The importance of mechanical and biological cues of tympanic membrane grafts to ensure optimal regeneration.

Chronic suppurative otitis media (CSOM) is often associated with permanent tympanic membrane (TM) perforation and conductive hearing loss. The current clinical gold standard, using autografts and allografts, suffers from several drawbacks. Artificial replacement materials can help to overcome these drawbacks. Therefore, scaffolds fabricated through digital light processing (DLP) were herein created to support TM regeneration. Various UV-curable printing inks, including gelatin methacryloyl (GelMA), gelatin-norbornene-norbornene (GelNBNB) (crosslinked with thiolated gelatin (GelSH)) and alkene-functionalized poly-ε-caprolactone (E-PCL) (crosslinked with pentaerythritol tetrakis(3-mercaptopropionate) (PETA4SH)) were optimized regarding photo-initiator (PI) and photo-absorber (PA) concentrations through viscosity characterization, photo-rheology and the establishment of working curves for DLP. Our material platform enabled the development of constructs with a range of mechanical properties (plateau storage modulus varying between 15 and 119 kPa). Excellent network connectivity for the GelNBNB and E-PCL constructs was demonstrated (gel fractions >95 %) whereas a post-crosslinking step was required for the GelMA constructs. All samples showed excellent biocompatibility (viability >93 % and metabolic activity >88 %). Finally, in vivo and ex vivo assessments, including histology, vibration and deformation responses measured through laser doppler vibrometry and digital image correlation respectively, were performed to investigate the effects of the scaffolds on the anatomical and physiological regeneration of acute TM perforations in rabbits. The data showed that the most efficient healing with the best functional quality was obtained when both mechanical (obtained with the PCL-based resin) and biological (obtained with the gelatin-based resins) material properties were taken into account.

Dermal Nipple-Areola Complex Perfusion through Circumareolar Scars: A Delay Model in Two-Stage Nipple-Sparing Mastectomy.

BACKGROUND: Nipple-sparing mastectomy (NSM) has evolved as a standard surgical option. The NSM complication rate remains high in large breasts. To reduce the risk of necrosis, several authors have proposed delayed procedures to enhance blood supply to the nipple-areola complex (NAC). The purpose of this study in a porcine model was to show adequate redirection of NAC perfusion by neoangiogenesis through circumareolar scars. METHODS: Delayed two-staged NSM was simulated in 52 nipples (six pigs) with a 60-day interval. The nipples underwent a full-thickness, circumareolar incision onto the muscular fascia, with preservation of underlying glandular perforators. After 60 days, NSM was performed through a radial incision. A silicone sheet was introduced in the mastectomy plane to prevent NAC revascularization by wound bed imbibition. Digital color imaging was used to assess necrosis. Near-infrared fluorescence with indocyanine green was used to assess perfusion patterns and perfusion in real time. RESULTS: No NAC necrosis was seen after 60 days' delay in any nipples. In all nipples, indocyanine green angiography showed complete alteration of the NAC vascular perfusion pattern from subjacent gland to a capillary fill following devascularization, exhibiting a predominant arteriolar capillary blush without distinct larger vessels. CONCLUSIONS: NAC delay reverses glandular perfusion to adequate dermal neovascularization. Neovascularization through full-thickness scars provides sufficient dermal perfusion after 60 days' delay. Identical staged delay in humans may be a surgically safe NSM option and could broaden therapeutic NSM indications in difficult breasts. Large clinical trials are necessary to provide identical results in human breasts. CLINICAL RELEVANCE STATEMENT: NAC delay reverses glandular perfusion to adequate dermal neovascularization. Neovascularization through full-thickness scars provides sufficient dermal perfusion after 60 days of delay. Identical staged delay in humans may be a surgically safe NSM option.

Sterile Pericarditis in Aachener Minipigs As a Model for Atrial Myopathy and Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia caused by structural remodeling of the atria, also called atrial myopathy. Current therapies only target the electrical abnormalities and not the underlying atrial myopathy. For the development of novel therapies, a reproducible large animal model of atrial myopathy is necessary. This paper presents a model of sterile pericarditis-induced atrial myopathy in Aachener minipigs. Sterile pericarditis was induced by spraying sterile talcum and leaving a layer of sterile gauze over the atrial epicardial surface. This led to inflammation and fibrosis, two crucial components of the pathophysiology of atrial myopathy, making the atria susceptible to the induction of AF. Two pacemaker electrodes were positioned epicardially on each atrium and connected to two pacemakers from different manufacturers. This strategy allowed for repeated non-invasive atrial programmed stimulation to determine the inducibility of AF at specified time points after surgery. Different protocols to test AF inducibility were used. The advantages of this model are its clinical relevance, with AF inducibility and the rapid induction of inflammation and fibrosis-both present in atrial myopathy-and its reproducibility. The model will be useful in the development of novel therapies targeting atrial myopathy and AF.