Calcium Phosphate Nanocrystals Research Articles

Immobilized Dipeptidase in Manganese Ion-Loaded Polyethylenimine-Induced Calcium Phosphate Nanocrystals for Carnosine Synthesis.

Carnosine is a natural bioactive dipeptide with important physiological functions widely used in food and medicine. Dipeptidase (PepD) from Serratia marcescens can catalyze the reverse hydrolytic reaction of β-alanine with l-histidine to synthesize carnosine in the presence of Mn2+. However, it remains challenging to practice carnosine biosynthesis due to the low activity and high cost of the enzyme. Therefore, the development of biocatalysts with high activity and stability is of significance for carnosine synthesis. Here, we proposed to chelate Mn2+ to polyethylenimine (PEI) that induced rapid formation of calcium phosphate nanocrystals (CaP), and Mn-PEI@CaP was used for PepD immobilization via electrostatic interaction. Mn-PEI@CaP as the carrier enhanced the stability of the immobilized enzyme. Moreover, Mn2+ loaded in the carrier acted as an in situ activator of the immobilized PepD for facilitating the biocatalytic process of carnosine synthesis. The as-prepared immobilized enzyme (PepD-Mn-PEI@CaP) kept similar activity with free PepD plus Mn2+ (activity recovery, 102.5%), while exhibiting elevated thermal stability and pH tolerance. Moreover, it exhibited about two times faster carnosine synthesis than the free PepD system. PepD-Mn-PEI@CaP retained 86.8% of the original activity after eight cycles of batch catalysis without the addition of free Mn2+ ions during multiple cycles. This work provides a new strategy for the co-immobilization of PepD and Mn2+, which greatly improves the operability of the biocatalysis and demonstrates the potential of the immobilized PepD system for efficient carnosine synthesis.

Self-assembled peptide P11-4 interacts with the type I collagen C-terminal telopeptide domain and calcium ions.

Evaluate molecularly the role of P11-4 self-assembly peptide in dentin remineralization and its interaction with collagen I. The calcium-responsive P11-4 peptide was analyzed by intrinsic fluorescence emission spectrum, circular dichroism spectrum (CD), and atomic force microscope (AFM). Differential light scattering was used to monitor the nucleation growth rate of calcium phosphate nanocrystals in the absence or in the presence of P11-4. AFM was used to analyze the radial size (nm) of calcium phosphate nanocrystals formed in the absence or in the presence of P11-4, as well as to verify the spatial structure of P11-4 in the absence or in the presence of Ca2+. The interaction of Ca2+ with the P11-4 (KD = 0.58±0.06mM) promotes the formation of β-sheet antiparallel structure, leads to its precipitation in saturated solutions of Ca/P=1.67 and induces the formation of parallel large fibrils (0.6 - 1.5µm). P11-4 organized the HAP nucleation by reducing both the growth rate and size variability of nanocrystals, analyzed by the F test (p<0.0001, N=30). P11-4 interacts (KD = 0.75±0.06μM) with the KGHRGFSGL motif present at the C-terminal collagen telopeptide domain. P11-4 also increased the amount of HAP and collagen in the MDPC-23 cells. The presented data propose a mechanism that will help future clinical and/or basic research to better understand a molecule able to inhibit structural collagen loss and help the impaired tissue to remineralize.

Incorporation/Enrichment of 3D Bioprinted Constructs by Biomimetic Nanoparticles: Tuning Printability and Cell Behavior in Bone Models.

Reproducing in vitro a model of the bone microenvironment is a current need. Preclinical in vitro screening, drug discovery, as well as pathophysiology studies may benefit from in vitro three-dimensional (3D) bone models, which permit high-throughput screening, low costs, and high reproducibility, overcoming the limitations of the conventional two-dimensional cell cultures. In order to obtain these models, 3D bioprinting offers new perspectives by allowing a combination of advanced techniques and inks. In this context, we propose the use of hydroxyapatite nanoparticles, assimilated to the mineral component of bone, as a route to tune the printability and the characteristics of the scaffold and to guide cell behavior. To this aim, both stoichiometric and Sr-substituted hydroxyapatite nanocrystals are used, so as to obtain different particle shapes and solubility. Our findings show that the nanoparticles have the desired shape and composition and that they can be embedded in the inks without loss of cell viability. Both Sr-containing and stoichiometric hydroxyapatite crystals permit enhancing the printing fidelity of the scaffolds in a particle-dependent fashion and control the swelling behavior and ion release of the scaffolds. Once Saos-2 cells are encapsulated in the scaffolds, high cell viability is detected until late time points, with a good cellular distribution throughout the material. We also show that even minor modifications in the hydroxyapatite particle characteristics result in a significantly different behavior of the scaffolds. This indicates that the use of calcium phosphate nanocrystals and structural ion-substitution is a promising approach to tune the behavior of 3D bioprinted constructs.

Sequentially co-immobilized PET and MHET hydrolases via Spy chemistry in calcium phosphate nanocrystals present high-performance PET degradation

Accumulation of polyethylene terephthalate (PET) has brought an enormous threat to the ecosystem. The recently reported PET hydrolase (DuraPETase) and MHET hydrolase (MHETase) can synergistically catalyze the complete PET degradation. Hence, this work was designed to develop a bienzymatic cascade catalysis by co-immobilizing the two enzymes for PET biodegradation. DuraPETase and MHETase were sequentially co-immobilized in calcium phosphate nanocrystals (CaP) through SpyTag/SpyCatcher system. MHETase-SpyCatcher was first embedded inside the nanocrystals via biomimetic mineralization, and DuraPETase-SpyTag was then conjugated on the outlayer (~1.5 µm). The bienzyme compartmentalization facilitated DuraPETase interaction with the solid substrate, and the layered structures of the nanocrystals protected the enzymes, thus enhancing their stability. The high specific surface area of the nanocrystals and the proximity effects from the bienzymatic cascade were beneficial to the improved enzyme activity. Experimental data and molecular dynamics simulations revealed the activation effect of Ca2+ on DuraPETase. Taken together, the final results indicate that the PET degradation efficiency of DuraPETase-MHETase@CaP increased by 6.1 and 1.5 times over the free bienzyme system within 10 d at 40 °C and 50 °C, with weight losses at 32.2% and 50.3%, respectively. The bienzymatic cascade with DuraPETase-MHETase@CaP can completely degrade PET, contributing to the recycling of PET.

Sequentially Co-Immobilized Pet and Mhet Hydrolases Via Spy Chemistry in Calcium Phosphate Nanocrystals Present High-Performance Pet Degradation

Sequentially Co-Immobilized Pet and Mhet Hydrolases Via Spy Chemistry in Calcium Phosphate Nanocrystals Present High-Performance Pet Degradation

Cyclic strain enhances the early stage mineral nucleation and the modulus of demineralized bone matrix.

The adaptive response of bones to mechanical loading is essential for musculoskeletal development. Despite the importance of collagen in bone mineralization, little is known about how cyclic strain influences physicochemical responses of collagen, especially at the early stage of mineralization when the levels of strain are higher than those in mature bones. The findings in this study show that, without any cell-mediated activity, cyclic strain increases nucleation rates of calcium phosphate (CaP) nanocrystals in highly-organized collagen matrices. The cyclic strain enhances the transport of mineralization fluids with nucleation precursors into the matrix, thus forming more CaP nanocrystals and increasing the elastic modulus of the collagen matrix. The results also suggest that the multiscale spatial distribution of nanocrystals in the fibrous collagen network determines tissue-level mechanical properties more critically than the total mineral content. By linking nano- and micro-scale observations with tissue-level mechanical properties, we provide new insights into designing better biomaterials.

Functionalization of the Parylene C Surface Enhances the Nucleation of Calcium Phosphate: Combined Experimental and Molecular Dynamics Simulations Approach.

Interactions at the solid–body fluid interfaces play a vital role in bone tissue formation at the implant surface. In this study, fully atomistic molecular dynamics (MD) simulations were performed to investigate interactions between the physiological components of body fluids (Ca2+, HPO42–, H2PO4–, Na+, Cl–, and H2O) and functionalized parylene C surface. In comparison to the native parylene C (−Cl surface groups), the introduction of −OH, −CHO, and −COOH surface groups significantly enhances the interactions between body fluid ions and the polymeric surface. The experimentally observed formation of calcium phosphate nanocrystals is discussed in terms of MD simulations of the calcium phosphate clustering. Surface functional groups promote the clustering of calcium and phosphate ions in the following order: −OH > −CHO > −Cl (parent parylene C) ≈ −COO–. This promoting role of surface functional groups is explained as stimulating the number of Ca2+ and HPO42– surface contacts as well as ion chemisorption. The molecular mechanism of calcium phosphate cluster formation at the functionalized parylene C surface is proposed.

Pulsed Electrical Stimulation Enhances Body Fluid Transport for Collagen Biomineralization.

Mechanical loads from physiologic activities such as walking and running generate bioelectricity in bones. By mimicking bioelectricity, external electrical stimulations have also been used therapeutically to stimulate bone-forming cells and, thus, to promote bone regeneration. However, little is known about the physicochemical mechanism(s) by which electrical stimulations drives calcium phosphate mineralization of collagen. Here, we showed that, during in vitro collagen mineralization in the absence of cells, application of pulsed electrical stimulation significantly enhanced the transport of ionic body fluid components through a micrometer-scale channel (∼100-200 μm gap space between the inner surfaces of tube-like collagen scaffolds and a cathode placed inside the collagen scaffolds). The enhanced transport of ionic precursors increased diffusion of the charged precursors from the channel to the inner collagen surface, where bone mineralization was otherwise restricted. The results indicate that pulsed electrical signals can locally accelerate the nucleation of calcium phosphate nanocrystals in or on collagen, allowing us to better control the spatial distribution of the nanocrystals at the microscale. The findings from this study provide insights into the utilization of electrical stimulation for applications such as facilitating bone-fracture healing and designing better bone-specific biomaterials.

Synergistic effects of Mg-substitution and particle size of chicken eggshells on hydrothermal synthesis of biphasic calcium phosphate nanocrystals

Magnesium (Mg2+) ion plays important roles in biomineralization of bone, teeth and calcium carbonate skeletons. Herein, chicken eggshells mainly comprising of Mg-calcite nanocrystals (Mg/(Mg + Ca) ∼2.0 mol.%) were used to fabricate biphasic calcium phosphate (BCP), a mixture of hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) nanocrystals, through hydrothermal reactions at 200 °C for 24 h. Our results indicated that β-TCP nanocrystals formed through the ion-exchange reactions of Mg-calcite, while HA nanocrystals were mainly produced by dissolution-reprecipitation reactions on the surfaces of eggshell samples in the hydrothermal system. Mg substitution in calcite resulted in formation of β-TCP nanocrystals instead of HA crystals through ion-exchange reactions. BCP samples with different compositions (∼28.6–77.8 wt.% β-TCP) were produced by controlling particle sizes of eggshells for hydrothermal reactions. The larger particles lead to the larger proportion of β-TCP in the BCP composition. Therefore, Mg substitution and particle size had synergetic effects on the hydrothermal synthesis of BCP using chicken eggshells through balance of ion-exchange and dissolution-reprecipitation reactions. Cell culture results showed that the BCP products were non-cytotoxic to MC3T3-E1 cells, which may be used for bone substitute materials in future.

Potential role of calcifying nanoparticles in the etiology of multiple sclerosis

Nanobacteria or calcifying nanoparticles are 80–500 nm sized nano-organisms that are physically associated with carbonate apatite mineral formations. They have been indicated in various diseases, including kidney stone formation, Alzheimer’s disease, and atherosclerosis. Nanoparticles contain calcium and apatite-binding protein fetuin-A, a calcification inhibitor. However, recent evidence indicates that fetuin-A can form nucleation seeds or nidi that grow in size through ion sedimentation to become larger amorphous nanoparticles in the presence of excess calcium and apatite ions.Fetuin-A also functions as an inhibitor of meprin, a metalloproteinase implicated in inflammation and neurodegenerative diseases. During inflammation, meprin functions to regulate chemokine activity of monocyte chemotactic protein 1, which is associated with chronic inflammatory diseases, including atherosclerosis, renal inflammatory diseases, and multiple sclerosis (MS). In addition, calcium phosphate nanocrystals that contain fetuin-A are pro-inflammatory to macrophages and promote vascular smooth muscle cell mineralization, potentiating a vicious cycle of inflammation and calcification. Thus, mineral stress and inflammation appear to be associated with each other. Furthermore, fetuin-A deficient mice exhibited reduced experimental autoimmune encephalomyelitis severity. Thus, fetuin-A plays a direct role in the neuroinflammatory response. Indeed, the level of fetuin-A in cerebrospinal fluid has been defined as a biomarker of disease activity in MS.MS is a chronic, inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) with an unknown etiology. The “inside-out” model of MS, supported by recent data, states that the initial axonal degeneration in the CNS occurs before demyelination, which then stimulates an auto-immune attack. It was shown very recently that influx of calcium from the extracellular space through nanoscale ruptures of the axonal plasma membrane predict axon degeneration in neuroinflammation. Calcium is an activator of calpains, proteases that function to break down the cytoskeleton, leading to neurodegeneration. Nanoruptures of the plasma membrane were suggested to occur at the early stages of axon damage, especially at nodes of Ranvier, which are devoid of myelin.Here, I propose that calcifying nanoparticles may have a role in the etiology and/or pathophysiology of MS. The initial event causing neurodegeneration may be due to the nanoparticles that have been suggested to easily cross the blood-brain barrier. Following this, the nanoparticles may create nanoruptures in the axonal membrane and also increase the calcium concentration around and within the neurons by forming nidi for calcification, eventually causing neurodegeneration. Nanoparticles can self-replicate; hence, they may represent an infectious causative agent for the development of MS.

Preparation and characterization of marine mineralized ASC nanocomposites through biomineralization

Mineralized collagen provides new solutions in the manufacture of porous scaffolds for tissue engineering. In this research, the use of biomimetic mineralization, the process of mineralization of acid soluble collagen (ASC) type I extracted from white fish (Rutilus frisii kutum) scales, in a body simulated fluid (SBF) in the presence and absence of an anionic surfactant, sodium dodecyl benzene sulphonate (SDBS) was thoroughly investigated. The formation of β-tricalcium phosphate (β-TCP) nanocrystals in mineralized nanocomposites was detected by XRD, TGA, and FT-IR techniques. The denaturation temperature (Td) of mineralized ASC was determined at 42.87 °C without surfactant, and at 70.2 °C with surfactant using DSC technique, which indicated a higher thermal stability of ASC without the SDBS surfactant. TEM images illustrated that the formation of β-TCP crystals on collagen nano-fibrils was in an irregular form in the absence of surfactant while it was more regular and in the form of rectangular sheets in the presence of surfactant. The results of UV/Vis spectrophotometer for turbidity measurements during the initial step of biomineralization revealed that SDBS while accelerating the self-assembly process of collagen nano-fibrills, delayed the process of nucleation and the growth of calcium phosphate nanocrystals by increasing the kinetic energy barrier.

Sol-gel synthesis of biocompatible Eu3+/Gd3+ co-doped calcium phosphate nanocrystals for cell bioimaging

Herein, a polyacrylic acid sol-gel method was presented to synthesize rare earth doped calcium phosphate nanocrystals (RE-CaP) as cell bioimaging agent. The effects of calcination temperature, calcination time and PAA concentration on phase composition, morphology, size and luminescence were discussed. In addition, the hemolysis, cytotoxicity, cell uptake and cell imaging of resulting RE-CaP nanocrystals were investigated. Results show that the increases in calcination temperature and time promote the transformation of product from impure crystalline phase (CaCO3, CaO) to pure CaP phase. The rise of calcination temperature results in significant enhancement of luminescence intensity. PAA concentration does not influence the crystalline phase composition and its increase leads to a little increase in luminescence intensity. In addition, the co-doping of Gd3+ improves the luminescence intensity of Eu3+ emissions. This method achieves the doping of Eu3+ ions in the crystallographic Ca2+ I and Ca2+ II sites of HAP with a preferable occupation at Ca2+ II site. The resulting RE-CaP nanocrystals (PAA: 0.6mg/mL, Eu/Gd = 2:1.5, 600°C, 3h) show good biocompatibility and can be easily uptaken by cancer cells. The internalized nanocrystals show stable and strong red luminescence under visible wavelengths excitation. In summary, PAA sol-gel method can be used to synthesize biocompatible RE-CaP luminescent nanomaterials for cell bioimaging.

Dispersion of hydroxyapatite nanocrystals stabilized by polymeric molecules bearing carboxy and sulfo groups

Calcium phosphate buildup is important for biological processes (e.g., bones and teeth growth) and negatively affects the efficiency and functioning of water systems (e.g., cooling water systems and boilers) as a result of scale buildup by salts precipitation. Thus, stable aqueous dispersions of calcium phosphate particles can effectively prevent the formation and buildup of scale in water systems. In this study, the stabilization of calcium phosphate nanocrystals (NCs) was studied by forming a supersaturated solution in the presence of poly acrylic acid/2-acrylamide-2-methylpropane sulfonic acid p(AA/AMPS) containing carboxy and sulfo group functionalities. Calcium phosphate NCs were formed and subsequently aggregated in a supersaturated aqueous solution containing 2-phosphonobutane-1,2,4-tricarboxylic acid without any copolymers. Aggregation of calcium phosphate NCs was suppressed in the presence of polymeric molecules containing carboxy groups, whereas molecules bearing sulfo groups were ineffective in dispersing calcium phosphate NCs. However, copolymers bearing both functional groups enhanced the dispersibility of calcium phosphate NCs. Using a combination of light scattering and surface charge measurements along with electron imaging, we found that the inhibition of calcium phosphate precipitation originates from hydroxyapatite nanocrystals (HANCs) with a size smaller than 100 nm in solution. While the carboxy groups in the copolymer adsorbed on the surface of the HANCs, the sulfo groups provided these species with an overall negative surface charge, thereby increasing their colloidal stability via electrostatic repulsion. These results indicated that the aggregation of the HANCs can be effectively hindered using sulfo/carboxy bifunctional copolymers.

Devitalized Stem Cell Microsheets for Sustainable Release of Osteogenic and Vasculogenic Growth Factors and Regulation of Anti‐Inflammatory Immune Response

The objective of this work was to investigate the effect of devitalized human mesenchymal stem cells (hMSCs) and endothelial colony-forming cells (ECFCs) seeded on mineralized nanofiber microsheets on protein release, osteogenesis, vasculogenesis, and macrophage polarization. Calcium phosphate nanocrystals were grown on the surface of aligned, functionalized nanofiber microsheets. The microsheets were seeded with hMSCs, ECFCs, or a mixture of hMSCs+ECFCs, cultured for cell attachment, differentiated to the osteogenic or vasculogenic lineage, and devitalized by lyophilization. The release kinetic of total protein, bone morphogenetic protein-2 (BMP2), and vascular endothelial growth factor (VEGF) from the devitalized microsheets was measured. Next, hMSCs and/or ECFCs were seeded on the devitalized cell microsheets and cultured in the absence of osteo-/vasculo-inductive factors to determine the effect of devitalized cell microsheets on hMSC/ECFC differentiation. Human macrophages were seeded on the microsheets to determine the effect of devitalized cells on macrophage polarization. Based on the results, devitalized undifferentiated hMSC and vasculogenic-differentiated ECFC microsheets had highest sustained release of BMP2 and VEGF, respectively. The devitalized hMSC microsheets did not affect M2 macrophage polarization while vascular-differentiated, devitalized ECFC microsheets did not affect M1 polarization. Both groups stimulated higher M2 macrophage polarization compared to M1.

Role of magnesium on the biomimetic deposition of calcium phosphate

Biomimetic depositions of calcium phosphate (CaP) are carried out using simulated body fluid (SBF), calcifying solution and newly developed magnesium containing calcifying solution. Calcium phosphate has a rich phase diagram and is well known for its excellent biocompatibility and bioactivity. The most common phase is hydroxyapatite (HAp), an integral component of human bone and tooth, widely used in orthopedic and dental applications. In addition, calcium phosphate nanoparticles show promise for the targeted drug delivery. The doping of calcium phosphate by magnesium, zinc, strontium etc. can change the protein uptake by CaP nanocrystals. This work describes the role of magnesium on the nucleation and growth of CaP on Ti and its oxide substrates. X-ray diffraction studies confirm formation of HAp nanocrystals which closely resemble the structure of bone apatite when grown using SBF and calcifying solution. It has been observed that magnesium plays crucial role in the nucleation and growth of calcium phosphate. A low magnesium level enhances the crystallinity of HAp while higher magnesium content leads to the formation of amorphous calcium phosphate (ACP) phase. Interestingly, the deposition of ACP phase is rapid when magnesium ion concentration in the solution is 40% of calcium plus magnesium ions concentration. Moreover, high magnesium content alters the morphology of CaP films.

Real-time observation of biomineralization process of calcium phosphate nanocrystals

Real-time observation of biomineralization process of calcium phosphate nanocrystals

Effects of calcium phosphate nanocrystals on osseointegration of titanium implant in irradiated bone.

Radiotherapy may compromise the integration of implant and cause implant loss. Implant surface modifications have the possibility of promoting cell attachment, cell growth, and bone formation which ultimately enhance the osseointegration process. The present study aimed to investigate the effects of calcium phosphate nanocrystals on implant osseointegration in irradiated bone. Sixteen rabbits were randomly assigned into control and nano-CaP groups, receiving implants with dual acid-etched surface or dual acid-etched surface discretely deposited of nanoscale calcium-phosphate crystals, respectively. The left leg of all the rabbits received 15 Gy radiation, followed by implants placement one week after. Four animals in each group were sacrificed after 4 and 12 weeks, respectively. Implant stability quotient (ISQ), ratio of bone volume to total volume (BV/TV), bone growth rate, and bone-to-implant contact (BIC) were evaluated. The nano-CaP group showed significantly higher ISQ (week 12, P = 0.031) and bone growth rate (week 6, P = 0.021; week 9, P = 0.001) than that in control group. No significant differences in BV/TV and BIC were found between two groups. Titanium implant surface modified with CaP nanocrystals provides a potential alternative to improve bone healing around implant in irradiated bone.

Fabrication of dispersible calcium phosphate nanocrystals via a modified Pechini method under non-stoichiometric conditions

Various techniques for preparing ceramic nanoparticles have been developed; however, most of them start from a preparation of precursor nanoparticles that are generally amorphous or in poorly crystallized phases. Thermal treatments used to obtain crystalline phases typically result in the sintering of the products into large polycrystals. In this study, we developed a process to fabricate dispersible hydroxyapatite (HAp; Ca10(PO4)6(OH)2) nanocrystals via a modified Pechini method, which is a sol–gel like solid-state synthesis method for the preparation of multicomponent oxides. We demonstrated that the HAp nanocrystals sintered into large polycrystals ranging in size from several tens to several hundreds of microns via a conventional Pechini method using the stoichiometric Ca/P molar ratio of 1.67. When the Ca/P molar ratio in the precursor was >1.67, a mixture of HAp nanocrystals and removable CaO matrix was obtained. The HAp nanocrystals were dispersed in aqueous media mostly in the form of nanoparticles when the amount of CaO matrix was sufficiently greater than the amount of HAp.

Topographic scale-range synergy at the functional bone/implant interface

We sought to explore the biological mechanisms by which endosseous implant surface topography contributes to bone anchorage. To address this experimentally, we implanted five groups of custom-made commercially pure titanium implants of varying surface topographical complexity in rat femora for 9 days; subjected them to mechanical testing; and then examined the interfacial bone matrix by electron microscopy. The five implant surfaces were prepared by combinations of dual acid etching and grit blasting the titanium substrates and, in some cases, modifying the created surfaces with the deposition of nanocrystals of calcium phosphate, which resulted in 10 samples per group. In parallel, we cultured rat bone marrow cells on surrogate implants constructed from polymer resin coated with the same calcium phosphate nanocrystals, and monitored the deposition of bone sialoprotein by transmission electron immunohisto-micrography. We found that implant samples modified with sub-micron scale crystals were bone-bonding, as described by the interdigitation of a mineralized cement line matrix with the underlying implant surface. The in vitro assay showed that bone sialoprotein could be deposited in the interstices between, and undercuts below, the nanocrystals. In addition, when mineralized, the cement line matrix globules occupied micron-sized pits in the implant surfaces, and in part obliterated them, creating an additional form of anchorage. Our results also showed that collagen, elaborated by the osteogenic cells, wrapped around the coarse-micron features, and became mineralized in the normal course of bone formation. This provided a mechanism by which coarse-micron implant features contributed to a functional interface, which we have previously described, that is capable of resisting the mechanical loading that increases as peri-implant bone matures. Thus, our findings provide mechanistic explanations for the biologically-relevant criteria that can be employed to assess the importance of implant surface topography at different scale-ranges.

Interactions Between Inorganic and Organic Phases in Bone Tissue as a Source of Inspiration for Design of Novel Nanocomposites

Mimicking the nanostructure of bone and understanding the interactions between the nanoscale inorganic and organic components of the extracellular bone matrix are crucial for the design of biomaterials with structural properties and a functionality similar to the natural bone tissue. Generally, these interactions involve anionic and/or cationic functional groups as present in the organic matrix, which exhibit a strong affinity for either calcium or phosphate ions from the mineral phase of bone. This study reviews the interactions between the mineral and organic extracellular matrix components in bone tissue as a source of inspiration for the design of novel nanocomposites. After providing a brief description of the various structural levels of bone and its main constituents, a concise overview is presented on the process of bone mineralization as well as the interactions between calcium phosphate (CaP) nanocrystals and the organic matrix of bone tissue. Bioinspired synthetic approaches for obtaining nanocomposites are subsequently addressed, with specific focus on chemical groups that have affinity for CaPs or are involved in stimulating and controlling mineral formation, that is, anionic functional groups, including carboxyl, phosphate, sulfate, hydroxyl, and catechol groups.