Silicone implant surface microtopography modulates inflammation and tissue repair in capsular fibrosis.

Excessive fibrous capsule formation around silicone mammary implants (SMI) involves immune reactions to silicone. Capsular fibrosis, a common SMI complication linked to host responses, worsens with specific implant topographies. Our study with 10 patients investigated intra- and inter-individually, reduced surface roughness effects on disease progression, wound responses, chronic inflammation, and capsular composition. The results illuminate the significant impact of surface roughness on acute inflammatory responses, fibrinogen accumulation, and the subsequent fibrotic cascade. The reduction of surface roughness to an average roughness of 4 µm emerges as a promising approach for mitigating detrimental immune reactions, promoting healthy wound healing, and curbing excessive fibrosis. The identified proteins adhering to rougher surfaces shed light on potential mediators of pro-inflammatory and pro-fibrotic processes, further emphasizing the need for meticulous consideration of surface design. The composition of the implant capsule and the discovery of intracapsular HSP60 expression highlight the intricate web of stress responses and immune activation that can impact long-term tissue outcomes.

Surface Topography, Microbial Adhesion, and Immune Responses in Silicone Mammary Implant-Associated Capsular Fibrosis.

Breast cancer is the most common cancer in women globally, often necessitating mastectomy and subsequent breast reconstruction. Silicone mammary implants (SMIs) play a pivotal role in breast reconstruction, yet their interaction with the host immune system and microbiome remains poorly understood. This study investigates the impact of SMI surface topography on host antimicrobial responses, wound proteome dynamics, and microbial colonization. Biological samples were collected from ten human patients undergoing breast reconstruction with SMIs. Mass spectrometry profiles were analyzed for acute and chronic wound proteomes, revealing a nuanced interplay between topography and antimicrobial response proteins. 16S rRNA sequencing assessed microbiome dynamics, unveiling topography-specific variations in microbial composition. Surface topography alterations influenced wound proteome composition. Microbiome analysis revealed heightened diversity around rougher SMIs, emphasizing topography-dependent microbial invasion. In vitro experiments confirmed staphylococcal adhesion, growth, and biofilm formation on SMI surfaces, with increased texture correlating positively with bacterial colonization. This comprehensive investigation highlights the intricate interplay between SMI topography, wound proteome dynamics, and microbial transmission. The findings contribute to understanding host-microbe interactions on SMI surfaces, essential for optimizing clinical applications and minimizing complications in breast reconstruction.

Targeted delivery of a vaccine protein to Langerhans cells in the human skin via the C-type lectin receptor Langerin.

Human skin is a preferred vaccination site as it harbors multiple dendritic cell (DC) subsets, which display distinct C-type lectin receptors (CLR) that recognize pathogens. Antigens can be delivered to CLR by antibodies or ligands to boost antigen-specific immune responses. This concept has been established in mouse models but detailed insights into the functional consequences of antigen delivery to human skin DC in situ are sparse. In this study, we cloned and produced an anti-human Langerin antibody conjugated to the EBV nuclear antigen 1 (EBNA1). We confirmed specific binding of anti-Langerin-EBNA1 to Langerhans cells (LC). This novel LC-based vaccine was then compared to an existing anti-DEC-205-EBNA1 fusion protein by loading LC in epidermal cell suspensions before coculturing them with autologous T cells. After restimulation with EBNA1-peptides, we detected elevated levels of IFN-γ- and TNF-α-positive CD4+ T cells with both vaccines. When we injected the fusion proteins intradermally into human skin explants, emigrated skin DC targeted via DEC-205-induced cytokine production by T cells, whereas the Langerin-based vaccine failed to do so. In summary, we demonstrate that antibody-targeting approaches via the skin are promising vaccination strategies, however, further optimizations of vaccines are required to induce potent immune responses.

Specific Protein Antigen Delivery to Human Langerhans Cells in Intact Skin.

Immune modulating therapies and vaccines are in high demand, not least to the recent global spread of SARS-CoV2. To achieve efficient activation of the immune system, professional antigen presenting cells have proven to be key coordinators of such responses. Especially targeted approaches, actively directing antigens to specialized dendritic cells, promise to be more effective and accompanied by reduced payload due to less off-target effects. Although antibody and glycan-based targeting of receptors on dendritic cells have been employed, these are often expensive and time-consuming to manufacture or lack sufficient specificity. Thus, we applied a small-molecule ligand that specifically binds Langerin, a hallmark receptor on Langerhans cells, conjugated to a model protein antigen. Via microneedle injection, this construct was intradermally administered into intact human skin explants, selectively loading Langerhans cells in the epidermis. The ligand-mediated cellular uptake outpaces protein degradation resulting in intact antigen delivery. Due to the pivotal role of Langerhans cells in induction of immune responses, this approach of antigen-targeting of tissue-resident immune cells offers a novel way to deliver highly effective vaccines with minimally invasive administration.

The questionable benefit of pectus excavatum repair on cardiopulmonary function: a prospective study.

OBJECTIVES: Since the introduction of the minimally invasive technique for repair of pectus excavatum (MIRPE), increasing numbers of patients are presenting for surgery. However, controversy remains regarding cardiopulmonary outcomes of surgical repair. Therefore, the aim of our prospective study was to investigate cardiopulmonary function, at rest and during exercise before surgery, first after MIRPE and then after pectus bar removal. METHODS: Forty-seven patients were enrolled in a prospective, open-label, single-arm, single-centre clinical trial (Impact of Surgical Treatments of Thoracic Deformation on Cardiopulmonary Function) [NCT02163265] between July 2013 and November 2019. All patients underwent a modified MIRPE technique for surgical correction of pectus excavatum (PE), called Minor Open Videoendoscopically Assisted Repair of Pectus Excavatum. The patients underwent pre- and postoperative chest X-ray, three-dimensional volume-rendering computer tomography thorax imaging, cardiopulmonary function tests at rest and during stepwise cycle spiroergometry (sitting and supine position) and Doppler echocardiography. Daily physical activity questionnaires were also completed. RESULTS: The study was completed by 19 patients (15 males, 4 females), aged 13.9-19.6 years at the time of surgery. The surgical patient follow-up was 5.7 ± 7.9 months after pectus bar removal. No significant differences in cardiopulmonary and exercise parameters were seen after placement of the intrathoracic bar, or after pectus bar removal, compared to presurgery. CONCLUSIONS: Our findings indicate that surgical correction of PE does not impair cardiopulmonary function at rest or during exercise. Therefore, no adverse effects on exercise performance should be expected from surgical treatment of PE via the modified MIRPE technique. CLINICAL TRIAL REGISTRATION NUMBER: clinicaltrials.gov [ClinicalTrials.gov number, NCT02163265].

Laser-assisted epicutaneous immunization to target human skin dendritic cells.

Dendritic cells (DC) are promising targets for immunotherapy of cancer. Clinically, immunization against cancer antigens by means of the most potent antigen-presenting cells, that is DC, remains an important treatment option in combination with the modern immune checkpoint approaches. Instead of adoptively transferring in vitro monocyte-derived DC, they can also be loaded in situ by antibody-mediated targeting of antigen. Conventionally, these vaccines are delivered by classical intradermal injections. Here, we tested an alternative approach, namely laser-assisted epicutaneous immunization. With an infrared laser ("Precise Laser Epidermal System"/P.L.E.A.S.E.® Laser System), we created micropores in human skin and applied monoclonal antibodies (mAbs) against C-type lectins, for example DEC-205/CD205 and Langerin/CD207. Optimal parameters for formation of pores in epidermis and dermis were determined. We could induce pores of defined depths without enhanced apoptosis around them. Antibodies applied epicutaneously to the laser-porated skin could be detected both in Langerhans cells (LC) in situ in the epidermis and in migratory skin DC subsets from short term human skin explant culture, demonstrating uptake and transport of Langerin and DEC-205 mAbs. Efficacy of targeting was similar between the different laser treatments and pore depths. Thus, laser-assisted epicutaneous immunization may be a valuable alternative to intradermal injection, yet the loading efficacy of DC needs to be further improved.

Impact of surgical treatment of pectus carinatum on cardiopulmonary function: a prospective study.

OBJECTIVES: The frequency of sternochondroplasty in cases of pectus carinatum (PC) has increased due to greater surgeon experience and modified surgical techniques. PC deformity does not usually cause cardiopulmonary malfunction or impairment. However, whether cardiopulmonary function changes after surgical repair remains a matter of controversy. The aim of our prospective study was to determine if surgery changes preoperative cardiopulmonary function. METHODS: Nineteen patients (16 males, 3 females) were enrolled in a prospective, open-label, single-arm, single-centre clinical trial (Impact of Surgical Treatments of Thoracic Deformation on Cardiopulmonary Function) (NCT02163265) between July 2013 and January 2017. All patients underwent PC repair via a modified Ravitch procedure and wore a lightweight, patient-controlled chest brace for 8 weeks postoperatively (the Innsbruck protocol). The average follow-up surgical examination was 8.3 months after surgery. In all enrolled patients, before surgery and not before 6 months postoperatively chest X-ray, 3-dimensional volume-rendered computed tomography thorax imaging, cardiopulmonary function tests with stepwise cycle spiroergometry (sitting and supine position) and Doppler echocardiography were performed; questionnaires about daily physical activity were also completed. RESULTS: Fourteen patients (aged 16.3 ± 2.6 years at study entry) completed the study. Changes in submaximal and peak power output were not detected during sitting, or when in the supine position. Also, no clinically relevant postoperative changes in spirometry or echocardiography were noted. CONCLUSIONS: Our findings confirm that surgical correction of PC does not impair cardiopulmonary function at rest or during physical exercise. CLINICAL REGISTRATION NUMBER: clinicaltrials.gov NCT02163265.

The effect on cardiopulmonary function after thoracoplasty in pectus carinatum: a systematic literature review.

OBJECTIVES: Creating an aesthetically appealing result using thoracoplasty, especially when correcting extensive deformities, but only causing low morbidity, is challenging. The frequency of thoracoplasties in cases of pectus carinatum (PC) has increased due to improved experience and modified surgical techniques, resulting in low morbidity and low complication rates. The indications for surgical treatment are still controversial and, in most cases, remain aesthetic or psychological rather than physiological. However, whether cardiopulmonary function changes after surgical repair remains a matter of controversy. We sought to investigate and shed light on published knowledge regarding this question. METHODS: We searched MEDLINE and PubMed databases, using various defined search phrases and inclusion criteria, to identify articles on pre- and postoperative cardiopulmonary evaluation and outcomes. RESULTS: Six studies met the inclusion criteria: 5 studies evaluated patients with PC for cardiopulmonary outcomes after chest wall surgery and 1 did so following conservative compression treatment. In these studies, surgical and conservative correction of PC did not reduce absolute lung volumes and spirometric measurements and consequently had no pathogenic effect on cardiopulmonary function. CONCLUSIONS: The results of this systematic review suggest that surgical correction of PC has no symptomatic pathogenic effect on cardiopulmonary function. The results, however, revealed both heterogeneity in the examinations used and inconsistent methods within each study. Further prospective trials with a stronger methodological design are necessary to objectively confirm that surgical correction of PC does not impair cardiopulmonary function.

Complications Related to Pectus Carinatum Correction: Lessons Learned from 15 Years' Experience. Management and Literature Review.

BACKGROUND: Various methods of corrective thoracoplasty for pectus carinatum deformity have been described, but to date no studies describe a review of complications and how to manage them. Complications are dependent not only on the technique used and the patient's age, but also on the experience of the treating surgeon. The authors present their 15 years' experience with surgical correction of pectus carinatum and the complications that have occurred. A literature review regarding complications with pectus carinatum surgery is performed. METHODS: A retrospective review of 95 patients (mean age, 19 years) was performed. One hundred four surgical procedures for repair of pectus carinatum were performed from July of 2000 to July of 2015 using a modified Ravitch technique, bioabsorbable material, postoperative bracing, and in some cases a diced rib cartilage graft technique. Intraoperative and postoperative complications were evaluated. RESULTS: The mean patient follow-up was 13.6 months (range, 4 months to 9.75 years). Intraoperative complications were pleura lesion and laceration of the internal mammary vein. Postoperative complications were recurrent mild protrusion, persistent protrusion of one or two costal cartilages, minor wound healing delay, skin ulcer, hypertrophic scar, transient intercostal dysesthesia, marginal pneumothorax, seroma, meningitis, and epidural hematoma. CONCLUSIONS: In our reported series of pectus carinatum repair, increasing experience and progressively less extensive techniques have resulted in fewer complications, low morbidity, and early return to activity. Complications were observed in the early period of application, predominantly because of a lack of experience, and usually subsided with increasing numbers of patients and frequency of surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.