Search Results (108)

Breast cancer (BC) frequently metastasizes to bone, leading to poor patient prognosis. The infiltration of cancer cells in bone impairs its homeostasis, triggering a pathological interaction between tumors and resident cells. Preclinical models able to mimic the bone microenvironment are needed to advance translational findings on BC mechanisms and treatments. We designed strontium-doped calcium phosphate cement to be employed for culturing cancer and bone cells and developed an in vitro bone metastasis model. The platform was established step by step, starting with the monoculture of cancer cells, mature osteoblasts (OBs) differentiated from mesenchymal stem cells, and mature osteoclasts (OCs) differentiated from Peripheral Blood Mononuclear Cells. The model was implemented with the co-culture of cancer cells with OBs or OCs, or the co-culture of OBs and OCs, allowing us to discriminate the interaction between the actors of the bone metastatic niche. The biomimetic material was further challenged with bone metastasis patient-derived material, showing good versatility and biocompatibility, suggesting its potential use as bone substitute. Overall, we developed a bone-mimicking model able to reproduce reciprocal interactions between cancer and bone cells in a biomimetic environment suitable for studying the biomolecular determinants of bone metastasis and, in the future, as a drug efficacy platform. Full article

Cranio-maxillofacial bone reconstruction, especially for large defects, remains challenging. Synthetic biomimetic materials are emerging as alternatives to autogenous grafts. Tissue engineering aims to create natural tissue-mimicking materials, with calcium phosphate-based scaffolds showing promise for bone regeneration applications. This study developed a porous calcium metaphosphate (CMP) scaffold with physicochemical properties mimicking natural bone, aiming to create a prevascularized synthetic bone graft. The scaffold, fabricated using sintered monocalcium phosphate with poly (vinyl alcohol) as a porogen, exhibited pore sizes ranging from 0 to 400 μm, with the highest frequency between 80 and 100 μm. The co-culture of endothelial cells (ECs) with human alveolar osteoblasts (aHOBs) on the scaffold led to the formation of tube-like structures and intrinsic VEGF release, reaching 10,455.6 pg/mL This level approached the optimal dose for vascular formation. Conversely, the co-culture with mesenchymal stem cells did not yield similar results. Combining ECs and aHOBs in the CMP scaffold offers a promising approach to developing prevascularized grafts for cranio-maxillofacial reconstruction. This innovative strategy can potentially enhance vascularization in large tissue-engineered constructs, addressing a critical limitation in current bone regeneration techniques. The prevascularized synthetic bone graft developed in this study could significantly improve the success rate of maxillofacial reconstructions, offering a viable alternative to autogenous grafts. Full article

Although SeO₃²⁻ ions have been loaded onto calcium phosphate to treat a wide range of cancers, the quest to promote bone tissue regeneration is still ongoing. Curcumin (cur), an herbal extraction, can selectively inhibit tumor cells and promote osteogenesis. In this study, SeO₃²⁻ ions were co-precipitated in biomimetic calcium phosphate (Se@BioCaP), and modified curcumin prodrug (mcur) was adsorbed on diverse Se@BioCaP surfaces (mcur-Se@BioCaP-Ads). Co-precipitation yielded Se@BioCaP with a significantly higher Se content and exhibited a tailorable micro-/nanostructure. The favorable pH-responsive release of Se and mcur from mcur-Se@BioCaP-Ads showed a synergistic anticancer efficiency in OS cells, enhancing OS cell inhibition more than a single dose of them, which might be associated with ROS production in OS cells. In addition, increased alkaline phosphatase activity and calcium nodule formation in MC3T3-E1 pre-osteoblasts were also verified. These results suggest this novel mcur-Se@BioCaP-Ads has promising and widespread potential in OS treatments. Full article

Bone defects caused by surgical interventions and the challenges of tumor recurrence and metastasis due to residual cancer cells significantly complicate the treatment of osteosarcoma (OS). To address these complex clinical challenges, we propose an innovative therapeutic strategy that centers on an ultrasound-activated multifunctional bioactive calcium phosphate (BioCaP) composite. A modified curcumin (mcur)-mediated wet biomimetic mineralization process was used to develop an anticancer-drug-integrated multifunctional BioCaP (mcur@BioCaP), exploring its potential biological effects for OS treatment activated by ultrasound (US). The mcur@BioCaP demonstrates a drug dose-dependent, tailorable alteration in its micro/nanostructure. The US stimulus significantly enhanced this composite to generate reactive oxygen species (ROS) in cancer cells. The results show that the OS cell viability of the mcur@BioCaP with US is 62.2% ± 6.3%, the migration distance is 63.9% ± 6.6%, and the invaded OS cell number is only 57.0 ± 3.7 OS cells per version, which were all significantly lower than US or mcur@BioCaP alone, suggesting that the anticancer, anti-migratory and anti-invasive effects of mcur@BioCaP on OS 143B cells were amplified by ultrasonic stimulation. This amplification can be attributed to the US-activated ROS production from the drug molecules, which regulates the wet biomimetic mineralization of the multifunctional composite. Furthermore, mcur@BioCaP with US increased calcium nodule formation by 1.8-fold, which was significantly higher than mcur@BioCaP or US group, indicating its potential in promoting bone regeneration. The anticancer and osteogenic potentials of mcur@BioCaP were found to be consistent with the mcur concentration in the multifunctional composite. Our research provides a novel therapeutic approach that leverages a multifunctional biomimetic mineral and ultrasonic activation, highlighting its potential applications in OS therapy. Full article

Calcium-based materials, such as calcium carbonate, calcium phosphate, and calcium silicate, have attracted significant attention in biomedical research, owing to their unique physicochemical properties and versatile applications. The distinctive characteristics of these materials, including their inherent biocompatibility and tunable structures, hold significant promise for applications in bone regeneration and tissue engineering. This review explores the biomedical applications of calcium-containing materials, particularly for bone regeneration. Their remarkable biocompatibility, tunable nanostructures, and multifaceted functionalities make them pivotal for advancing regenerative medicine, drug delivery system, and biomimetic scaffold applications. The evolving landscape of biomedical research continues to uncover new possibilities, positioning calcium-based materials as key contributors to the next generation of innovative biomaterial scaffolds. Full article

Simulated body fluid (SBF) and artificial saliva (AS) are used in biomedical and dental research to mimic the physiological conditions of the human body. In this study, the biomimetic precipitation of double-doped amorphous calcium phosphate in SBF and AS are compared by thermodynamic modelling of chemical equilibrium in the SBF/AS-CaCl₂-MgCl₂-ZnCl₂-K₂HPO₄-H₂O and SBF/AS-CaCl₂-MgCl₂-ZnCl₂-K₂HPO₄-Glycine/Valine-H₂O systems. The saturation indices (SIs) of possible precipitate solid phases at pH 6.5, close to pH of AS, pH 7.5, close to pH of SBF, and pH 8.5, chosen by us based on our previous experimental data, were calculated. The results show possible precipitation of the same salts with almost equal SIs in the two biomimetic environments at the studied pHs. A decrease in the saturation indices of magnesium and zinc phosphates in the presence of glycine is a prerequisite for reducing their concentrations in the precipitates. Experimental studies confirmed the thermodynamic predictions. Only X-ray amorphous calcium phosphate with incorporated Mg (5.86–8.85 mol%) and Zn (0.71–2.84 mol%) was obtained in the experimental studies, irrespective of biomimetic media and synthesis route. Solid-state nuclear magnetic resonance (NMR) analysis showed that the synthesis route affects the degree of structural disorder of the precipitates. The lowest concentration of dopant ions was obtained in the presence of glycine. Further, the behaviour of the selected amorphous phase in artificial saliva was studied. The dynamic of Ca²⁺, Mg²⁺, and Zn²⁺ ions between the solid and liquid phases was monitored. Both direct excitation ³¹P NMR spectra and ¹H-³¹P CP-MAS spectra proved the increase in the nanocrystalline hydroxyapatite phase upon increasing the incubation time in AS, which is more pronounced in samples with lower additives. The effect of the initial concentration of doped ions on the solid phase transformation was assessed by solid-state NMR. Full article

Carbonated apatite (CAp), known as the main mineral that makes up human bone, can be utilized in conjunction with scaffolds to increase their bioactivity. Various methods (e.g., co-precipitation, hydrothermal, and biomimetic coatings) have been used to provide bioactivity by forming CAp on surfaces similar to bone minerals. Among them, the use of simulated body fluids (SBF) is the most popular biomimetic method for generating CAp, as it can provide a mimetic environment. However, coating methods using SBF require at least a week for CAp formation. The long time it takes to coat biomimetic scaffolds is a point of improvement in a field that requires rapid regeneration. Here, we report a step-wise biomimetic coating method to form CAp using calcium carbonate vaterite (CCV) as a precursor. We can manufacture CCV-transformed CAp (V-CAp) on the surface in 4 h at least by immersing CCV in a phosphate solution. The V-CAp deposited surface was analyzed using scanning electron microscopy (SEM) images according to the type of phosphate solutions to optimize the reaction conditions. X-ray diffraction (XRD) and attenuated total reflection-Fourier transform infrared (ATR-FTIR) analysis validated the conversion of CCV to V-CAp on surfaces. In addition, the bioactivity of V-CAp coating was analyzed by the proliferation and differentiation of osteoblasts in vitro. V-CAp showed 2.3-folded higher cell proliferation and 1.4-fold higher ALP activity than the glass surface. The step-wise method of CCV-transformed CAp is a biocompatible method that allows the environment of bone regeneration and has the potential to confer bioactivity to biomaterial surfaces, such as imparting bioactivity to non-bioactive metal or scaffold surfaces within one day. It can rapidly form carbonated apatite, which can greatly improve time efficiency in research and industrial applications. Full article

Mineralized materials are gaining increased interest recently in a number of fields, especially in bone tissue engineering as bone replacement materials as well as in the architecture-built environment as structural building materials. Until the moment, there has not been a unified sustainable approach that addresses this multi-scale application objective by developing a self-mineralized material with minimum consumption of materials and processes. Thus, in the current study, a hydrogel developed from sodium alginate, gelatine, and calcium phosphate dibasic (CPDB) was optimized in terms of rheological properties and mineralization capacity through the formation of hydroxyapatite crystals. The hydrogel composition process adopted a three-stage, thermally induced chemical cross-linking to achieve a stable and enhanced hydrogel. The 6% CPDB-modified SA–gelatine hydrogel achieved the best rheological properties in terms of elasticity and hardness. Different concentrations of epigallocatechin gallate were tested as well as a rheological enhancer to optimize the hydrogel and to boost its anti-microbial properties. However, the results from the addition of EPGCG were not considered significant; thus, the 6% CPDB-modified SA–gelatine hydrogel was further tested for mineralization by incubation in various media, without and with cells, for 7 and 14 days, respectively, using scanning electron microscopy. The results revealed significantly enhanced mineralization of the hydrogel by forming hydroxyapatite platelets of the air-incubated hydrogel (without cells) in non-sterile conditions, exhibiting antimicrobial properties as well. Similarly, the air-incubated bioink with osteosarcoma SaOs-2 cells exhibited dense mineralized topology with hydroxyapatite crystals in the form of faceted spheres. Finally, the FBS-incubated hydrogel and FBS-incubated bioink, incubated for 7 and 14 days, respectively, exhibited less densely mineralized topology and less distribution of the hydroxyapatite crystals. The degradation rate of the hydrogel and bioink incubated in FBS after 14 days was determined by the increase in dimensions of the 3D-printed samples, which was between 5 to 20%, with increase in the bioink samples dimensions in comparison to their dimensions post cross-linking. Meanwhile, after 14 days, the hydrogel and bioink samples incubated in air exhibited shrinkage: a 2% decrease in the dimensions of the 3D-printed samples in comparison to their dimensions post cross-linking. The results prove the capacity of the developed hydrogel in achieving mineralized material with anti-microbial properties and a slow-to-moderate degradation rate for application in bone tissue engineering as well as in the built environment as a structural material using a sustainable approach. Full article

This study aims to develop multi-functional bio-safe dental resin composites with capabilities for mineralization, high in vitro biocompatibility, and anti-biofilm properties. To address this issue, experimental resin composites consisting of UDMA/TEGDMA-based dental resins and low quantities (1.9, 3.8, and 7.7 vol%) of 45S5 bioactive glass (BAG) particles were developed. To evaluate cellular responses of resin composites, MC3T3-E1 cells were (1) exposed to the original composites extracts, (2) cultured directly on the freshly cured resin composites, or (3) cultured on preconditioned composites that have been soaked in deionized water (DI water), a cell culture medium (MEM), or a simple HEPES-containing artificial remineralization promotion (SHARP) solution for 14 days. Cell adhesion, cell viability, and cell differentiation were, respectively, assessed. In addition, the anti-biofilm properties of BAG-loaded resin composites regarding bacterial viability, biofilm thickness, and biofilm morphology, were assessed for the first time. In vitro biological results demonstrated that cell metabolic activity and ALP expression were significantly diminished when subjected to composite extracts or direct contact with the resin composites containing BAG fillers. However, after the preconditioning treatments in MEM and SHARP solutions, the biomimetic calcium phosphate minerals on 7.7 vol% BAG-loaded composites revealed unimpaired or even better cellular processes, including cell adhesion, cell proliferation, and early cell differentiation. Furthermore, resin composites with 1.9, 3.8, and 7.7 vol% BAG could not only reduce cell viability in S. mutans biofilm on the composite surface but also reduce the biofilm thickness and bacterial aggregations. This phenomenon was more evident in BAG7.7 due to the high ionic osmotic pressure and alkaline microenvironment caused by BAG dissolution. This study concludes that multi-functional bio-safe resin composites with mineralization and anti-biofilm properties can be achieved by adding low quantities of BAG into the resin system, which offers promising abilities to mineralize as well as prevent caries without sacrificing biological activity. Full article

β-tricalcium phosphate (β-TCP) is a promising material in regenerative traumatology for the creation of bone implants. Previously, it was established that doping the structure with certain cations can reduce the growth of bacterial activity. Recently, much attention has been paid to co-doped β-TCP, that is explained by their ability, on the one hand, to reduce cytotoxicity for cells of the human organism, on the other hand, to achieve a successful antibacterial effect. Sr, Cu-co-doped solid solutions of the composition Ca_9.5–xSr_xCu(PO₄)₇ was obtained by the method of solid-phase reactions. The Rietveld method of structural refinement revealed the presence of Sr²⁺ ions in four crystal sites: M1, M2, M3, and M4. The M5 site is completely occupied by Cu²⁺. Isomorphic substitution of Ca²⁺ → (Sr²⁺and Cu²⁺) expands the concentration limits of the existence of the solid solution with the β-TCP structure. No additional phases were formed up to x = 4.5 in Ca_9.5–xSr_xCu(PO₄)₇. Biocompatibility tests were performed on cell lines of human bone marrow mesenchymal stromal cells (hMSC), human fibroblasts (MRC-5) and osteoblasts (U-2OS). It was demonstrated that cytotoxicity exhibited a concentration dependence, along with an increase in osteogenesis and cell proliferation. Ca_9.5–xSr_xCu(PO₄)₇ powders showed significant inhibitory activity against pathogenic strains Escherichia coli and Staphylococcus aureus. Piezoelectric properties of Ca_9.5–xSr_xCu(PO₄)₇ were investigated. Possible ways to achieve high piezoelectric response are discussed. The combination of bioactive properties of Ca_9.5–xSr_xCu(PO₄)₇ renders them multifunctional materials suitable for bone substitutes. Full article

This study investigates the profound impact of the ZrO₂ inclusion volume on the characteristics of Al₂O₃/ZrO₂ nanocomposites, particularly influencing the formation of calcium phosphates on the surface. This research, aimed at advancing tissue engineering, prepared nanocomposites with 5, 10, and 15 vol% ZrO₂, subjecting them to chemical surface treatment for enhanced calcium phosphate deposition sites. Biomimetic coating with Sr-enriched simulated body fluid (SBF) further enhanced the bioactivity of nanocomposites. While the ZrO₂ concentration heightened the oxygen availability on nanocomposite surfaces, the quantity of Sr-containing phosphate was comparatively less influenced than the formation of calcium phosphate phases. Notably, the coated nanocomposites exhibited a high cell viability and no toxicity, signifying their potential in bone tissue engineering. Overall, these findings contribute to the development of regenerative biomaterials, holding promise for enhancing bone regeneration therapies. Full article

Hybrid materials based on calcium phosphates and synthetic polymers can potentially be used for caries protection due to their similarity to hard tissues in terms of composition, structure and a number of properties. This study is focused on the biomimetic synthesis of hybrid materials consisting of hydroxiapatite and the zwitterionic polymers polysulfobetaine (PSB) and polycarboxybetaine (PCB) using controlled media conditions with a constant pH of 8.0–8.2 and Ca/P = 1.67. The results show that pH control is a dominant factor in the crystal phase formation, so nano-crystalline hydroxyapatite with a Ca/P ratio of 1.63–1.71 was observed as the mineral phase in all the materials prepared. The final polymer content measured for the synthesized hybrid materials was 48–52%. The polymer type affects the final microstructure, and the mineral particle size is thinner and smaller in the synthesis performed using PCB than using PSB. The final intermolecular interaction of the nano-crystallized hydroxyapatite was demonstrated to be stronger with PCB than with PSB as shown by our IR and Raman spectroscopy analyses. The higher remineralization potential of the PCB-containing synthesized material was demonstrated by in vitro testing using artificial saliva. Full article

Natural and renewable sources of calcium carbonate (CaCO₃), also referred to as “biogenic” sources, are being increasingly investigated, as they are generated from a number of waste sources, in particular those from the food industry. The first and obvious application of biogenic calcium carbonate is in the production of cement, where CaCO₃ represents the raw material for clinker. Overtime, other more added-value applications have been developed in the filling and modification of the properties of polymer composites, or in the development of biomaterials, where it is possible to transform calcium carbonate into calcium phosphate for the substitution of natural hydroxyapatite. In the majority of cases, the biological structure that is used for obtaining calcium carbonate is reduced to a powder, in which instance the granulometry distribution and the shape of the fragments represent a factor capable of influencing the effect of addition. As a result of this consideration, a number of studies also reflect on the specific characteristics of the different sources of the calcium carbonate obtained, while also referring to the species-dependent biological self-assembly process, which can be defined as a more “biomimetic” approach. In particular, a number of case studies are investigated in more depth, more specifically those involving snail shells, clam shells, mussel shells, oyster shells, eggshells, and cuttlefish bones. Full article

Coating layers consisting of a crystalline apatite matrix with immobilized basic fibroblast growth factor (bFGF) can release bFGF, thereby enhancing bone regeneration depending on their bFGF content. We hypothesized that the incorporation of fluoride ions into apatite crystals would enable the tailored release of bFGF from the coating layer depending on the layer’s fluoride content. In the present study, coating layers consisting of fluoride-incorporated apatite (FAp) crystals with immobilized bFGF were coated on a porous collagen sponge by a precursor-assisted biomimetic process using supersaturated calcium phosphate solutions with various fluoride concentrations. The fluoride content in the coating layer increased with the increasing fluoride concentration of the supersaturated solution. The increased fluoride content in the coating layer reduced its solubility and suppressed the burst release of bFGF from the coated sponge into a physiological salt solution. The bFGF release was caused by the partial dissolution of the coating layer and, thus, accompanied by the fluoride release. The concentrations of released bFGF and fluoride were controlled within the estimated effective ranges in enhancing bone regeneration. These findings provide useful design guidelines for the construction of a mineralized, bFGF-releasing collagen scaffold that would be beneficial for bone tissue engineering, although further in vitro and in vivo studies are warranted. Full article

This study examined the effectiveness of coating demineralized bone matrix (DBM) with amorphous calcium phosphate (DBM + CaP), as well as a composite of DBM, calcium phosphate, and serum albumin (DBM + CaP + BSA). The intact structure of DBM promotes the transformation of amorphous calcium phosphate (CaP) into dicalcium phosphate dihydrate (DCPD) with a characteristic plate shape and particle size of 5–35 µm. The inclusion of BSA in the coating resulted in a better and more uniform distribution of CaP on the surface of DBM trabeculae. MG63 cells showed that both the obtained forms of CaP and its complex with BSA did not exhibit cytotoxicity up to a concentration of 10 mg/mL in vitro. Ectopic (subcutaneous) implantation in rats revealed pronounced biocompatibility, as well as strong osteoconductive, osteoinductive, and osteogenic effects for both DBM + CaP and DBM + CaP + BSA, but more pronounced effects for DBM + CaP + BSA. In addition, for the DBM + CaP + BSA samples, there was a pronounced full physiological intrafibrillar biomineralization and proangiogenic effect with the formation of bone-morrow-like niches, accompanied by pronounced processes of intramedullary hematopoiesis, indicating a powerful osteogenic effect of this composite. Full article