Ultrafast and Reproducible Synthesis of Tailor-Made Octacalcium Phosphate.

Octacalcium phosphate (OCP) has excellent bone formation ability and a good resorption rate as compared to the commercial bone substitutes [e.g., Bio-Oss (Geistlich Pharma AG) and MBCP+ (Biomatlante)], as well as synthesized biomaterials (hydroxyapatite and tricalcium phosphate). The synthesis approach to obtain phase-pure OCP possesses a great challenge due to its complex reaction mechanism and narrow synthesis window. Thus, the current study aimed to overcome the synthesis challenges and to define the precise reaction conditions required for controllable and reproducible synthesis of OCP. Using the principles of the coprecipitation method, novel synthesis protocols were developed ensuring ultrafast synthesis of OCP within minutes. XRD analysis confirmed that phase-pure OCP was obtained. These processing schemes enabled the synthesis of tailor-made OCP with specific surface areas ranging from 16 to 91 m2/g. The synthesized OCPs exhibited plate-like morphology. The interaction of the synthesized OCPs with MC3T3-E1 cells was found to be nontoxic, confirming their cytocompatibility. The synthesis approach developed in this study indicates that challenges such as the reaction volume, stirring rate, and flow rate need to be addressed in the future to upscale the technology.

The role of collagen and crystallinity in the physicochemical properties of naturally derived bone grafts.

Xenografts are commonly used for bone regeneration in dental and orthopaedic domains to repair bone voids and other defects. The first-generation xenografts were made through sintering, which deproteinizes them and alters their crystallinity, while later xenografts are produced using cold-temperature chemical treatments to maintain the structural collagen phase. However, the impact of collagen and the crystalline phase on physicochemical properties have not been elucidated. We hypothesized that understanding these factors could explain why the latter provides improved bone regeneration clinically. In this study, we compared two types of xenografts, one prepared through a low-temperature chemical process (Treated) and another subsequently sintered at 1100°C (Sintered) using advanced microscopy, spectroscopy, X-ray analysis and compressive testing. Our investigation showed that the Treated bone graft was free of residual blood, lipids or cell debris, mitigating the risk of pathogen transmission. Meanwhile, the sintering process removed collagen and the carbonate phase of the Sintered graft, leaving only calcium phosphate and increased mineral crystallinity. Microcomputed tomography revealed that the Treated graft exhibited an increased high porosity (81%) and pore size compared to untreated bone, whereas the Sintered graft exhibited shrinkage, which reduced the porosity (72%), pore size and strut size. Additionally, scanning electron microscopy displayed crack formation around the pores of the Sintered graft. The Treated graft displayed median mechanical properties comparable to native cancellous bone and clinically available solutions, with an apparent modulus of 166 MPa, yield stress of 5.5 MPa and yield strain of 4.9%. In contrast, the Sintered graft exhibited a lower median apparent modulus of 57 MPa. It failed in a brittle manner at a median stress of 1.7 MPa and strain level of 2.9%, demonstrating the structural importance of the collagen phase. This indicates why bone grafts prepared through cold-temperature processes are clinically favourable.

Role of carboxylic organic molecules in interfibrillar collagen mineralization.

Bone is a composite material made up of inorganic and organic counterparts. Most of the inorganic counterpart accounts for calcium phosphate (CaP) whereas the major organic part is composed of collagen. The interfibrillar mineralization of collagen is an important step in the biomineralization of bone and tooth. Studies have shown that synthetic CaP undergoes auto-transformation to apatite nanocrystals before entering the gap zone of collagen. Also, the synthetic amorphous calcium phosphate/collagen combination alone is not capable of initiating apatite nucleation rapidly. Therefore, it was understood that there is the presence of a nucleation catalyst obstructing the auto-transformation of CaP before entering the collagen gap zone and initiating rapid nucleation after entering the collagen gap zone. Therefore, studies were focused on finding the nucleation catalyst responsible for the regulation of interfibrillar collagen mineralization. Organic macromolecules and low-molecular-weight carboxylic compounds are predominantly present in the bone and tooth. These organic compounds can interact with both apatite and collagen. Adsorption of the organic compounds on the apatite nanocrystal governs the nucleation, crystal growth, lattice orientation, particle size, and distribution. Additionally, they prevent the auto-transformation of CaP into apatite before entering the interfibrillar compartment of the collagen fibril. Therefore, many carboxylic organic compounds have been utilized in developing CaP. In this review, we have covered different carboxylate organic compounds governing collagen interfibrillar mineralization.

Amorphous Calcium Phosphate and Amorphous Calcium Phosphate Carboxylate: Synthesis and Characterization.

Amorphous calcium phosphate (ACP) is the first solid phase precipitated from a supersaturated calcium phosphate solution. Naturally, ACP is formed during the initial stages of biomineralization and stabilized by an organic compound. Carboxylic groups containing organic compounds are known to regulate the nucleation and crystallization of hydroxyapatite. Therefore, from a biomimetic point of view, the synthesis of carboxylate ions containing ACP (ACPC) is valuable. Usually, ACP is synthesized with fewer steps than ACPC. The precipitation reaction of ACP is rapid and influenced by pH, temperature, precursor concentration, stirring conditions, and reaction time. Due to phosphates triprotic nature, controlling pH in a multistep approach becomes tedious. Here, we developed a new ACP and ACPC synthesis approach and thoroughly characterized the obtained materials. Results from vibration spectroscopy, nuclear magnetic resonance (NMR), X-ray photoelectron spectroscopy (XPS), true density, specific surface area, and ion release studies have shown a difference in the physiochemical properties of the ACP and ACPC. Additionally, the effect of a carboxylic ion type on the physiochemical properties of ACPC was characterized. All of the ACPs and ACPCs were synthesized in sterile conditions, and in vitro analysis was performed using MC-3T3E1 cells, revealing the cytocompatibility of the synthesized ACPs and ACPCs, of which the ACPC synthesized with citrate showed the highest cell viability.

Small organic molecules containing amorphous calcium phosphate: synthesis, characterization and transformation.

As the primary solid phase, amorphous calcium phosphate (ACP) is a pivotal precursor in cellular biomineralization. The intrinsic interplay between ACP and Howard factor underscores the significance of understanding their association for advancing biomimetic ACP development. While organic compounds play established roles in biomineralization, this study presents the synthesis of ACP with naturally occurring organic compounds (ascorbate, glutamate, and itaconate) ubiquitously found in mitochondria and vital for bone remodeling and healing. The developed ACP with organic compounds was meticulously characterized using XRD, FTIR, and solid-state 13C and 31P NMR. The morphological analysis revealed the characteristic spherical morphology with particle size close to 20 nm of all synthesized ACP variants. Notably, the type of organic compound strongly influences true density, specific surface area, particle size, and transformation. The in vitro analysis was performed with MC3T3-E1 cells, indicating the highest cell viability with ACP_ASC (ascorbate), followed by ACP_ITA (itaconate). The lowest cell viability was observed with 10 %w/v of ACP_GLU (glutamate); however, 1 %w/v of ACP_GLU was cytocompatible. Further, the effect of small organic molecules on the transformation of ACP to low crystalline apatite (Ap) was examined in Milli-Q® water, PBS, and α-MEM.

Advances in Sintering Techniques for Calcium Phosphates Ceramics.

Calcium phosphate (CaP) biomaterials are extensively used to reconstruct bone defects. They resemble a chemical similarity to the inorganic mineral present in bones. Thus, they are termed as the key players in bone regeneration. Sintering is a heat treatment process applied to CaP powder compact or fabricated porous material to impart strength and integrity. Conventional sintering is the simplest sintering technique, but the processing of CaPs at a high temperature for a long time usually leads to the formation of secondary phases due to their thermal instability. Furthermore, it results in excessive grain growth that obstructs the densification process, limiting the application of CaP's ceramics in bone regeneration. This review focuses on advanced sintering techniques used for the densification of CaPs. These techniques utilize the synergy of temperature with one or more parameters such as external pressure, electromagnetic radiation, electric current, or the incorporation of transient liquid that boosts the mass transfer while lowering the sintering temperature and time.

Permanent photodoping of plasmonic gallium-ZnO nanocrystals.

Donor dopants in oxide semiconductors are compensated not only by valuable electrons but also by other point defects, leading to a decrease in electric conductivity and infrared absorption. We demonstrate that the electron compensation mechanism in Ga doped ZnO nanocrystals can be promoted by photodoping. Unexpectedly, the electrons from photodoping are stable in the open air for months.

Strong, Rapid, and Reversible Photochromic Response of Nb Doped TiO2 Nanocrystal Colloids in Hole Scavenging Media.

Understanding photochromicity is essential for developing new means of modulating the optical properties and optical response of materials. Here, we report on the synthesis and exciting new photochromic behavior of Nb5+ doped TiO2 nanoparticle colloids (NCs). We find that, in hole scavenging media, Nb5+ doping significantly improves the photochromic response time of TiO2 nanoparticles. In the infrared regime, Nb-doped TiO2 NCs exhibit 1 order of magnitude faster photoresponse kinetics than the pristine TiO2. Enhanced photochromic response is observed in the visible light regime as well. The transmittance of Nb-doped TiO2 NCs drops to 10% in less than 2 min when irradiated by UV-light in the 500 nm range. The photochromic reaction is fully reversible. The physical origin of the high reaction rate is the high Nb5+ concentration. As a donor dopant, Nb5+ builds up a significant positive charge in the material, which leads to highly efficient electron accumulation during the UV irradiation and results in a rapid photoresponse. EPR experiments identify a new defect type from Nb5+ doping, which alters the physical mechanisms available for transmittance modulation. Our new NCs are economic to synthesize and highly suitable for switchable photochromic applications, e.g., smart windows for modulating visible light and infrared transmittance in built-environments.