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The development of magnesium calcium phosphate bone cements (MCPCs) has garnered substantial attention. MCPCs are bioactive and biodegradable and have appropriate mechanical and antimicrobial properties for use in reconstructive surgery. In this study, the cement powders based on a (Ca + Mg)/P = 2 system doped with Zn2+ at 0.5 and 1.0 wt.% were obtained and investigated. After mixing with a cement liquid, the structural and phase composition, morphology, chemical structure, setting time, compressive strength, degradation behavior, solubility, antibacterial activities, and in vitro behavior of the cement materials were examined. A high compressive strength of 48 ± 5 MPa (mean ± SD) was achieved for the cement made from Zn2+ 1.0 wt.%-substituted powders. Zn2+ introduction led to antibacterial activity against Staphylococcus aureus and Escherichia coli strains, with an inhibition zone diameter of up to 8 mm. Biological assays confirmed that the developed cement is cytocompatible and promising as a potential bone substitute in reconstructive surgery.

The development of magnesium calcium phosphate bone cements (MCPCs) have garnered big attention. MCPCs are bioactive and biodegradable and have appropriate mechanical and antimicrobial properties for use in reconstructive surgery. In this study, the cement powders based on a (Ca + Mg)/P = 2 system doped with Zn2+ at 0.5 and 1.0 wt.% were obtained and investigated. After the mixing with a cement liquid, structural and phase composition, morphology, chemical structure, setting time, compressive strength, degradation behavior, solubility, antibacterial activities, and in vitro behaviour of the cement materials were examined. A high compressive strength of 48 ± 5 MPa (mean ± SD) was achieved for the cement made from Zn2+ 1.0-wt.%-substituted powders. The Zn2+ introduction led to antibacterial activity against Staphylococcus aureus and Escherichia coli strains, with an inhibition zone diameter up to 8 mm. Biological assays confirmed that the developed cements are cytocompatible and promising as a potential bone substitute in reconstructive surgery.

Mineral-polymer composites based on PVP and hydroxyapatite (HA) are obtained by in situ deposition in solutions of polyvinylpyrrolidone (PVP). The composites are presented in the form of films of hydrogels. During the in situ formation of HA, according to TEM data, round particles up to 10 nm in size are formed. For HA particles, the CSR values ​​are close to the size of crystals obtained from the TEM data, and for the PVP–HA composites, the particle size obtained from the TEM data significantly exceeds the CSR value. The swelling of the obtained films is studied by the gravimetric method: the swelling curve of the mineral-polymer film containing 1.96% HA has a form characteristic of the swelling of hydrogels. Biological studies of polymers and composites of polymers with HA deposited in situ have shown that by-products of the HA formation reaction have a negative effect on cell viability. However, the obtained materials are promising for use as membranes in osteoplastic surgery.

Gold nanoparticles as part of vaccines greatly increase antigen stability, antigen accumulation in the lymph nodes, and antigen uptake by antigen-presenting cells. The use of such particles as part of anticancer vaccines based on heat shock proteins to increase vaccine effectiveness is timely. We prepared and characterized nanoconjugates based on 15-nm gold nanoparticles and thermostable tumor antigens isolated from MH22a murine hepatoma cells. The whole-cell lysate of MH22a cells contained the main heat shock proteins. BALB/c mice were injected with the conjugates and then received transplants of MH22a cells. The highest titer was produced in mice immunized with the complex of gold nanoparticles + antigen with complete Freund’s adjuvant. The immunized mice showed no signs of tumor growth for 24 days. They also showed a decreased production of the INF-γ, IL-6, and IL-1 proinflammatory cytokines compared to the mice immunized through other schemes. This study is the first to show that it is possible in principle to use gold nanoparticles in combination with thermostable tumor antigens for antitumor vaccination. Antitumor vaccines based on thermostable tumor antigens can be largely improved by including gold nanoparticles as additional adjuvants.

Recently, there has been increased interest in the synthesis of nanoparticles by using natural polysaccharides. These polysaccharides are eco-friendly, nontoxic, and cheap to prepare. On the other hand, the attention in hydrocolloids and films has significantly enhanced, and their application is very promising in the food, pharmaceutical, perfumery and cosmetics, oil, paper, and textile industries. In this context, the present study is aimed to prepare silver nanoparticles by using viscous and superviscous exopolysaccharides of the rhizobacterium Paenibacillus polymyxa strains, CCM 1465 and 88A, and examined the properties of the resultant nanoparticles. We examined the synthesis and properties of silver nanoparticles under variable synthetic conditions by using exopolysaccharides of the rhizobacteria Paenibacillus polymyxa CCM 1465 and 88A. To prepare nanoparticles, we used different combinations of exopolysaccharide and silver nitrate concentrations: 1-10 mg/mL and 1-40 mM, respectively. The resulting solutions were alkalinized from pH 7.5-12 and heated for 15, 30, and 60 min to determine the optimal synthetic conditions. We found that the exopolysaccharides of strains CCM 1465 and 88A reduced silver ions and acted as nanoparticle stabilizers. The prepared spherical, oval, and triangular particles were stable and ranged in size from 2 to 40 nm, depending on the strain and on the experimental conditions. The nanoparticles showed antibacterial and antifungal activity against Escherichia coli K-12, Pseudomonas aeruginosa 50.3, Bacillus subtilis 26-D, and Fusarium oxysporum. In addition, the nanoparticles were active against SK-MEL-2 human melanoma cells. This finding shows the promise of further research on the exopolysaccharides of P. polymyxa 1465 and 88А in different fields of science, including medicine.

The interaction of microbial cells with antibody-gold nanoparticle conjugates in conductive suspensions was experimentally studied by using an acoustic slot-mode sensor. The sensor consisted of a piezoelectric plate with a propagating acoustic wave and a liquid container located above this plate with a given gap. An analysis of the measured parameters of the sensor revealed that the specific interaction of bacterial cells with the conjugates led to a stronger change in the sensor output signal than the specific interaction of bacterial cells with antibodies. The measurements were made for Azospirillum brasilense Sp7 cells in buffer with an initial conductivity of 5-30 μS/cm. The limit of cell detection with the conjugates was 103 cells/mL, and the analysis took about 4 min. The advantage of the sensor is the possibility of repeated use and cleaning of the liquid container without damaging the sensor's elements. These results are promising for use in rapid test systems for the direct detection of microbial cells in actual samples of liquids in medical diagnostics.

We have studied manganese-containing calcium phosphates differing in manganese content and phase composition. At a manganese content of 0.15 wt %, the whitlockite content is ~90 wt % and the calcium pyrophosphate content is ~10 wt %. Increasing the manganese content to 1.49 wt % reduces the whitlockite content to ~70 wt % and increases the calcium pyrophosphate content to ~30 wt %. IR spectroscopy results show that the samples calcined at 400°C have the apatite structure, whereas raising the calcination temperature to 900°C leads to the formation of the whitlockite structure and calcium pyrophosphate. Active sintering begins in the range 920–1050°C. Raising the firing temperature to 1200°C leads to the formation of a densely sintered structure, with melted regions and an average grain size from 15 to 25 μm. With increasing manganese content, the grain size of the ceramics decreases. Our results on cytotoxic properties demonstrate that the samples are not cytotoxic and maintain cell proliferation and spreading. The cytotoxicity of the samples is insensitive to the calcium pyrophosphate and manganese concentrations. The powders and ceramics prepared in this study can be used as key components of novel materials for bone tissue engineering.

The review deals with chitosan and polyvinylpyrrolidone and its composite materials with calcium phosphates for medical application. The approaches to obtain the composite materials from chitosan and polyvinylpyrrolidone containing nanosized calcium phosphates are examined, and their physicochemical and biological properties and the areas of possible application are discussed.

This review is devoted to methylcellulose and starch also to its composite materials with calcium phosphates for application in medicine. The techniques of manufacturing the composite materials from methylcellulose and starch containing nanosized calcium phosphate are examined, and their physicochemical and biological properties and the areas of possible application are discussed.

Powders based on β-tricalcium phosphate (β-TCP) containing sulphate groups at up to 12.0 mol.% were synthesised by chemical precipitation from aqueous solutions. The obtained materials were characterised by X-ray phase analysis, Fourier transform infrared spectroscopy, measurement of specific surface area, scanning electron microscopy, energy dispersive analysis, synchronous thermal analysis, mass spectra investigations and biological assays. It was established that during the synthesis, the obtained materials lose the sulphate groups in the course of heat treatment at 900 or 1200 °C. These groups stabilise low-temperature β-TCP, but when introduced at a high concentration, the sulphate groups contribute to the formation of hydroxyapatite during the heat treatment. Specific surface area of the powders proved to be in the range 81.7–96.5 m2/g. Results of biological assays showed cytocompatibility of both pure β-TCP and samples of sulphate-containing β-TCP. Additionally, matrix properties in the culture of MG-63 cells were revealed in all samples. Thus, the obtained materials are promising for biomedical applications.

Silymarin (Sil) was conjugated to selenium nanoparticles (SeNPs) to increase Sil bioavailability. The conjugates were monodisperse; the average diameter of the native SeNPs was ~ 20-50 ± 1.5 nm, whereas that of the conjugates was 30-50 ± 0.5 nm. The use of SeNPs to increase the bioavailability of Syl was examined with the MH-22a, EPNT-5, HeLa, Hep-2, and SPEV-2 cell lines. The EPNT-5 (glioblastoma) cells were the most sensitive to the conjugates compared to the conjugate-free control. The conjugates increased the activity of cellular dehydrogenases and promoted the penetration of Sil into the intracellular space. Possibly, SeNPs play the main part in Sil penetration of cells and Sil penetration is not associated with phagocytosis. Thus, SeNPs are promising for use as a Sil carrier and as protective antigens.

Hydroxyapatite (HA)–polyvinylpyrrolidone (PVP) nanocomposites with the HA/PVP ratio of 3.6–14.5 were synthesized by chemical precipitation from solutions of calcium nitrate and ammonium hydrogen phosphate in a PVP solution. The phase composition, size of coherent scattering regions, and size and morphology of HA particles were determined after heat treatment of the products of synthesis. The chemical interaction of the composite components was established by ESR spectroscopy on exposure to laser radiation at 355 nm.

An original method is proposed for the production of methylcellulose-based film materials. The method is based on obtaining a homogeneous MC mixture with sodium alginate in an aqueous solution and subsequently crosslinking the mixture of the polymers with iron salts owing to their interaction with the blocks of L-guluronic acid in the alginate.

The results of studies concerning ceramics made of substituted (silver, zinc, copper, iron) tricalcium phosphate (TCP) powders are presented. It is shown that the pores in the obtained ceramics are interrelated, the size of macropores ranges from 200 to 400 μm, the size of micropores ranges from 1 to 5 μm, and there are nanopores between the ceramic grains. Such pore sizes can provide the penetration of biological fluxes and cells required for the subsequent formation and growth of new bone tissue into the ceramic matrix. According to the solubility in the physiological solution, the ceramics composed of cation-substituted TCP can be arranged in the following order: Ag ≈ Fe < Cu < Zn. According to the results of studies on the antimicrobial activity with respect to a strain of E. coli bacteria, it has been established that cation-substituted TCPs exhibit a pronounced antimicrobial activity. The highest antimicrobial activity has been shown by the samples of zinc-substituted TCP.

Methylcellulose (MC) is now widely used in medicine to fill defects of damaged tissues. A new method is proposed to improve the stability of MC-based materials in aqueous media using non-toxic reagents. MC–alginate blend films are crosslinked by iron(II) and iron(III) ions using different iron salts. The resulting films are stable in physiological solution for about 14 days. Mechanical tests of the dried films show an increase in the Young's modulus with iron concentration in solutions. Mossbauer spectroscopy data show that the films contain Fe3+ ions alone irrespective of whether chlorides of Fe2+ or Fe3+ are applied as crosslinking agents. The use of ascorbic acid as a complexing agent prevents Fe2+ from oxidation. The obtained materials are stable for at least half a year. The resulting films facilitate the growth of human fibroblasts on their surface.

Brushite cement based on alpha-tricalcium phosphate (α-TCP) and its composite with polylactide (PL) frame with a Kelvin structure were developed. The composite was obtained by filling the PL frame with liquid cement paste by extrusion. A 30% aqueous solution of magnesium dihydrogen phosphate was used as a cement liquid. The cement phase composition was studied before soaking in a physiological solution: the main phases are dicalcium phosphate dihydrate (DCPD), tricalcium phosphate, and amorphous calcium phosphate. It was found that magnesium does not form a separate phase but, probably, is a part of a DCPD crystal lattice. During soaking of cement in a physiological solution, two processes occur simultaneously, namely, the release of calcium ions into the solution, mostly through the dissolution DCPD, and the precipitation of calcium ions from the solution on the cement surface in the form of apatite, which is confirmed by the data of X-ray phase analysis and microstructure studies. After the exposure in a physiological solution, the apatite phase becomes the main phase and the DCPD content decreases, which is related to the transformation of DCPD into the apatite phase. The solubility was studied in a physiological solution containing a Tris buffer. In the absence of a buffer, the solution pH increased and, as a result, the solubility of the composite increased too. In the presence of a buffer, the solubilities of cement and composite varied insignificantly.

Nanotechnology is actively used for diagnosis, treatment and prophylaxis against coronaviruses. To date, methods for producing antibodies and prototypes of vaccines for four types of coronaviruses have been developed. These are: transmissible gastroenteritis coronavirus, avian coronavirus, severe acute respiratory syndrome coronavirus, and SARSCoV-2 coronavirus. Gold nanoparticles can be used as adjuvants to increase the effectiveness of vaccines by stimulating antigen-presenting cells and ensuring controlled antigen release. Thus, gold nanoparticles, which have adjuvant properties, can be an excellent tool in the design of effective vaccines against infectious diseases.

A sensor system based on a piezoelectric resonator with a lateral electric field in the frequency range 6-7 MHz of the electric field for virus detection is described. Through use of the transmissible virus causing gastroenteritis in pigs and specific antibodies, the possibility of detecting the virus in suspension in real time was determined. It was found that the frequency dependence of the real and imaginary parts of the electrical impedance of such a resonator loaded with a virus suspension changes significantly after the addition of specific antibodies to the suspension. No changes are observed if the antibodies are not specific. Thus, the results obtained illustrate the possibility of detecting viruses in situ, directly in the liquid phase, if the change in the real or imaginary parts of the electrical impedance after the addition of antibodies is used as an analytical signal. The possibility of virus detection in the presence of foreign viral particles has been illustrated.

Mesoporous hydroxyapatite (HA) and iron(III)-doped HA (Fe-HA) are attractive materials for biomedical, catalytic, and environmental applications. In the present study, the nanopowders of HA and Fe-HA with a specific surface area up to 194.5 m2/g were synthesized by a simple precipitation route using iron oxalate as a source of Fe3+ cations. The influence of Fe3+ amount on the phase composition, powders morphology, Brunauer–Emmett–Teller (BET) specific surface area (S), and pore size distribution were investigated, as well as electron paramagnetic resonance and Mössbauer spectroscopy analysis were performed. According to obtained data, the Fe3+ ions were incorporated in the HA lattice, and also amorphous Fe oxides were formed contributed to the gradual increase in the S and pore volume of the powders. The Density Functional Theory calculations supported these findings and revealed Fe3+ inclusion in the crystalline region with the hybridization among Fe-3d and O-2p orbitals and a partly covalent bond formation, whilst the inclusion of Fe oxides assumed crystallinity damage and rather occurred in amorphous regions of HA nanomaterial. In vitro tests based on the MG-63 cell line demonstrated that the introduction of Fe3+ does not cause cytotoxicity and led to the enhanced cytocompatibility of HA.

A method for the rapid detection of coronaviruses is presented on the example of the transmissible gastroenteritis virus (TGEV) directly in aqueous solutions with different conductivity. An acoustic sensor based on a slot wave in an acoustic delay line was used for the research. The addition of anti-TGEV antibodies (Abs) diluted in an aqueous solution led to a change in the depth and frequency of resonant peaks on the frequency dependence of the insertion loss of the sensor. The difference in the output parameters of the sensor before and after the biological interaction of the TGE virus in solutions with the specific antibodies allows drawing a conclusion about the presence/absence of the studied viruses in the analyzed solution. The possibility for virus detection in aqueous solutions with the conductivity of 1.9–900 μs/cm, as well as in the presence of the foreign viral particles, has been demonstrated. The analysis time did not exceed 10 min.

Background: The liver disease problem prompts investigators to search for new methods of liver treatment. Introduction: Silymarin (Sil) protects the liver by reducing the concentration of free radicals and the extent of damage to the cell membranes. A particularly interesting method to increase the bioavailability of Sil is to use synthesized gold nanoparticles (AuNPs) as reagents. The study considered whether it was possible to use the silymarin-AuNP conjugate as a potential liver-protecting drug. Methods: AuNPs were conjugated to Sil and the liver-protecting activity of the conjugate was examined. Experimental hepatitis and hepatocyte cytolysis after carbon tetrachloride action were used as a model system, and the experiments were conducted with laboratory animals. Result: For the first time, silymarin was conjugated to colloidal gold nanoparticles (AuNPs). Electron microscopy showed that the resultant preparations were monodisperse and that the mean conjugate diameter was 18-30 nm ± 0.5 nm (mean diameter of the native nanoparticles, 15 ± 0.5 nm). In experimental hepatitis in mice, conjugate administration interfered with glutathione depletion in hepatocytes in response to carbon tetrachloride. It also was conducive to an increase in energy metabolism and stimulated the monocyte-macrophage function of the liver. The results were confirmed by the high respiratory activity of the hepatocytes in cell culture. Conclusion: We conclude that the silymarin-AuNP conjugate holds promise as a liver-protecting agent in acute liver disease caused by carbon tetrachloride poisoning.

Carbonated hydroxyapatite (CHA) owing to its chemical and phase composition that is similar to that of the inorganic component of native bone tissue is a promising material for reconstructive surgery to heal bone defects that are caused by trauma and extensive surgery. An original method for obtaining porous CHA ceramic granules was developed. To obtain a system of interconnected pores, a protein foam with sucrose was used. The optimum ratio of the protein foam to the ceramic CHA powder was found to be 3: 1 for production of porous ceramics with a homogeneous structure. The mechanical properties of the porous CHA ceramics that we obtained at different ratios between the protein foam and ceramic CHA powder were studied: as the concentration of the ceramic CHA powder increased in the mixture, the compressive strength of the CHA ceramics decreased from 6–7 to 2–3 MPa. The microstructure of the CHA ceramics is characterized by the presence of pores that are different in size, from fractions to tens of microns. In vitro studies of the porous CHA ceramics were performed. The evaluation of the influence of the granules on the growth of rat MMSCs in vitro revealed a decrease in the cell viability with an increase in the concentration of the granules. The reduced viability of the MMSCs in the presence of the granules can be associated with alkalization of the environment by the sintering additive.

Gold nanoparticles (AuNPs) are successfully used as an adjuvant in the design of effective vaccines and in the preparation of high-affinity antibodies to haptens and complete antigens. Here, we assessed the adjuvant properties of AuNPs conjugated to a synthetic M2e peptide of the influenza A virus capsid. The resulting conjugate, a commercial influenza vaccine, and M2e in combination with different adjuvants were used to immunize laboratory mice. The highest titer was detected in the sera of mice immunized with two adjuvants: AuNPs and AuNP-conjugated CpG oligodeoxynucleotide 1826. With this combination, we also recorded increases in the respiratory activity of splenic lymphocytes, in the respiratory activity of peritoneal macrophages, and in the production of proinflammatory cytokines (IL-6 and IFN-γ). The results indicate that simultaneous immunization of the animals with two conjugates—M2e + AuNPs and CpG + AuNPs—activates antibody development. Therefore, the use of AuNPs as an antigen carrier leads to a complete and coordinated immune response from both cellular and humoral immunity.

The electro-acoustical sensor for the real-time identification of the bacteriophage FAl-SR65 is described. The polyclonal antibodies specific to the bacteriophage FAl-SR65 were for the first time obtained, and the possibility of their application to the bacteriophage detection by using the electro-acoustical method of analysis was also studied for the first time. The electro-acoustical sensor was based on the lateral electric field excited piezoelectric resonator. The frequency dependences of the real and imaginary parts of the electrical impedance of such a resonator, loaded with the virus-antibody suspension, significantly differed from those measured for the same resonator with the same virus suspension but without antibodies (control). The limit for the reliable bacteriophage detection during their interaction with the antibodies (sensitivity level) was determined to be 106 phages ml-1. The obtained results demonstrate the possibility to record the bacteriophage-antibody interactions and can be used as the basis for the development of the biological sensor for the quantitative virus detection.

Brushite cement obtained from α-Ca3(PO4)2 and orthophosphoric acid in the presence of Mg(H2PO4)2 with compressive strength of 18 MPa was armored with a framework with the Kelvin architecture made of polylactide by thermoextrusion 3D printing. It is shown that armoring of cement with polylactide framework allows one not only to increase the compressive strength of such a structure (up to 35 MPa) but also to significantly improve its deformability (up to 15%).

The possibility of detecting bacteriophages using phage mini-antibodies by the electroacoustic analysis method using bacteriophages FA1-59b was shown. It was found that the frequency dependence of the real and imaginary parts of the electrical impedance of a resonator with a suspension of phages and the appropriate antibodies significantly differs from that of the resonator with a control virus suspension without addition of mini-antibodies. The amount of FAl-Sp59b bacteriophage in the analyzed suspension varied from ~1010 to 106 phage/mL; the analysis did not take longer than 5 min. The change in the real or imaginary parts of the electrical impedance at the fixed frequency near the resonance after addition of specific mini-antibodies in the suspension appeared to be an optimal information parameter to obtain reliable information. These results may allow the development of a biological sensor to identify and quantify viruses in the liquid phase.

The phase composition of brushite cement that is based on β-tricalcium phosphate (β-TCP) and monocalcium phosphate monohydrate (MCPM) is optimized. It is shown that an increase in the β-TCP/MCPM ratio from 1.0 to 1.35 leads to a 20% increase in the cement compressive strength. We assume that this is due to reinforcement of the cement with ceramic particles of β-TCP. Carbonated hydroxyapatite (CHA) granules that are introduced into the cement composition in the amount of 10 wt % also lead to a 20% increase in the cement compressive strength. The cement that is investigated is promising for use in osteoplastic surgery for healing of bone tissue defects that result from trauma and extensive surgery.

This paper examines the physicochemical properties and microstructure of brushite calcium phosphate cements possessing strength acceptable for application in surgery (15–20 MPa) and ensuring an optimal acidity (pH 6.5–7.5) of solutions in contact with them. Holding in a physiological saline produces significant changes in the microstructure of the cement relative to that before immersion in the solution: it causes a transformation of the most soluble components into platelike hydroxyapatite crystals.

Intrinsically disordered proteins play a central role in dynamic regulatory and assembly processes in the cell. Recently, a human &kappa, casein proteolytic fragment called lactaptin (8.6 kDa) was found to induce apoptosis of human breast adenocarcinoma MCF-7 and MDA-MB-231 cells with no cytotoxic activity toward normal cells. Earlier, we had designed some recombinant analogs of lactaptin and compared their biological activity. Among these analogs, RL2 has the highest antitumor activity, but the amino acid residues and secondary structures that are responsible for RL2&prime, s activity remain unclear. To elucidate the structure&ndash, activity relations of RL2, we studied the structural and aggregation features of this fairly large intrinsically disordered fragment of human milk &kappa, casein by a combination of physicochemical methods: NMR, paramagnetic relaxation enhancement (PRE), Electron Paramagnetic Resonance (EPR), circular dichroism, dynamic light scattering, atomic force microscopy, and a cytotoxic activity assay. It was found that in solution, RL2 exists as stand-alone monomeric particles and large aggregates. Whereas the disulfide-bonded homodimer turned out to be more prone to assembly into large aggregates, the monomer predominantly forms single particles. NMR relaxation analysis of spin-labeled RL2 showed that the RL2 N-terminal region, which is essential not only for multimerization of the peptide but also for its proapoptotic action on cancer cells, is more ordered than its C-terminal counterpart and contains a site with a propensity for &alpha, helical secondary structure.

Succeeding in the substitution of pharmaceutical compounds with ions deliverable with the use of resorbable biomaterials could have far-reaching benefits for medicine and economy. Calcium phosphates are known as excellent accommodators of foreign ions. Manganese, the fifth most abundant metal on Earth was studied here as an ionic dopant in ?-tricalcium phosphate (?-TCP) ceramics. ?-TCP containing different amounts of Mn2+ ions per MnxCa3-x(PO4)2 formula (x = 0, 0.001, 0.01, and 0.1) was investigated for a range of physicochemical and biological properties. The results suggested the role of Mn2+ as a structure booster, not breaker. Mn2+ ions increased the size of coherent X-ray scattering regions averaged across all crystallographic directions and also lowered the temperature of transformation of the hydroxyapatite precursor to ?-TCP. The particle size increased fivefold, from 20 to 100 nm, in the 650-750 °C region, indicating that the reaction of formation of ?-TCP was accompanied by a considerable degree of grain growth. The splitting of the antisymmetric stretching mode of the phosphate tetrahedron occurred proportionally to the Mn2+ content in the material, while electron paramagnetic resonance spectra suggested that Mn2+ might substitute for three out of five possible calcium ion positions in the unit cell of ?-TCP. The biological effects of Mn free ?-TCP and Mn-doped ?-TCP were selective: moderately proliferative to mammalian cells, moderately inhibitory to bacteria, and insignificant to fungi. Unlike pure ?-TCP, ?-TCP doped with the highest concentration of Mn2+ ions significantly inhibited the growth of all bacterial species tested: Staphylococcus aureus, Salmonella typhi, Escherichia coli, Pseudomonas aeruginosa, and Enterococcus faecalis. The overall effect against the Gram-positive bacteria was more intense than against the Gram-negative microorganisms. Meanwhile, ?-TCP alone had an augmentative effect of the viability of adipose-derived mesenchymal stem cells (ADMSCs) and the addition of Mn2+ tended to reduce the extent of this augmentative effect, but without imparting any toxicity. For all Mn-doped ?-TCP concentrations except the highest, the cell viability after 72 h incubation was significantly higher than that of the negative control. Assays evaluating the effect of Mn2+-containing ?-TCP formulations on the differentiation of ADMSCs into three different lineages: osteogenic, adipogenic, and chondrogenic - demonstrated no inhibitory or adverse effects compared to pure ?-TCP and powder-free positive controls. Still, ?-TCP delivering the lowest amount of Mn2+ seemed most effective in sustaining the differentiation process toward all three phenotypes, indicating that the dose of Mn2+ in ?-TCP need not be excessive to be effective.