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The abstract of the paper is here:

The increasing use of TiO2 nanomaterials (TiNMs) in bone tissue engineering raises
concerns about their biocompatibility. To date, majority of biological testing was focused on the cytotoxicity of TiO2 nanoparticles and their composites. However, evaluation of immunocompatibility and effects on hemostasis is crucial for successful clinical applications of bone regeneration materials. Such data are scarce for TiNMs.  
To fill this gap, this study aimed to investigate impact of TiNMs with different
morphologies and their composites with calcium deficient hydroxyapatite (CaDHA/TiNMs) on hemostasis, as well as the cell viability and inflammatory response of Jurkat T cells. Four different TiNMs, nanoparticles (TiNPs), nanoplates (TiNPls), nanotubes (TiNTs), nanowires (TiNWs), and their composites with CaDHA were studied.
Among investigated materials, the least effect was observed for CaDHA. Effect on plasma coagulation was observed only for TiNPs, which shortened the prothrombin time. All TiNMs affected global hemostasis, especially the elongated TiNWs. Coating TiNMs with CaDHA resulted in a less pronounced effect compared to TiNMs. No significant effect on the viability of Jurkat T cells was observed for TiNMs, while composites increased it. Analysis of the expression of pro- inflammatory (IL-6, IL-8 and TNFa) and anti-inflammatory (IL-10) cytokines indicated inflammatory potential of investigated materials. Among TiNMs, TiNWs had the most pronounced pro-inflammatory effect, while CaDHA/TiNTs and CaDHA/TiNWs showed the most pronounced effect among composites.  
The obtained results confirm the potential of investigated materials for biomedical
applications. However, further studies are needed to establish a more precise relationship between the materials’ physico-chemical properties and their biological effects, thus ensuring their safe application.

The paper is authored by: Suzana Inkret, Ina Erceg, Marija Ćurlin, Nikolina Kalčec, Nikolina Peranić, Ivana Vinković Vrček, Darija Domazet Jurašin and Maja Dutour Sikirić

The article is available here:
Comparison of bovine serum albumin and chitosan effects on calcium phosphate formation in the presence of silver nanoparticles – RSC Advances (RSC Publishing)

Abstract:
The precipitation of calcium phosphates (CaPs) in the presence of more than one type of additive is of interest both from a fundamental point of view and as a possible biomimetic route for the preparation of multicomponent composites in which the activity of the components is preserved. In this study, the effect of bovine serum albumin (BSA) and chitosan (Chi) on the precipitation of CaPs in the presence of silver nanoparticles (AgNPs) stabilized with sodium bis(2-ethylhexyl)sulfosuccinate (AOT-AgNPs), poly(vinylpyrrolidone) (PVP-AgNPs), and citrate (cit-AgNPs) was investigated. In the control system, the precipitation of CaPs occurred in two steps. Amorphous calcium phosphate (ACP) was the first precipitated solid, which transformed into a mixture of calcium-deficient hydroxyapatite (CaDHA) and a smaller amount of octacalcium phosphate (OCP) after 60 min of ageing. Both biomacromolecules inhibited ACP transformation, with Chi being a stronger inhibitor due to its flexible molecular structure. As the concentration of the biomacromolecules increased, the amount of OCP decreased both in the absence and presence of AgNPs. In the presence of cit-AgNPs and two highest BSA concentrations, a change in the composition of the crystalline phase was observed. Calcium hydrogen phosphate dihydrate was formed in the mixture with CaDHA. An effect on the morphology of both the amorphous and crystalline phases was observed. The effect depended on the specific combination of biomacromolecules and differently stabilized AgNP. The results obtained suggest a simple method for fine-tuning the properties of precipitates using different classes of additives. This could be of interest for the biomimetic preparation of multifunctional composites for bone tissue engineering.

This publication was authored by Ina Erceg, Vida Strasser, Nicolas Somers, Marta Jurković, Jasminka Kontrec, Damir Kralj, Rinea Barbir, Ivana Vinković Vrčeg, Marie Lasgorceix, Anne Leriche and Maja Dutour Sikirić as corresponding author.

The abstract of the publication is as follows:

Among key factors determining the fate of biomaterials in vivo are their interactions with blood serum proteins, which can lead to either successful integration or rejection/encapsulation. Although there are a number of studies investigating the interactions between proteins and bioimplants, comparable data for different types of biomaterials are lacking. To fill this gap, the adsorption kinetics and binding interactions of bovine serum albumin (BSA) with calcium phosphates (CaPs), namely hydroxyapatite (HA) and calcium deficient apatite (CaDHA), different TiO2 nanomaterials (TiNMs) presenting various morphologies such as nanoparticles (TiNPs), nanoplatelets (TiNPls), nanotubes (TiNTs) and nanowires (TiNWs), as well as their composites with CaDHA (CaDHA/TiNMs) were investigated. The kinetics of BSA adsorption on all studied materials was best described by pseudo-second order kinetics. The rate coefficient values obtained for the composites were lower than those for CaDHA and the corresponding TiNMs, while the adsorption density was higher for the composites than for CaDHA, except for the composites with TiNTs. Adsorption on TiNWs, CaDHA and all composites involved intraparticle diffusion, which was the rate- limiting step only for CaDHA/TiNTs. Fluorimetric titration experiments revealed that the number of binding sites was in larger than 1, except for TiNTs and TiNWs, indicating positive binding cooperativity. Interestingly, the values of the binding constants were lower for the TiNMs with a higher adsorption rate coefficient. Overall, BSA adsorption on the studied materials proved to be a complex process, which depended on the different surface properties of the adsorbents. Which property had a dominant role depended on the chemical identity of the adsorbent. The obtained comparable data for
different types of materials point to the way of modifying their protein adsorption and binding properties.

The publication is published on 21. February 2023 in open access. You can read the whole paper on this link:
Materials | Free Full-Text | Can Differently Stabilized Silver Nanoparticles Modify Calcium Phosphate Precipitation? (mdpi.com)

The abstract of this study is here:

Calcium phosphates (CaPs) composites with silver nanoparticles (AgNPs) attract attention as a possible alternative to conventional approaches to combating orthopedic implant-associated infections. Although precipitation of calcium phosphates at room temperatures was pointed out as an advantageous method for the preparation of various CaP-based biomaterials, to the best of our knowledge, no such study exists for the preparation of CaPs/AgNP composites. Motivated by this lack of data in this study we investigated the influence of AgNPs stabilized with citrate (cit-AgNPs), poly(vinylpyrrolidone) (PVP-AgNPs), and sodium bis(2-ethylhexyl) sulfosuccinate (AOT-AgNPs) in the concentration range 5–25 mg dm⁻³ on the precipitation of CaPs. The first solid phase to precipitate in the investigated precipitation system was amorphous calcium phosphate (ACP). The effect of AgNPs on ACP stability was significant only in the presence of the highest concentration of AOT-AgNPs. However, in all precipitation systems containing AgNPs, the morphology of ACP was affected, as gel-like precipitates formed in addition to the typical chain-like aggregates of spherical particles. The exact effect depended on the type of AgNPs. After 60 min of reaction time, a mixture of calcium-deficient hydroxyapatite (CaDHA) and a smaller amount of octacalcium phosphate (OCP) formed. PXRD and EPR data point out that the amount of formed OCP decreases with increasing AgNPs concentration. The obtained results showed that AgNPs can modify the precipitation of CaPs and that CaPs properties can be fine-tuned by the choice of stabilizing agent. Furthermore, it was shown that precipitation can be used as a simple and fast method for CaP/AgNPs composites preparation which is of special interest for biomaterials preparation.Keywords: calcium phosphates; silver nanoparticles; amorphous calcium phosphate; transformation; composites

The seminar took place on 20 and 21 of January 2023 at Daytona Beach, Florida, USA.

To be able to go in USA, Suzana recieved additional financial help from Croatian and European ceramic Societies.

Here is the certificate of her attendance:

The study was published on 2 December 2022 in open access. You can read the whole article on this link:
Minerals | Free Full-Text | Influence of Biomacromolecules on Calcium Phosphate Formation on TiO2 Nanomaterials (mdpi.com)

The abstract of the publication is here:

Calcium phosphates (CaP) composites with biomacromolecules and/or nanomaterials have recently emerged as a potential solution to improve the poor mechanical properties and biological response of CaP. Among the methods available for preparation of such composites, precipitation at low temperatures attracts special interest as it allows preservation of the activity of biomacromolecules. However, precipitation of CaP in the presence of two additives is a complex process that needs to be studied in detail to rationalize composite preparation. This study aimed to investigate co-precipitation of CaP on different TiO₂ nanomaterials (TiNMs), including nanoparticles (TiNPs), nanoplates (TiNPls), nanotubes (TiNTs), and nanowires (TiNWs), in the presence of bovine serum albumin (BSA) and chitosan (Chi). The obtained results have shown that both BSA and Chi inhibited transformation of amorphous to crystalline CaP, even in the presence of TiNMs at concentrations that promoted transformation. Chi proved to be a stronger inhibitor due to its more flexible structure. The presence of BSA and Chi did not influence the composition of the CaP formed as calcium-deficient hydroxyapatite (CaDHA) was formed in all the systems. However, both macromolecules influenced the morphology of the formed CaDHA in different ways depending on the type of TiNM used. BSA and Chi adsorbed on all the TiNMs, as confirmed by zeta potential measurements, but this adsorption reduced the amount of CaP formed on TiNMs only in the case of TiNWs. The obtained results contribute to the understanding of the influence of BSA and Chi on CaP precipitation in the presence of nanomaterials and thus to the rational design of CaP-based multi-composite materials.Keywords: calcium-deficient hydroxyapatite; bovine serum albumin; chitosan; precipitation

The conference was held from 8 till 11 November 2011 at Sveti Martin na Muri, Croatia.

She had a poster presentation about the influence of differently stabilized silver nanoparticles on calcium phosphate formation.

The abstract of this poster is here:

The thesis was held on 23. September 2022 at Faculty of Science, Department of Chemistry, University of Zagreb. Supervisor of her thesis was Maja Dutour Sikirić.

We congratulate to you Ina!

Here is an abstract of her thesis:

Calcium phosphates and TiO2 nanomaterials composites are attracting attention as advanced
materials for bone regeneration due to the complementary properties of the components. Current studies
of such composites focus on coating TiO2 nanostructures with calcium phosphate layers to improve their
bioactivity.
The aim of this doctoral thesis was to systematically investigate the biomimetic preparation of
nanocomposites based on calcium phosphate and titania nanomaterials under physiological conditions.
Two methods of nanocomposite synthesis were compared, immersion in simulated body fluid and
precipitation from a suspension. In addition, the influence of biologically active molecules, bovine
serum albumin and chitosan, was determined. To evaluate the in vivo behavior of the prepared
composites, the adsorption and binding parameters of serum albumin were determined, since this protein
is the first to interact with the implant materials after implantation.
The obtained results showed that precipitation from solution is a rapid and versatile method for
preparing TiO2 and calcium phosphate composites, in which no changes in the composition or structure
of the calcium phosphate phase depending on the type of titanium nanomaterials was observed. Such
composites exhibit improved protein adsorption properties, indicating their potential for biomedical
applications.
(186 + XV pages, 90 figures, 34 + XXVII tables, 397 references, original in Croatian)

Thesis deposited in Central Chemical Library, Horvatovac 102A, Zagreb, Croatia and National and
University Library, Hrvatske bratske zajednice 4, Zagreb, Croatia.

Keywords: bovine serum albumin / calcium phosphates / chitosan / nanocomposites / precipitation /
simulated body fluid / titanate nanomaterials

The Regional Biophysics Conference was held in Pecs, Hungary from 22 to 26 August 2022. The whole programme of conference is available on this link:
Programme . RBC 2022

Here is an abstract of this lecture:

Multiscale view on calcium phosphate formation – a route for rationalizing the design of novel bioimplant materials

Maja Dutour Sikirić

Ruđer Bošković Institute, Division of Physical Chemistry, Zagreb, HR

Calcium phosphates (CaPs) attract attention due to their role in biological and pathological mineralization, as well as in different industrial processes. At conditions close to physiological, the formation of calcium phosphates usually proceeds in two steps, the first of which is the formation of an amorphous precursor (ACP). The formation of ACP can be envisioned as a series of aggregation steps, Posners clusters aggregate to form primary particles that in turn grow and aggregate into chain-like aggregates that in contact with mother liquor grow and transform into crystalline phase. [1] Dynamic light scattering and laser scattering studies have revealed that the aggregation of ACP particles is a process which from the earliest stages simultaneously takes place at wide length scales, from nanometres to micrometres, resulting in a highly polydisperse precipitation system. [2]

Such behaviour offers the possibility to regulate ACP, and consequently crystalline CaP, formation by controlling ACP formation at the scale of interest. A possible way to achieve this is to precipitate CaPs in the presence of nanostructured materials.

Motivated by this, we investigated the influence of different materials, surfactant micelles [3], liposomes [4], TiO₂ nanomaterials of different dimensionality [5,6] and silver nanoparticles on CaP’s precipitation. It was shown that nanomaterials can exert a variety of the effects on the formation of CaPs and in certain cases the effect on the precipitation process observed at the microscale could be the result of different pathways at the nanoscale. As some of nanomaterials exhibit biological activities, this opens a pathway for biomimetic preparation of multifunctional bioimplant materials.

Acknowledgments

Financial support from Croatian Science Foundation, Grant HRZZ- IP-2018-01-1493 and Marie Sklodowska-Curie Grant Agreement No. 861138 is greatly acknowledged.

References

1. L. Brečević et al. Colloids Surf., 1987, 28, 301.
2. V. Čadež et al., Crystals, 2018, 8, 254.
3. A. Selmani et al. CrystEngComm, 2015, 17, 8529.
4. I. Erceg et al., Minerals, 2022, 12, 208.
5. I. Erceg et al., Colloids and Surfaces A, 2020, 593, 124615
6. I. Erceg et al., Nanomaterials, 2021, 11, 1523.