ACS Applied Bio Materials最新文献

{"title":"Manufacturing Route-Dependent Biointerface Modulation in 3D-Printed and Conventional Dental Implant Systems.","authors":"Maria Helena Rossy Borges, Marcio da Costa Marques, Julia Nascimento Souza, Luis Rafael Mangueira Ribeiro, Catia Sufia Alves Freire de Andrade, Agnaldo R de Souza Junior, Aljomar José Vechiato-Filho, Valentim A R Barão, Jamil A Shibli, João Gabriel S Souza","doi":"10.1021/acsabm.6c00473","DOIUrl":"https://doi.org/10.1021/acsabm.6c00473","url":null,"abstract":"<p><p>Implant manufacturing routes determine surface architecture and, consequently, modulate biointerface interactions that govern early biological responses. Although additive manufacturing has emerged as a promising alternative to conventional subtractive techniques, direct comparisons among commercially available systems remain limited. In this study, a commercially available additively manufactured dental implant was compared with four market-available conventionally machined systems to elucidate manufacturing route-dependent biointerface modulation. Physicochemical properties, surface topography, and electrochemical behavior were evaluated alongside biological responses. Protein adsorption profiles were characterized by liquid chromatography-tandem mass spectrometry (LC-MS/MS), while polymicrobial accumulation was quantified and profiled. Microbially induced surface degradation was assessed by titanium ion release. The additively manufactured implant and the market-leading conventional system exhibited higher surface roughness and distinctive topographical features, which were associated with reduced polymicrobial biofilm accumulation, lower titanium ion release following microbial challenge, and stable electrochemical behavior. Although conventionally machined implants exhibited broader proteomic profiles, functional enrichment analyses revealed overlapping biological categories among implant systems. Collectively, the findings demonstrate that the manufacturing route critically modulates implant biointerface characteristics, with additive manufacturing achieving performance comparable to established commercial systems.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"iRGD-Functionalized Graphene-Silver Nanohybrids for Enhanced Blood-Brain Barrier Transport and Tumor Penetration in Glioma Models.","authors":"Vianni Chopra, Jocelyn Alexandra Gómez Siono, Carlos Eduardo Fajardo Barocio, Gaurav Chauhan","doi":"10.1021/acsabm.6c00709","DOIUrl":"https://doi.org/10.1021/acsabm.6c00709","url":null,"abstract":"<p><p>Efficient drug delivery across both the tumor microenvironment and the blood-brain barrier (BBB) remains a major challenge in glioblastoma therapy, where dense cellular architecture and endothelial restriction severely limit treatment efficacy. Here, we report the rational design of a multifunctional nanoplatform, Dox[iRGD-GO@AgNP], integrating graphene oxide (GO), silver nanoparticles (AgNPs), and a cyclic iRGD tumor-penetrating peptide to enhance doxorubicin (Dox) transport, tumor penetration, and intracellular delivery. Comprehensive physicochemical characterization confirmed successful synthesis, surface functionalization, colloidal stability, and efficient drug loading. In two-dimensional C6 glioma cell monolayers, cyclic iRGD-functionalized nanohybrids demonstrated significantly enhanced intracellular Dox accumulation compared to free drug and nontargeted controls. These effects were further amplified in three-dimensional glioma spheroids, where Dox[iRGD-GO@AgNP] achieved deep tumor penetration (>80 µm) and more homogeneous intratumoral distribution. Enhanced delivery translated into superior therapeutic efficacy, as evidenced by reduced cell viability, increased membrane damage, upregulation of apoptosis-related markers (p53 and caspase-3 &9), and pronounced morphological disruption confirmed by fluorescence imaging and electron microscopy. To evaluate endothelial transport, a Transwell-based bEnd.3 BBB model was established and validated by transendothelial electrical resistance measurements and tight junction imaging. Cyclic iRGD-functionalized nanohybrids exhibited significantly enhanced transendothelial transport while preserving BBB integrity, indicating ligand-mediated transport rather than nonspecific barrier disruption. Importantly, improved BBB traversal resulted in increased drug accumulation in downstream glioma cells and spheroids. These composites showed anti-angiogenic properties in ovo CAM model. Overall, this study integrates rational nanocomposite design with a hierarchical in vitro evaluation framework spanning material characterization, tumor-relevant 2D and 3D models, and BBB transport. The Dox[iRGD-GO@AgNP] platform addresses key delivery and efficacy barriers in glioblastoma and provides a translationally relevant strategy for the development of BBB-penetrating nanotherapeutics.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple-Session Magnetic Fluid Hyperthermia: Augmented MNPs Penetration Led to Complete Eradication of Hetero-Multicellular Breast Tumor Spheroids via Apoptosis.","authors":"Tushar Patel, Gaurang Gajjar, Kaid Johar, Kinnari H Parekh, Neeraj Jain","doi":"10.1021/acsabm.6c00915","DOIUrl":"https://doi.org/10.1021/acsabm.6c00915","url":null,"abstract":"<p><p>Magnetic fluid hyperthermia (MFH) is an emerging localized cancer therapy that uses magnetic nanoparticles to selectively induce 42 to 45 °C mild hyperthermia within tumor tissues under alternating magnetic field to kill cancer cells. Despite encouraging clinical outcomes in glioblastoma and prostate cancer, the broader clinical translation of MFH across various tumor types remains limited by heterogeneous nanoparticle distribution, inconsistent tumor heating, and the frequent use of poorly predictive preclinical two-dimensional (2D) cultures. These conventional cultures fail to recapitulate the structural and stromal complexity of solid tumors and often overestimate therapeutic efficacy. In an attempt to recreate the cellular heterogeneity of clinical breast tumors to some extent, we developed a hetero-multicellular spheroid of breast cancer by co-culturing breast adenocarcinoma cells MCF-7, with non-cancerous murine fibroblasts McCoy. This approach generated heterospheroids that mimic certain key features of the breast tumor microenvironment, including heterogeneous cell population, fibroblast activation, collagen-rich extracellular matrix deposition, and the spatial arrangement of proliferative, quiescent, and necrotic cells. Following histologic validation, the hyperthermic potential of poly(acrylic acid)-coated Mn0.9Zn0.1Fe2O4 nanoparticle-based magnetic fluid on the heterospheroids was assessed under a 10 kA/m magnetic field strength and 332 kHz frequency. A single-session MFH inhibited heterospheroid growth and induced apoptosis; however, it did not significantly ablate the spheroids. Subsequently, two MFH sessions led to the complete elimination of the spheroids, accompanied by pronounced apoptotic activity. These findings suggest that repeated MFH can overcome thermotolerance, thereby augmenting therapeutic potential against stromal-rich breast tumors.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiscale Computational Insights into Bergenin Encapsulation by Modified γ-Cyclodextrins: Conformational and Energetic Investigations via QM/MM and Molecular Dynamics.","authors":"Pramod Kumar, Rituraj Purohit","doi":"10.1021/acsabm.6c01652","DOIUrl":"https://doi.org/10.1021/acsabm.6c01652","url":null,"abstract":"<p><p>Despite bergenin (BER) having significant therapeutic benefits, its medicinal potential is hindered by its low natural abundance and poor aqueous solubility. Through host-guest complexation with cyclodextrins (CDs), this work offers an economical molecular approach to increase the bioavailability of BER. For the three native CDs (α-, β-, and γ-CD), γ-CD showed superior encapsulation properties. Octakis(6-O-sulfo)-γ-CD and Octakis(2,3,6-tri-O-methyl)-γ-CD were found to be the most suitable hosts for BER after additional screening of γ-CD derivatives. Strong non-bonded interactions and improved conformational stability were found for both complexes in microsecond-scale (2 μs) molecular dynamics (MD) simulations. Counterpoise-corrected DFT calculations at the B3LYP/6-31+G level showed more favorable complexation energy for the Octakis-methyl-γ-CD/BER complex (-52.34 kJ/mol) than for the Octakis-sulfo-γ-CD/BER complex (-33.81 kJ/mol), a trend that was consistently reproduced using the ωB97X-D/6-31G level of theory. Steered MD simulations demonstrated the unbinding mechanism of BER from CD. Higher electronic stability for the methylated complex (8.42 eV gap) than the sulfonated complex (7.01 eV) was shown by HOMO-LUMO orbital energy analysis. This higher stability of Octakis(2,3,6-tri-O-methyl)-γ-CD/BER was supported by two hydrogen bonds and one carbon-hydrogen interaction, as determined by IGMH analysis. The IR and UV-vis spectra of BER were also calculated and systematically compared with the corresponding experimental spectra. These molecular insights demonstrate that Octakis(2,3,6-tri-O-methyl)-γ-CD serves as a superior encapsulation host for BER, enhancing its therapeutic applicability.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulation-Driven Optimization of Nanocomposite Auxetic Intervertebral Disc Substitutes Mimicking Native Mechanics.","authors":"Sumit Suryakant Kolte, Vinayak Vijayan, Lihua Lou","doi":"10.1021/acsabm.6c00702","DOIUrl":"https://doi.org/10.1021/acsabm.6c00702","url":null,"abstract":"<p><p>Intervertebral disc degeneration remains a leading cause of chronic low back pain, and current disc replacement designs often fail to reproduce the behavior of the native intervertebral disc. This study evaluated chiral auxetic disc replacements incorporating polymeric and nanocomposite cores and compared them with a native L4-L5 disc model and a representative commercial implant. The finite element model included cancellous vertebral cores with cortical shells and was subjected to 2.8 mm axial compression and 7.5 N·m pure moments in flexion, extension, and lateral bending. Interfacial pressure, tangential contact stress, and sliding distance were evaluated under compression using pointwise agreement mapping, while posterior anterior-posterior displacement and strain energy were evaluated across all loading modes. The ultra-high molecular-weight polyethylene (UHMWPE) auxetic design provided the strongest overall performance among the proposed designs, with 31.25% pressure agreement and 49.33% sliding-distance agreement with the native disc, compared with 1.01% and 11.47%, respectively, for the commercial design. Graphene-reinforced UHMWPE produced the highest tangential contact stress agreement (34.06%) but reduced pressure and sliding-distance agreement relative to UHMWPE. UHMWPE also provided the closest strain energy response among the auxetic designs and closely reproduced the native posterior displacement during flexion. However, its range of motion remained substantially lower than the native disc, revealing a tradeoff between favorable compressive behavior and rotational compliance. These findings identify the UHMWPE chiral architecture as the most promising design evaluated while demonstrating the need for further geometric optimization to reduce bending stiffness.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biopolymer Silica Hybrids as Superior Nanocarriers for Anticancer Drug Delivery.","authors":"Sumiya Iqbal, Shaista Ilyas, Aya A Ezzat, Menna Hassan, Samar Mansour, Sanjay Mathur","doi":"10.1021/acsabm.6c01527","DOIUrl":"https://doi.org/10.1021/acsabm.6c01527","url":null,"abstract":"<p><p>Liposomal carriers are widely used for anticancer drug delivery due to their biocompatible nature in the biological milieu. Liposome-based drugs often face premature leakage, uncontrolled release, and insufficient control over long-term drug availability. Here, we present poly(lactic-co-glycolic acid) (PLGA)-coated mesoporous silica nanocarriers (PLGA-mSiO2, polysilomes) as an efficient and stable alternative to PEGylated liposomes. Such hybrid transporters are capable of efficiently encapsulating both hydrophilic [doxorubicin (DOX)] and hydrophobic [tamoxifen (TAM)] drugs. Investigation on drug loading, release kinetics, cellular uptake, and therapeutic response confirms the superior drug encapsulation and delivery of polysilomes efficiently. In liposomes, TAM was localized within the lipid bilayer, whereas DOX was actively loaded into the aqueous core through a transmembrane pH gradient. While this architecture enabled coloading, liposomes showed rapid drug release and pronounced cytotoxicity. In contrast, the core-shell structure of PLGA-mSiO2 polysilome carriers retained hydrophilic DOX within the mesoporous silica core and hydrophobic TAM within the PLGA shell. This compartmentalization ensures higher encapsulation efficiencies of both DOX (77.3%) and TAM (60.5%), with loading capacities of 59.3 and 50.4%, respectively. The PLGA-silica interface is a degradable diffusion barrier, enabling pH-responsive sustained release under acidic conditions. Moreover, PLGA-mSiO2 showed enhanced cellular uptake in MDA-MB-231 breast cancer cells and prolonged (up to 144 h) suppression of cell viability. These results present PLGA-coated mesoporous silica nanocarriers as a promising alternative to liposomal delivery by converting rapid drug release into sustained therapeutic activity.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Tumor-Targeting Perovskite Quantum Dot with High Luminescence and Stability for Radiotherapy Sensitization through X-ray-Activated Photoelectrocatalysis.","authors":"Yu Zhang, Jian Li, Rongrong Yan, Siyu Chen, Ruohao Li, Yuanyuan Li, Xin Chen, Yinan Jiao, Hui Bu","doi":"10.1021/acsabm.6c01224","DOIUrl":"https://doi.org/10.1021/acsabm.6c01224","url":null,"abstract":"<p><p>Radiotherapy (RT) remains a cornerstone in lung cancer management, yet its efficacy is often compromised by radiation resistance and off-target toxicity. Metal halide perovskites exhibit high potential for biomedical applications owing to their exceptional fluorescence imaging and photoelectric conversion capabilities, offering distinct radiosensitization advantages via high-Z elements and radiation-excited electron‒hole pairs. However, their poor physiological stability and limited biocompatibility have hindered biomedical translation. Herein, we construct an optimized multifunctional perovskite quantum dot (PQD) modified with chitosan-folate (CS-FA) (Cs-Sn-Pb-Br@CS-FA), which maintains long-term retention of photoluminescence and optical absorption properties in water for over 200 days, enabling specific tumor lesion tracing. Upon X-ray irradiation, the Cs-Sn-Pb-Br@CS-FA can promote the generation of multiple reactive oxygen species (ROS) through photoelectrocatalytically-induced electron‒hole pair separation and triplet energy transfer (TET). Moreover, the generated holes can simultaneously deplete endogenous glutathione (GSH), amplifying ROS accumulation and enhancing radiotherapeutic efficiency to promote tumor cell death. Biosafety assessment verified minimal toxicity to normal tissues at therapeutic doses, with intact fluorescent nanoparticles excreted via feces in their undecomposed perovskite form. In vivo study further underscored the dual functionality of the Cs-Sn-Pb-Br@CS-FA for precise tumor fluorescence imaging and effective radiosensitization in anti-tumor therapy. This work expands the biomedical application horizons of metal halide perovskites.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aloe-Emodin Interaction Study with Human Telomeric G-Quadruplex DNA under K+ and Na+ Conditions.","authors":"Priya Kumari, Manish S Sengar, Kumud Pandav, Ritu Barthwal, Surat Kumar, Arvind K Singh Chandel","doi":"10.1021/acsabm.6c01554","DOIUrl":"https://doi.org/10.1021/acsabm.6c01554","url":null,"abstract":"<p><p>Aloe-emodin (AED), a naturally occurring anthraquinone, was examined for its interaction with two model human telomeric G-quadruplex systems: wHTel26 adopting a hybrid-2 topology in K+-containing buffer and HTel22 adopting an antiparallel basket topology in Na+-containing buffer. UV-visible absorption, fluorescence, and circular dichroism spectroscopy showed concentration-dependent changes consistent with AED association with both G4 models. The apparent binding constants varied among the analytical techniques, spanning approximately 103 M-1-105 M-1, reflecting the distinct optical and conformational observables monitored by each method and the non-linear nature of the titration profiles. The limited wavelength shifts and preservation of the major CD signatures were consistent with a non-intercalative interaction, although the precise binding geometry and stoichiometry could not be resolved. AED produced an apparent thermal stabilization of approximately 14 °C for wHTel26 under the tested K+ condition, whereas no comparable stabilization was observed for HTel22 under the tested Na+ condition. Because the systems differed simultaneously in sequence, flanking residues, topology, and cation, this difference cannot be attributed solely to the ionic environment. Docking generated plausible AED association poses was used only as supportive, hypothesis-generating evidence. AED also reduced MCF-7 metabolic viability with an estimated IC50 of 18.82 µM; however, telomerase inhibition and intracellular G4 target engagement were not investigated. Thus, establishing sequence- and cation-controlled G4 selectivity and confirming intracellular target engagement remain important challenges. Future studies employing matched-sequence/cross-cation comparisons, direct cellular G4-target engagement, and telomerase-based mechanistic assays will be required to establish the molecular and biological significance of AED-G4 interactions.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticle Reinforcement of Poly(diol citrate)-Based Coacervate Adhesives","authors":"Maoyi Lian,&nbsp;Xindi Gao,&nbsp;Kai Liang,&nbsp;Yali Ji","doi":"10.1021/acsabm.6c01521","DOIUrl":"10.1021/acsabm.6c01521","url":null,"abstract":"<p>Tannic acid (TA)-based coacervate adhesives rely primarily on hydrogen-bonding interactions to maintain cohesion. However, these relatively weak hydrogen-bonds easily trigger cohesive failure in practical bonding applications, particularly under wet conditions. To address this limitation, a nanoparticle reinforcement strategy was employed in this study. A poly(diol citrate)-based coacervate adhesive (PN) was first synthesized via one-pot melt polycondensation of citric acid (CA), 1,8-octanediol (OD), and polyethylene glycol (PEG), followed by coupling with N-hydroxysuccinimide (NHS). Subsequently, TA-modified silica (TA-SiO₂) and TA-modified chitin nanocrystals (TA-ChNC) were separately blended with PN and TA in aqueous solution to fabricate two types of nanocomposite coacervate adhesives, denoted as PNTS and PNTC, respectively. The results demonstrated that the cohesive strength, represented by peak stress, was significantly enhanced from 762.4 ± 94.1 kPa (pristine PNT) to 1266.1 ± 63.0 kPa (PNTS-3) and 2201.5 ± 187.6 kPa (PNTC-5), accompanied by a pronounced improvement in lap-shear adhesion strength: for the gel-type adhesives, from 36.6 ± 9.4 kPa (pristine PNT) to 56.4 ± 4.5 kPa (PNTS-3) and 74.4 ± 13.4 kPa (PNTC-3); for powder-type adhesives, from 27.1 ± 5.2 kPa (pristine PNT) to 36.3 ± 7.5 kPa (PNTS-3) and 73.3 ± 8.0 kPa (PNTC-3). Notably, TA-ChNC showed superior reinforcing effects in both gel and powder forms. Furthermore, the nanocomposite adhesives exhibited favorable cytocompatibility and antibacterial activity. Specifically, the PNTC adhesive achieved a hemolysis rate below 5%, together with shortened blood coagulation time and a low blood clotting index (BCI). In summary, the nanoparticle composite strategy effectively improved the overall performance of the coacervate adhesives.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 19","pages":"9248–9257"},"PeriodicalIF":5.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Effects and Medium-Induced Transformations of Non-Apatitic Calcium Phosphates in Relation to Breast Tumor Microcalcifications","authors":"Lorenzo Degli Esposti,&nbsp;Amit Cohen,&nbsp;Adriana Carolina Torres-Mansilla,&nbsp;Netta Vidavsky,&nbsp;Michele Iafisco","doi":"10.1021/acsabm.6c01460","DOIUrl":"10.1021/acsabm.6c01460","url":null,"abstract":"<p>Breast tumor microcalcifications (MCs), primarily composed of calcium phosphates (CaPs), exhibit significant heterogeneity in composition, crystallinity, and ionic substitution. To date, apatite and magnesium-rich whitlockite are the only CaP phases identified in clinical breast tissue samples, while other phases potentially related to pathological biomineralization, such as brushite and monetite, were reported only for other pathologies. Magnesium is frequently incorporated in CaPs formed under physiological or pathological conditions, where it strongly influences crystal structure, crystallinity, solubility, and surface chemistry. Expanding the understanding of magnesium effects beyond apatite-based systems is therefore essential to elucidate phase-dependent cellular behavior. Here, we engineered a panel of synthetic CaP phases, including brushite, low- and high-Mg-doped brushite, whitlockite, monetite, and Mg-doped monetite, which serve as simplified model CaP systems to investigate structure–property–cellular response relationships. Characterization in the cell-free medium revealed Mg/Ca-dependent morphological variations, partial dissolution, reprecipitation, and surface modifications prior to cellular exposure, indicating that cells interact with a dynamic, medium-transformed material system. Upon interaction with non-tumorigenic and precancerous human breast epithelial cells, cellular responses were dependent on both crystal phase and malignancy stage. Under the tested conditions, monetite and high-Mg brushite led to a lower relative proliferation rate in precancerous cells compared to non-malignant cells. Within brushite samples, higher Mg content correlated with reduced proliferation in precancerous cells, whereas this trend was absent for monetite, suggesting that particle effects depend on both chemical composition and crystal phase. These findings demonstrate that magnesium incorporation into non-apatitic CaP phases differentially regulates breast epithelial cell behavior, supporting the view that minerals function as active components of the microenvironment rather than passive deposits.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 19","pages":"9211–9221"},"PeriodicalIF":5.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}