Construction of Processable Ultrastiff Hydrogel for Periarticular Fracture Strutting and Healing.

Development of bioactive bone and joint implants that offer superior mechanical properties to facilitate personalized surgical procedures remains challenging in the field of biomedical materials. As for the hydrogel, mechanical property and processability are major obstructions hampering its application as load-bearing scaffolds in orthopedics. Herein, we constructed implantable composite hydrogels with appealing processability and ultrahigh stiffness. Central to our design is the incorporation of a thixotropic composite network into an elastic polymer network via dynamic interactions to synthesize a percolation-structured double-network (DN) hydrogel with plasticity, followed by in situ strengthening and self-strengthening mechanisms for fostering the DN structure to the cojoined-network structure and subsequently mineralized-composite-network structure to harvest excellent stiffness. The ultrastiff hydrogel is shapeable and can reach a compressive modulus of 80-200 MPa together with a fracture energy of 6-10 MJ/m3, comparable to the mechanical performance of cancellous bone. Moreover, the hydrogel is cytocompatible, osteogenic, and showed almost no volume shrinkage within 28 days in simulated body fluid or culture medium. Such characteristics enabled the utility of a hydrogel in the reduction and stabilization of periarticular fracture treatment on a distal femoral AO/OTA B1 fracture rabbit model and successfully avoided the recollapse of the articular surface.

Diagnostic value of nerve conduction study in NOTCH2NLC-related neuronal intranuclear inclusion disease.

BACKGROUND AND AIMS: Neuronal intranuclear inclusion disease (NIID) is a rare progressive neurodegenerative disorder mainly caused by abnormally expanded GGC repeats within the NOTCH2NLC gene. Most patients with NIID show polyneuropathy. Here, we aim to investigate diagnostic electrophysiological markers of NIID. METHODS: In this retrospective dual-center study, we reviewed 96 patients with NOTCH2NLC-related NIID, 94 patients with genetically confirmed Charcot-Marie-Tooth (CMT) disease, and 62 control participants without history of peripheral neuropathy, who underwent nerve conduction studies between 2018 and 2022. RESULTS: Peripheral nerve symptoms were presented by 53.1% of patients with NIID, whereas 97.9% of them showed peripheral neuropathy according to electrophysiological examinations. Patients with NIID were characterized by slight demyelinating sensorimotor polyneuropathy; some patients also showed mild axonal lesions. Motor nerve conduction velocity (MCV) of the median nerve usually exceeded 35 m/s, and were found to be negatively correlated with the GGC repeat sizes. Regarding the electrophysiological differences between muscle weakness type (n = 27) and non-muscle weakness type (n = 69) of NIID, nerve conduction abnormalities were more severe in the muscle weakness type involving both demyelination and axonal impairment. Notably, specific DWI subcortical lace sign was presented in only 33.3% of muscle weakness type, thus it was difficult to differentiate them from CMT. Combining age of onset, distal motor latency, and compound muscle action potential of the median nerve showed the optimal diagnostic performance to distinguish NIID from major CMT (AUC = 0.989, sensitivity = 92.6%, specificity = 97.4%). INTERPRETATION: Peripheral polyneuropathy is common in NIID. Our study suggest that nerve conduction study is useful to discriminate NIID.

Repair of critical diaphyseal defects of lower limbs by 3D printed porous Ti6Al4V scaffolds without additional bone grafting: a prospective clinical study.

The repair of critical diaphyseal defects of lower weight-bearing limbs is an intractable problem in clinical practice. From December 2017, we prospectively applied 3D printed porous Ti6Al4V scaffolds to reconstruct this kind of bone defect. All patients experienced a two-stage surgical process, including thorough debridement and scaffold implantation. With an average follow-up of 23.0 months, ten patients with 11 parts of bone defects were enrolled in this study. The case series included three females and seven males, their defect reasons included seven parts of osteomyelitis and four parts of aseptic nonunion. The bone defects located at femur (five parts) and tibia (six parts), with an average defect distance of 12.2 cm. Serial postoperative radiologic follow-ups displayed a continuous process of new bone growing and remodeling around the scaffold. One patient suffered tibial varus deformity, and he underwent a revision surgery. The other nine patients achieved scaffold stability. No scaffold breakage occurred. In conclusion, the implantation of 3D printed Ti6Al4V scaffold was feasible and effective to reconstruct critical bone defects of lower limbs without additional bone grafting. Graphical abstract.

An innovative strategy to treat large metaphyseal segmental femoral bone defect using customized design and 3D printed micro-porous prosthesis: a prospective clinical study.

Five patients with segmental irregular-shaped bone defect of the femur were recruited in this study from 2017.12 to 2018.11. All patients were treated by customized design and 3D printed micro-porous prosthesis. And the procedure was divided into stages: radical debridement and temporary fixation (the first stage); the membrane formation and virtual surgery (intervening period for 6-8 weeks); definite reconstruction the defects (the second stage). Routine clinical follow-up and radiographic evaluation were done to assess bone incorporation and complications of internal fixation. The weight-bearing time and the joint function of the patients were recorded. The patients were followed up for an average of 16.4 months. The average length of bone defect and the distal residual bone was 12 cm and 6.5 cm. The average time of partial weight-bearing and full weight-bearing was 12.7 days and 2.6 months. X-ray demonstrated good osseous integration of the implant/bone interface. No complications occurred such as implant loosening, subsidence, loss of correction and infection. At the last follow-up, Harris score of hip joint was excellent in 2 cases, good in 2 cases, fair in 1 case; HSS score of knee joint was good in 4 cases, middle in 1 case. From our study, we concluded that meticulous customized design 3D printed micro-porous prosthesis combined with intramedullary nail may be a promising and an alternative strategy to treat metaphyseal segmental irregular-shaped femoral bone defect, especially for cases with massive juxta-articular bone loss.

A novel self-assembled oligopeptide amphiphile for biomimetic mineralization of enamel.

BACKGROUND: Researchers are looking for biomimetic mineralization of ena/mel to manage dental erosion. This study evaluated biomimetic mineralization of demineralized enamel induced by a synthetic and self-assembled oligopeptide amphiphile (OPA). RESULTS: The results showed that the OPA self-assembled into nano-fibres in the presence of calcium ions and in neutral acidity. The OPA was alternately immersed in calcium chloride and sodium hypophosphate solutions to evaluate its property of mineralization. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed nucleation and growth of amorphous calcium phosphate along the self-assembled OPA nano-fibres when it was repetitively exposed to solutions with calcium and phosphate ions. Energy dispersive spectrometry (EDS) confirmed that these nano-particles contained calcium and phosphate. Furthermore, electron diffraction pattern suggested that the nano-particles precipitated on OPA nano-fibres were comparable to amorphous calcium phosphate. Acid-etched human enamel slices were incubated at 37°C in metastable calcium phosphate solution with the OPA for biomimetic mineralization. SEM and X-ray diffraction indicated that the OPA induced the formation of hydroxyapatite crystals in organized bundles on etched enamel. TEM micrographs revealed there were 20-30 nm nano-amorphous calcium phosphate precipitates in the biomimetic mineralizing solution. The particles were found separately bound to the oligopeptide fibres. Biomimetic mineralization with or without the oligopeptide increased demineralized enamel microhardness. CONCLUSIONS: A novel OPA was successfully fabricated, which fostered the biomimetic mineralization of demineralized enamel. It is one of the primary steps towards the design and construction of novel biomaterial for future clinical therapy of dental erosion.

Low vertebral CT Hounsfield units: a risk factor for new osteoporotic vertebral fractures after the treatment of percutaneous kyphoplasty.

PURPOSES: To identify the characteristics of the vertebral HU in the elderly patient with new osteoporosis vertebral compression fractures (OVCF) after treatment of percutaneous kyphoplasty (PKP), which may help us to preliminarily evaluate the risk of a new OVCF after the treatment of PKP. METHODS: We retrospectively analyzed the patients who received PKP treatments in our hospital to find out the patients suffered new OVCFs after the treatment of PKP and set an age-, sex-, first fracture vertebrae-, surgical segment-, and comorbidity-matched control group without new fractures. We measured the axial and sagittal L1-HU values to compare their differences. RESULTS: There were 32 patients who suffered new OVCFs and received another PKP surgery in our department. In the study group, the average L1 sagittal and axial HU values were 46.17 ± 21.31 HU and 47.77 ± 22.38 HU, and they had no statistical difference (P > 0.05). For the control group, the average L1 sagittal and axial HU values were 75.69 ± 29.72 HU and 80.23 ± 30.26 HU, and their difference was not significant (P > 0.05). No matter from the axial or sagittal evaluation, the L1 HU value in the study group was significantly lower than that in the control group (P < 0.001). The AUC of using the L1 axial HU value to differentiate patients with new fractures from controls was 0.85 while the sagittal one was 0.82. In axial (and sagittal) evaluation, the cutoff value (adjusted to the multiple of five) had high specificity of 90% or high sensitivity of 90% to identify patients with new fractures of 45 HU and 75 HU (50 HU and 75 HU), respectively. CONCLUSIONS: The lower the vertebral HU value is, the more likely the patients suffer new OVCFs after PKP treatment.

Transcriptomic and metabonomic insights into the biocontrol mechanism of Trichoderma asperellum M45a against watermelon Fusarium wilt.

Watermelon (Citrullus lanatus) is one of the most popular fruit crops. However, Fusarium wilt (FW) is a serious soil-borne disease caused by Fusarium oxysporum f. sp. niveum (FON) that severely limits the development of the watermelon industry. Trichoderma spp. is an important plant anti-pathogen biocontrol agent. The results of our previous study indicated that Trichoderma asperellum M45a (T. asperellum M45a) could control FW by enhancing the relative abundance of plant growth-promoting rhizobacteria (PGPR) in the rhizosphere of watermelon. However, there are few studies on its mechanism in the pathogen resistance of watermelon. Therefore, transcriptome sequencing of T. asperellum M45a-treated watermelon roots combined with metabolome sequencing of the rhizosphere soil was performed with greenhouse pot experiments. The results demonstrated that T. asperellum M45a could stably colonize roots and significantly increase the resistance-related enzymatic activities (e.g., lignin, cinnamic acid, peroxidase and peroxidase) of watermelon. Moreover, the expression of defense-related genes such as MYB and PAL in watermelon roots significantly improved with the inoculation of T. asperellum M45a. In addition, KEGG pathway analysis showed that a large number of differentially expressed genes were significantly enriched in phenylpropane metabolic pathways, which may be related to lignin and cinnamic acid synthesis, thus further inducing the immune response to resist FON. Furthermore, metabolic analysis indicated that four differential metabolic pathways were enriched in M45a-treated soil, including six upregulated compounds and one down-regulated compound. Among them, galactinol and urea were significantly positively correlated with Trichoderma. Hence, this study provides insight into the biocontrol mechanism of T. asperellum M45a to resist soil-borne diseases, which can guide its industrial application.

Additive manufacturing of Zn-Mg alloy porous scaffolds with enhanced osseointegration: In vitro and in vivo studies.

Biodegradable metals (BM) and additive manufacturing (AM) are regarded revolutionary biomaterials and biofabrication technologies for bone repairing metal implants, the combination of both, namely AM of BM, is thus expected to solve the dual technical difficulties including "conventional medical metals are biologically inert and exist in the human body permanently" and "conventional manufacturing processes are inadequate to fabricate personalized implants of complicated structure". This work additively manufactured biodegradable Zn-Mg alloy porous scaffolds by laser powder bed fusion (L-PBF). By using the pre-alloyed Zn-xMg (x = 1, 2 and 5 wt.%) powder and the optimized processing conditions, high fusion quality with the relative density greater than 99.5% was confirmed for the L-PBF parts. The influence of Mg content on microstructure, mechanical properties, in vitro corrosion, cytocompatibility, in vivo degradation, biocompatibility and osteogenic effect was investigated. Fine α-Zn grains and precipitation phases including Mg2Zn11 and MgZn2 were observed in the Zn-xMg L-PBF parts. The hardness increased, and the strength increases firstly and then decreased with increasing the Mg content. The compressive strength and elastic modulus of Zn-1Mg porous scaffolds reached the highest as 40.9 ± 0.4 MPa and 1.17 ± 0.11 GPa, respectively, equivalent to those of cancellous bone. The corrosion rate and cell viability slightly rose with increasing the Mg content. Histological analysis after 6-week and 12-week implantation in rabbit femurs showed enhanced bone formation around the Zn-1Mg porous scaffolds compared with pure Zn counterparts. In summary, Zn-1Mg porous scaffolds produced by L-PBF presented promising results to fulfill customized requirements of biodegradable bone implants. STATEMENT OF SIGNIFICANCE: Additive manufacturing of biodegradable metal porous scaffolds is expected to solve the dual challenges from customized structures and bioactive function required for bone implants. It was the first to present a systematic in vitro and in vivo investigation into the compositions, microstructure, mechanical properties, biodegradation, biocompatibility and osteogenic effect of additively manufactured Zn-Mg alloy porous scaffolds. Reliable formation quality and performance evaluation was achieved by using the pre-alloyed Zn-xMg (x = 1, 2 and 5 wt.%) powder and the optimized laser powder bed fusion process. Although the Zn-1Mg scaffolds exhibited promising mechanical strength, biocompatibility, and osteogenic effect, their degradation rate needs to be further accelerated compared with the term of bone reconstruction.

Processing optimization, mechanical properties, corrosion behavior and cytocompatibility of additively manufactured Zn-0.7Li biodegradable metals.

Biodegradable Zn-Li alloys exhibit superior mechanical performance and favorable osteogenic capability for load-bearing bone devices. Additive manufacturing (AM) endows freedom for the fabrication of bone implants of personalized structure to satisfy patient-specific needs. In this paper, AM of Zn-Li alloys was attempted for the first-time using laser powder bed fusion (LPBF), and the fabricated samples exhibited good fusion quality and high dimensional accuracy. The processing optimization, mechanical properties, in vitro corrosion behavior and cytocompatibility were investigated by using Zn-0.7Li bulk and porous samples. The ultimate tensile strength and elastic modulus of bulk samples respectively reached 416.5 MPa and 83.3 GPa, and both were the highest among various additively manufactured Zn alloys reported so far. Porous samples achieved compressive strength (18.2 MPa) and elastic modulus (298.0 MPa), which were comparable to those of cancellous bone. Porous samples exhibited a higher corrosion rate and alleviated the problem of slow degradation of Zn-Li alloys. Nevertheless, osteoblastic cells showed a more spreading and healthier morphology when adhering to the porous samples compared to the bulk samples, thus a better cytocompatibility was confirmed. This work shows tremendous potential to precisely design and modulate biodegradable Zn alloys to fulfill clinical needs by using AM technology. STATEMENT OF SIGNIFICANCE: This paper firstly studied processing optimization during laser powder bed fusion of Zn-Li alloy. Bulk and porous Zn-0.7Li samples in customized design were obtained with high formation quality. The tensile strength of bulk samples reached 416.5 MPa, while the compressive strength and modulus of porous samples reduced to 18.2 MPa and 298.0 MPa, comparable to those of bone. The weight loss of porous samples was roughly 5 times that of bulk samples; osteoblastic cells showed a more spreading and healthier morphology at porous samples, indicating improved biodegradation rate and cytocompatibility. This work shows tremendous potential to precisely design and modulate biodegradable Zn alloy porous scaffolds to fulfill clinical needs by using additive manufacturing technology.

A shape memory alloy actuated release device using non-self-locking thread.

This paper proposes a novel non-explosive and resettable release device driven by shape memory alloy (SMA), which can replace the commonly used pyrotechnic device. In the scheme, a flywheel nut with bidirectional thread is connected with two screws through the non-self-locking thread, and the target adapters are fixed with the two screws and then locked into a hole by the flywheel nut. When unlocking, the offset SMA actuator releases the flywheel nut by triggering the pulley assembly and multi-level levers. Under the pulling force of the pre-tightening load of the screws, the flywheel nut rotates at high speed to unlock the screws, thus releasing the target adapters. After separation, the device can be quickly reset with the reset tool without replacing any parts. The prototype of the release device is fabricated and tested; according to the performance test results, the device can bear the maximum bi-directional preload of 10 kN and the average unlocking force is 9.73 N. The unlocking time decreases with the increase in driving voltage, and the average unlocking response time is 342 ms under 9 V voltage. Furthermore, the actuator can function well with a lifetime of more than 50 cycles. It is concluded that this scheme has potential advantages to replace the traditional non-reusable explosive driving device.

Improved osseointegration with rhBMP-2 intraoperatively loaded in a specifically designed 3D-printed porous Ti6Al4V vertebral implant.

Three-dimensional (3D)-printed porous Ti6Al4V implants are commonly used for reconstructing bone defects in the treatment of orthopaedic diseases owing to their excellent osteoconduction. However, to achieve improved therapeutic outcomes, the osteoinduction of these implants requires further improvement. The aim of this study was to investigate the combined use of recombinant human BMP-2 (rhBMP-2) with a 3D-printed artificial vertebral implant (3D-AVI) to improve the osteoinduction. Eight male Small Tail Han sheep underwent cervical corpectomy, and 3D-AVIs with or without loaded rhBMP-2 in cavities designed at the center were implanted to treat the cervical defect. Radiographic, micro-computed tomography, fluorescence labelling, and histological examination revealed that the osseointegration efficiency of the rhBMP-2 group was significantly higher than that of the blank control group. The biomechanical test results suggested that rhBMP-2 reduced the range of motion of the cervical spine and provided a more stable implant. Fluorescence observations revealed that the bone tissue grew from the periphery to the center of the 3D-AVIs, first growing into the pore space and then interlocking with the Ti6Al4V implant surface. Therefore, we successfully improved osseointegration of the 3D-AVI by loading rhBMP-2 into the cavity designed at the center of the Ti6Al4V implant, realizing earlier and more stable fixation of implants postoperatively in a simple manner. These benefits of rhBMP-2 are expected to expand the application range and reliability of 3D-printed porous Ti6Al4V implants and improve their therapeutic efficacy.

Structure elucidation and formation mechanistic study of a methylene-bridged pregabalin dimeric degradant in pregabalin extended-release tablets.

During the pharmaceutical development of pregabalin extended-release tablets, an unknown degradant at a relative retention time (RRT) of 11.7 was observed and its nominal amount exceeded the ICH identification threshold in an accelerated stability study. The aim of this study is to identify the structure and investigate the formation mechanism of this impurity for the purpose of developing a chemically stable pharmaceutical product. By utilizing multi-stage LC-MS analysis in conjunction with mechanism-based stress study, the structure of the RRT 11.7 impurity was rapidly identified as a dimeric degradant that is caused by dimerization of two pregabalin molecules with a methylene bridging the two pregabalin moieties. The structure of the dimer was confirmed by 1D and 2D NMR measurement. The formation pathway of the dimeric degradant was also inferred from the mechanism-based stress study, which implicated that the bridging methylene could originate from formaldehyde which might be the culprit that triggers the dimerization in the first place. The subsequent API-excipients compatibility study indicated that the degradant was indeed formed in the compatibility experiments between pregabalin API and two polymeric excipients (PEO and PVPP) that are known to contain residual formaldehyde, but only in the co-presence of another excipient, colloidal silicon dioxide (SiO2). The kinetic behavior of the degradant formation was also investigated and two kinetic models were utilized based on the Arrhenius and Eyring equations, respectively, to calculate the activation energy (Ea) as well as the enthalpy of activation (△H‡), entropy of activation (△S‡), and Gibbs free energy (△G‡) of the degradation reaction. The results of this study would be useful for the understanding of similar dimeric degradant formation in finished products of drug substances containing primary or secondary amine moieties.

Sustainable release of vancomycin from micro-arc oxidised 3D-printed porous Ti6Al4V for treating methicillin-resistant Staphylococcus aureus bone infection and enhancing osteogenesis in a rabbit tibia osteomyelitis model.

Elimination of infection and enhancement of osteogenesis by orthopaedic implants are two critical factors in the treatment of complex bone infections. A prolonged and expensive procedure requiring two surgical steps and a 6-8-week period of joint immobilisation is utilised as a primary treatment for revision arthroplasty of an infected prosthesis, greatly affecting long-term patient care for the ageing population. Here, we evaluated the effects of vancomycin-loaded in micro-arc oxidised (MAO) three-dimensional (3D) printed porous Ti6Al4V scaffolds on osteogenesis. This system showed a high loading capacity and sustained vancomycin release kinetics, as demonstrated using high-performance liquid chromatography. In vivo, 0.1 mL of 108 colony forming units (CFU) methicillin-resistant Staphylococcus aureus was injected into the tibias of rabbits to induce severe osteomyelitis. Physical, haematological, radiographic, microbiological, and histopathological analyses were performed to evaluate the effects of treatment. Rabbits with vancomycin-loaded in MAO scaffolds showed the inhibition of bone infection and enhancement of osteogenesis, resulting in better outcomes than in the other groups. Overall, these findings demonstrated the potential of this 3D printed porous Ti6Al4V, with good osteogenesis and sustained vancomycin release properties, for application in the treatment of complex bone infections.

Magnetic cilia carpets with programmable metachronal waves.

Metachronal waves commonly exist in natural cilia carpets. These emergent phenomena, which originate from phase differences between neighbouring self-beating cilia, are essential for biological transport processes including locomotion, liquid pumping, feeding, and cell delivery. However, studies of such complex active systems are limited, particularly from the experimental side. Here we report magnetically actuated, soft, artificial cilia carpets. By stretching and folding onto curved templates, programmable magnetization patterns can be encoded into artificial cilia carpets, which exhibit metachronal waves in dynamic magnetic fields. We have tested both the transport capabilities in a fluid environment and the locomotion capabilities on a solid surface. This robotic system provides a highly customizable experimental platform that not only assists in understanding fundamental rules of natural cilia carpets, but also paves a path to cilia-inspired soft robots for future biomedical applications.

Novel beta-cyclodextrin derivative functionalized polymethacrylate-based monolithic columns for enantioselective separation of ibuprofen and naproxen enantiomers in capillary electrochromatography.

A novel enantioselective polymethacrylate-based monolithic column for capillary electrochromatography was prepared by ring-opening reaction of epoxy groups from poly(glycidyl methacrylate-co-ethylene dimethacrylate) monolith with a novel beta-cyclodextrin derivative bearing 4-dimethylamino-1,8-naphthalimide functionalities. Conditions for the ring-opening reaction with respect to different reaction parameters were thoroughly optimized to obtain high electroosmotic flow, separation efficiency and enantioselectivity for the analytes. The nonaqueous mobile phase composition regarding acetonitrile-methanol ratio and the concentration of electrolyte were examined to manipulate the hydrophobic inclusion and anion-exchange interaction between the analytes and chiral stationary phase. It was observed that in addition to beta-cyclodextrin cavity, the electrostatic interaction exhibited pronounced influence on the enantioseparation of acidic analytes. Acidic enantiomers (ibuprofen and naproxen) could be separated with separation factor (alpha) values up to 1.08 and a maximum separation efficiency of 86000 plates/m could be achieved.

Cyclen-based side-chain homopolymer self-assembly with plasmid DNA: protection of DNA from enzymatic degradation.

In this study, a 1,4,7,10-tetraazacyclododecane (cyclen)-based side-chain homopolymer was developed for the first time; this polymer can self-assembly with plasmid DNA to form polyelectrolyte complexes (polyplex), which can protect DNA from enzymatic degradation. Moreover, the polyplex can disassembly and release free DNA when NaCl solution is added to this system. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) are used for imaging of the surface structure of the polyplex, and results indicated that the polyplex structures respond to the polymer concentration. Circular dichroism (CD) spectrum suggested that the DNA configuration in the polyplex was retained.

An Injectable Strong Hydrogel for Bone Reconstruction.

For treating bone defects in periarticular fractures, there is a lack of biomaterial with injectable characteristics, tough structure, and osteogenic capacity for providing a whole-structure support and osteogenesis in the defect area. An injectable hydrogel is an ideal implant, however is weak as load-bearing scaffolds. Herein, a new strategy, i.e., an in situ formation of "active" composite double network (DN), is raised for the preparation of an injectable strong hydrogel particularly against compression. As a demonstration, 4-carboxyphenylboronic acid grafted poly(vinyl alcohol) (PVA) is crosslinked using calcium ions to provide a tough frame while bioactive glass (BG) microspheres are associated by poly(ethylene glycol) to obtain an interpenetrated inorganic network for reinforcement. The injected PVA/BG DN hydrogel gains compressive strength, modulus, and fracture energy of 34 MPa, 0.8 MPa, and 40 kJ m-2 , respectively. Then, the properties can be "autostrengthened" to 57 MPa, 2 MPa, and 65 kJ m-2 by mineralization in 14 days. In vivo experiments prove that the injected DN hydrogel is more efficient to treat femoral supracondylar bone defects than the implanted bulk DN gel. The work suggests a facile way to obtain a strong hydrogel with injectability, cytocompatibility, and tailorable functionality.

Matryoshka-Inspired Micro-Origami Capsules to Enhance Loading, Encapsulation, and Transport of Drugs.

Stimuli-responsive hydrogels are promising candidates for use in the targeted delivery of drugs using microrobotics. These devices enable the delivery and sustained release of quantities of drugs several times greater than their dry weight and are responsive to external stimuli. However, existing systems have two major drawbacks: (1) severe drug leakage before reaching the targeted areas within the body and (2) impeded locomotion through liquids due to the inherent hydrophilicity of hydrogels. This article outlines an approach to the assembly of hydrogel-based microcapsules in which one device is assembled within another to prevent drug leakage during transport. Inspired by the famous Russian stacking dolls (Matryoshka), the proposed scheme not only improves drug-loading efficiency but also facilitates the movement of hydrogel-based microcapsules driven by an external magnetic field. At room temperature, drug leakage from the hydrogel matrix is 90%. However, at body temperature the device folds up and assembles to encapsulate the drug, thereby reducing leakage to a mere 6%. The Matryoshka-inspired micro-origami capsule (MIMC) can disassemble autonomously when it arrives at a targeted site, where the temperature is slightly above body temperature. Up to 30% of the encapsulated drug was shown to diffuse from the hydrogel matrix within 1 h when it unfolds and disassembles. The MIMC is also shown to enhance the movement of magnetically driven microcapsules while navigating through media with a low Reynolds number. The translational velocity of the proposed MIMC (four hydrogel-based microcapsules) driven by magnetic gradients is more than three times greater than that of a conventional (single) hydrogel-based microcapsule.

A Simple, Time-Saving Dye Staining of Proteins in Sodium Dodecyl Sulfate-Polyacrylamide Gel Using Coomassie Blue.

Most traditional post-electrophoretic processes need several hours to several days to finish the whole staining process and traditional staining solutions all contain methanol, acetic acid, or phosphoric acid, which not only produce the unpleasant smell but also cause environmental pollution. Here a fixation-free, fast protein staining method in sodium dodecyl sulfate-polyacrylamide gel electrophoresis using Coomassie blue is described. The protocol includes only staining and quick washing steps, can be completed in 0.5 h. It has a sensitivity of 10 ng. In addition, the dye stain does not contain any acid or methanol.

Development of oral dispersible tablets containing prednisolone nanoparticles for the management of pediatric asthma.

The purpose of the present study was to develop oral dispersible tablets containing prednisolone (PDS)-loaded chitosan nanoparticles using microcrystalline cellulose (MCC 101), lactose, and croscarmellose sodium (CCS). The PDS-loaded chitosan nanoparticles were formulated by ionotropic external gelation technique in order to enhance the solubility of PDS in salivary pH. Prepared nanoparticles were used for the development of oral fast disintegrating tablets by direct compression method. The prepared tablets were evaluated for disintegration time (DT), in vitro drug release (DR), thickness, weight variation, drug content uniformity, friability, and hardness. The effect of concentrations of the dependent variables (MCC, lactose, CCS) on DT and in vitro DR was studied. Fast disintegrating tablets of PDS can be prepared by using MCC, CCS, and lactose with enhanced solubility of PDS. The minimum DT was found to be 15 seconds, and the maximum DR within 30 minutes was 98.50%. All independent variables selected for the study were statistically significant. Oral fast disintegrating tablets containing PDS nanoparticles could be the better choice for the pediatric patients that would result in better patient compliance. From this study, it can be concluded that fast disintegrating tablets could be a potential drug delivery technology for the management of asthma in pediatrics.