Biomaterials

Full-thickness wounds have always been one of the serious clinical problems that require a series of highly developed wound dressings to offer structural support, angiogenesis, and tissue regeneration. In the present study, an asymmetric bilayer wound dressing made up of a PVDF microfibrous top layer (TL) and a deferoxamine (Def)-loaded soluplus (Sol)-silk fibroin (SF) nanofibrous bottom layer (BL) was fabricated and characterized. After morphological and physical characterization, it was found that the presence of PVDF microfibrous layer increased tensile strength (from 3.0 ± 0.2 to 6.8 ± 0.5 MPa), elastic modulus (from 35.3 ± 3.0 to 77.9 ± 4.3 MPa), and failure strain (from 52.4 ± 2.9 to 66.8 ± 3.2 %). The swelling capability and biodegradability of the fabricated wound dressing resulted in a sustained release of Def up to approximately 88.1 ± 5.2 % in 168 h. The PVDF/Sol-SF-Def dressing showed high levels of cytocompatibility, and its superior angiogenic potential was confirmed by chicken chorioallantoic membrane assay. Histological examination demonstrated that in vivo fullthickness wounds treated with PVDF/SF-Sol-Def had superior re-epithelialization, increased granulation tissue thickness, enhanced collagen deposition, and increased COL1/COL3 ratio indicative of advanced wound remodeling. Therefore, the bilayer structure with its protective and bioactive properties represents a comprehensive approach toward the treatment of full-thickness wounds.

The aim of this study was to evaluate the fracture resistance of 2 different types of all-ceramic crown using immediate dentin sealing (IDS), obtained using a CAD/CAM system on molars with different preparations. Forty extracted lower molars were endodontically treated and divided into four groups (n = 10) according to the dental preparation. Group 1 (SP0) was prepared without filling the pulp chamber and crown-root junction was located at the cementoenamel junction (CEJ). Group 2 (SP1) was prepared without filling the pulp chamber and crown-root junction was located 1-mm above the CEJ. Groups 3 and 4 contained a flat preparation surface with no axial wall height. Group 3 (CP0) was made IDS with complete filling of the pulp chamber with composite resin and crown-root junction was located at the CEJ. Group 4 (CP1) was prepared with complete filling of the pulp chamber and crown-root junction was located 1-mm above the CEJ. All groups were restored with CAD/CAM lithium disilicate ceramic crowns. Specimens were subjected to the fracture test and statistically analyzed using analysis of variance (ANOVA). Fracture mode was determined using a stereoscopic microscope, classified as repairable or nonrepairable, and analyzed using Fischer's exact test. Results indicated that there were no significant differences between the groups in terms of fracture resistance or fracture pattern (p >0.05). Fracture resistance was the lowest in the SP0 group, followed by the SP1 group (1634.38 N) of CP0 (1821.50 N), and it was the highest in the CP1 group. There was a predominance of nonrepairable fractures and there were no significant differences in the fracture resistance and fracture mode of CAD/CAM lithium disilicate molar all-ceramic crowns. Endodontically treated molars teeth might be restored with endocrowns or all-ceramic crowns on flat preparation; however tooth fracture failures that affect reliability of these types of restorations should be considered.

The aim of this study was to evaluate the fracture resistance of 2 different types of all-ceramic crown using immediate dentin sealing (IDS), obtained using a CAD/CAM system on molars with different preparations. Forty extracted lower molars were endodontically treated and divided into four groups (n = 10) according to the dental preparation. Group 1 (SP0) was prepared without filling the pulp chamber and crown-root junction was located at the cementoenamel junction (CEJ). Group 2 (SP1) was prepared without filling the pulp chamber and crown-root junction was located 1-mm above the CEJ. Groups 3 and 4 contained a flat preparation surface with no axial wall height. Group 3 (CP0) was made IDS with complete filling of the pulp chamber with composite resin and crown-root junction was located at the CEJ. Group 4 (CP1) was prepared with complete filling of the pulp chamber and crown-root junction was located 1-mm above the CEJ. All groups were restored with CAD/CAM lithium disilicate cera...

The biological control of inorganic crystal formation, morphology and assembly is of interest to biologists and biotechnologists studying hard tissue growth and regeneration, as well as to materials scientists using biomimetic approaches for control of inorganic material fabrication and assembly. Biomimetics requires an accurate understanding of natural mechanisms at the molecular level. Such understanding can be derived from the use of metal surfaces to study surface recognition by proteins together with combinatorial genetics techniques for selection of suitable peptides. Polymerization of these peptides produces engineered polypeptides large enough to encode their own folding information with low structural complexity while enhancing binding affinity to surfaces. The low complexity of such polypeptides can aid in analyses leading to modeling and eventual manipulation of the structure of the folded polypeptide. Here we present structure predictions for gold-binding protein sequences, originally selected by combinatorial techniques. Molecular dynamics simulations lasting 5 ns were carried out using solvated polypeptides at the gold surface to assess the dynamics of the binding process and the effects of surface topography on the specificity of protein binding.

The biological control of inorganic crystal formation, morphology and assembly is of interest to biologists and biotechnologists studying hard tissue growth and regeneration, as well as to materials scientists using biomimetic approaches for control of inorganic material fabrication and assembly. Biomimetics requires an accurate understanding of natural mechanisms at the molecular level. Such understanding can be derived from the use of metal surfaces to study surface recognition by proteins together with combinatorial genetics techniques for selection of suitable peptides. Polymerization of these peptides produces engineered polypeptides large enough to encode their own folding information with low structural complexity while enhancing binding affinity to surfaces. The low complexity of such polypeptides can aid in analyses leading to modeling and eventual manipulation of the structure of the folded polypeptide. Here we present structure predictions for gold-binding protein sequences, originally selected by combinatorial techniques. Molecular dynamics simulations lasting 5 ns were carried out using solvated polypeptides at the gold surface to assess the dynamics of the binding process and the effects of surface topography on the specificity of protein binding.

Hydroxyapatite (HAp, Ca10(PO4)6(OH)2) is the major inorganic component of bones, with high bioactivity and biocompatibility, and pores in the 50-200 μm range can facilitate cell anchorage and proliferation. HAp was synthesised through a rapid sol-gel method, avoiding the usual long aging process typically required for sol-gel HAp. Acetate and nitrate precursor salts were compared, to produce bioceramics having different porosities induced via the addition of hydrogen peroxide (H2O2) pore-forming agent. 3-10 wt% H2O2 was added, and the resulting bioceramics calcined at 400 and 700 °C. Microstructure, composition, specific surface area and macro/mesoporosity were analysed, and bioactivity and cytotoxicity/biocompatibility evaluated by immersion in simulated body fluid (SBF) and MTT assays on MG63 osteoblast cell lines. When heated to 400 °C HAp was the only calcium phosphate phase present, but after heating to 700 °C they were a mixture of HAp and β-tricalcium phosphate (β-TCP, Ca3(PO4)2). The bioceramics exhibit high bioactivity, crystallising HAp from SBF, and most were biocompatible, with cell viabilities of 110-139% for samples with 3 wt% H2O2 derived from nitrates, or from acetates heated to 700 °C. This is the first time that HAp-based bioceramics derived from a rapid sol-gel process have been produced with such induced porosity.

Redox-responsive polymer dot (PD) were synthesized from disulfide cross-linked polymers in a carbonized process to allow quenching effects by loading of boron-dipyrromethene (BODIPY) onto the matrix. The disulfide linkage facilitated degradation of the PD system by intracellular glutathione (GSH), leading to fluorescence recovery by BODIPY and intracellular drug release. The paclitaxel release profile showed that approximately 100% of the drug escaped from the matrix in response to 10 mM GSH, whereas less than 10% was released in the absence of GSH. In vitro studies showed that quenching produced by BODIPY loading enabled visual monitoring of cancer cell death, as the quenching disappeared when BODIPY was released by GSH inside of cancer cells. The PD contain disulfide bonds representing a GSH-triggered ligand; thus, nanocarriers presented enhanced in vivo chemotherapeutic inhibition in xenograft tumor-bearing mice localized at the cancer location, guided by fluorescent off-on syste...

The ability of bacteria to develop antibiotic resistance and colonize abiotic surfaces by forming biofilms is a major cause of medical implant-associated infections and results in prolonged hospitalization periods and patient mortality. This raises the urgent need to develop compounds that can inhibit bacterial colonization of surfaces. In this study, we present an unreported microwave-based synthesis of MgF 2 nanoparticles (Nps) using ionic liquid. We demonstrate the antimicrobial activity of these fluoride nanomaterials and their ability to restrict biofilm formation of common bacterial pathogens. Scanning and transmission electron microscopic techniques indicated that the MgF 2 $Nps attach and penetrate into the cells. Flow cytometry analysis revealed that the Nps caused a disruption in the membrane potential. The MgF 2 $Nps also induced membrane lipid peroxidation and once internalized can interact with chromosomal DNA. Based on these findings we further explored the possibility of using the MgF 2 $Nps to coat surfaces and inhibit biofilm formation. A microwave synthesis and coating procedure was utilized to coat glass coupons. The MgF 2 coated surfaces effectively restricted biofilm formation of the tested bacteria. Taken together these results highlight the potential for developing MgF 2 nanoparticles in order to inhibit bacterial infections.

Background The application of tissue engineering and stem cells has not yet reached clinical reality. In many cases, such as cell selection, delivery, viability and stability, the time-consuming nature of treatments, regulatory issues, high costs and the need to obtain licenses from health regulatory agencies for compliance with medical ethics have created limitations for tissue engineering. Objective This study aims to describe the fabrication and use of bioscaffolds and biologically simulated bone materials and investigate the different methods used, their structures and scales from micro to macro levels in bone regeneration. Methods In this review study, related articles from 2008 to 2023 were searched in the Web of Science, PubMed, Scopus and Google Scholar databases using the keywords bioscaffold, bone materials, biological materials, and bone repair. Finally, 95 eligible articles were selected and reviewed. Results Studies showed that biomimetic methods, by combining structural design, surface modification, and the use of external physical stimuli, have created a great potential for bone regeneration. However, there are still significant challenges in this field at the clinical level. Conclusion Based on the studies, in vivo bone regeneration may be possible through the combination of tissue structural simulation and external physical stimulation, reducing the dependence on exogenous cells and biochemical factors in bone tissue engineering. Scaffold-based bone tissue engineering therapies that are safe, convenient and, most importantly, cost-effective will have significant advantages in clinical applications.

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

β-Amyloid peptide (Aβ), the primary protein component in senile plaques associated with Alzheimer's disease (AD), has been implicated in neurotoxicity associated with AD. Previous studies have shown that the Aβ-neuronal membrane interaction plays a crucial role in Aβ toxicity. More specifically, it is thought that Aβ interacts with ganglioside rich and sialic acid rich regions of cell surfaces. In light of such evidence, we have hypothesized that the Aβ-membrane sialic acid interaction could be inhibited through use of a biomimic multivalent sialic acid compound that would compete with the cell surface for Aβ binding. To explore this hypothesis, we synthesized a series of photocrosslinked sialic acid containing oligosaccharides and tested their ability to bind Aβ and attenuate Aβ toxicity in cell culture assays. We show that a polymer prepared via the photocrosslinking of disialyllacto-N-tetraose (DSLNT) was able to attenuate Aβ toxicity at low micromolar concentrations without adversely affecting the cell viability. Polymers prepared from mono-sialyl-oligosaccharides were less effective at Aβ toxicity attenuation. These results demonstrate the feasibility of using photocrosslinked sialyl-oligosaccharides for prevention of Aβ toxicity in vitro and may provide insight into the design of new materials for use in attenuation of Aβ toxicity associated with AD.

β-Amyloid peptide (Aβ), the primary protein component in senile plaques associated with Alzheimer's disease (AD), has been implicated in neurotoxicity associated with AD. Previous studies have shown that the Aβ-neuronal membrane interaction plays a crucial role in Aβ toxicity. More specifically, it is thought that Aβ interacts with ganglioside rich and sialic acid rich regions of cell surfaces. In light of such evidence, we have hypothesized that the Aβ-membrane sialic acid interaction could be inhibited through use of a biomimic multivalent sialic acid compound that would compete with the cell surface for Aβ binding. To explore this hypothesis, we synthesized a series of photocrosslinked sialic acid containing oligosaccharides and tested their ability to bind Aβ and attenuate Aβ toxicity in cell culture assays. We show that a polymer prepared via the photocrosslinking of disialyllacto-N-tetraose (DSLNT) was able to attenuate Aβ toxicity at low micromolar concentrations without adversely affecting the cell viability. Polymers prepared from mono-sialyl-oligosaccharides were less effective at Aβ toxicity attenuation. These results demonstrate the feasibility of using photocrosslinked sialyl-oligosaccharides for prevention of Aβ toxicity in vitro and may provide insight into the design of new materials for use in attenuation of Aβ toxicity associated with AD.

Silica (SiO2)/chitosan (CS) composite aerogels are bioactive when they are submerged in simulated body fluid (SBF), causing the formation of bone-like hydroxyapatite (HAp) layer. Silica-based hybrid aerogels improve the elastic behavior, and the combined CS modifies the network entanglement as a crosslinking biopolymer. Tetraethoxysilane (TEOS)/CS is used as network precursors by employing a sol-gel method assisted with high power ultrasound (600 W). Upon gelation and aging, gels are dried in supercritical CO2 to obtain monoliths. Thermograms provide information about the condensation of the remaining hydroxyl groups (400–700 °C). This step permits the evaluation of the hydroxyl group’s content of 2 to 5 OH nm−2. The formed Si-OH groups act as the inductor of apatite crystal nucleation in SBF. The N2 physisorption isotherms show a hysteresis loop of type H3, characteristic to good interconnected porosity, which facilitates both the bioactivity and the adhesion of osteoblasts cells. ...

In this study, we present and characterize a fiber deposition technique for producing three-dimensional poly(ethylene glycol)terephthalate-poly(butylene terephthalate) (PEGT/PBT) block co-polymer scaffolds with a 100% interconnecting pore network for engineering of articular cartilage. The technique allowed us to ''design-in'' desired scaffold characteristics layer by layer by accurately controlling the deposition of molten co-polymer fibers from a pressure-driven syringe onto a computer controlled x2y2z table. By varying PEGT/PBT composition, porosity and pore geometry, 3D-deposited scaffolds were produced with a range of mechanical properties. The equilibrium modulus and dynamic stiffness ranged between 0.05-2.5 and 0.16-4.33 MPa, respectively, and were similar to native articular cartilage explants (0.27 and 4.10 MPa, respectively). 3D-deposited scaffolds seeded with bovine articular chondrocytes supported a homogeneous cell distribution and subsequent cartilage-like tissue formation following in vitro culture as well as subcutaneous implantation in nude mice. This was demonstrated by the presence of articular cartilage extra cellular matrix constituents (glycosaminoglycan and type II collagen) throughout the interconnected pore volume. Similar results were achieved with respect to the attachment of expanded human articular chondrocytes, resulting in a homogenous distribution of viable cells after 5 days dynamic seeding. The processing methods and model scaffolds developed in this study provide a useful method to further investigate the effects of scaffold composition and pore architecture on articular cartilage tissue formation.

Heart valve replacements fabricated from glutaraldehyde (Glut)-crosslinked heterograft materials, porcine aortic valves or bovine pericardium, have been widely used in cardiac surgery to treat heart valve disease. However, these bioprosthetic heart valves often fail in long-term clinical implants due to pathologic calcification of the bioprosthetic leaflets, and for stentless porcine aortic valve bioprostheses, bioprosthetic aortic wall calcification also typically occurs. Previous use of the epoxide-based crosslinker, Triglycidyl amine (TGA), on cardiac bioprosthetic valve materials demonstrated superior biocompatibility, mechanics, and calcification resistance for porcine aortic valve cusps (but not porcine aortic wall) and bovine pericardium, versus Glut-prepared controls. However, TGA preparation did not completely prevent long-term calcification of cusps or pericardium. Herein we report further mechanistic investigations of an added therapeutic component to this system, 2-Mercaptoethylidene-1,1-bisphosphonic acid (MABP), a custom synthesized thiol bisphosphonate, which has previously been shown in a preliminary report to prevent bioprosthetic heterograft biomaterial calcification when used in combination with initial TGA crosslinking for 7 days. In the present studies we have further investigated the effectiveness of MABP in experiments that examined: 1) The use of MABP after optimal TGA crosslinking, in order to avoid any competitive interference of MABP-reactions with TGA during crosslinking; 2) Furthermore, recognizing the importance of alkaline phosphatase in the formation of dystrophic calcific nodules, we have investigated the hypothesis that the mechanism by which MABP primarily functions is through the reduction of alkaline phosphatase activity. Results from cell-free model systems, cell culture studies, and rat subcutaneous implants, show that materials functionalized with MABP after TGA crosslinking have reduced alkaline phosphatase activity, and in vivo have no significant calcification in long term implant studies. It is concluded that bioprosthetic heart valves prepared in this fashion are compelling alternatives for Glut-prepared bioprostheses.

Some treatments of metals and alloys in electrolyte give opportunities to modify their surfaces. The surface layers after electrical discharge treatment in electrolyte have different structure in comparison with the metal matrix, determining different properties such as higher hardness, strength and corrosion resistance. In this study altering of the surface of tool steels after electrical discharge treatment in electrolyte is investigated. Different process conditions are compared and resultant microstructures are investigated by optical microscopy and XRD. Results show improved surface properties and change in microstructure and chemical composition of the modified surfaces.

In order to improve their bacterial antifouling property, silicone surfaces were functionalized through the plasma polymerization (PP) technique using diethyl phosphite as the precursor. The functionalized surfaces were characterized using contact angle measurements, contact angle titration, Fourier transform infrared–attenuated total reflection spectroscopy and in vitro cytotoxicity assay. The amount of non-specific protein adsorption and the conformational changes of surface-adsorbed proteins were investigated. Antifouling properties of the surfaces were evaluated in vitro and in vivo. PP functionalization generated a hydrophilic and amphoteric surface with a very good protein and bacterial antifouling property and caused less conformational changes on the secondary structure of surface-adsorbed proteins. In in vivo conditions, no slime layer was formed around bacteria that adhered on the PP-functionalized surface. It is concluded that the amphoteric nature of the PP-functionalize...

S ome weaknesses of conventional glass ionomer cement (GIC) as dental materials, for instance the lack of bioactive potential and poor mechanical properties, remain unsolved. Objective: The purpose of this study was to investigate the effects of the partial replacement of CaO with MgO or ZnO on the mechanical and biological properties of the H[SHULPHQWDO JODVV LRQRPHU FHPHQWV 0DWHULDO DQG 0HWKRGV &DOFLXP ÀXRURDOXPLQR silicate glass was prepared for an experimental glass ionomer cement by melt quenching WHFKQLTXH 7KH JODVV FRPSRVLWLRQ ZDV PRGL¿HG E\ SDUWLDO UHSODFHPHQW PRO RI &D2 ZLWK 0J2 RU =Q2 1HW VHWWLQJ WLPH FRPSUHVVLYH DQG ÀH[XUDO SURSHUWLHV DQG in vitro rat dental pulp stem cells (rDPSCs) viability were examined for the prepared GICs and compared to a commercial GIC. Results: The experimental GICs set more slowly than the commercial product, but their extended setting times are still within the maximum limit PLQ VSHFL¿HG LQ ,62 &RPSUHVVLYH VWUHQJWK RI WKH H[SHULPHQWDO *,& ZDV QRW increased by the partial substitution of CaO with either MgO or ZnO, but was comparable WR WKH FRPPHUFLDO FRQWURO )RU ÀH[XUDO SURSHUWLHV DOWKRXJK WKHUH ZDV QR VLJQL¿FDQFH EHWZHHQ WKH EDVH DQG WKH PRGL¿HG JODVV DOO SUHSDUHG *,&V PDUNHG D VWDWLVWLFDOO\ KLJKHU ÀH[XUDO VWUHQJWK S DQG FRPSDUDEOH PRGXOXV WR FRQWURO 7KH PRGL¿HG FHPHQWV VKRZHG LQFUHDVHG FHOO YLDELOLW\ IRU U'36&V &RQFOXVLRQV 7KH H[SHULPHQWDO *,&V PRGL¿HG with MgO or ZnO can be considered bioactive dental materials.

The individual contributions of pH and chloride concentration to the corrosion kinetics of bioabsorbable magnesium (Mg) alloys remain unresolved despite their significant roles as driving factors in Mg corrosion. This study demonstrates and quantifies hitherto unknown separate effects of pH and chloride content on the corrosion of Mg alloys pertinent to biomedical implant applications. The experimental setup designed for this purpose enables the quantification of the dependence of corrosion on pH and chloride concentration. The in vitro tests conclusively demonstrate that variations in chloride concentration, relevant to biomedical applications, have a negligible effect on corrosion kinetics. The findings identify pH as a critical factor in the corrosion of bioabsorbable Mg alloys. A variationally consistent phase-field model is developed for assessing the degradation of Mg alloys in biological fluids. The model accurately predicts the corrosion performance of Mg alloys observed during the experiments, including their dependence on pH and chloride concentration. The capability of the framework to account for mechano-chemical effects during corrosion is demonstrated in practical orthopedic applications considering bioabsorbable Mg alloy implants for bone fracture fixation and porous scaffolds for bone tissue engineering. The strategy has the potential to assess the in vitro and in vivo service life of bioabsorbable Mg-based biomedical devices.

Brain tissue loss following stroke is irreversible with current treatment modalities. The use of an acellular extracellular matrix (ECM), formulated to produce a hydrogel in situ within the cavity formed by a stroke, was investigated as a method to replace necrotic debris and promote the infiltration of host brain cells. Based on magnetic resonance imaging measurements of lesion location and volume, different concentrations of ECM (0, 1, 2, 3, 4, 8 mg/mL) were injected at a volume equal to that of the cavity (14 days post-stroke). Retention of ECM within the cavity occurred at concentrations >3 mg/mL. A significant cell infiltration into the ECM material in the lesion cavity occurred with an average of ∼36,000 cells in the 8 mg/mL concentration within 24 h. An infiltration of cells with distances of >1500 μm into the ECM hydrogel was observed, but the majority of cells were at the tissue/hydrogel boundary. Cells were typically of a microglia, macrophage, or neural and oligoden...

Replacing the tissue lost after a stroke potentially provides a new neural substrate to promote recovery. However, significant neurobiological and biotechnological challenges need to be overcome to make this possibility into a reality. Human neural stem cells (hNSCs) can differentiate into mature brain cells, but require a structural support that retains them within the cavity and affords the formation of a de novo tissue. Nevertheless, in our previous work, even after a week, this primitive tissue is void of a vasculature that could sustain its long-term viability. Therefore, tissue engineering strategies are required to develop a vasculature. Vascular endothelial growth factor (VEGF) is known to promote the proliferation and migration of endothelial cells during angio-and arteriogenesis. VEGF by itself here did not affect viability or differentiation of hNSCs, whereas growing cells on poly(D,L-lactic acid-co-glycolic acid) (PLGA) microparticles, with or without VEGF, doubled astrocytic and neuronal differentiation. Secretion of a burst and a sustained delivery of VEGF from the microparticles in vivo attracted endothelial cells from the host into this primate tissue and in parts established a neovasculature, whereas in other parts

Transplantation of human neural stem cells (hNSCs) is emerging as a viable treatment for stroke related brain injury. However, intraparenchymal grafts do not regenerate lost tissue, but rather integrate into the host parenchyma without significantly affecting the lesion cavity. Providing a structural support for the delivered cells appears important for cell based therapeutic approaches. The non-invasive monitoring of therapeutic methods would provide valuable information regarding therapeutic strategies but remains a challenge. Labeling transplanted cells with metalbased 1 H-magnetic resonance imaging (MRI) contrast agents affects the visualization of the lesion cavity. Herein, we demonstrate that a 19 F-MRI contrast agent can adequately monitor the

A hipersensibilidade dentinaria, comumente denominada de sensibilidade dentaria, tem como seu principal fator etiologico a exposicao de dentina radicular, caracterizada por uma sensacao dolorosa oriunda de estimulos termicos, quimicos, mecânicos ou osmoticos que nao pode ser atribuida a outra patologia como a carie dentaria. O presente estudo objetiva tratar sobre sensibilidade dentinaria e suas implicacoes. Clinicamente, a dor se manifesta de forma aguda, localizada, desenvolvida rapidamente e com curta duracao frente ao estimulo. Existem no mercado dessensibilizantes que ajudam a combater sensibilidade dentaria, normalmente estes sao bastante efetivos, porem o tratamento prolongado e essencial para melhor ser o seu efeito. Um dos inumeros disponiveis no mercado e o Dessensibilizante e Remineralizante Dessensibilize Nano P (FMG), o qual apresenta caracteristicas quimicas e estruturais semelhantes as da hidroxiapatita, o qual possui biocompatibilidade agindo na remineralizacao da es...

Electrospinning is a promising technique for the production of scaffolds aimed at the regeneration of soft tissues. The aim of this work was to develop electrospun bundles mimicking the architecture and mechanical properties of the fascicles of the human Achille tendon. Two different blends of poly(L-lactic acid) (PLLA) and collagen (Coll) were tested, PLLA/Coll-75/25 and PLLA/Coll-50/50, and compared with bundles of pure PLLA. First, a complete physico-chemical characterization was performed on non-woven mats made of randomly arranged fibers. The presence of collagen in the fibers was assessed by thermogravimetric analysis, differential scanning calorimetry and water contact angle measurements. The collagen release in phosphate buffer solution (PBS) was evaluated for 14 days: results showed that collagen loss was about 50% for PLLA/Coll-75/25 and 70% for PLLA/Coll-50/50. In the bundles, the individual fibers had a diameter of 0.48± 0.14 µm (PLLA), 0.31±0.09 µm (PLLA/Coll-75/25), 0.33±0.08 µm (PLLA/Coll-50/50), whereas bundle diameter was in the range 300-500 µm for all samples. Monotonic tensile tests were performed to measure the mechanical properties of PLLA bundles (as-spun) and of PLLA/Coll-75/25 and PLLA/Coll-50/50 bundles (as-spun, and after 48 hour, 7 days and 14 days in PBS). The most promising material was the PLLA/Coll-75/25 blend with a Young modulus of 98.6±12.4 MPa (as-spun) and 205.1±73.0 MPa (after 14 days in PBS). Its failure stress was 14.2±0.7 MPa (as-spun) and 6.8±0.6 MPa (after 14 days in PBS). Pure PLLA withstood slightly lower stress than the PLLA/Coll-75/25 while PLLA/Coll-50/50 had a brittle behavior. Humanderived tenocytes were used for cellular tests. A good cell adhesion and viability after 14 day culture was observed. This study has therefore demonstrated the feasibility of fabricating electrospun bundles with multiscale structure and mechanical properties similar to the human tendon.

In this study, the mechanical properties of porous glass-ceramic scaffolds are investigated by means of three-dimensional finite element models based on micro-computed tomography (micro-CT) scan data. In particular, the quantitative relationship between the morpho-architectural features of the obtained scaffolds, such as macroscopic porosity and strut thickness, and elastic properties, is sought. The macroscopic elastic properties of the scaffolds have been obtained through numerical homogenization approaches using the mechanical characteristics of the solid walls of the scaffolds (assessed through nanoindentation) as input parameters for the numerical simulations. Anisotropic mechanical properties of the produced scaffolds have also been investigated by defining a suitable anisotropy index. A comparison with morphological data obtained through the micro-CT scans is also presented. The proposed study shows that the produced glass-ceramic scaffolds exhibited a macroscopic porosity ranging between 29% and 97% which corresponds to an average stiffness ranging between 42.4 GPa and 36 MPa. A quantitative estimation of the isotropy of the macroscopic elastic properties has been performed showing that the samples with higher solid fractions were those closest to an isotropic material.

Low accumulation of chemotherapeutic agent in tumor tissue and multidrug resistance (MDR) present a major obstacle to curing cancer treatment. Therefore, how to combine several therapeutics in one system is a key issue to overcome the problem. Here, we demonstrate epidermal growth factor receptor (EGFR) antibody-conjugated PEGylated nanographene oxide (PEG-NGO) to carry epirubicin (EPI) for tumor targeting and triple-therapeutics (growth signal blocking, chemotherapy, photothermal therapy) in tumor treatment. This synergistic targeted treatment simultaneously enhances the local drug concentration (6.3-fold) and performs the ultra-efficient tumor suppression to significantly prolong the mice survival (over the course of 50 days).

Human embryonic stem cells (hESCs) have the potential to offer a virtually unlimited source of chondrogenic cells for use in cartilage repair and regeneration. We have recently shown that expandable chondrogenic cells can be derived from hESCs under selective growth factor-responsive conditions. In this study, we explore the potential of these hESC-derived chondrogenic cells to produce an extracellular matrix (ECM)-enriched cartilaginous tissue construct when cultured in hyaluronic acid (HA)-based hydrogel, and further investigated the long-term reparative ability of the resulting hESC-derived chondrogenic cell-engineered cartilage (HCCEC) in an osteochondral defect model. We hypothesized that HCCEC can provide a functional template capable of undergoing orderly remodeling during the repair of critical-sized osteochondral defects (1.5 mm in diameter, 1 mm depth into the subchondral bone) in a rat model. In the process of repair, we observed an orderly spatial-temporal remodeling of HCCEC over 12 weeks into osteochondral tissue, with characteristic architectural features including a hyaline-like neocartilage layer with good surface regularity and complete integration with the adjacent host cartilage and a regenerated subchondral bone. By 12 weeks, the HCCEC-regenerated osteochondral tissue resembled closely that of age-matched unoperated native control, while only fibrous tissue filled in the control defects which left empty or treated with hydrogel alone. Here we demonstrate that transplanted hESC-derived chondrogenic cells maintain long-term viability with no evidence of tumorigenicity, providing a safe, highly-efficient and practical strategy of applying hESCs for cartilage tissue engineering.

Spinal cord injury (SCI) causes permanent paralysis below the damaged area. SCI is linked to neuronal death, demyelination, and limited ability of neuronal fibers to regenerate. Regeneration capacity is limited by the presence of many inhibitory factors in the spinal cord environment. The use of poly(lactide-co-glycolide) (PLG) bridges has demonstrated the ability to sustain long-term regeneration after SCI in a cervical hemisection mouse model. Critically, imaging of regenerating fibers and the myelination status of these neuronal filaments is a severe limitation to progress in SCI research. We used a transgenic mouse model that selectively expresses fluorescent reporters (eGFP) in the neuronal fibers of the spinal cord. We implanted a PLG bridge at C5 vertebra after hemisection and evaluated in live animals' neuronal fibers at the bridge interface and within the bridge 8 weeks postimplant. These in vivo observations were correlated with in situ evaluation 12 weeks postimplanta...

The current research was undertaken to study the improvement of the tribological behavior of nanocrystalline bioceramic, α-alumina sample, produced by the calculations of gibbsite at different temperatures (300 to 1200°C), followed by uniaxial pressing, sintering and HIP treatment. The improved friction and wear resistance is attributed to the fine microstructure of the sample calcined at 1400 °C. 1. MATERIALS AND METHODS The calcined alunminas powders were uniaxially pressed at 150 MPa into discs of 17 mm in diameter and 4 mm thickness. The compaction was carried out at a constant strain rate. After ejecting from the die, the samples were measured and weighed to calculate the density. Green compacts were placed into an alumina crucible with Al2O3 powder and sintered at different temperatures of 1250, 1300, 1350, 1400 and 1450 °C for 2 h at a heating rate of 30 K min in order to obtain a closed porosity (high density) as observed by M.H. Bocangera [1, 2]. The sintered samples were t...

In order efficiently to target therapies intending to stop or reverse degenerative processes of articular cartilage, it would be crucial to diagnose osteoarthritis (OA) earlier and more sensitively than is possible with the existing clinical methods. Unfortunately, current clinical methods for OA diagnostics are insensitive for detecting the early degenerative changes, e.g., arising from collagen network damage or proteoglycan depletion. We have recently investigated several novel quantitative biophysical methods, including ultrasound indentation, quantitative ultrasound techniques and magnetic resonance imaging, for diagnosing the degenerative changes of articular cartilage, typical for OA. In this study, the combined results of these novel diagnostic methods were compared with histological (Mankin score, MS), compositional (proteoglycan, collagen and water content) and mechanical (dynamic and equilibrium moduli) reference measurements of the same bovine cartilage samples. Receiver operating characteristics (ROC) analysis was conducted to judge the diagnostic performance of each technique. Indentation and ultrasound techniques provided the most sensitive measures to differentiate samples of intact appearance (MS= 0) from early (1<MS<3) or more advanced (MS>3) degeneration. Furthermore, these techniques were good predictors of tissue composition and mechanical properties. The specificity and sensitivity analyses revealed that the mechano-acoustic methods, when further developed for in vivo use, may provide more sensitive probes for OA diagnostics than the prevailing qualitative X-ray and arthroscopic techniques. Noninvasive quantitative MRI measurements showed slightly lower diagnostic performance than mechano-acoustic techniques. The compared methods could possibly also be used for the quantitative monitoring of success of cartilage repair.

Injectable hydrogel biomaterials are promising therapies to promote repair and regeneration postmyocardial infarction (MI). However, the timing of delivery and the mechanisms through which biomaterial treatments confer their benefits are translational issues that remain to be addressed. We assessed the efficacy of an injectable collagen matrix at 3 different delivery time points post-MI. Infarcted mice received the matrix or control (saline) treatment at 3 h, 1 week or 2 weeks after MI. The earlier treatment delivery better prevented negative ventricular remodeling and long-term deterioration of cardiac function (up to 3 months), whereas waiting longer to administer the matrix (1 and 2 weeks post-MI) reduced the therapeutic effects. Collagen matrix delivery did not stimulate an inflammatory response acutely and favorably modulated inflammation in the myocardium long-term. We found that the matrix interacts with the host tissue to alter the myocardial cytokine profile, promote angiogenesis, and reduce fibrosis and cell death. This work highlights that the timing of delivery can significantly affect the ability of an injectable hydrogel to protect the post-MI environment, which will be an important consideration in the clinical translation of cardiac biomaterial therapy.

In this research, composites based on treated tropical sawdust and polypropylene (PP) were prepared using hot press molding machine. Raw sawdust was chemically treated with monomer, 2-ethylhexyl methacrylate in order to improve the mechanical properties of the composites. The influence of the chemically treated sawdust on the physical and mechanical properties of sawdust-PP composites were investigated at various loading level from 10 wt% up to 30 wt%. Results indicate that the mechanical properties of the chemically treated sawdust-PP composites were found to be higher than those of the raw ones respectively. The surface morphology obtained from scanning electron microscopy (SEM) showed that raw sawdust-PP composites possess surface roughness and weak interfacial adhesion between the matrix and the filler while the chemically treated one showed improved filler-matrix interaction. This indicates that better dispersion of the filler with the PP matrix has occurred upon chemical treatment of the filler. Water absorption tests showed that composites prepared from the chemically treated sawdust absorb lower amount of water compared to the ones prepared from raw sawdust, suggesting that hydrophilic nature of the cellulose in the sawdust has significantly decreased upon chemical treatment.

and foremost, I want to thank my parents for their love and continuous support through all of my endeavors and for always telling me I can achieve whatever I want. I also have to especially thank my brother, Burns, for wanting to pursue a degree in engineering, and thus forcing me to sit through college recruitment visits, listening to talks on engineering programs as a high school senior. It was during this time that I stumbled upon the Biological Engineering program at Mississippi State, and the rest is history. I also have to thank my other two siblings, Drew and Caroline, for keeping me grounded and always findings ways to tease me about my "Kathryn"isms. My progression over the past four years would not have been possible without the guidance from my graduate advisors. I would like to thank Ken Gall for taking on a young student who had never heard of a glass transition temperature and providing me with not only a plethora of knowledge on materials science but also instilling many invaluable skills I can apply in becoming an exciting, successful researcher. Whenever I would hit a road block or feel lost in my work, Ken's encouraging words and sage advice always put me back on track feeling ever the more motivated. I would like to thank Barbara Boyan for always lending her opinions on the convergence of materials science and biology, and for serving not only as an amazing mentor, but also as an outstanding role model to women trying to pave their own career paths in the science community. I would also like to acknowledge my other committee members, Andres Garcia, Johnna v Temenoff, and Yonathan Thio for giving their time and consideration towards my research. This work would not have been possible without the strong relationships I have formed with my labmates. I have to particularly thank Matthew DiPrima for his patience in helping me whenever the Insight went down or for laser-cutting obscene amounts of material; Walter Voit for helping me work through those tough critical problems and introducing me to Siedtlers and Set; and Scott Kasprzak for his handy machine shop skills and shared love of Diet Coke. Also, I would like to give a special thank you to Sharon Hyzy for all of her work with assisting me with the cell culture and biochemical assays. In addition, this work would never have reached fruition without the numerous undergraduates who assisted with making material and running tests: Hillary Harris,

Targeting the spleen with nanoparticles could increase the efficacy of vaccines and cancer immunotherapy, and have the potential to treat intracellular infections including leishmaniasis, trypanosome, splenic TB, AIDS, malaria, and hematological disorders. Although, nanoparticle capture in both the liver and spleen has been well documented, there are only a few examples of specific capture in the spleen alone. It is proposed that the larger the nanoparticle size (> 400 nm) the greater the specificity and capture within the spleen. Here, we synthesized five nanostructures with different shapes (ranging from spheres, worms, rods, nanorattles and toroids) and poly(N-isopropylacrylamide), PNIPAM, surface coating using the temperature-directed morphology transformation (TDMT) method. Globular PNIPAM (i.e. water insoluble) surface coatings have been shown to significantly increase cell uptake and enhanced enzyme activity. We incorporated a globular component of PNIPAM on the nanostructure surface, and examined the in vivo biodistribution of these nanostructures and accumulation in various tissues and organs in a mouse model. The in vivo biodistribution as a function of time was influenced by the shape and PNIPAM surface composition, in which organ capture and retention was the highest in the spleen. The rods (~150 nm in length and 15 nm in width) showed the highest capture and retention of greater than 35% to the initial injection amount compared to all other nanostructures. It was found that the rods specifically targeted the cells in the red pulp region of the spleen due to the shape and PNIPAM coating of the rod. This remarkable accumulation and selectively into the spleen represents new nanoparticle design parameters to develop new splenotropic effects for vaccines and other therapeutics.

MgAl-layered double hydroxide (MgAl-LDH) nanoparticles have great protentials in drug and siRNA delivery. In this work, we used a nanodot-coating strategy to prepare SiO 2 dot-coated layered double hydroxide (SiO 2 @MgAl-LDH) nanocomposites with good dispersibility and controllable size for drug delivery. The optimal SiO 2 @MgAl-LDH nanocomposite was obtained by adjusting synthetic parameters including the mass ratio of MgAl-LDH to SiO 2 , the mixing temperature and time. The optimal SiO 2 @MgAl-LDH nanocomposite was shown to have SiO 2 nanodots (10-15 nm in diameter) evenly deposited on the surface of MgAl-LDHs (110 nm in diameter) with the plate-like morphology and the average hydrodynamic diameter of 170 nm. We further employed SiO 2 @MgAl-LDH nanocomposite as a nanocarrier to deliver methotrexate (MTX), a chemotherapy drug, to the human osteosarcoma cell (U2OS) and found that MTX delivered by SiO 2 @MgAl-LDH nanocomposite apparently inhibited the U2OS cell growth.

Nanoporous materials with uniform and adjustable pore sizes (1-100 nm) have important applications in modern biotechnology. Many biomolecules, such as peptides and proteins, have crucial functions in biological systems and exist in nanoscale sizes (1-100 nm) at extremely low concentrations. In order to separate or identify biomolecules in biological systems, nanoporous materials with carefully designed pore structures and pore sizes are ideal hosts. By further manipulating the composition, surface chemistry, and morphology of nanoporous materials, their applications in diverse biological areas are promising but as yet require further exploration. Enrichment of peptidome fractions is a key to identify which peptides control molecular and cellular pathways in life science. Mass spectrometry (MS)-based peptide mapping is one of the fundamental tools for current peptidome research. Detection of functional peptides in biosystems (e.g., in serum and on the cell surface) is currently an important but extremely challenging topic. Serum consists of a complex biological fluid, in which the target peptide may exist in a very low abundance and is mixed with a large number of other peptides and proteins, making detection in such a biosystem difficult. For one example, the enrichment and detection of the cytotoxic lymphocyte (CTL) epitope of E7 (a functional peptide residue) in biosystems is of significant importance in the immunotherapy of human papillomavirus (HPV)-related diseases, and has consequently attracted intensive attention in pathological and clinical studies. Very recently, the E7 peptide has been shown effective as a preventive therapeutic vaccine to generate immune responses and eliminate tumour growth in clinical-phase trials. For

Modulation of the immune response is an important step in the induction of protective humoral and cellular immunity against pathogens. In this study, we investigated the possibility of using a nanomaterial conjugated with the toll-like receptor (TLR) ligand CpG to modulate the immune response towards the preferred polarity. MgAl-layered double hydroxide (LDH) nanomaterial has a very similar chemical composition to Alum, an FDA approved adjuvant for human vaccination. We used a model antigen, ovalbumin (OVA) to demonstrate that MgAl-LDH had comparable adjuvant activity to Alum, but much weaker inflammation. Conjugation of TLR9 ligand CpG to LDH nanoparticles significantly enhanced the antibody response and promoted a switch from Th2 toward Th1 response, demonstrated by a change in the IgG2a:IgG1 ratio. Moreover, immunization of mice with CpG-OVA-conjugated LDH before challenge with OVA-expressing B16/F10 tumor cells retarded tumor growth. Together, these data indicate that LDH nanomaterial can be used as an immune adjuvant to promote Th1 or Th2 dominant immune responses suitable for vaccination purposes.

Understanding the influences of particle properties of antigen-adjuvant complexes on immunity is crucial in designing highly active adjuvants for new-generation of vaccines. This paper briefly revisits the current opinions on the size-dependent immunity of various adjuvant particles and then comprehensively discusses a few immunity-determining processes that are affected by the antigen-adjuvant particle properties. These include particle size, surface charge, surface hydrophilicity/lipophilicity, and antigen-adjuvant binding strength. Based on current understandings, we hypothesize that a maximum immune response occurs at a certain antigen-adjuvant particle size. This hypothesis clearly explains the paradoxical opinions on the size-dependent immunity and has also been supported by the data reported by several research groups. Finally, we further hypothesize that there is a similar relationship between any immune response and any measureable antigen-adjuvant particle property, and that there is a maximum immune response when all measureable antigen-adjuvant particle properties are optimized. We believe more attention should be paid to this issue when designing and developing effective adjuvants in future research.

MgAl-layered double hydroxide (MgAl-LDH) nanoparticles have great potentials in drug and siRNA delivery. In this work, we used a nanodot-coating strategy to prepare SiO2 dot-coated layered double hydroxide (SiO2@MgAl-LDH) nanocomposites with good dispersibility and controllable size for drug delivery. The optimal SiO2@MgAl-LDH nanocomposite was obtained by adjusting synthetic parameters including the mass ratio of MgAl-LDH to SiO2, the mixing temperature and time. The optimal SiO2@MgAl-LDH nanocomposite was shown to have SiO2 nanodots (10-15nm in diameter) evenly deposited on the surface of MgAl-LDHs (110nm in diameter) with the plate-like morphology and the average hydrodynamic diameter of 170nm. We further employed SiO2@MgAl-LDH nanocomposite as a nanocarrier to deliver methotrexate (MTX), a chemotherapy drug, to the human osteosarcoma cell (U2OS) and found that MTX delivered by SiO2@MgAl-LDH nanocomposite apparently inhibited the U2OS cell growth.

Although liposomes are widely used as carriers of drugs and imaging agents, they suffer from a lack of stability and the slow release of the encapsulated contents at the targeted site. Polymersomes (vesicles of amphiphilic polymers) are considerably more stable compared to liposomes; however, they also demonstrate a slow release for the encapsulated contents, limiting their efficacy as a drug-delivery tool. As a solution, we prepared and characterized echogenic polymersomes which are programmed to release the encapsulated drugs rapidly when incubated with cytosolic concentrations of glutathione. These vesicles encapsulated air bubbles inside and efficiently reflected diagnostic frequency ultrasound. Folate-targeted polymersomes showed an enhanced uptake by breast and pancreatic-cancer cells in a monolayer as well as in threedimensional spheroid cultures. Polymersomes encapsulated with the anticancer drugs gemcitabine and doxorubicin showed significant cytotoxicity to these cells. With further improvements, these vesicles hold the promise to serve as multifunctional nanocarriers, offering a triggered release as well as diagnostic ultrasound imaging.

Human bone marrow-derived mesenchymal stem cells (hMSCs) are promising cell candidates for cartilage regeneration. Building the appropriate microenvironment for cell differentiation in response to exogenous stimuli is a critical step towards the clinical utilization of hMSCs. In this study, the effects of RGD peptide immobilization onto macro-porous alginate scaffolds on TGF-b1-induced hMSC chondrogenesis were evaluated. The results revealed different cell morphology, viability and proliferation extent in the RGD-immobilized vs. un-modified scaffolds. The TGF-b1-induced activation of both Smaddependent (SMAD2) and Smad-independent (ERK1/2) signaling pathways was stronger and persisted for over 3 weeks in the RGD-immobilized scaffolds, indicating greater accessibility of the cells to the inducer. By contrast, in the un-modified alginate scaffolds, the cells aggregated into compacted clusters resulting in lesser effects of TGF-b1. The efficient and prolonged exposure to the chondrogenic inducer in the RGDmodified scaffolds ensured the appropriate progression of MSC differentiation from the initial phase of cell condensation until the appearance of committed chondrocytes, at 3 weeks of cultivation. Taken together, our results highlight the fundamental importance of the microenvironment design of the scaffold as well as the presentation of the inductive cue for inducing efficient stem-cell controlled differentiation.

Mixed metallic Au-Pd nanoparticles (NPs) supported on rice husk ash silica was successfully developed through immobilization of imidazolium chloride (Im) ionic liquid. Au-PdNPs_Me-IM ionic liquid at RHA silica catalytic system was prepared by the method of reduction using NaBH 4 as reducing agent at controlled feed rate and used as effective catalyst for ligand free Suzuki coupling reaction in ethanol at 80 °C. Synthesized catalytic system was characterized by using FT-IR, NMR, XRD, SEM-EDS and TGA-DSC analysis. Mixed metallic Au-PdNPs catalytic system provides better catalytic activity than mono metallic nanoparticles. Ionic liquid and mixed metallic nanoparticles hybrid system supported on natural waste rice husk ash silica provides better stability with high efficiency, enhances the physicochemical properties through intermolecular interactions and consequently provides ease in recyclability up to next seven turns without loss in catalytic efficiency.

The growing global demand for meat consumption, especially for poultry, has led to an increase in bone waste production that necessitates sustainable waste management strategies. This study proposes a new processing method for Chicken Bone Waste (CBW) and evaluates the reactant's potential usage. The novel approach to this issue consists of the integration of an enzymatic pretreatment to CBW before being subjected to the pyrolysis process. First, the CBW were classically processed (CBW classic) and then underwent a novel enzymatic pretreatment that consisted of a mixture of protease, lipase, and amylase (CBW enzymes). The pretreated CBW were slowly pyrolyzed (10 • C/min) at temperatures between 500-900 • C. The increase in temperature led to a decrease in biochar yield of 45 ± 3 wt%. In addition, the biochar thermal stability increased with the augmentation of process temperature. The pyro-gas primary consists of CO 2 and ≥ C 2 , CO, CH 4, and H 2. Higher process temperatures enhanced the production of ≥ C 2 and H 2. The maximum oil yields were 45.3 wt% (600 • C, CBW classic) and 38.5 wt% (500 • C, CBW enzymes). The bio-oil obtained from CBW enzymes at 600 • C exhibits higher yielding valuable compounds. Chemicals identified in the main groups can be used as scaffolds for plant protection products, waxes and polishes, fireproofing, textiles, rubber, jet fuel, biodiesel, etc. The study concludes that the novel integrated processing enhances the potential functionalities of pyrolysis products by producing green, renewable chemicals and resources.

Bone tissue engineering has mainly focused on generating 3D grafts to repair bone defects. However, the underlying signaling mechanisms responsible for development of such 3D bone equivalents have largely been ignored. Here we describe the crucial aspects of embryonic osteogenesis and bone development including cell sources and general signaling cascades that guide mesenchymal progenitors towards osteogenic lineage. Drawing from the knowledge of developmental biology, we then review how silk biomaterial can regulate osteogenic signaling by focusing on the expression of cell surface markers, functional genomic information (mRNA) of stem cells cultured on silk matrices. In an attempt to recapitulate exact in vivo microenvironment of osteogenesis, role of scaffold architecture and material chemistry in regulating cellular differentiation is elaborated. The generated knowledge will not only improve our understanding of cell-material interactions but reveal newer strategies beyond a conventional tissue engineering paradigm and open new prospects for developing silk-based therapies against clinically relevant bone disorders.

Bone tissue engineering has mainly focused on generating 3D grafts to repair bone defects. However, the underlying signaling mechanisms responsible for development of such 3D bone equivalents have largely been ignored. Here we describe the crucial aspects of embryonic osteogenesis and bone development including cell sources and general signaling cascades that guide mesenchymal progenitors towards osteogenic lineage. Drawing from the knowledge of developmental biology, we then review how silk biomaterial can regulate osteogenic signaling by focusing on the expression of cell surface markers, functional genomic information (mRNA) of stem cells cultured on silk matrices. In an attempt to recapitulate exact in vivo microenvironment of osteogenesis, role of scaffold architecture and material chemistry in regulating cellular differentiation is elaborated. The generated knowledge will not only improve our understanding of cell-material interactions but reveal newer strategies beyond a conventional tissue engineering paradigm and open new prospects for developing silk-based therapies against clinically relevant bone disorders.

Unexpectedly, the solubility of CeO 2 nanoparticles (NPs) at 25 °C does not depend on particle size, but is significantly affected by the sample's thermal pre-treatment. The classical interpretation of NPs' solubility proposed by the Gibbs-Thompson or Kelvin equations fails to describe the experimental data on CeO 2 solubility obtained in this study. Thermal treatment did not change the samples' morphological characteristics, while slightly affecting NP hydroxylation and local crystallinity. The differences in the solubility of dried and non-treated CeO 2 particles were most noticeable at pH < 4, and dissolved cerium concentration was much lower in the case of the dried sample. After prolonged storage (up to 4.5 years) of CeO 2 NPs in aqueous media, the solubility of dried samples gradually increased, while for non-treated samples it remained unchanged. Based on the example of CeO 2 , the dissolution laws of other less soluble nanomaterials should be reconsidered.