In vitro model assesses the susceptibility of polymeric scaffolds for material-driven heart valve regeneration to calcification

In Vitro Model. 2025 Jul 15;4(2):157-175. doi: 10.1007/s44164-025-00090-x. eCollection 2025 Aug.

ABSTRACT

PURPOSE: Material driven in situ heart valve tissue engineering (HVTE) prospects an alternative to non-living replacements. HVTE exploits bioresorbable (synthetic) scaffolds that guide neo-tissue formation. Proper scaffold design assesses and mitigates potential material-related risks, such as calcific nodule formation. Herein, we establish an in vitro model to investigate the calcification risk of materials for HVTE.

METHODS: Calcification was studied by culturing 3D scaffolds with porcine valvular interstitial cells in a phosphate-enhanced calcification medium (CM) for 3 weeks. The model was applied by testing three electrospun polymeric Tissue engineering (TE) scaffolds (PCL, PCL-BU, and PC-BU) against a bovine pericardial patch control. Additionally, the model included a 10% cyclic strain environment to evaluate hemodynamic effects.

RESULTS: TE constructs showed significantly less calcification compared to the pericardial tissue control, mirroring in vivo animal model findings. No differences in calcification were observed among the TE constructs, and cyclic strain did not affect calcification.

CONCLUSION: The 3D in vitro model established in this study effectively mimics calcification in TE material constructs, aiding in systematic testing and comparison of cardiovascular TE materials. It can help understand calcification principles and evaluate potential risk factors (e.g., strain). As such, the model will support the design of biomaterials for in situ HVTE in particular and implantable polymer grafts in general.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s44164-025-00090-x.

PMID:40708815 | PMC:PMC12283539 | DOI:10.1007/s44164-025-00090-x

Bovine pericardial patch with reduced crosslinking time preserves matrix integrity and mitigates calcification in rat subcutaneous tissue

Cell Tissue Bank. 2025 Aug 27;26(3):37. doi: 10.1007/s10561-025-10188-x.

ABSTRACT

Prosthetic valves derived from bovine pericardium (BP) are crucial for heart valve replacement, yet current crosslinking methods with glutaraldehyde can lead to immune responses and calcification. This study evaluated the effects of reducing the glutaraldehyde crosslinking time from 10 to 5 days in bovine pericardial patches for use as heart valve substitutes. In addition to examining the physical properties of the BP, the study analyzed the biocompatibility, tissue structure, and calcification of the pericardial tissue. BPs were processed using two protocols based on the fixation time with glutaraldehyde: BP10d (10 days) and BP5d (5 days). All samples were treated with glutamic acid to neutralize residual aldehyde groups from the glutaraldehyde. Subsequently, the resulting material was assessed for mechanical and thermal properties and histologically using light and scanning electron microscopy. Post-implantation histological evaluation and calcium content determination were conducted after 7, 14, 30, 60 and 120 days. The calcification was a rare occurrence. However, some samples from the BP10d group displayed positive Von Kossa staining, indicating mineral deposition. Chemical analysis using ICP-OES revealed low calcium concentrations in the explants of both groups, with higher concentrations observed in the BP10d group during the later analysis periods. Mechanical and thermal stability assessments showed no significant differences between experimental groups. Histological examination revealed more collagen and elastic fibers deformation, and inflammation in the BP10d group compared to the BP5d group. The revised manufacturing protocol, with a 5-day fixation time, showed promising anti-calcifying activity, biocompatibility, and tissue preservation.

PMID:40864226 | DOI:10.1007/s10561-025-10188-x

A Self-Generated Electricity-Driven Sclera reinforcement bionic piezoelectric patch for Management of High Myopia

J Nanobiotechnology. 2025 Jul 1;23(1):470. doi: 10.1186/s12951-025-03493-w.

ABSTRACT

BACKGROUND: High myopia (HM) is a progressive ocular condition characterized by excessive axial elongation and severe refractive errors, often leading to sight-threatening complications. The underlying pathological driver of HM is the weakening of scleral biomechanics, making the sclera a key therapeutic target. While posterior scleral reinforcement (PSR) has been established as an effective intervention to strengthen the sclera, currently available PSR materials often fail to fully meet clinical demands.

RESULTS: Inspired by the electric eel, which generates surface electrolytes to facilitate electric discharge and influence interactions with its surroundings, we developed a biomimetic piezoelectric patch (BPP@PVDF) for HM treatment. This patch integrates a bovine pericardium (BPP) scaffold with a piezoelectric polyvinylidene fluoride (PVDF) film, endowing the BPP with electrical properties and improved cell adhesion. Through electrical activation, the BPP enhances scleral mechanical strength and promotes collagen synthesis, effectively mitigating axial elongation in myopia.

CONCLUSIONS: Both in vitro and in vivo experiments demonstrate that our precisely designed patch provided a stable and effective solution for reducing progressive axial elongation in HM. By leveraging nanotechnology, electrical stimulation, and scleral reinforcement surgery, this study offers a groundbreaking approach with significant implications for both scientific research and clinical practice. Our strategy paves the way for enhanced surgical outcomes in HM treatment, offering a promising avenue for future therapeutic advancements.

PMID:40598551 | PMC:PMC12211304 | DOI:10.1186/s12951-025-03493-w

Trimethylamine N-oxide drives bioprosthetic heart valve calcification via macrophage pyroptosis in juvenile rats

Cardiovasc Pathol. 2025 Jul 4;79:107750. doi: 10.1016/j.carpath.2025.107750. Online ahead of print.

ABSTRACT

Bioprosthetic heart valves (BHVs) constructed from bovine pericardium (BP) are widely used in valve replacement due to their favorable biocompatibility. However, early structural degeneration, particularly in younger recipients, remains a critical challenge, primarily driven by calcification. Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite elevated by high-choline diets, has been implicated in vascular and valvular calcification, but its role in BHV deterioration remains unclear. This study aimed to evaluate the effects of TMAO on BP calcification. Three-week-old Sprague-Dawley rats were assigned to six diet groups: Normal Chow Diet (NCD), High Choline Diet (HCD), High Fat Diet (HFD), combined High Fat and Choline Diet (HFD+HCD), HFD with TMAO supplementation (HFD+TMAO), and HFD with both HCD and the TMAO inhibitor 3,3-dimethyl-1-butanol (DMB). BHVs made of BP were implanted subcutaneously, and after 8 weeks, we assessed calcium deposition, osteogenic markers, plasma metabolites, inflammatory cytokines, inflammatory cell proportions, and macrophage pyroptosis using techniques such as colorimetry, immunohistochemistry, ELISA, flow cytometry, and immunofluorescence. In vitro, RAW264.7 macrophages were exposed to TMAO, and pyroptosis was assessed by Western blotting, ELISA, and electron microscopy. Results indicated that HCD and HFD significantly increased BP calcification, osteogenic marker expression, and inflammatory responses in BHVs. The HFD+HCD and HFD+TMAO groups exhibited pronounced calcific and inflammatory effects, which were reduced by DMB. In vitro, TMAO induced macrophage pyroptosis, contributing to calcification. These findings suggest that TMAO promotes BP calcification through pyroptosis-driven inflammation, and that targeting TMAO via dietary or microbial modulation may offer a promising strategy to improve BHV durability, particularly in young patients.

PMID:40619044 | DOI:10.1016/j.carpath.2025.107750

Delayed recurrence of complete atrioventricular block following ablation for premature ventricular complexes

A 77-year-old man was admitted for catheter ablation due to frequent premature ventricular complexes (PVCs). Activation mapping revealed that the earliest ventricular activation during the PVC was recorded on …  Read More

Delayed Cardiac Partial Herniation after Right-sided Pneumonectomy:Report of a Case

Kyobu Geka. 2025 Aug;78(8):626-629.

ABSTRACT

Cardiac herniation is a rare complication after pulmonary surgery. A 59-year-old woman underwent right-sided pneumonectomy for right pulmonary squamous cell carcinoma, pulmonary vein was ligated intrapericardialy and the pericardial defect, which mesasured about 2 cm was not repaired. After four months, the patient complained of bilateral lower leg edema and dyspnea on effort. Computed tomography (CT) showed the right atrial herniation into the right-sided thoracic cavity. We diagnosed with symptomatic cardiac herniation and performed opration with small thoracotomy. At operation it was found that the right atrium herniated into the right-sided thoracic cavity. There were no adhesions between the pericardium and the right atrium. We placed the right atrium back within the pericardium and repaired using a bovine pericardial patch. The postoperative course was uneventful. Bilateral lower leg edema and cardiac herniation disappeared. Cardiac herniation did not recur over four years postoperatively.

PMID:40840886