Aptamer-conjugated mesoporous polydopamine for docetaxel targeted delivery and synergistic photothermal therapy of prostate cancer.

OBJECTIVES: It is imperative to develop efficient strategies on the treatment of prostate cancer. Here, we constructed multifunctional nanoparticles, namely AS1411@MPDA-DTX (AMD) for targeted and synergistic chemotherapy/photothermal therapy of prostate cancer. MATERIALS AND METHODS: Mesoporous polydopamine (MPDA) nanoparticles were prepared by a one-pot synthesis method, DTX was loaded through incubation, and AS1411 aptamer was modified onto MPDA by the covalent reaction. The prepared nanoparticles were characterized by ultra-micro spectrophotometer, Fourier transform infrared spectra, transmission electron microscope, and so on. The targeting ability was detected by selective uptake and cell killing. The mechanism of AMD-mediated synergistic therapy was detected by Western blot and immunofluorescence. RESULTS: The prepared nanoparticles can be easily synthesized and possessed excellent water solubility, stability, and controlled drug release ability, preferentially in acidic context. Based on in vitro and in vivo results, the nanoparticles can efficiently target prostate cancer cells, promote DTX internalization, and enhance the antitumor effects of chemo-photothermal therapy strategies under the NIR laser irradiation. CONCLUSIONS: As a multifunctional nanoplatform, AS1411@MPDA-DTX could efficiently target prostate cancer cells, promote DTX internalization, and synergistically enhance the antiprostate cancer efficiency by combining with NIR irradiation.

Porous Biphasic Calcium Phosphate Granules from Oyster Shell Promote the Differentiation of Induced Pluripotent Stem Cells.

Oyster shells are rich in calcium, and thus, the potential use of waste shells is in the production of calcium phosphate (CaP) minerals for osteopathic biomedical applications, such as scaffolds for bone regeneration. Implanted scaffolds should stimulate the differentiation of induced pluripotent stem cells (iPSCs) into osteoblasts. In this study, oyster shells were used to produce nano-grade hydroxyapatite (HA) powder by the liquid-phase precipitation. Then, biphasic CaP (BCP) bioceramics with two different phase ratios were obtained by the foaming of HA nanopowders and sintering by two different two-stage heat treatment processes. The different sintering conditions yielded differences in structure and morphology of the BCPs, as determined by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Brunauer-Emmett-Teller (BET) surface area analysis. We then set out to determine which of these materials were most biocompatible, by co-culturing with iPSCs and examining the gene expression in molecular pathways involved in self-renewal and differentiation of iPSCs. We found that sintering for a shorter time at higher temperatures gave higher expression levels of markers for proliferation and (early) differentiation of the osteoblast. The differences in biocompatibility may be related to a more hierarchical pore structure (micropores within macropores) obtained with briefer, high-temperature sintering.

To Close or to Collapse: The Role of Charges on Membrane Stability upon Pore Formation.

Resealing of membrane pores is crucial for cell survival. Membrane surface charge and medium composition are studied as defining regulators of membrane stability. Pores are generated by electric field or detergents. Giant vesicles composed of zwitterionic and negatively charged lipids mixed at varying ratios are subjected to a strong electric pulse. Interestingly, charged vesicles appear prone to catastrophic collapse transforming them into tubular structures. The spectrum of destabilization responses includes the generation of long-living submicroscopic pores and partial vesicle bursting. The origin of these phenomena is related to the membrane edge tension, which governs pore closure. This edge tension significantly decreases as a function of the fraction of charged lipids. Destabilization of charged vesicles upon pore formation is universal-it is also observed with other poration stimuli. Disruption propensity is enhanced for membranes made of lipids with higher degree of unsaturation. It can be reversed by screening membrane charge in the presence of calcium ions. The observed findings in light of theories of stability and curvature generation are interpreted and mechanisms acting in cells to prevent total membrane collapse upon poration are discussed. Enhanced membrane stability is crucial for the success of electroporation-based technologies for cancer treatment and gene transfer.

The Effect of Stromal-Derived Factor 1α on Osteoinduction Properties of Porous ß-Tricalcium Phosphate Bioceramics.

ß-Tricalcium phosphate (TCP) is a type of bioceramic material which is commonly used for hard tissue repair and famous of its remarkable biocompatibility and osteoconductivity with similar composition to natural bone. However, TCP lacks osteoindcutive properties. Stromal-derived factor 1α (SDF-1α) can promote bone regeneration with excellent osteoinduction effect. In this study, SDF-1α was loaded into TCP to investigate the in vitro effects of SDF-1α on the osteoinductive properties of TCP. In vitro studies showed that SDF-1α/TCP scaffold significantly stimulated the expression of osteopontin and osteocalcin. As to the in vivo studies, the rabbit bone defect model showed that SDF-1α stimulated more new bone formation. In conclusion, SDF-1α/TCP bioceramic scaffolds could further promote bone regeneration compared to pure TCP bioceramics.

Adenine-induced chronic kidney disease induces a similar skeletal phenotype in male and female C57BL/6 mice with more severe deficits in cortical bone properties of male mice.

Chronic kidney disease (CKD) causes bone loss, particularly in cortical bone, through formation of cortical pores which lead to skeletal fragility. Animal models of CKD have shown variability in the skeletal response to CKD between males and females suggesting sex may play a role in this variation. Our aim was to compare the impact of adenine-induced CKD on cortical parameters in skeletally mature male and female C57Bl/6 mice. After 10-weeks of adenine-induced CKD, both male and female adenine mice had high serum parathyroid hormone (PTH), high bone turnover, and cortical porosity compared to non-CKD controls. Both sexes had lower cortical thickness, but only male mice had lower cortical bone area. CKD imparted greater deficits in mechanical properties of male mice compared to female mice. These data demonstrate that both male and female mice develop high PTH/high bone turnover in response to adenine-induced CKD and that cortical bone phenotypes are slightly more severe in males, particularly in mechanical properties deficits.

Pinus roxburghii alleviates bone porosity and loss in postmenopausal osteoporosis by regulating estrogen, calcium homeostasis and receptor activator of nuclear factor-κB, osteoprotegerin, cathepsin bone markers.

OBJECTIVES: The study was aimed to evaluate the potential of hydroalcoholic extract of Pinus roxburghii (PRE) stem bark in post-menopausal osteoporosis and its underlying mechanisms. METHODS: In silico docking of the markers was done using AutoDock version 4.2. for molecular targets: receptor activator of nuclear factor-κB (RANK), osteoprotegerin (OPG) and Cathepsin. Female Wistar rats of bodyweight 200-250 g were employed and surgical ovariectomy (OVX) was performed. PRE was administered at a dose of 100 and 200 mg/kg whereas standard drug, raloxifene given at 1 mg/kg orally for eight weeks. KEY FINDINGS: PRE (20 and 40 µg/mL) significantly increased the cellular proliferation in osteoblastic UMR cell lines 11.58 and 15.09% respectively. Eight weeks after surgical removal of ovaries, a significant bone porosity was confirmed by modulation in bone breaking strength of tibia, lumber, and femur; bone mineral density (BMD), calcium, phosphorus, hydroxyproline levels in OVX group. Treatment with PRE 100 and 200 mg/kg significantly restored the bone loss. Real-time polymerase chain reaction (RT-PCR) analysis of molecular markers RANK, OPG and cathepsin and histology also confirmed the attenuation of bone loss. The quantification of quercetin, gallic acid, caffeic acid, catechin, tannic acid and ascorbic acid was done by high-performance liquid chromatography (HPLC) and high performance thin layer chromatography. CONCLUSIONS: P. roxburghii produced anti-osteoporotic effect possibly due to estrogenic modulation, and improved bone remodeling.

Physical characterization of biphasic bioceramic materials with different granulation sizes and their influence on bone repair and inflammation in rat calvaria.

Biphasic calcium phosphate bioceramics (BCP) consist of a mixture of hydroxyapatite (HA) and beta-tricalcium phosphate (ß-TCP) within the same particle. Due to their osteoconductive properties, biocompatibility and resemblance to natural bone, these materials have become a promising and suitable alternative to autologous bone grafting. First, the topography characteristics, specific surface area, and total pore volume of BCP were evaluated using scanning electron microscopy and the BET and BJH methods. Next, this study aimed to evaluate the intensity of the inflammatory process and the bone neoformation capacity of various particle sizes of BCP in the repair of critical defects in the calvaria of rats. A xenogeneic biomaterial was used in the control group. After 30, 60, and 90 days, the animals were euthanized, followed by the processing of the samples to measure the intensity of inflammatory infiltrates and the areas of bone neoformation. Our results indicate that no considerable differences were observed in the inflammatory scores in sites treated with distinct BCP grain sizes. A greater area of bone neoformation was measured in the xenogeneic group at all analysis times, with no substantial differences in bone formation between the BCP particle size in the range of 250-500 µm and 500-1000 µm.

Investigations of the effect of the amount of biochar on soil porosity and aggregation and crop yields on fertilized black soil in northern China.

The combination of chemical fertilizer and biochar is regarded as a useful soil supplement for improving the properties of soil and crop yields, and this study describes how the biochar of maize straw can be used to improve the quality of the degraded black soil. This has been achieved by examining the effects of combining different amounts of biochar with chemical fertilizer on the porosities and aggregate formation of soil and exploring how these changes positively impact on crop yields. A field trial design combining different amounts of maize straw biochar [0 (NPK), 15.75 (BC1), 31.5 (BC2), and 47.25 t ha-1 (BC3)] with a chemical fertilizer (NPK) has been used to investigate changes in the formation of soil aggregate, clay content, soil organic carbon (SOC), and crop yields in Chinese black soil over a three year period from 2013 to 2015. The results of this study show that the addition of fertilizer and biochar in 2013 to black soil results in an increased soybean and maize yields from 2013 to 2015 for all the treatments, with BC1/BC2 affording improved crop yields in 2015, while BC3 gave a lower soybean yield in 2015. Total porosities and pore volumes were increased for BC1 and BC2 treatments but relatively decreased for BC3, which could be attributed to increased soil capillary caused by the presence of higher numbers of fine soil particles. The addition of biochar had a positive influence on the numbers and mean weight diameters (MWD) of soil macroaggregates (>0.25 mm) that were present, with the ratio of SOC to TN in soil macroaggregates found to be greater than in the microaggregates. The most significant amount of carbon present in macroaggregates (>2 mm and 0.25-2 mm) was observed when BC2 was applied as a soil additive. Increasing the levels of maze straw biochar to 47.25 t ha-1 led to an increase in the total organic carbon of soil, however, the overall amount of macroaggregates and MWD were decreased, which is possibly due to localized changes in microbial habitat. The supplementation of biochar increased in the amount of aromatic C present (most significant effect observed for BC2), with the ratio of aliphatic C to aromatic C found to be enhanced due to a relative reduction in the aliphatic C content with >2 mm particle fraction. These changes in organic carbon content and soil stability were analyzed using univariate quadratic equations to explain the relationship between the type of functional groups (polysaccharide C, aliphatic C, aromatic C, aliphatic C/aromatic C) present in the soil aggregates and their MWDs, which were found to vary significantly. Overall, the results of this study indicate that the use of controlled amounts of maize-straw biochar in black soil is beneficial for improving crop yields and levels of soil aggregation, however, the use of excessive amounts of biochar results in unfavorable aggregate formation which negatively impacts the yields of crop growth. The data produced suggest that aromatic C content can be used as a single independent variable to characterize the stability of soil aggregate when biochar/fertilizer mixtures are used as soil additives to boost growth yields. Analysis of soil and crop performance in black soil revealed that the application of maize-straw biochar at a rate of 15.75 and 31.5 t ha-1 had positive effects on crop yields, soil aggregation and accumulation of aromatic C in the aggregate fractions when a soybean-maize rotation system was followed over three years.

Effects of hydroxyapatite on PMMA-HAp cement for biomedical applications.

OBJECTIVE: The main goal of this study was to examine the influence of hydroxyapatite (HAp) macroaggreate concentrations on thermal and mechanical properties of radioactive bone cement and to study the relation of glass transition Tg with its mechanical properties. METHODS: The bone cement as (1-x)PMMA-xHAp binary system was prepared in six [x] distinct concentration parameters of 0.0 up to 0.5. The HAp was synthesized using a solgel procedure following calcination by thermal treatment. The composite was prepared in cold based (non-radioactive) mixing polymethyl methacrylate (PMMA) and HAp. Differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and mechanical compressive strength (CS) were used to measure the thermal and mechanical properties. RESULTS: The DSC and TGA thermal profiles in function to concentration parameter [x] were presented. The CS lies in a range of 3.71-7.37 MPa and the glass transition temperature Tg = 126.27 °C. There was a direct relationship between the PMMA-HAp thermoplastic properties with mechanical and thermal properties in function of HAp concentrations. CONCLUSION: The specific PMMA-HAp composite, with a concentration ratio of 1:1 and HAp thermal treatment at the Tg, provides a material with a compression strength of 7.37 MPa and a suitable amount of porous similar to a trabecular bone, possible to apply in bone cement implants, regardless of whether they are radioactive or not.

Simultaneous investigation of the liquid transport and swelling performance during tablet disintegration.

Fast disintegrating tablets have commonly been used for fast oral drug delivery to patients with swallowing difficulties. The different characteristics of the pore structure of such formulations influence the liquid transport through the tablet and hence affect the disintegration time and the release of the drug in the body. In this work, terahertz time-domain spectroscopy and terahertz pulsed imaging were used as promising analytical techniques to quantitatively analyse the impact of the structural properties on the liquid uptake and swelling rates upon contact with the dissolution medium. Both the impact of porosity and formulation were investigated for theophylline and paracetamol based tablets. The drug substances were either formulated with functionalised calcium carbonate (FCC) with porosities of 45% and 60% or with microcrystalline cellulose (MCC) with porosities of 10% and 25%. The terahertz results reveal that the rate of liquid uptake is clearly influenced by the porosity of the tablets with a faster liquid transport observed for tablets with higher porosity, indicating that the samples exhibit structural similarity in respect to pore connectivity and pore size distribution characteristics in respect to permeability. The swelling of the FCC based tablets is fully controlled by the amount of disintegrant, whereas the liquid uptake is driven by the FCC material and the interparticle pores created during compaction. The MCC based formulations are more complex as the MCC significantly contributes to the overall tablet swelling. An increase in swelling with increasing porosity is observed in these tablets, which indicates that such formulations are performance-limited by their ability to take up liquid. Investigating the effect of the microstructure characteristics on the liquid transport and swelling kinetics is of great importance for reaching the next level of understanding of the drug delivery, and, depending on the surface nature of the pore carrier function, in turn controlling the performance of the drug mainly in respect to dissolution in the body.

Simplification of fused deposition modeling 3D-printing paradigm: Feasibility of 1-step direct powder printing for immediate release dosage form production.

Direct powder three-dimensional (3D)-printing (DPP) of tablets to simplify fused deposition modelling (FDM) was explored. The FDM paradigm involving hot-melt extrusion for making 3D-printable drug-loaded filaments as intermediate products for tablet manufacturing has been gaining attention for the decentralized on-site production of personalized dosage forms. For direct 3D-printing, powder blends were loaded into a cartridge-like head and were successfully printed with honeycomb design following heating of the extrusion cartridge. This 1-step DPP with incorporation of in-built porosity providing higher surface area served as proof of concept for manufacture of rapid release dosage forms. Water soluble hydroxypropylcellulose SSL was chosen as matrix former and caffeine as model drug. The effect of PEG4000 as plasticizer/pore former and Kollidon VA64 as rapidly dissolving polymer on DPP processability and dissolution rate was investigated. Directly 3D-printed tablets with low (30%) infill density showed rapid dissolution independently of the formulation, whereas for high (80%) infill density a combination of PEG4000 and Kollidon VA64 was required to achieve rapid release. The obtained tablets demonstrated good uniformity of percent drug content but had variable weight. Caffeine was present in crystalline state and in the stable polymorph in the tablets. Hence, DPP feasibility for immediate release dosage form manufacture was demonstrated. This technique might create an opportunity to avoid hot-melt extrusion allowing 3D-printing independently of mechanical properties of a filament and potentially prolonging product shelf life by reducing thermal stress.

Development of an Anti-Inflammatory Drug-Incorporated Biomimetic Scaffold for Corneal Tissue Engineering.

Purpose: The aim of this study was to design naproxen sodium (NS)-containing, biomimetic, porous poly(lactide-co-glycolide) (PLGA) scaffolds for regeneration of damaged corneal epithelium. Methods: NS-incorporated PLGA scaffolds were prepared using the emulsion freeze-drying method and then coated with collagen or poly-l-lysine. Porosity measurements of the scaffolds were performed by the gas adsorption/desorption method and the scaffolds demonstrated highly porous, open-cellular pore structures with pore sizes from 150 to 200 µm. Results: The drug loading efficiency of scaffolds was found to be higher than 84%, and about 90%-98% of NS was released at the end of 7 days with a fast drug release rate at the initial period of time and then in a slow and sustained manner. The corneal epithelial cells were isolated from New Zealand white rabbits. The obtained cells were seeded onto scaffolds and continued to increase during the time period of the study, indicating that the scaffolds might promote corneal epithelial cell proliferation without causing toxic effects for at least 10 days. Conclusions: The NS-loaded PLGA scaffolds exhibited a combination of controlled drug release and biomimetic properties that might be attractive for use in treatment of corneal damage both for controlled release and biomedical applications.

Regulating water binding capacity and improving porous carbohydrate matrix's humectant and moisture proof functions by mixture of sucrose ester and Polygonatum sibiricum polysaccharide.

The moisture stability of tobacco shred, a typical porous carbohydrate material, is very important during its processing, storage and smoking, moreover, it is sensitive to environmental conditions. Therefore, effect of sucrose esters (SEs) and sucrose ester/Polygonatum sibiricum polysaccharide mixture (SPMs) on the moisture retention and moisture resistance of tobacco shred was assessed. When SEs were added to tobacco shred, moisture resistance was significantly enhanced, whereas moisture holding capacity was attenuated. Contrarily, the addition of SPMs made moisture retention index (MRI) and moisture proof index (MPI) increase from 1.8910 to 2.1612 and from 1.9489 to 2.0665, respectively, revealing that SPMs improved the moisture retention and moisture proof ability of tobacco shred simultaneously. The monolayer moisture content (M0) was decreased by SEs and increased by SPMs. Low-field nuclear magnetic resonance (LF-NMR) analysis showed that during adsorption, SPMs reduced the interaction between tobacco shred and water via hydrophobic property of SEs; during desorption, SPMs promoted the interaction between tobacco shred and water through hydrophilic binding of polysaccharide, leading to the migration of immobilized water to bound state. The modeling of the isotherms and LF-NMR analysis clarified the mechanism why SPMs could improve moisture stability of tobacco.

Efficient and prolonged antibacterial activity from porous PLGA microparticles and their application in food preservation.

Simple addition of a minute quantity of non-toxic mustard oil in water/oil/water (W/O/W) double emulsion led to a porous morphology at the surface as well as in the interior of the biodegradable PLGA (Poly(l-lactide-co-glycolide)) microparticles. An attempt was made to understand the mechanism of pore formation by analyzing optical micrographs and SEM images in addition to solution viscosity of organic phase and interfacial tension values between organic and aqueous phases. The origin of surface porosity was thought to come from the inclusion of inner water droplet, stabilized by heteroaggregation of mustard oil and PLGA chains along with PVA (polyvinyl alcohol), to the solidifying polymer skin. The surface pores did not arise in absence of mustard oil. The encapsulation and release of antibacterial active (benzoic acid) from porous PLGA particles was studied in PBS buffer (pH 7) at 37 °C for 60 days. The release profiles were well-controlled in nature, and found to be influenced by surface porosity of the particles that can be manipulated by varying the amount of mustard oil. The release mechanism can well be explained with the help of power law model. Strikingly, in liquid medium, porous particles were found completely suppressing the growth of Escherichia coli and Staphylococcus aureus for a prolonged period of 60 days. The strong antimicrobial activity (100% inhibition of bacterial growth) in porous particles can be linked to the enhanced surface area due to the formation of micro/nano pores which accelerate the hydrolytic degradation of PLGA to release lactic acid/glycolic acid (antibacterial) in addition to encapsulated antibacterial (benzoic acid). In a food model system, the shelf life of the water melon juice was also found to be enhanced by suppressing the growth of the natural microbes in comparison to control.

Dermal smartPearls - Optimized silica particles for commercial products & mechanistic considerations.

The amorphous state of actives can be long-term stabilized by incorporation into mesoporous particles, thus the increase in the saturation solubility by amorphicity can be exploited to improve the bioavailability. In this study 5 different silica particles were investigated regarding loading capacity and long-term stability of the amorphous form. Five different silica were used ranging in pore mean size from 3 to 25 nm, pore volume 0.4 to 1.8 mL/g, and BET surface from 740 to 320 m2/g. As model active avobenzone was used, because it is a challenging molecule by its high crystallisation tendency. To be industrially feasible, a loading capacity of about 50% pore volume was investigated. The particles were loaded by an immersion evaporation method, being able to be used in industrial production. A theory of the active precipitation in the pores was developed based on the Ostwald-Miers range. The 25 nm pore-sized particles showed a crystalline fraction directly after loading, the 3 nm and 17 nm pore-sized particles after 1 month of storage. Long-term stability of 1 year had the silica with 6 nm and 10 nm pore size, thus being ideal for products. By nitrogen sorption studies, primarily filling of the pores from bottom to top was identified as loading mechanism. HPLC analysis showed some active remaining in the pores due to strong interaction with the pore surface, which needs to be considered when developing dermal products. Interestingly, the increase in saturation solubility Cs - determined in carrageenan gels - remained also for silica particles showing a minor partial crystalline avobenzone fraction. Thus, limited crystallinity does not impair the shelf-life and performance of dermal formulations.

Formulation and optimization of drug-loaded mesoporous silica nanoparticle-based tablets to improve the dissolution rate of the poorly water-soluble drug silymarin.

Porous carriers have been put forward as a promising alternative for stabilizing the amorphous state of loaded drugs, and thus significantly improving the dissolution rate of poorly soluble compounds. The purpose of this study was to enhance the saturation solubility, dissolution rate and drug loading of the poorly water-soluble drug silymarin via incorporation into mesoporous silica nanospheres within a lyophilized tablet to obtain a unique formulation. 32 full factorial design was applied to study the effect of both independent variables, polyvinyl alcohol (PVA) as stabilizer and binder and sucrose as cryoprotectant and disintegrant; and on the dependent variables that included the mean particle size (Y1), disintegration time (Y2), tablet strength (Y3) and % of drug release after 2 min, R2min,Y4. The drug-loaded mesoporous silica nanospheres and the optimized formula was evaluated by different characterization methods: scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry, X-ray diffractometry and Fourier transform infrared spectroscopy; as well as drug content, saturation solubility and moisture content. The evaluation demonstrated that the loaded mesoporous silica nanospheres and the optimized formula are in amorphous state without any chemical interaction with the silica matrix or the stabilizer. Moreover, the drug was stably maintained in nanosize range with narrow particle size distribution. Furthermore, the optimized lyophilized tablets had highly porous structure, low friability (less than 1%), fast disintegration (less than 30 s), high tablet strength, low moisture content (less than 1%), remarkably increased dissolution rate and noticeable improvement in saturation solubility.

Elevations in Cortical Porosity Occur Prior to Significant Rise in Serum Parathyroid Hormone in Young Female Mice with Adenine-Induced CKD.

Chronic kidney disease (CKD) leads to significant bone loss primarily through the development of cortical porosity. In both patients and animal models of CKD, sustained elevations in serum parathyroid hormone (PTH) are associated with cortical porosity. In this study, we aimed to track the progression of cortical porosity and increased PTH utilizing the adenine-induced CKD model. Young female mice (8 weeks) were given 0.2% adenine to induce CKD. Tissues were collected from groups of adenine and age-matched control mice after 2, 6, and 10 weeks. Serum blood urea nitrogen was elevated at all time points in adenine mice, but serum PTH was only statistically elevated at the 10-week time point. Cortical porosity was sevenfold higher in 6-week adenine mice compared to age-matched controls and 14-fold higher in 10-week adenine mice vs. controls. Additionally, osteocyte receptor activator of nuclear factor κB ligand (RANKL) was elevated in adenine-fed mice, while annexin V, an early marker of cellular apoptosis, was mildly decreased in osteocytes in adenine-fed mice. Based on these results, we hypothesize high serum PTH signals to osteocytes prolonging their lifespan resulting in sustained RANKL which drives osteoclastic bone resorption in the cortex. In conclusion, our data show time-dependent elevations in serum PTH and cortical porosity in adenine-induced CKD mice and demonstrate changes in osteocyte RANKL and apoptosis which may contribute to the development of cortical pores.

Evaluation of the biomedical properties of a Ca+-conjugated silk fibroin porous material.

Hemostatic materials could reduce avertible death from bleeding during surgery and emergency treatment. To this end, silk fibroin (SF) loaded with Ca2+ (1.8, 3.6 5.4, or 7.2%, w:w) was tested as a new hemostatic material (designated as SF1.8, SF3.6, SF5.4, or SF7.2), and the Ca2+ release rate, platelet adhesion, blood coagulation, cytocompatibility, and antimicrobial properties were investigated. Platelet adhesion on SF1.8 was improved significantly compared with pure SF porous material, and increased with increasing Ca2+ concentration. For SF3.6, platelet adhesion was greater than observed for gelatin and calcium alginate porous materials, clotting occurred earlier, and the complete coagulation time was shorter. Additionally, rabbit ear wound studies revealed that the hemostatic time for SF3.6 was significantly shorter than for gelatin, and similar to that for calcium alginate. The shed blood weight was lowest when SF was loaded with 7.2% Ca2+. The SF3.6 porous material displayed no obvious cytotoxicity, and exhibited satisfactory antibacterial activity against Escherichia coli and Staphylococcus aureus.

Three-dimensional Printed Mg-Doped ß-TCP Bone Tissue Engineering Scaffolds: Effects of Magnesium Ion Concentration on Osteogenesis and Angiogenesis In Vitro.

Background: Three-dimensional (3D) printed bone tissue engineering scaffolds have been widely used in research and clinical applications. ß-TCP is a biomaterial commonly used in bone tissue engineering to treat bone defects, and its multifunctionality can be achieved by co-doping different metal ions. Magnesium doping in biomaterials has been shown to alter physicochemical properties of cells and enhance osteogenesis. Methods: A series of Mg-doped TCP scaffolds were manufactured by using cryogenic 3D printing technology and sintering. The characteristics of the porous scaffolds, such as microstructure, chemical composition, mechanical properties, apparent porosity, etc., were examined. To further study the role of magnesium ions in simultaneously inducing osteogenesis and angiogenesis, human bone marrow mesenchymal stem cells (hBMSCs) and human umblical vein endothelial cells (HUVECs) were cultured in scaffold extracts to investigate cell proliferation, viability, and expression of osteogenic and angiogenic genes. Results: The results showed that Mg-doped TCP scaffolds have the advantages of precise design, interconnected porous structure, and similar compressive strength to natural cancellous bone. hBMSCs and HUVECs exhibit high proliferation rate, cell morphology and viability in a certain amount of Mg2+. In addition, this concentration of magnesium can also increase the expression levels of osteogenic and angiogenic biomarkers. Conclusion: A certain concentration of magnesium ions plays an important role in new bone regeneration and reconstruction. It can be used as a simple and effective method to enhance the osteogenesis and angiogenesis of bioceramic scaffolds, and support the development of biomaterials and bone tissue engineering scaffolds.

Cryoprotectant enables structural control of porous scaffolds for exploration of cellular mechano-responsiveness in 3D.

Despite the wide applications, systematic mechanobiological investigation of 3D porous scaffolds has yet to be performed due to the lack of methodologies for decoupling the complex interplay between structural and mechanical properties. Here, we discover the regulatory effect of cryoprotectants on ice crystal growth and use this property to realize separate control of the scaffold pore size and stiffness. Fibroblasts and macrophages are sensitive to both structural and mechanical properties of the gelatin scaffolds, particularly to pore sizes. Interestingly, macrophages within smaller and softer pores exhibit pro-inflammatory phenotype, whereas anti-inflammatory phenotype is induced by larger and stiffer pores. The structure-regulated cellular mechano-responsiveness is attributed to the physical confinement caused by pores or osmotic pressure. Finally, in vivo stimulation of endogenous fibroblasts and macrophages by implanted scaffolds produce mechano-responses similar to the corresponding cells in vitro, indicating that the physical properties of scaffolds can be leveraged to modulate tissue regeneration.