Magnesium Whitlockite Research Articles

Low-temperature aqueous synthesis and biocompatibility of manganese whitlockite

In this work, manganese whitlockite (Mn-WH, Ca18Mn2(HPO4)2(PO4)12) was successfully synthesized and comprehensively characterized. This material is a manganese-containing analog of the biomineral magnesium whitlockite (Mg-WH, Ca18Mg2(HPO4)2(PO4)12). The synthesis was performed via a low-temperature dissolution-precipitation process in aqueous medium under ambient pressure at 75 °C using dicalcium phosphate dehydrate and manganese acetate tetrahydrate as starting materials. The crystal structure of the synthesized powder was determined by powder X-ray diffraction, FTIR and Raman spectroscopies, demonstrating the presence of characteristic structural units. Morphological features and elemental distribution within the synthesized powder were studied by SEM/EDX analysis. XPS, EPR and magnetic studies confirmed the presence of Mn ions in a divalent state. Temperature-dependent magnetic measurements revealed a paramagnetic behavior of Mn-WH down to 5 K. In vitro cytotoxicity experiments were performed with MC3T3-E1 preosteoblastic cell line.

Magnesium whitlockite nanoparticles: Hydrothermal synthesis, anti-inflammatory and anti-cancer potential

This study revealed the potential of magnesium whitlockite [WH: Ca18Mg2(HPO4)2(PO4)12] nanoparticles (WH NPs) for anti-inflammatory and anti-cancer therapies. Although magnesium whitlockite possesses promising biological properties, its effects on inflammation and cancer remain unexplored. In this study, we address this gap by synthesizing WH NPs and demonstrating their multifaceted functionalities. Through detailed characterization, we revealed the synthesis pathway involving brushite as a precursor, with magnesium ions incorporated during hydrothermal treatment. WH NPs exhibited anti-inflammatory properties by significantly reducing the production of key inflammatory markers (NO, TNF-α, and IL-6). Furthermore, they display promising anti-cancer activity by inhibiting the proliferation of MDA-MB-231 breast cancer cells. Our findings not only establish a deeper understanding of WH NP synthesis but also highlight their potential for the development of innovative cancer and inflammatory treatments.

Large-Scale Green Synthesis of Magnesium Whitlockite from Environmentally Benign Precursor.

Magnesium whitlockite (Mg-WH) powders were synthesized with remarkable efficiency via the dissolution-precipitation method by employing an environmentally benign precursor, gypsum. Under optimized conditions, each 5.00 g of initial gypsum yielded an impressive amount of 3.00 g (89% yield) of Mg-WH in a single batch. Remarkably, no XRD peaks attributable to impurity phases were observed, indicating the single-phase nature of the sample. FT-IR analysis confirmed the presence of the PO43- and HPO42- groups in the obtained Mg-WH phase. The SEM-EDX results confirmed that Mg-WH crystals with homogeneous Ca, Mg, P, and O distributions were obtained. In previously published research papers, the synthesis of Mg-WH has been consistently described as a highly intricate process due to material formation within a narrow pH and temperature range. Our proposed synthesis method is particularly compelling as it eliminates the need for meticulous monitoring, presenting a notable improvement in the quest for a more convenient and efficient Mg-WH synthesis. The proposed procedure not only emphasizes the effectiveness of the process, but also highlights its potential to meet significant demands, providing a reliable solution for large-scale production needs in various promising applications.

A copper-containing analog of the biomineral whitlockite: dissolution-precipitation synthesis, structural and biological properties.

In the present work, copper whitlockite (Cu-WH, Ca18Cu2(HPO4)2(PO4)12) was successfully synthesized and comprehensively characterized, founding the base knowledge for its future studies in medicine, particularly for bone regeneration. This material is a copper-containing analog of the well-known biomineral magnesium whitlockite (Mg-WH, Ca18Mg2(HPO4)2(PO4)12). The synthesis of powders was performed by a dissolution-precipitation method in an aqueous medium under hydrothermal conditions. Phase conversion from brushite (CaHPO4·2H2O) to Cu-WH took place in an acidic medium in the presence of Cu2+ ions. Optimization of the synthesis conditions in terms of medium pH, temperature, time, Ca/Cu molar ratio and concentration of starting materials was performed. The crystal structure of the synthesized products was confirmed by XRD, FTIR and Raman spectroscopy, 1H and 31P solid-state NMR, and EPR. Morphological features and elemental distribution of the synthesized powders were studied by means of SEM/EDX analysis. The ion release in SBF solution was estimated using ICP-OES. Cytotoxicity experiments were performed with MC3T3-E1 cells. The study on thermal stability revealed that the synthesized material is thermally unstable and gradually decomposes upon annealing to Cu-substituted β-Ca3(PO4)2 and Ca2P2O7.

Phase transformations during the dissolution-precipitation synthesis of magnesium whitlockite nanopowders from gypsum

In the present work, magnesium whitlockite (Mg-WH) powders were synthesized via a low-temperature dissolution-precipitation process using gypsum as a starting material. The suggested synthetic approach is cost-effective and environmentally friendly solution, promoting sustainable manufacturing practises. The phase evolution and formation of Mg-WH in an aqueous medium in the presence of magnesium and phosphate ions under static and rotating conditions were investigated. Powder XRD patterns, FTIR spectra and SEM images were obtained for samples synthesized for different times to monitor the gradual phase transformation. It was found that single-phase Mg-WH can be obtained using both synthetic approaches, however, the reaction under rotating conditions favors faster formation of Mg-WH crystals. Samples obtained under static conditions had larger crystallite size and higher crystallinity, while those prepared under rotating conditions had smaller crystallites and lower crystallinity. The Rietveld refinement confirmed the structural parameters of the synthesized samples, indicating a slight change in the lattice parameters and magnesium occupancy with an extended synthesis time. We state that the phase composition, crystallite size, crystallinity, and powder morphology can be facilely controlled by regulating the synthesis time and selecting the synthesis setup.

The many facets of micropetrosis - Magnesium whitlockite deposition in bisphosphonate-exposed human alveolar bone with osteolytic metastasis.

The lacuno-canalicular space of apoptotic osteocytes eventually becomes mineralised in vivo. This condition is known as micropetrosis and is a fundamental characteristic of ageing bone. Increased prevalence of such hypermineralised osteocyte lacunae is viewed as a structural marker of impaired bone function - both mechanical and biological. Within the lacuno-canalicular space, mineralised apoptotic debris typically occurs as micrometre-sized, spherical nodules of magnesium-rich, carbonated apatite. Moreover, characteristically facetted, rhomboidal nodules of magnesium whitlockite [Mg-whitlockite; Ca18Mg2(HPO4)2(PO4)12] have been reported in human alveolar bone exposed to the bisphosphonate alendronate. This work provides supporting evidence for Mg-whitlockite formation in the alveolar bone of a 70-year-old male exposed to the bisphosphonate zoledronic acid to suppress osteolytic changes in skeletal metastasis. Backscattered electron scanning electron microscopy (BSE-SEM) revealed spherical and rhomboidal nodules within the lacuno-canalicular space. A variant of spherical nodules exhibited a fuzzy surface layer comprising radially extending acicular crystallites. The rhomboidal nodules ranged between ∼200nm to ∼2.4µm across the widest dimension (652±331nm). Micro-Raman spectroscopy and energy dispersive X-ray spectroscopy confirmed that rhomboidal nodules are compositionally distinct from spherical nodules, exhibiting higher Mg content and lower Ca/P ratio. Formation of Mg-whitlockite within osteocyte lacunae is multifactorial in nature and suggests altered bone biomineralisation. Nevertheless, the underlying mechanism(s) and sequence of events remain poorly understood and warrant further investigation. The possibility to discriminate between carbonated apatite and Mg-whitlockite nodules within osteocyte lacunae, based on particle morphology, attests to the diagnostic potential of BSE-SEM with or without additional analyses of material composition.

Abstract 5561: Molecular imaging of calcification and soft tissue defines prognosis of DCIS to invasive breast cancer

Abstract Introduction: Ductal carcinoma in situ (DCIS) is a non-obligatory precursor to invasive breast cancer (IBC). Currently there are no reliable markers to indicate if DCIS will progress IBC after an initial treatment, or if it will remain as DCIS. Because of this uncertainty, standard treatment for DCIS includes surgery with or without radiotherapy. Breast microcalcifications are a common feature in the mammographic detection of DCIS and occur in around 80% of DCIS and 50% of IBC. Despite this, their potential role in the development of DCIS and with progression to IBC remains largely unexplored. The main aim of the study is to identify novel biomarkers for DCIS prognosis, based on chemical and molecular compositional changes of calcifications and their surrounding soft tissue in DCIS. Methods: Consecutive tissue section from 422 patients were analyzed using mid-infrared and Raman hyperspectral imaging and X-ray diffraction (XRD) and included (i) ‘DCIS controls’ (DCIS without recurrence) (n=193), (ii) ‘DCIS cases’ (DCIS which subsequently recurred as an invasive disease) (n=123), (iii) ‘synchronous DCIS with invasive cancer’ (n=44) and ‘benign’ (n=62) groups. Both parametrized and data mining approaches including cluster analysis, unsupervised and supervised multivariate statistical analysis and biomodelling based on leave-one-sample-out cross-validation were used to classify the data and develop DCIS prediction models. Results: Prediction modelling of 314 calcification and soft tissue spectral images from 170 patients (‘DCIS controls’=118 versus ‘DCIS cases’=52) showed an AUROC mean value of 0.85 in distinguishing DCIS that did not recur from DCIS that recurred as IBC. Prediction modelling of XRD data from 124 patients (‘DCIS controls’=67 versus ‘DCIS cases’=57) showed an AUROC mean value of 0.80. The calcification spectral features showed pathology specific changes in phosphate to carbonate ratio as well as changes in magnesium whitlockite content. The epithelial features showed changes in protein secondary structure and content indicating structural remodeling between the two groups. XRD parametrized data analysis corroborated these observations in terms of difference in whitlockite, as well as crystallinity/unit axis of the measured calcifications. The prediction models are currently being tested independently on the remaining sample data. Conclusion: Complementary chemical and molecular analysis of breast calcifications and soft tissue using spectroscopy and XRD imaging predicts the likely progression of DCIS to IBC. Subject to the ongoing validation of biomarkers, these approaches appear as promising DCIS risk assessment tools that can inform diagnosis, prognosis and treatment options. Citation Format: Jayakrupakar Nallala, Doriana Calabrese, Sarah Gosling, Esther Lips, Rachel Factor, Allison Hall, Sarah Pinder, Ihssane Bouybayoune, Elinor Sawyer, Lorraine King, Jeffrey Marks, Thomas Lynch, Donna Pinto, Jelle Wesseling, Shelley Hwang, Keith Rogers, Nick Stone, Grand Challenge PRECISION consortium. Molecular imaging of calcification and soft tissue defines prognosis of DCIS to invasive breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5561.

Production of Nano Hydroxyapatite and Mg-Whitlockite from Biowaste-Derived products via Continuous Flow Hydrothermal Synthesis: A Step towards Circular Economy.

Biowastes from agriculture, sewage, household wastes, and industries comprise promising resources to produce biomaterials while reducing adverse environmental effects. This study focused on utilising waste-derived materials (i.e., eggshells as a calcium source, struvite as a phosphate source, and CH3COOH as dissolution media) to produce value-added products (i.e., calcium phosphates (CaPs) derived from biomaterials) using a continuous flow hydrothermal synthesis route. The prepared materials were characterised via XRD, FEG-SEM, EDX, FTIR, and TEM analysis. Magnesium whitlockite (Mg-WH) and hydroxyapatite (HA) were produced by single-phase or biphasic CaPs by reacting struvite with either calcium nitrate tetrahydrate or an eggshell solution at 200 °C and 350 °C. Rhombohedral-shaped Mg-WH (23-720 nm) along with tube (50-290 nm diameter, 20-71 nm thickness) and/or ellipsoidal morphologies of HA (273-522 nm width) were observed at 350 °C using HNO3 or CH3COOH to prepare the eggshell and struvite solutions, and NH4OH was used as the pH buffer. The Ca/P (atomic%) ratios obtained ranged between 1.3 and 1.7, indicating the formation of Mg-WH and HA. This study showed that eggshells and struvite usage, along with CH3COOH, are promising resources as potential sustainable precursors and dissolution media, respectively, to produce CaPs with varying morphologies.

Abstract P4-02-22: Breast microcalcification chemistry predicts DCIS prognosis

Abstract Introduction: Microcalcifications are a common feature in mammographic detection of ductal carcinoma in situ (DCIS), and occur in >80% of cases. Known to be present as type I (calcium oxalate-CaO) and type II (carbonated calcium hydroxyapatite-CHAP) microcalcifications, their association with DCIS and their role in the progression of DCIS to invasive breast cancer (IBC) remains unexplored. In an effort to understand the factors involved in DCIS prognosis, it is hypothesized that changes in the chemical composition of calcifications, in tandem with molecular changes in the surrounding soft tissue, will define patients with DCIS who will progress to develop IBC from those who remain with a stable DCIS phenotype. To this end, a novel label-free approach of hyperspectral imaging using mid-infrared (mid-IR) and Raman spectroscopy was used to probe calcification chemistry and molecular composition of the surrounding ductal and stromal soft tissue. The main aim of the work is to identify biomarkers for DCIS prognosis, based on chemical and molecular compositional changes of calcifications and the surrounding soft tissue. It is anticipated that the spectral biomarkers will provide patients and clinicians an informed risk assessment whether to undertake treatment for DCIS or to be placed under active surveillance. Methods: Tissue samples from 422 patient have been obtained and include (i) ‘pure DCIS’ (DCIS without recurrence) (n=193), (ii) ‘DCIS with invasive recurrence’ (DCIS from patients who subsequently were known to develop invasive disease) (n=123), (iii) ‘DCIS plus contemporaneous invasive cancer’ (n=44) and ‘benign’ (n=62) samples. Serial tissue sections were measured using mid-IR and Raman hyperspectral imaging approaches targeting the same calcification and soft tissue regions from specific DCIS ducts. Hyperspectral imaging data was initially pre-processed to digitally remove paraffin and unintended spectral interferences. The pre-processed data was subjected to cluster analysis followed by unsupervised and supervised machine learning classification models to identify spectral features associated with DCIS and its progression to IBC. Results: Cluster analysis based segmentation of hyperspectral images revealed histopathological features including calcifications, epithelium, necrotic areas, connective tissue and stroma. Spectra were extracted from each of the histopathological features using image coordinates, and biomodelling analysis was performed. Initial analysis of 314 calcification images from 170 patients with (i) ‘pure DCIS’ (n=118) and (ii) ‘DCIS with invasive recurrence’ (n=52) showed an area under the receiver operating characteristic (AUROC) mean value of 85% in distinguishing pure DCIS from DCIS that later recurred as IBC. The calcification features appeared to indicate pathology specific changes in phosphate and carbonate content as well as changes in magnesium whitlockite content. Similar analysis of the surrounding soft tissue spectral features showed an AUROC mean value of 85% (necrotic regions surrounding calcifications) and 76% (epithelium) respectively. The epithelial features showed changes in protein secondary structure and content, which together with the calcification changes indicate structural remodelling in DCIS that progresses to IBC, from those that do not. Perspectives: In the ongoing analyses of imaging data from 422 patients, it is anticipated that molecular/structural features from calcification and soft tissue imaging data will provide important cues in understanding DCIS prognosis and could be a promising way forward in determining management of DCIS risk and treatment underpinned by the identification of specific discriminatory spectral markers. Acknowledgments: This work was supported by Cancer Research UK and by KWF Kankerbestrijding (ref. C38317/A24043). Citation Format: Jayakrupakar Nallala, Doriana Calabrese, Sarah Gosling, Esther Lips, Rachel Factor, Allison Hall, Sarah E. Pinder, Ihssane Bouybayoune, Lorraine King, Jeffrey Marks, Thomas Lynch, Donna Pinto, Jelle Wesseling, E Shelley Hwang, Keith Rogers, Nick Stone. Breast microcalcification chemistry predicts DCIS prognosis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-22.

Dissolution–precipitation synthesis and thermal stability of magnesium whitlockite

Thermally induced degradation and phase transformation of magnesium whitlockite (Ca18Mg2(HPO4)2(PO4)12) powders were investigated in detail by combining XRD analysis, FTIR and Raman spectroscopy as well as 1H and 31P NMR.

Preparation, characterization and protein adsorption properties of nanostructured magnesium whitlockite

Preparation, characterization and protein adsorption properties of nanostructured magnesium whitlockite

Inorganic Powders Prepared from Fish Scales

A mixture of abramis brama (freshwater bream), carassius carassius (crucian carp), and sander lucioperca (pike perch) scales was used for the preparation of fish scale powder containing constituents of organic and inorganic nature. The mixture of the mentioned fish scales was washed, dried, and ground for the preparation of fish scale powder. Vibration sieving was used to prepare fish scale powder enriched with inorganic components. According to thermal analysis data, this fish scale powder enriched with inorganic components included about 36.5 wt.% components removed when heating, primarily those of organic nature, and 63.5 wt.% mineral components. Inorganic powders consisting of hydroxyapatite and magnesium whitlockite were obtained via heat treatment of this fish scale powder at 800–1000 °C. Particles of these inorganic powders consisted of sintered grains with dimensions less than 100 nm after heat treatment at 800 °C, less than 200 nm after heat treatment at 900 °C, and 100–1000 nm after heat treatment at 1000 °C. Fish scale powder enriched with inorganic components as well as heat-treated inorganic powders consisting of hydroxyapatite and magnesium whitlockite can be recommended for the production of different materials, such as ceramics or composites.

Synthesis of whitlockite nanopowders with different magnesium content

Recently, synthetic magnesium whitlockite (Ca18Mg2(HPO4)2(PO4)12, WH) has received much attention for being used as a bone substitute. The present research explores the possibility of tailoring Ca to Mg ratio in WH structure material, which might subsequently affect its biological properties. A dissolution-precipitation synthesis of nanocrystalline WH samples was performed at 65 °C using brushite as a starting material in the presence of Mg2+ ions. The change in the stoichiometry of synthesized samples was reflected in the variation of lattice parameters: the decrement of crystallographic constants was attributed to the difference in ionic radius of Ca and Mg ions. The synthesized powders were characterized to determine the phase purity, crystallographic parameters, functional groups, and morphology under altered Ca to Mg molar ratios.

Abstract P2-08-07: Predicting DCIS prognosis using infrared and raman spectroscopy of breast calcifications and soft-tissue microstructure

Abstract Introduction: Ductal carcinoma in situ (DCIS) is a potential precursor of invasive breast cancer. The uncertain trajectory of DCIS, to progress to invasive disease or to remain in situ, currently drives treatment, despite lack of proven benefit. Therefore, understanding the molecular features of the DCIS trajectory may prevent overtreatment of this disease. Breast calcifications are a common feature in DCIS and are seen mammographically in over 80% of cases. Calcifications have been largely characterised based only on x-ray morphology; their chemical composition, their association with the surrounding soft tissue and role in DCIS and invasive breast cancer biology is largely unexplored. In this regard, a bio-photonic approach, based on infrared (IR) and Raman spectroscopy in combination with machine learning, was used to study DCIS by probing the chemical composition of calcifications and the surrounding soft tissue in breast lesions. The main aim of the work is to identify molecular compositional changes in calcifications and in soft tissue that potentially accompany or drive the progression of DCIS to invasive breast cancer, or indicates a stable DCIS phenotype. Methods: Serial tissue sections from 303 patients with (i) ‘pure DCIS’ (DCIS without recurrence) (n=158), (ii) ‘DCIS with invasive recurrence’ (DCIS from a patient who subsequently was known to develop invasive disease) (n=123) and (iii) ‘DCIS plus invasive cancer contemporaneously’ (n=22), were measured using mid-IR imaging and Raman mapping. The same calcifications and soft tissue regions from specific DCIS ducts were targeted across the techniques on the serial sections. Spectral images were analysed using cluster analysis followed by unsupervised and supervised machine learning classification models to identify spectral features associated with the progression of DCIS to invasive breast cancer. Results: Segmentation of IR and Raman spectral images based on cluster analysis identified important histopathological features including calcifications, epithelium, necrotic areas, connective tissue and stroma based on the spectral heterogeneity. Based on analysis of Raman calcification data from 145 patients with (i) ‘pure DCIS’ (n=90) and (ii) ‘DCIS with invasive recurrence’ (n=55), an area under the receiver operating characteristic (AUROC) mean value of 85% was obtained in distinguish pure DCIS from DCIS that later recurred as invasive cancer. The calcification features appeared to indicate pathology specific changes in phosphate and carbonate content and appearance of magnesium whitlockite. Similar analysis of the surrounding soft tissue spectral features showed an AUROC mean value of 76%, which showed changes in protein secondary structure and content, particularly in the necrotic regions surrounding calcifications. In addition, classification models are being developed and refined from the IR spectral data, the initial results of which have shown an AUROC value of only 54% from the same patients’ data. Perspectives: It is anticipated that the current novel approaches allowing label-free measurement of calcifications and soft tissue will provide important cues in understanding DCIS prognosis and could be a promising way forward in determining DCIS management. Current and future efforts include identification of specific discriminatory spectral features for molecular and pathological correlation. Acknowledgments: This work was supported by Cancer Research UK and by KWF Kankerbestrijding (ref. C38317/A24043). Citation Format: Jayakrupakar Nallala, Doriana Calabrese, Sarah Gosling, Allison Hall, Sarah Pinder, Ihssane Bouybayoune, Lorraine King, Jeffrey Marks, Esther Lips, Thomas Lynch, Donna Pinto, Jelle Wesseling, Shelley Hwang, Keith Rogers, Nick Stone, on behalf of the Grand Challenge PRECISION consortium. Predicting DCIS prognosis using infrared and raman spectroscopy of breast calcifications and soft-tissue microstructure [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-07.

Кристаліндукований остеоартрит: роль кристалів основного фосфату кальцію

Кристали основних фосфатів кальцію вже давно асоціюються з патогенезом остеоартриту. Основні фосфати кальцію з великою частотою визначаються в синовіальній рідині і суглобовому хрящі при цьому захворюванні. У той час як осадження основних фосфатів кальцію розглядається багатьма вченими як наслідок прогресуючого перебігу остеоартриту, з’явилися суттєві докази того, що ці кристали можуть виступати активними патогенними медіаторами остеоартриту. «Кристали основних фосфатів кальцію» — загальний термін для опису декількох видів фосфатів кальцію, у тому числі карбонатапатиту, гідроксиапатиту, три- і октакальцієвих фосфатів, кристалів вітлокіта магнію. Кристали основних фосфатів кальцію патогенетично пов’язані з остеоартритом, кальцинуючим тендинітом, гострим кристалічним артритом та атеросклерозом. Кристали кальцію визначаються в синовіальній рідині в 65 % випадків остеоартриту колінного суглоба, вони з високою частотою виявляються в гіаліновому хрящі при остеоартриті, а також у 100 % пацієнтів у суглобовому хрящі при проведенні операції тотального ендопротезування. Кристали основних фосфатів кальцію також були виявлені в синовіальній рідині та синовіальній мембрані пацієнтів із легким, помірним і тяжким ураженням колінного суглоба при артроскопії. Основні фосфати кальцію проявляють множинні біологічні ефекти in vitro, у тому числi здатність стимулювати мітогенез, продукцію простагландинів, цитокінів і матриксних металопротеїназ у різних типах клітин, включаючи синовіоцити, хондроцити і макрофаги. Кристали основних фосфатів кальцію також обумовлюють запалення при остеоартриті шляхом прямої взаємодії з вродженою імунною системою. У цьому огляді обговорюються останні досягнення в цій галузі і підбиваються підсумки сучасного розуміння ролі кристалів основних фосфатів кальцію в патогенезі остеоартриту. Погляди на роль кристалів основних фосфатів кальцію в патогенезі остеоартриту продовжують розширюватися, проте вже сьогодні існує достатньо експериментальних і клінічних доказів найважливішої ролі кальційумісних кристалів у розвитку цього захворювання і прогресуючій дегенерації суглобового хряща.

Citrate-based mussel-inspired magnesium whitlockite composite adhesives augmented bone-to-tendon healing.

Citrate-based mussel-inspired whitlockite composite adhesives (CMWAs) were developed and administered to the bone-tendon interface in anterior cruciate ligament (ACL) reconstruction. CMWAs could improve the initial bone-tendon bonding strength, promote the bony inward growth from the bone tunnel and enhance the chondrogenesis and osteogenesis of the bone-tendon interface, thus augmenting bone-to-tendon healing.

A rapid way to synthesize magnesium whitlockite microspheres for high efficiency removing heavy metals

A rapid way to synthesize magnesium whitlockite microspheres for high efficiency removing heavy metals

Micrometer-Sized Magnesium Whitlockite Crystals in Micropetrosis of Bisphosphonate-Exposed Human Alveolar Bone.

Osteocytes are contained within spaces called lacunae and play a central role in bone remodelling. Administered frequently to prevent osteoporotic fractures, antiresorptive agents such as bisphosphonates suppress osteocyte apoptosis and may be localized within osteocyte lacunae. Bisphosphonates also reduce osteoclast viability and thereby hinder the repair of damaged tissue. Osteocyte lacunae contribute to toughening mechanisms. Following osteocyte apoptosis, the lacunar space undergoes mineralization, termed "micropetrosis". Hypermineralized lacunae are believed to increase bone fragility. Using nanoanalytical electron microscopy with complementary spectroscopic and crystallographic experiments, postapoptotic mineralization of osteocyte lacunae in bisphosphonate-exposed human bone was investigated. We report an unprecedented presence of ∼80 nm to ∼3 μm wide, distinctly faceted, magnesium whitlockite [Ca18Mg2(HPO4)2(PO4)12] crystals and consequently altered local nanomechanical properties. These findings have broad implications on the role of therapeutic agents in driving biomineralization and shed new insights into a possible relationship between bisphosphonate exposure, availability of intracellular magnesium, and pathological calcification inside lacunae.

Elemental vs. phase composition of breast calcifications

Despite the importance of calcifications in early detection of breast cancer, and their suggested role in modulating breast cancer cell behaviour, very little detail is known about their chemical composition or how this relates to pathology. We measured the elemental composition of calcifications contained within histological sections of breast tissue biopsies, and related this to both crystallographic parameters measured previously in the same specimens, and to the histopathology report. The Ca:P ratio is of particular interest since this theoretically has potential as a non-invasive aid to diagnosis; this was found to lie in a narrow range similar to bone, with no significant difference between benign and malignant. The Mg:Ca ratio is also of interest due to the observed association of magnesium whitlockite with malignancy. The initially surprising inverse correlation found between whitlockite fraction and magnesium concentration can be explained by the location of the magnesium in calcified tissue. Sodium was also measured, and we discovered a substantial and significant difference in Na:Ca ratio in the apatite phase between benign and malignant specimens. This has potential for revealing malignant changes in the vicinity of a core needle biopsy.

Relationships between pathology and crystal structure in breast calcifications: an in situ X-ray diffraction study in histological sections.

Calcifications are not only one of the most important early diagnostic markers of breast cancer, but are also increasingly believed to aggravate the proliferation of cancer cells and invasion of surrounding tissue. Moreover, this influence appears to vary with calcification composition. Despite this, remarkably little is known about the composition and crystal structure of the most common type of breast calcifications, and how this differs between benign and malignant lesions. We sought to determine how the phase composition and crystallographic parameters within calcifications varies with pathology, using synchrotron X-ray diffraction. This is the first time crystallite size and lattice parameters have been measured in breast calcifications, and we found that these both parallel closely the changes in these parameters with age observed in fetal bone. We also discovered that these calcifications contain a small proportion of magnesium whitlockite, and that this proportion increases from benign to in situ to invasive cancer. When combined with other recent evidence on the effect of magnesium on hydroxyapatite precipitation, this suggests a mechanism explaining observations that carbonate levels within breast calcifications are lower in malignant specimens.