anhydride) conjugated with 1.8 kDa bPEI resulted in nanofibers of diameters 486 ± 9 nm. NASFs inhibited the NF-κB response stimulated by the negatively charged agonists, CpG and poly(I:C), in Ramos-blue cells but not Pam3CSK4, a nonanionic agonist. Moreover, NASFs significantly impeded NF-κB activation in cells stimulated with damage-associated molecular pattern molecules (DAMPs) released from doxorubicin killed cancer cells. In vivo application of NASFs to open wounds demonstrated nucleic acid scavenging in wounds of diabetic mice infected with Pseudomonas aeruginosa, suggesting the in vivo efficacy of NASFs. This simple technique of generating NASF results in effective localized anti-inflammation in vitro and local nucleic acid scavenging in vivo.

Modifying hernia mesh design to improve device mechanical performance and promote tension-free repair.

PURPOSE: Approximately 348,000 ventral hernia repairs are performed annually in the United States and the incisional hernia recurrence rate is approximately 20% as a result of suture and mesh device failure. Device failure is related to changes at the suture/tissue interface that leads to acute or chronic suture pull-through and surgical failure. To better manage mechanical tension, we propose a modified mesh design with extensions and demonstrate its mechanical superiority. METHODS: Comparative uniaxial static tensile testing was conducted on polypropylene suture and a modified mesh. Subsequently, a standard of care (SOC) mesh and modified mesh were evaluated using a tensometer in an acute hernia bench-top model. RESULTS: Modified mesh breaking strength, extension knot breaking strength, extension disruption, and extension anchoring were superior to suture (p < .05). Modified mesh ultimate tensile strength of anchoring was superior to SOC mesh (p < .05). Various stitch patterns and modifications in device design significantly improved device tension-free performance far beyond clinically relevant benchmarks (p < .05). CONCLUSIONS: Testing demonstrates that the modified mesh outperforms SOC mesh and suture in all tested failure modes. SOC hernia mesh tears through tissue at stress levels below maximum physiologic stress, whereas, the modified hernia mesh is up to 200% stronger than SOC mesh at resisting suture tearing through tissue and maintains anchoring at stresses far beyond clinically relevant benchmarks. Modifying hernia mesh design significantly improves device mechanical performance and enhances tension-free repair.

Forearm-Based Turnover Muscle Flaps for Elbow Soft-Tissue Reconstruction: A Comparison of Regional Coverage Based on Distal Flap Perfusion.

BACKGROUND: Elbow wounds pose a reconstructive challenge. Prior studies have described the vascular anatomy of both the brachioradialis and flexor carpi ulnaris muscle flaps. The goal of this study was to describe the distal flap perfusion of the flexor carpi radialis, with a direct comparison of the brachioradialis, flexor carpi ulnaris, and flexor carpi radialis muscle flaps for coverage around the elbow. METHODS: Six fresh-frozen upper extremity specimens were dissected for brachioradialis, flexor carpi radialis, and flexor carpi ulnaris flaps. Vascular data from prior studies were combined with our anatomical measurements to determine the area of perfused coverage around the elbow for the brachioradialis and flexor carpi ulnaris. The flexor carpi radialis flap distal vascular perfusion was examined separately with transverse sections at 1-cm intervals after India ink injections to determine distal flap perfusion and elbow coverage. Perfusion data were plotted on x and y axes over the posterior elbow. RESULTS: The brachioradialis muscle covered an average of 56 percent of the x axis and 7.4 percent of the y axis. The flexor carpi ulnaris muscle covered an average of 90 percent of the elbow along the x axis and 23.3 percent of elbow along the y axis. The flexor carpi radialis covered an average of 34 percent of the x axis and 4.8 percent of the y axis. CONCLUSION: The flexor carpi ulnaris muscle provides the most versatile and robust coverage over the posterior elbow, followed by the brachioradialis muscle, which consistently provides coverage over the lateral epicondyle.

Association Between Targeted HER-2 Therapy and Breast Reconstruction Outcomes: A Propensity Score-Matched Analysis.

BACKGROUND: Current treatment for HER-2+ breast cancer includes chemotherapy and targeted HER-2 therapy with trastuzumab and/or pertuzumab. Evidence is lacking on the safety of breast reconstructive operations in these patients. We hypothesized that targeted HER-2 therapy was not associated with post-mastectomy reconstructive outcomes. STUDY DESIGN: Women receiving chemotherapy and post-mastectomy reconstruction at Duke University Medical Center from 2006 to 2016 were retrospectively identified. Patients receiving targeted HER-2 therapy with trastuzumab and/or pertuzumab within 6 weeks before breast reconstruction were propensity score-matched 1:1 to patients who did not receive targeted HER-2 therapy, based on the following factors: age, obesity, diabetes, tobacco use, receipt of neoadjuvant chemotherapy, chemotherapy regimen, and radiation therapy. Primary study outcomes included the occurrence of hematoma, seroma, infection, wound breakdown, mastectomy skin flap necrosis, and postoperative flap thrombosis. RESULTS: A total of 481 women were identified, resulting in 107 propensity score-matched pairs. Administration of combined trastuzumab and pertuzumab therapy before breast reconstruction was independently associated with increased risk of postoperative wound breakdown requiring operative intervention for closure, compared with patients not undergoing targeted HER-2 therapy (odds ratio 65.29; 95% CI 1.63 to 2,611.50; p = 0.03). In addition, larger tumor size (2 to 5 cm) was significantly associated with a reduced risk of postoperative wound breakdown, compared with smaller tumors (<2 cm) (odds ratio 0.41; 95% CI 0.19 to 0.87; p = 0.02). Single-agent targeted HER-2 therapy with trastuzumab was not significantly associated with reconstructive complications. CONCLUSIONS: Our study suggests that trastuzumab therapy in conjunction with breast reconstructive operation is not associated with reconstructive complications, and breast reconstruction does not need to be delayed due to the administration of trastuzumab. Future studies are needed to evaluate the impact of pertuzumab on surgical outcomes.

In Vivo RNAi screening identifies a leukemia-specific dependence on integrin beta 3 signaling.

We used an in vivo small hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells in vivo and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation via the intracellular kinase Syk. In contrast, loss of Itgb3 in normal hematopoietic stem and progenitor cells did not affect engraftment, reconstitution, or differentiation. Finally, using an Itgb3 knockout mouse model, we confirmed that Itgb3 is dispensable for normal hematopoiesis but is required for leukemogenesis. Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML.