Pathological Mineralization Research Articles

Lipids and Minerals, Interplay in Biomineralization: Nature's Alchemy.

The main focus of this article is the role of lipids in biomineralization. Much of the discussion on biomineralization focuses on proteins in these decades. Indeed, collagen and acidic noncollagenous proteins effectively serve as templates for mineralization. However, other macromolecules such as lipids and polysaccharides have received less attention despite their abundance at mineralization sites. The matrix vesicle (MV) theory is widely accepted as the induction of early mineralization. Although ion concentration within the vesicles has been discussed in the initial mineralization in this theory, the role of phospholipids that constitute the vesicle membrane has not been discussed much. Comprehensive considerations, including pathological mineralization, exist regardless of the localization of MVs, the involvement of bacteria in dental calculus formation, and biomineralization caused by marine organisms such as corals, suggesting that initial mineralization found in these biological conditions might be a common reaction relating to lipids. In contrast, despite the abundance of lipids, mineralization occurs only in the limited tissue within our body. In other words, gathering knowledge and creating a path to understanding about lipid-based mineralization is extremely important in proposing new bone disease treatment methods. This article describes how lipids influence nucleation, mineralization, and expansion during hard tissue formation.

A new perspective on intervertebral disc calcification-from bench to bedside.

Disc degeneration primarily contributes to chronic low back and neck pain. Consequently, there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis, ectopic calcification, herniation, or mixed phenotypes. Amongst these phenotypes, disc calcification is the least studied. Ectopic calcification, by definition, is the pathological mineralization of soft tissues, widely studied in the context of conditions that afflict vasculature, skin, and cartilage. Clinically, disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment. It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics: hypertrophic chondrocyte-like cell differentiation; TNAP, ENPP1, and ANK upregulation; cell death; altered Pi and PPi homeostasis; and local inflammation. Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype. It is essential to recognize that the presentation and nature of mineralization differ between AF, NP, and EP compartments. Moreover, the combination of anatomic location, genetics, and environmental stressors, such as aging or trauma, govern the predisposition to calcification. Lastly, the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis, along with disc cell death and differentiation status. While there is limited understanding of this phenotype, understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.

Application of a calcium and phosphorus biomineralization strategy in tooth repair: a systematic review.

Biomineralization is a natural process in which organisms regulate the growth of inorganic minerals to form biominerals with unique layered structures, such as bones and teeth, primarily composed of calcium and phosphorus. Tooth decay significantly impacts our daily lives, and the key to tooth regeneration lies in restoring teeth through biomimetic approaches, utilizing mineralization strategies or materials that mimic natural processes. This review delves into the types, properties, and transformations of calcium and phosphorus minerals, followed by an exploration of the mechanisms behind physiological and pathological mineralization in living organisms. It summarizes the mechanisms and commonalities of biomineralization and discusses the advancements in dental biomineralization research, guided by insights into calcium and phosphorus mineral biomineralization. This review concludes by addressing the current challenges and future directions in the field of dental biomimetic mineralization.

Проточная ячейка для исследования кристаллизации на подложках

Recently, a flow-type cell has been innovatively designed for the detailed study of the precipitation process on various substrates. This unique cell allows the manipulation of critical parameters involved in biomineralization processes. Notably, the cell design permits 3D printing in a standard lab setup. It is equipped with transparent windows that enable the use of ex situ techniques to analyze precipitates once they have been extracted from the cell due to its convenient disassembling feature. Furthermore, the cell supports in situ methods of studying such as optical microscopy and X-ray diffraction. Two versions of the cell are available: one with passive mixing and the other with active mixing of reactant solutions. Through the case study focusing on the biomimetic precipitation of calcium carbonate on eggshell membranes, the cell demonstrated its functionality by enabling the precipitation of vaterite and calcite mixtures with changes in CaCO3 polymorph ratios depending on the mixing mode. This versatile cell is not limited to studying calcium carbonate; it can be used to investigate the precipitation of various other substances. It holds potential for modeling biomineral formation processes and pathological mineral formation in organisms. Additionally, the cell can be adapted for the study of antisolvent and other precipitation techniques.

Effect of ambient gas and crystal features on Doppler ultrasound twinkling of pathological mineralizations.

Color Doppler twinkling on kidney stones and other pathological mineralizations is theorized to arise from stable microbubbles, which suggests twinkling will be sensitive to ambient gas. Here, lab-grown cholesterol, calcium phosphate, and uric acid crystals were imaged with ultrasound in water while varying oxygen, carbon dioxide, and nitrogen levels. Twinkling was found to increase on cholesterol in elevated oxygen, cholesterol and calcium phosphate in elevated carbon dioxide, and no crystals in elevated nitrogen. These results support the crevice microbubble theory of twinkling and suggest gases may be varied to enhance twinkling on some mineralizations.

Annexin A5 stabilizes matrix vesicle-biomimetic lipid membranes: unravelling a new role of annexins in calcification

Matrix vesicles are a special class of extracellular vesicles thought to actively contribute to both physiologic and pathologic mineralization. Proteomic studies have shown that matrix vesicles possess high amounts of annexin A5, suggesting that the protein might have multiple roles at the sites of calcification. Currently, Annexin A5 is thought to promote the nucleation of apatitic minerals close to the inner leaflet of the matrix vesicles’ membrane enriched in phosphatidylserine and Ca2+. Herein, we aimed at unravelling a possible additional role of annexin A5 by investigating the ability of annexin A5 to adsorb on matrix-vesicle biomimetic liposomes and Langmuir monolayers made of dipalmitoylphosphatidylserine (DPPS) and dipalmitoylphosphatidylcholine (DPPC) in the absence and in the presence of Ca2+. Differential scanning calorimetry and dynamic light scattering measurements showed that Ca2+ at concentrations in the 0.5–2.0 mM range induced the aggregation of liposomes probably due to the formation of DPPS-enriched domains. However, annexin A5 avoided the aggregation of liposomes at Ca2+ concentrations lower than 1.0 mM. Surface pressure versus surface area isotherms showed that the adsorption of annexin A5 on the monolayers made of a mixture of DPPC and DPPS led to a reduction in the area of excess compared to the theoretical values, which confirmed that the protein favored attractive interactions among the membrane lipids. The stabilization of the lipid membranes by annexin A5 was also validated by recording the changes with time of the surface pressure. Finally, fluorescence microscopy images of lipid monolayers revealed the formation of spherical lipid-condensed domains that became unshaped and larger in the presence of annexin A5. Our data support the model that annexin A5 in matrix vesicles is recruited at the membrane sites enriched in phosphatidylserine and Ca2+ not only to contribute to the intraluminal mineral formation but also to stabilize the vesicles’ membrane and prevent its premature rupture.

Gene Expression Analyses in Models of Rosiglitazone-Induced Physiological and Pathological Mineralization Identify Novel Targets to Improve Bone and Vascular Health.

Clinical studies revealed detrimental skeletal and vascular effects of the insulin sensitizer rosiglitazone. We have shown earlier that rosiglitazone accelerates osteoblast differentiation from human mesenchymal stem cells (hMSC) at the expense of increased oxidative stress and cell death. In calcifying human vascular cells, rosiglitazone stimulates pathological mineralization, an effect diminished by the antioxidant resveratrol. Here, we aimed to elucidate transcriptional networks underlying the rosiglitazone-enhanced mineralization phenotype. We performed genome-wide transcriptional profiling of osteogenic hMSCs treated with rosiglitazone for short-term periods of 1 up to 48 h during the first two days of differentiation, a phase that we show is sufficient for rosiglitazone stimulation of mineralization. Microarray-based mRNA expression analysis revealed 190 probes that were differently expressed in at least one condition compared to vehicle-treated control. This rosiglitazone gene signature contained well-known primary PPAR targets and was also endogenously regulated during osteogenic hMSC differentiation and osteoblast-like differentiation of vascular smooth muscle cells (VSMCs) into calcifying vascular cells (CVCs). Comparative analysis revealed rosiglitazone targets that were commonly enriched in osteoblasts and CVCs or specifically enriched in either osteoblasts or CVCs. Finally, we compared expression patterns of CVC-specific genes with patient expression data from carotid plaque versus intact adjacent tissue, and identified five rosiglitazone targets to be differentially regulated in CVCs and carotid plaque but not osteoblasts when compared to their non-mineralizing counterparts. These targets, i.e., PDK4, SDC4, SPRY4, TCF4 and DACT1, may specifically control extracellular matrix mineralization in vascular cells, and hence provide target candidates for further investigations to improve vascular health.

The Biomineralization Conundrum of Calcified Extraradicular Deposits on the Apical Root Surface of Teeth: A Case Report

Background: Calcified extraradicular deposits on the apical root surface of teeth (CEDARST) are rarely seen in the dental field, compared with dental calculus deposits, which are very frequent. However, the exact biomineralization process of this entity has remained unclear until now. Objective: To report a case of an exuberant calcified extraradicular deposit on the apical root surface of an anterior tooth with apical periodontitis and propose for the first time some potential mechanisms involved in this pathological mineralization, and thereby suggest directions for future research. Case Presentation: In brief, a root-canal-treated canine displaying a radiographic periapical radiolucency was treated, and the sinus tract persisted despite root canal retreatment in which high endodontic standards were maintained. Endodontic surgery was performed, and the curettage of the pathologic tissue revealed an exuberant calculus-like material attached to the outer root surface, around the exit of the apical foramen. Two-year follow-up radiography revealed complete bone healing, and the patient´s tooth was asymptomatic and functional. Conclusion: The development of CEDARST seems to depend on a fine synergic control exerted by specific microorganisms (mainly bacteria) on this pathological mineralization, as well as on the local chemical microenvironment of the apical lesion of the affected tooth. Microbial implications and inhibitors of mineralization seem to play a dominant role in CEDARST biomineralization.

Recurrence of follicular dendritic cell sarcoma in tonsils after 7 years: a rare case report

Dystrophic calcifications are pathological mineral precipitates which occur in degenerative or dead tissue, despite normal serum calcium and phosphate levels, mostly seen in subcutaneous tissues secondary to infection or trauma. Chronic inflammation of the tonsils may lead to the formation of calcifications called tonsilloliths. The prevalence amongst the population is 2% to 16%, in age groups ranging from 10 years to 77 years of age, with a male/female ratio of 1:1. These calcifications display radiopaque images that are single or multiple, round or irregular, unilateral or bilateral and are superimposed upon the mandibular ramus. Computed tomography (CT) can be the investigation of choice for definitive diagnosis. The treatment of tonsilloliths is dependent on the size and presence of symptoms. It’s preferable to remove a single, large tonsillolith, as they can cause recurrent episodes of tonsillitis. Usually manual compression, curettage or a simple incision to release the calcified body should suffice for the relief. In case of numerous tonsilloliths, an attempt to remove them individually is not a feasible approach. Hence, bilateral tonsillectomy is opted.

Bone-matrix mineralization dampens integrin-mediated mechanosignalling and metastatic progression in breast cancer.

In patients with breast cancer, lower bone mineral density increases the risk of bone metastasis. Although the relationship between bone-matrix mineralization and tumour-cell phenotype in breast cancer is not well understood, mineralization-induced rigidity is thought to drive metastatic progression via increased cell-adhesion forces. Here, by using collagen-based matrices with adjustable intrafibrillar mineralization, we show that, unexpectedly, matrix mineralization dampens integrin-mediated mechanosignalling and induces a less proliferative stem-cell-like phenotype in breast cancer cells. In mice with xenografted decellularized physiological bone matrices seeded with human breast tumour cells, the presence of bone mineral reduced tumour growth and upregulated a gene-expression signature that is associated with longer metastasis-free survival in patients with breast cancer. Our findings suggest that bone-matrix changes in osteogenic niches regulate metastatic progression in breast cancer and that in vitro models of bone metastasis should integrate organic and inorganic matrix components to mimic physiological and pathologic mineralization.

Physicochemical understanding of biomineralization by molecular vibrational spectroscopy: From mechanism to nature.

The process and mechanism of biomineralization and relevant physicochemical properties of mineral crystals are remarkably sophisticated multidisciplinary fields that include biology, chemistry, physics, and materials science. The components of the organic matter, structural construction of minerals, and related mechanical interaction, etc., could help to reveal the unique nature of the special mineralization process. Herein, the paper provides an overview of the biomineralization process from the perspective of molecular vibrational spectroscopy, including the physicochemical properties of biomineralized tissues, from physiological to applied mineralization. These physicochemical characteristics closely to the hierarchical mineralization process include biological crystal defects, chemical bonding, atomic doping, structural changes, and content changes in organic matter, along with the interface between biocrystals and organic matter as well as the specific mechanical effects for hardness and toughness. Based on those observations, the special physiological properties of mineralization for enamel and bone, as well as the possible mechanism of pathological mineralization and calcification such as atherosclerosis, tumor micro mineralization, and urolithiasis are also reviewed and discussed. Indeed, the clearly defined physicochemical properties of mineral crystals could pave the way for studies on the mechanisms and applications.

A crystallin mutant cataract with mineral deposits

Connexin mutant mice develop cataracts containing calcium precipitates. To test whether pathologic mineralization is a general mechanism contributing to the disease, we characterized the lenses from a nonconnexin mutant mouse cataract model. By cosegregation of the phenotype with a satellite marker and genomic sequencing, we identified the mutant as a 5-bp duplication in the γC-crystallin gene (Crygcdup). Homozygous mice developed severe cataracts early, and heterozygous animals developed small cataracts later in life. Immunoblotting studies showed that the mutant lenses contained decreased levels of crystallins, connexin46, and connexin50 but increasedlevels of resident proteins of the nucleus, endoplasmic reticulum, and mitochondria. The reductions in fiber cell connexins were associated with a scarcity of gap junction punctae as detected by immunofluorescence and significant reductions in gap junction-mediated coupling between fiber cells in Crygcdup lenses. Particles that stained with the calcium deposit dye, Alizarin red, were abundant in the insoluble fraction from homozygous lenses but nearly absent in wild-type and heterozygous lens preparations. Whole-mount homozygous lenses were stained with Alizarin red in the cataract region. Mineralized material with a regional distribution similar to the cataract was detected in homozygous lenses (but not wild-type lenses) by micro-computed tomography. Attenuated total internal reflection Fourier-transform infrared microspectroscopy identified the mineral as apatite. These results are consistent with previous findings that loss of lens fiber cell gap junctional coupling leads to the formation of calcium precipitates. They also support the hypothesis that pathologic mineralization contributes to the formation of cataracts of different etiologies.

Zebrafish Models to Study Ectopic Calcification and Calcium-Associated Pathologies.

Ectopic calcification refers to the pathological accumulation of calcium ions in soft tissues and is often the result of a dysregulated action or disrupted function of proteins involved in extracellular matrix mineralization. While the mouse has traditionally been the go-to model organism for the study of pathologies associated with abnormal calcium deposition, many mouse mutants often have exacerbated phenotypes and die prematurely, limiting the understanding of the disease and the development of effective therapies. Since the mechanisms underlying ectopic calcification share some analogy with those of bone formation, the zebrafish (Danio rerio)-a well-established model for studying osteogenesis and mineralogenesis-has recently gained momentum as a model to study ectopic calcification disorders. In this review, we outline the mechanisms of ectopic mineralization in zebrafish, provide insights into zebrafish mutants that share phenotypic similarities with human pathological mineralization disorders, list the compounds capable of rescuing mutant phenotypes, and describe current methods to induce and characterize ectopic calcification in zebrafish.

The effect of crystal composition and environment on the color Doppler ultrasound twinkling artifact

Objective. Pathological mineralizations form throughout the body and can be difficult to detect using conventional imaging methods. Color Doppler ultrasound twinkling highlights ∼60% of kidney stones with a rapid color shift and is theorized to arise from crevice microbubbles as twinkling disappears on kidney stones at elevated pressures and scratched acrylic balls in ethanol. Twinkling also sometimes appears on other pathological mineralizations; however, it is unclear whether the etiology of twinkling is the same as for kidney stones. Approach. In this study, five cholesterol, calcium phosphate, and uric acid crystals were grown in vitro and imaged in Doppler mode with a research ultrasound system and L7-4 transducer in water. To evaluate the influence of pressure on twinkling, the same crystals were imaged in a high-pressure chamber. Then, the effect of surface tension on twinkling was evaluated by imaging crystals in different concentrations of surfactant (1%, 2%, 3%, 4%) and ethanol (10%, 30%, 50%, 70%), artificial urine, bovine blood, and a tissue-mimicking phantom. Main results. Results showed that all crystals twinkled in water, with cholesterol twinkling significantly more than calcium phosphate and uric acid. When the ambient pressure was increased, twinkling disappeared for all tested crystals when pressures reached 7 MPa (absolute) and reappeared when returned to ambient pressure (0.1 MPa). Similarly, twinkling across all crystals decreased with surface tension when imaged in the surfactant and ethanol (statistically significant when surface tension <22 mN m−1) and decreased in blood (surface tension = 52.7 mN m−1) but was unaffected by artificial urine (similar surface tension to water). In the tissue-mimicking phantom, twinkling increased for cholesterol and calcium phosphate crystals with no change observed in uric acid crystals. Significance. Overall, these results support the theory that bubbles are present on crystals and cause twinkling, which could be leveraged to improve twinkling for the detection of other pathological mineralizations.

The pathophysiology and management of vascular calcification in chronic kidney disease patients

ABSTRACT Introduction Vascular calcification (VC) which is the pathological mineral deposition in the vascular system, predominantly at the intimal and medial layer of the vessel wall, is an important comorbidity in patients with chronic kidney disease (CKD) leading to significant morbidity and mortality while necessitating appropriate treatment. Our review aims to provide an in-depth analysis of the current understanding of VC. Areas covered In this review, we first discuss the pathophysiology of VC in CKD patients, then we explain the methods to predict and assess VC. Afterwards, we provide the currently available as well as the potential therapeutic approaches of VC. We finally discuss our understanding regarding the current situation surrounding VC in our expert opinion section. Expert opinion Predicting, assessing and treating VC is crucial and the future advances in the field of research surrounding VC will potentially occur in one or more of these three areas of clinical management. There is a current lack of evidence and consensus regarding specific therapeutic options for alleviating VC and this situation may not necessitate VC to be determined, detected, and documented before the available options are implemented. Regardless, the prediction and assessment of VC is still important and requires further improvement together with the developments in therapeutic alternatives. The future has the potential to bring better research which would guide and improve the management of this patient group. A more specialized approach consisting of targeted therapies and more tailored management plans for patients with CKD and VC is on the horizon.

Heterotopic mineral deposits in intact rat Achilles tendons are characterized by a unique fiber-like structure

Heterotopic mineralization entails pathological mineral formation inside soft tissues. In human tendons mineralization is often associated with tendinopathies, tendon weakness and pain. In Achilles tendons, mineralization is considered to occur through heterotopic ossification (HO) primarily in response to tendon pathologies. However, refined details regarding HO deposition and microstructure are unknown. In this study, we characterize HO in intact rat Achilles tendons through high-resolution phase contrast enhanced synchrotron X-ray tomography. Furthermore, we test the potential of studying local tissue injury by needling intact Achilles tendons and the relation between tissue microdamage and HO. The results show that HO occurs in all intact Achilles tendons at 16 weeks of age. HO deposits are characterized by an elongated ellipsoidal shape and by a fiber-like internal structure which suggests that some collagen fibers have mineralized. The data indicates that deposition along fibers initiates in the pericellular area, and propagates into the intercellular area. Within HO deposits cells are larger and more rounded compared to tenocytes between unmineralized fibers, which are fewer and elongated. The results also indicate that multiple HO deposits may merge into bigger structures with time by accession along unmineralized fibers. Furthermore, the presence of unmineralized regions within the deposits may indicate that HOs are not only growing, but mineral resorption may also occur. Additionally, phase contrast synchrotron X-ray tomography allowed to distinguish microdamage at the fiber level in response to needling. The needle injury protocol could in the future enable to elucidate the relation between local inflammation, microdamage, and HO deposition.

Progress in the regulation of pathological crystallization

The regulation of pathological crystallization had made great progress during the last two decades. The inhibitor of pathological mineralization and its mechanisms are overviewed.

In grapevine decline, microbiomes are affected differently in symptomatic and asymptomatic soils

Grapevine decline affects viticulture worldwide. It is caused by a wide range of individual and combined biotic and abiotic factors. Some declines remain unexplained because they are not associated with known pathological symptoms or mineral dysregulation. Vineyard microbiological quality is an important area of study, since grapevine-associated microbiome primarily originates in vineyard soils and determines host health and development. To understand the decrease of growth and yield, and the high mortality of plants in vineyards affected by these declines, a multisite study investigated soil microbial communities. Spatial (terroir: two distinct geographical locations) and temporal (season: autumn and spring) dimensions were added to the inter-row soil status factor (S for areas with symptomatic vines and AS for those with asymptomatic vines). The microbiomes of AS and S soils were analyzed using high-throughput sequencing based on the bacterial 16S rRNA gene, the fungal ITS1 region (Internal Transcribed Spacer), or the fungal 18S rRNA gene for Glomeromycota family. Geographical location was the strongest driver of bacterial and fungal microbial communities, while the seasonal factor primarily influenced bacterial community. Based on metabarcoding analysis, symptomatic soils presented enriched bacterial taxa that can be potentially beneficial for grapevine growth. In addition, fungal diversity and richness, including Glomeromycota division, were greater in symptomatic soils. Fungal genera associated with grapevine diseases were detected across all conditions, with higher abundances in symptomatic soils. These findings reveal that vineyard soils affected by unexplained decline are a potential source of both fungal pathogens and beneficial microorganisms.

人体生物矿化与病态结晶研究进展

<p indent="0mm">In the chemical industry, crystallization is an indispensable unit operation in the separation of the solid-liquid phase and a ubiquitous method to manufacture high-value crystal products. In nature, crystallization resulting in mineralization is a more general phenomenon in organisms. Modern crystallization technology is gradually expanding into the field of biomolecular engineering. However, biomineralization, in which organisms form tissues with biological functions by controlling the precipitation and crystallization of inorganic nanocrystals in organic matrices, is a dynamic, complex process that accompanies the organism throughout its life. But, when abnormal fluctuations occur in the body’s internal chemical environment, pathological mineralization occurs, resulting in the precipitation of inorganic or organic salt crystals which are aberrant crystallizations, a process known as pathological crystallization, causing disease and endangering human health, such as kidney stones, gall stones, malaria, and gout. Compared to the conventional crystallization from solution in chemical engineering which contains crystal nucleation, growth, and aggregation, biomineralization involves many microscopic and macroscopic processes such as ion/molecular assembly into nuclei, crystal-liquid interface mass transfer, and particle aggregation, which strongly couples with the physiological environment. The limitation of conventional crystallization hinders the advancement in understanding the mechanism of the ion/molecular crystallization process and the regulation of complex environments <italic>in vivo</italic>, resulting in the blindness of the screening and development of drugs for the treatment and prevention of such diseases. The study of biomineralization is a frontier research field and their discoveries in pathological crystallization are supposed to promote the development of clinical medicine. Based on the latest research in crystal engineering and crystallography, we take the common pathological mineralization-induced diseases (malaria, kidney stones, atherosclerosis, gall stones, gout) as examples, and select recent representative and significant findings from the perspective of understanding the mechanism of the crystallization process. The mechanisms of inorganic and organic crystal crystallization processes related to these diseases are reviewed, focusing on the molecular mechanisms of crystal nucleation, growth, agglomeration, and adhesion at diverse scales during different stages of the disease. The mechanisms of the crystallization inhibitors (molecules that inhibit the nucleation, growth, aggregation, or agglomeration process of pathological crystal) are also reviewed. The aim of the research on the crystallization and inhibition mechanisms is to build up guidelines for the screening and designing of effective inhibitors. Based on these findings, researchers have successfully designed many potent molecules that hold promise as a novel therapeutic modality. At the end of the review, the key research challenges and future directions in pathological mineralization are given. To meet the practical needs of clinical drug development, pathological mineralization researchers still face many challenges in understanding the mechanism of the crystallization process, screening drugs, establishing platforms and models, and building guidelines for medical advancement. Due to the complex environments <italic>in vivo</italic>, it is difficult to understand the mechanism of crystallization under the interaction between multiple ions/molecules and drugs, where molecular recognition plays important role in specific binding to crystal surface sites. The research on crystallization mechanism aims to screen potential pathological crystal inhibitors. Because considerable studies are based on <italic>in vitro</italic> experiments, more attention should be paid to the building platforms and models that can mimic human environments and use molecular design tools to selectively inhibit the crystallization process, which is believed to be the most potent strategy to find the specific drug for the biomineralization-induced disease. Finally, it is necessary to establish scientific and efficient guidelines for medicine development and provide effective therapeutic and preventive measures for biomineralization-induced diseases.

Method for non-invasive assessment of the structure of a heart valve bioprosthesis

Background. The study of explanted heart valve bioprostheses is a valuable source of information about the destructive processes in their components that develop as a result of prolonged contact with the recipient’s body. An analysis of the morphology, staging and degree of involvement of various valve prosthesis materials in the prevalence of pathological processes – calcification, mechanical damage, growth of the connective tissue capsule, is the basis for developing potential methods for increasing the service life of these products and reducing the risk of re-interventions. The aim of the study was to evaluate the potential of computed microtomography to analyze the internal structure of a biological prosthetic heart valve explanted due to dysfunction. Material and methods. In this work, we investigated the prevalence of pathological mineralization of the PeriCor bioprosthesis, explanted as a result of the developed dysfunction of the leaflet apparatus with a clinical picture of grade 2B prosthetic insufficiency. The material was described macroscopically, after which it was subjected to high-resolution computed microtomography. In the structure of the sample, X-ray dense areas of pathological mineralization were identified and described, and the volume of the material involved in calcification was assessed. Results. It was shown that the main pathological changes that led to prosthetic dysfunction were degenerative changes in the biomaterial with signs of calcification, thickening and rupture of the leaflets. It was quantitatively determined that the areas of radiologically dense inclusions (calcifications) occupy 11.1 % of the volume of the material. It has been established that the described areas are associated with the sheathing of the frame and with the elements of the suture material used in the production of this bioprosthesis. Conclusion. The method of non-destructive analysis of the internal structure of altered materials of a biological prosthesis studied in this work has demonstrated the possibility of а qualitative and quantitative assessment of areas of pathological mineralization, their distribution and connection with other processes leading to the development of prosthetic dysfunction. The method makes it possible to visualize macro- and microsites of calcification and can become a valuable tool to complement existing approaches to the study of explanted bioprostheses.