Core–shell molecularly imprinted polymer nanoparticles with assistant recognition polymer chains for effective recognition and enrichment of natural low-abundance protein

Core–shell molecular imprinting of nanomaterials overcomes difficulties with template transfer and achieves higher binding capacities for macromolecular imprinting, which are more important to the imprinting of natural low-abundance proteins from cell extracts. In the present study, a novel strategy of preparing core–shell nanostructured molecularly imprinted polymers (MIPs) was developed that combined the core–shell approach with assistant recognition polymer chains (ARPCs). Vinyl-modified silica nanoparticles were used as support and ARPCs were used as additional functional monomers. Immunoglobulin heavy chain binding protein (BiP) from the endoplasmic reticulum (ER) was chosen as the model protein. The cloned template protein BiP was selectively assembled with ARPCs from their library, which contained numerous limited-length polymer chains with randomly distributed recognition and immobilization sites. The resulting complex was copolymerized onto the surface of vinyl-modified silica nanoparticles under low concentrations of the monomers. After template removal, core–shell-structured nanoparticles with a thin imprinted polymer layer were produced. The particles demonstrated considerably high adsorption capacity, fast adsorption kinetics and selective binding affinities toward the template BiP. Furthermore, the synthesized MIP nanoparticles successfully isolated cloned protein BiP from protein mixtures and highly enriched BiP from an ER extract containing thousands of kinds of proteins. The enrichment reached 115-fold and the binding capacity was 5.4 μg g⁻¹, which were higher than those achieved by using traditional MIP microspheres. The advantageous properties of MIP nanoparticles hold promise for further practical applications in biology, such as protein analysis and purification.     

Cyclodextrin-functionalized biomaterials loaded with miconazole prevent Candida albicans biofilm formation in vitro

Polyethylene (PE) and polypropylene (PP) were functionalized at their surfaces with cyclodextrins (CDs) in order to prevent the adhesion and proliferation of Candida albicans on medical devices made from these polymers. The surface functionalization involved the grafting of glycidyl methacrylate (GMA) after oxidative γ-ray pre-irradiation, followed by the attachment of β-CD and HP-β-CD to PE-g-GMA and PP-g-GMA surfaces. The yield of CD functionalization directly depended on the amount of GMA grafted. The presence of CDs on the surface of the polymers did not compromise their cell compatibility, but remarkably changed their protein adsorption profile. In contrast to unmodified PE and PP that adsorb significant amounts of fibrinogen (～0.047 mg cm^?2) but not albumin, the CD-modified polyethers promoted the adsorption of albumin (between 0.015 and 0.155 mg cm^?2) and reduced the adsorption of fibrinogen. Furthermore, functionalization with CDs provided PE and PP with the capability to incorporate the anti-fungal drug miconazole (up to 0.27 mg cm^?2), leading to reduced biofilm formation by C. albicans in an in vitro biofilm model system. Overall, the results of the work indicate that the novel approach for functionalization of PE and PP is potentially useful to reduce the likelihood of foreign body-related infections.     

Via zinc(II) protoporphyrin to the synthesis of poly(ZnPP-MAA-EGDMA) for the imprinting and selective binding of bilirubin

Poly(zinc protoporphyrin-methacrylic acid-ethyl glycol dimethylacrylate) (poly(ZnPP-MAA-EGDMA)) imprinted with α-bilirubin can cause spectroscopic change in wavelength and absorption intensity due to the metal–ion coordination between ZnPP and bilirubin. The fluorescent imprinted polymer was able to selectively bind α-bilirubin. The corresponding imprinted polymer monolith was synthesized by using the functional monomer, methacrylic acid and the fluorescent monomer, zinc(II) protoporphyrin. Although the imprinted polymers (MIPs) using methacrylic acid, protoporphyrin, or zinc(II) protoporphyrin alone as the only functional monomer could bind bilirubin, the imprinting effects were all comparably inferior to the imprinted poly(ZnPP-MAA-EGDMA). Therefore, it revealed that via the combined utilization of ZnPP and MAA for the fluorescent and functional effect, the MIPs thus prepared were then able to create the highly selective cavities. The optimal condition for the heated polymerization of the imprinted poly(ZnPP-MAA-EGDMA) was found to be 60 °C for 6 h. The imprinting factor of 3.069 could be achieved from the fluorescent imprinted polymer by comparing the binding results obtained from the MIP and the NIP (non-imprinted polymer). The imprinting factor obtained from bilirubin/biliverdin mixture solution was reduced to 2.111 because of the presence of biliverdin. The selectivity toward bilirubin of 2.269 from the bilirubin/biliverdin mixture was obtained. Therefore, to utilize ZnPP for the preparation of the imprinted materials confirmed the selective binding and detection of bilirubin via the fluorescent approach.     

Low-density polypropylene meshes coated with resorbable and biocompatible hydrophilic polymers as controlled release agents of antibiotics

The application of bioactive meshes in abdominal surgery for the repair of hernias is an increasing clinical activity in a wide sector of the population. The main secondary effect is the appearance of infections from bacteria, specifically Staphylococcus aureus and S. epidermidis. This paper describes the development and application of low-density polypropylene meshes coated with a biocompatible and resorbable polymer as a controlled release system of the antibiotic vancomycin. The polymeric coating (a non-cross-linked copolymer of 2-hydroxyethyl methacrylate and 2-acrylamido-2-methylpropanesulfonic acid) has a thickness of 14–15 μm and contains 0.32 mg cm^?2 of the antibiotic vancomycin. The in vitro experiments demonstrate the excellent inhibitory character of the coated meshes loaded with the antibiotic, following the standard protocol of inhibition of halo in agar diffusion test. This inhibitory effect is maintained for a relatively long period (at least 14 days) with a low concentration of antibiotic. The acrylic polymer system regulates the release of the antibiotic with a rate of 24 μg h^?1, due to its slow dissolution in the medium. Experiments in vivo, based on the implantation of coated meshes, demonstrate that the system controls the infection in the animal (rabbits) for at least 30 days. The concentration of antibiotic in the blood stream of the rabbits was below the detection limit of the analytical technique (<1–2 μg ml^?1), which demonstrates that the antibiotic is released in the local area of the implant and remains concentrated at the implantation site, without diffusion to the blood stream. The systems can be applied to other medical devices and implants for the application of new-generation antibiotics in a controlled release and targeted applications.     

Toxico-pathological changes induced by cypermethrin in broiler chicks: Their attenuation with Vitamin E and selenium

Ninety 1-day old broiler chicks of mixed gender (as hatched) procured from a local hatchery were randomly divided into five equal groups. All the treatments were given through crop tubing. Groups 1–4 received cypermethrin (CY) (600 mg kg^?1 b. wt.) daily for 30 days. In addition to CY (group 1), groups 2–4 received Vit E (150 mg kg^?1 b. wt.), Se (0.25 mg kg^?1 b. wt.), and Vit E (150 mg kg^?1 b. wt.)+Se (0.25 mg kg^?1 b. wt.), respectively. Group 5 served as control andreceived normal saline (2 ml kg^?1 b. wt.) for 30 days. Randomly selected six broiler chicks from each group were slaughtered at experimental days 10, 20 and 30 for the collection of serum/plasma and morbid tissues. Absolute organ weights were recorded. Total plasma proteins, fibrinogen and creatinine were significantly (P<0.05) increased while alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and urea decreased significantly (P<0.05) in CY-treated group when compared with the control group. Kidneys were swollen grossly in treated broiler chicks. In liver, necrosis of hepatocytes, cytoplasmic vacuolation, bile duct hyperplasia and mononuclear cellular infiltration were observed. In kidneys, necrosis of tubular epithelial cells, cytoplasmic vacuolation, cellular infiltration and atrophy of glomeruli were observed. Sub-arachnoid space was much dilated in CY-treated broiler chicks. It can be concluded that CY induces biochemical and histopathological alterations in broilers chicks; however, these toxic effects can be ameliorated by Vit E or Se. Combination of Vit E and Se was more effective in ameliorating toxic effects of cypermethrin in broilers chicks.     

Cyclodextrin-containing hydrogels for contact lenses as a platform for drug incorporation and release

Poly(2-hydroxyethyl methacrylate) hydrogels containing β-cyclodextrin (pHEMA/β-CD) have been investigated as a platform for sustained release of ophthalmic drugs. First of all, pHEMA/β-CD hydrogel membranes and contact lenses were prepared by photopolymerization of HEMA, mono-methacrylated β-CD (mono-MA-β-CD) and trimethylolpropane trimethacrylate using a cast molding process. The hydrogels were characterized by Fourier transform infrared spectroscopy, equilibrium swelling ratio (ESR) and tensile tester. The results showed that the incorporation of β-CD in the hydrogels increased the ESR and tensile strength. Then, puerarin was used as a model to evaluate drug loading and in vitro and in vivo release behavior of the pHEMA/β-CD hydrogels. It was revealed that puerarin loading and in vitro release rate were dependent on β-CD content in the pHEMA/β-CD hydrogels. In rabbit eyes the pHEMA/β-CD hydrogel contact lenses exhibited longer mean residence times (MRT_F) of puerarin in tear fluid than that of pHEMA contact lenses and 1% puerarin eye drops. The puerarin concentration in the aqueous humor of rabbit reached a maximum of 0.81 μg ml^?1 after wearing the pHEMA/β-CD contact lens, which had been presoaked in 0.802 mg ml^?1 puerarin solution for 4.81 h. Also, the pHEMA/β-CD contact lenses had a higher drug bioavailability in aqueous humor than puerarin eye drops. The data demonstrate that pHEMA/β-CD hydrogel contact lenses can effectively deliver puerarin through the cornea.     

In vitro cytotoxicity of porous silicon microparticles: Effect of the particle concentration,surface chemistry and size

We report here the in vitro cytotoxicity of mesoporous silicon (PSi) microparticles on the Caco-2 cells as a function of particle size fractions (1.2–75 μm), particle concentration (0.2–4 mg ml^?1) and incubation times (3, 11 and 24 h). The particle size (smaller PSi particles showed higher cytotoxicity) and the surface chemistry treatment of the PSi microparticles were considered to be the key factors regarding the toxicity aspects. These effects were significant after the 11 and 24 h exposure times, and were explained by cell–particle interactions involving mitochondrial disruption resulting from ATP depletion and reactive oxygen species production induced by the PSi surface. These events further induced an increase in cell apoptosis and consequent cell damage and cell death in a dose-dependent manner and as a function of the PSi particle size. These effects were, however, less pronounced with thermally oxidized PSi particles. Under the experimental conditions tested and at particle sizes >25 μm, the non-toxic threshold concentration for thermally hydrocarbonized and carbonized PSi particles was <2 mg ml^?1, and for thermally oxidized PSi microparticles was <4 mg ml^?1.     

Clinico-hematological and micronuclear changes induced by cypermethrin in broiler chicks: Their attenuation with vitamin E and selenium

This study was carried out on 90 one-day-old broiler chicks to know clinico-hematological alterations, DNA damage caused by cypermethrin (CY), and attenuation of toxic effects by vitamin E (Vit E) and selenium (Se). Birds were randomly divided into five equal groups. Groups 1–4 received CY (600 ml kg^?1 b.wt) daily for 30 days by crop tubing. In addition to CY, groups 2, 3 and 4 received Vit E (150 mg kg^?1 b.wt), Se (0.25 mg kg^?1 b.wt), and Vit E (150 mg kg^?1 b.wt)+Se (0.25 mg kg^?1 b.wt), respectively. Group 5 served as control. Birds were monitored twice daily for clinical signs. They were weighed and blood samples were collected at experimental days 10, 20 and 30 for hematological studies. CY-treated birds showed more prominent signs of toxicity compared to CY+Vit E, CY+Se and CY+Vit E+Se birds. Body weight in groups 1–3 was significantly (P<0.05) smaller at days 20 and 30 when compared with the control group. Significantly (P<0.001) higher numbers of micronuclei appeared in chicks treated with CY compared to CY+Vit E- and CY+Se-treated birds. Significantly decreased total erythrocyte counts (TEC), hemoglobin (Hb) concentration and packed cell volume (PCV) in all treated groups were recorded. Treated birds suffered from macrocytic hypochromic anemia. Leukocytosis in early stage and later leucopenia was seen in treated birds. It can be concluded that CY induces toxic effects in broilers chicks; however, these toxic effects can be ameliorated by Vit E or Se. Combination of Vit E and Se was more effective to ameliorate toxic effects of cypermethrin.     

Hemocompatibility evaluation of different silver nanoparticle concentrations employing a modified Chandler-loop in vitro assay on human blood

Due to their antibacterial effects, the use of silver nanoparticles (AgNPs) in a great variety of medical applications like coatings of medical devices has increased markedly in the last few years. However, blood in contact with AgNPs may induce adverse effects, thereby altering hemostatic functions. The objective of this study was to investigate the hemocompatibility of AgNPs in whole blood. Human whole blood (n = 6) was treated with different AgNPs concentrations (1, 3 and 30 mg l^?1) or with saline/blank solutions as controls before being circulated in an in vitro Chandler-loop model for 60 min at 37 °C. Before and after circulation, various hematologic markers were investigated. Based on the hematologic parameters measured, no profound changes were observed in the groups treated with AgNP concentrations of 1 or 3 mg l^?1. AgNP concentrations of 30 mg l^?1 induced hemolysis of erythrocytes and α-granule secretion in platelets, increased CD11b expression on granulocytes, increased coagulation markers thrombin–antithrombin-III complex, kallikrein-like and FXIIa-like activities as well as complementing cascade activation. Overall, we provide for the first time a comprehensive evaluation including all hematologic parameters required to reliably assess the hemocompatibility of AgNPs. We strongly recommend integrating these hemocompatibility tests to preclinical test procedures prior to in vivo application of new AgNP-based therapies.     

Vegetable oil thermosets reinforced by tannin–lipid formulations

Totally bio-based thermosetting polymers which are comparable to synthetic polyester thermosets have been prepared from copolymerization of condensed tannin–fatty acid esters with vegetable oils. Oxidative copolymerization of tannin linoleate/acetate mixed esters with linseed oil and tung oil produced polymer films ranging from soft rubbers to rigid thermosets. Tannin incorporation into the formulations was essential for the final product to achieve necessary mechanical strength. Films had ambient modulus values between 0.12 and 1.6 GPa, with glass transition temperatures ranging from 32 to 72 °C and calculated crosslink densities of 1020–57,700 mol m^?3. Film stiffness, T_g and crosslink density increase with greater tannin linoeate/acetate content due mainly to this tannin component providing rigidity through polyphenolic aromatic rings and unsaturated chains as crosslinking sites.     

Preventive effect of a galactoglucomannan (GGM) from Dendrobium huoshanense on selenium-induced liver injury and fibrosis in rats

This study was carried out to investigate the preventive effects of galactoglucomannan (GGM), a homogeneous polysaccharide from Dendrobium huoshanense, on liver injury and fibrosis induced by sodium selenite. Sprague–Dawley rats injected subcutaneously with sodium selenite at the dosage of 3.28 mg kg^?1 b. wt. were set as the model groups. Rats treated with sodium selenite at the dosage of 3.28 mg kg^?1 b. wt. and GGM at 50–200 mg kg^?1 b. wt. were set as the prevention groups. Biochemical and histological analysis showed that GGM significantly ameliorated selenite-induced liver injury and fibrosis in rats. Oral administration of GGM effectively attenuated the toxicity of selenite to liver tissue, which was judged both by the decreased activities of serum hepatic enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), and by liver histopathological examination. Meanwhile, GGM also reduced the levels of H₂O₂ and malondialdehyde (MDA), elevated the levels of GSH, restored the fluidity of hepatic plasma membrane, and retained the activities of endogenous enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST). The prevention of selenite-induced liver injury and fibrosis by GGM was further supported by the reduced expression of transforming growth factor-β1 (TGF-β1) and type I collagen. These results suggested that GGM may be developed into a novel antifibrotic agent for the prevention of liver injury and fibrosis.     

Toxicity of methimazole on femoral bone in suckling rats: Alleviation by selenium

AimsSelenium has a pharmacological properties and it is well considered as an antioxidant. The present study investigated the potential ability of selenium, used as a nutritional supplement, to alleviate bone impairments in suckling rats whose mothers were treated with methimazole, an antithyroid drug.Main methodsFemale Wistar rats were randomly divided into four groups of six each: group I served as control which received standard diet; group II were rendered hypothyroid by administration of methimazole (250 mg L^?1 in their drinking water); group III received both methimazole (250 mg L^?1 in their drinking water) and selenium (0.5 mg kg^?1 of diet); group IV received 0.5 Na₂SeO₃ mg kg^?1 of diet. Treatments were started from the 14th day of pregnancy until day 14 after delivery.Key findingsMethimazole treatment decreased femur length and weight in 14-day-old rats, when compared to controls. Femur antioxidant enzyme activities, superoxide dismutase, catalase and glutathione peroxidase decreased. Lipid peroxidation recorded an increase revealed by high femur malondialdehyde levels. Methimazole also caused a significant decrease in calcium and phosphorus levels in bone. Yet, in plasma and urine, they increased and decreased inversely. Besides, plasma total tartrate-resistant acid phosphatase was enhanced, while total alkaline phosphatase was reduced. Co-administration of selenium through diet improved the biochemical parameters cited above. Nevertheless, distorted histoarchitecture revealed in hypothyroid rat femur was alleviated by Se treatment.SignificanceThe present study suggests that selenium is an important protective element that may be used as a dietary supplement protecting against bone impairments.     

High density type I collagen gels for tissue engineering of whole menisci

This study investigates the potential of high density type I collagen gels as an injectable scaffold for tissue engineering of whole menisci, and compares these results with previous strategies using alginate as an injectable scaffold. Bovine meniscal fibrochondrocytes were mixed with collagen and injected into micro-computed tomography-based molds to create 10 and 20 mg ml^?1 menisci that were cultured for up to 4 weeks and compared with cultured alginate menisci. Contraction, histological, confocal microscopy, biochemical and mechanical analysis were performed to determine tissue development. After 4 weeks culture, collagen menisci had preserved their shape and significantly improved their biochemical and mechanical properties. Both 10 and 20 mg ml^?1 menisci maintained their DNA content while significantly improving the glycosaminoglycan and collagen content, at values significantly higher than the alginate controls. Collagen menisci matched the alginate control in terms of the equilibrium modulus, and developed a 3- to 6-fold higher tensile modulus than alginate by 4 weeks. Further fibrochondrocytes were able to reorganize the collagen gels into a more fibrous appearance similar to native menisci.     

Poly-l-lysine-coated albumin nanoparticles: Stability,mechanism for increasing in vitro enzymatic resilience,and siRNA release characteristics

Enzymatic degradation of nanoparticle (NP)-based drug delivery vehicles is a major factor influencing the administration routes as well as the site-specific delivery of NPs. To understand the stability of albumin NPs in an aggressive proteolytic environment, bovine serum albumin (BSA) NPs were fabricated via a coacervation technique and stabilized by coating using different molecular weights (MWs: 0.9–24 kDa) and concentrations (0.1–1.0 mg ml^?1) of the cationic polymer, poly-l-lysine (PLL). A short interfering ribonucleic acid (siRNA) was used as a model drug for encapsulation in the BSA NPs. The generated NPs were characterized for morphology (with atomic force microscopy), size (with photon correlation spectroscopy) and charge (zeta-potential). The size range of formed BSA particles (155 ± 11 to 3800 ± 1600 nm) was effectively controlled by the MW and concentration of the PLL used for coating. The aqueous solution stability of NPs increased with an increasing MW and PLL concentration. However, in the presence of trypsin, NPs coated with higher MW PLL were not as stable as those formed using lower MW PLL. This trend was also confirmed based on the release pattern of siRNA in the presence of trypsin. We conclude that, when designing stabilizing coatings for soft protein-based NPs, smaller molecules may be more suitable for particle coating if enhanced proteolytic resistance and more stable NPs are desired for targeted drug delivery applications.     

Differential expression of androgen and estrogen receptors in PCB (Aroclor 1254)-exposed rat ventral prostate: Impact of alpha-tocopherol

Polychlorinated biphenyls (PCBs) are environmental toxicants, which affect male fertility by altering the androgen and estrogen levels. PCB-induced toxic manifestations are associated with the production of reactive oxygen species. Vitamin E (α-tocopherol) is a major lipophilic chain breaking antioxidant, which protects polyunsaturated fatty acids in tissues against peroxidation, a property that could be beneficial in the male reproductive biology. The purpose of this study was to determine the impact of α-tocopherol on PCB (Aroclor 1254)-induced changes in androgen receptor (AR) and estrogen receptors (ERs) expression in Wistar rat ventral prostate. Rats were divided into 3 groups of 6 animals each. Group I rats were administered corn oil (vehicle) intraperitoneally (i.p.); Group II rats were treated with 2 mg kg^?1 day^?1 of PCB (i.p.); Group III rats were treated with 2 mg kg^?1 day^?1 of PCB (i.p.) along with simultaneous oral supplementation of 50 mg kg^?1 day^?1 of α-tocopherol. Serum testosterone and estradiol titers were assayed. Prostatic acid phosphatase activity (PAcP), citric acid concentration, generation of hydrogen peroxide (H₂O₂) and lipid peroxides (LPO) were estimated. mRNA and protein expression of AR, ER-α and ER-β in ventral prostate were quantified. Serum testosterone, estradiol, PAcP, citric acid levels, AR and ER-α expressions were significantly decreased while H₂O₂ generation, LPO, ER-β were increased in PCB-exposed animals. Simultaneous supplementation of α-tocopherol in PCB-exposed rats resulted in significant restoration of all the parameters to the control. The results suggest that α-tocopherol has definite protective effect against PCB-induced toxicity in ventral prostatic dysfunction.     

Control of cellular adhesiveness in an alginate-based hydrogel by varying peroxidase and H2O2 concentrations during gelation

An aqueous solution of alginate possessing phenolic hydroxyl (Alg-Ph) groups is gellable via a horseradish peroxidase (HRP)-catalyzed oxidative crosslinking reaction between Ph groups, consuming H₂O₂ as an electron acceptor. This study evaluates the effect of H₂O₂ and HRP concentrations on cellular adhesiveness and proliferation on the resultant enzymatically crosslinked Alg-Ph gels. After 4 h of seeding, 81.1% of L929 fibroblast cells adhere to an Alg-Ph hydrogel prepared with 1 U ml^?1 HRP and 1 mM H₂O₂. Increasing the concentration of H₂O₂ to 15 mM decreases the percentage of adhering cells to 28.4%. The cellular adhesion at this H₂O₂ concentration is increased to 82.6% by increasing the HRP concentration to 10 U ml^?1. The cells adhering to the Alg-Ph hydrogels with higher cellular adhesiveness establish a confluent monolayer during 168 h of culture. A cell sheet can then be harvested within 5 min of immersion in a medium containing alginate lyase at 1.0 mg ml^?1. The harvested cell sheet re-adhere, and the cells contained in the sheet proliferate after being transferred to another cell culture dish.     

An explanation of the mineralization mechanism in osteoblasts induced by calcium hydroxide

Calcium hydroxide (Ca(OH)₂) has been broadly used in endodontics, including apexification to obtain apical closure by mineralization. However, the detailed mechanism of mineralization induced by Ca(OH)₂ is still unclear. This study focuses on the function of calcium and hydroxyl ions which dissociate from Ca(OH)₂ during the mineralization process. Though primary osteoblasts cultured in the medium without or with 0.025 mg ml^?1 Ca(OH)₂ did not show mineralization, they did exhibit mineralization when they were cultured with a higher concentration of Ca(OH)₂ (0.25 mg ml^?1). Mineralization induced in the presence of 0.25 mg ml^?1 Ca(OH)₂ was greater at pH 7.4 than at pH 8.5. The high mineralization activity observed under neutral conditions was caused by the prolonged activation of p38 and JNK. Hydroxyl ions did not have any effect on the mineralization. The results demonstrate that calcium ions dissociated from Ca(OH)₂ are critical for inducing the mineralization of osteoblasts.     

Synthesis and characterization of degradable bioconjugated hydrogels with hyperbranched multifunctional cross-linkers

Hyperbranched poly(ester amide) polymer (Hybrane? S1200, M_n 1200 g mol^?1) was functionalized with maleic anhydride (MA) and propylene sulfide, to obtain multifunctional cross-linkers with fumaric and thiol end groups, S1200MA and S1200SH, respectively. The degree of substitution (DS) of maleic acid groups was controlled by varying the molar ratio of MA to S1200 in the reaction mixture. Hydrogels were obtained by UV cross-linking of functionalized S1200 and poly(ethylene glycol) diacrylate in aqueous solutions. Compressive modulus increased with decreasing S1200/PEG ratio and also depended on the DS of the multifunctional cross-linker (S1200). Also, heparin-based macromonomers together with functionalized hyperbranched polymers were used to construct novel functional hydrogels. The multivalent hyperbranched polymers allowed high cross-linking densities in heparin modified gels while introducing biodegradation sites. Both heparin presence and acrylate/thiol ratio had an impact on degradation profiles and morphologies. Hyperbranched cross-linked hydrogels showed no evidence of cell toxicity. Overall, the multifunctional cross-linkers afford hydrogels with promising properties that suggest that these may be suitable for tissue engineering applications.     

Volumetric analysis of osteoclastic bioresorption of calcium phosphate ceramics with different solubilities

Commonly, to determine osteoclastic resorption of biomaterials only the resorbed area is measured. The depth of the resorption pit, however, may also be important for the performance of a material. To generate such data we used two calcium phosphate ceramics (Ca₁₀ and Ca₂). The solubility of the materials was determined according to DIN EN ISO 10993-14. They were scanned three-dimensionally using infinite focus microscopy and subsequently cultivated for 4 weeks in simulated body fluid without (control) or with human osteoclasts. After this cultivation period osteoclasts number was determined and surface changes were evaluated two- and three-dimensionally. Ca₁₀ and Ca₂ showed solubilities of 11.0 ± 0.5 and 23.0 ± 2.2 mg g^?1, respectively. Both materials induced a significant increase in osteoclast number. While Ca₁₀ did not show osteoclastic resorption, Ca₂ showed an increased pit area and pit volume due to osteoclastic action. This was caused by an increased average pit depth and an increased number of pits, while the average area of single pits did not change significantly. The deduced volumetric osteoclastic resorption rate (vORR) of Ca₂ (0.01–0.02 μm³ μm^?2 day^?1) was lower than the remodelling speed observed in vivo (0.08 μm³ μm^?2 day^?1), which is in line with the observation that implanted resorbable materials remain in the body longer than originally expected. Determination of volumetric indices of osteoclastic resorption might be valuable in obtaining additional information about cellular resorption of bone substitute materials. This may help facilitate the development of novel materials for bone substitution.     

The mechanical stress–strain properties of single electrospun collagen type I nanofibers

Knowledge of the mechanical properties of electrospun fibers is important for their successful application in tissue engineering, material composites, filtration and drug delivery. In particular, electrospun collagen has great potential for biomedical applications due to its biocompatibility and promotion of cell growth and adhesion. Using a combined atomic force microscopy (AFM)/optical microscopy technique, the single fiber mechanical properties of dry, electrospun collagen type I were determined. The fibers were electrospun from a 80 mg ml^?1 collagen solution in 1,1,1,3,3,3-hexafluro-2-propanol and collected on a striated surface suitable for lateral force manipulation by AFM. The small strain modulus, calculated from three-point bending analysis, was 2.82 GPa. The modulus showed significant softening as the strain increased. The average extensibility of the fibers was 33% of their initial length, and the average maximum stress (rupture stress) was 25 MPa. The fibers displayed significant energy loss and permanent deformations above 2% strain.