Development of biomedical hydrogels for rheumatoid arthritis treatment.

Rheumatoid Arthritis (RA) is an autoimmune disorder that hinders the normal functioning of bones and joints and reduces the quality of human life. Every year, millions of people are diagnosed with RA worldwide, particularly among elderly individuals and women. Therefore, there is a global need to develop new biomaterials, medicines and therapeutic methods for treating RA. This will improve the Healthcare Access and Quality Index and also relieve administrative and financial burdens on healthcare service providers at a global scale. Hydrogels are soft and cross-linked polymeric materials that can store a chunk of fluids, drugs and biomolecules for hydration and therapeutic applications. Hydrogels are biocompatible and exhibit excellent mechanical properties, such as providing elastic cushions to articulating joints by mimicking the natural synovial fluid. Hence, hydrogels create a natural biological environment within the synovial cavity to reduce autoimmune reactions and friction. Hydrogels also lubricate the articulating joint surfaces to prevent degradation of synovial surfaces of bones and cartilage, thus exhibiting high potential for treating RA. This work reviews the progress in injectable and implantable hydrogels, synthesis methods, types of drugs, advantages and challenges. Additionally, it discusses the role of hydrogels in targeted drug delivery, mechanistic behaviour and tribological performance for RA treatment.

Multi-functional bioactive silver- and copper-doped diamond-like carbon coatings for medical implants.

Diamond-like carbon (DLC) coatings doped with bioactive elements of silver (Ag) and copper (Cu) have been receiving increasing attention in the last decade, particularly in the last 5 years, due to their potential to offer a combination of enhanced antimicrobial and mechanical performance. These multi-functional bioactive DLC coatings offer great potential to impart the next generation of load-bearing medical implants with improved wear resistance and strong potency against microbial infections. This review begins with an overview of the status and issues with current total joint implant materials and the state-of-the art in DLC coatings and their application to medical implants. A detailed discussion of recent advances in wear resistant bioactive DLC coatings is then presented with a focus on doping the DLC matrix with controlled quantities of Ag and Cu elements. It is shown that both Ag and Cu doping can impart strong antimicrobial potency against a range of Gram-positive and Gram-negative bacteria, but this is always accompanied so far by a reduction in mechanical performance of the DLC coating matrix. The article concludes with discussion of potential synthesis methods to accurately control bioactive element doping without jeopardising mechanical properties and gives an outlook to the potential long-term impact of developing a superior multifunctional bioactive DLC coating on implant device performance and patient health and wellbeing. STATEMENT OF SIGNIFICANCE: Multi-functional diamond-like carbon (DLC) coatings doped with bioactive elements of silver (Ag) and copper (Cu) offer great potential to impart the next generation of load-bearing medical implants with improved wear resistance and strong potency against microbial infections. This article provides a critical review of the state-of-the-art in Ag and Cu doped DLC coatings, beginning with an overview of the current applications of DLC coatings in implant technology followed by a detailed discussion of Ag/Cu doped DLC coatings with particular focus on the relationship between their mechanical and antimicrobial performance. Finally, it ends with a discussion on the potential long-term impact of developing a truly multifunctional ultra-hard wearing bioactive DLC coating to extend the lifetime of total joint implants.

Exploring the robustness of DNA nanotubes framework for anticancer theranostics toward the 2D/3D clusters of hypopharyngeal respiratory tumor cells.

This study aimed to develop a robust approach for the early diagnosis and treatment of tumors. Short circular DNA nanotechnology synthesized a stiff and compact DNA nanotubes (DNA-NTs) framework. TW-37, a small molecular drug, was loaded into DNA-NTs for BH3-mimetic therapy to elevate the intracellular cytochrome-c levels in 2D/3D hypopharyngeal tumor (FaDu) cell clusters. After anti-EGFR functionalization, the DNA-NTs were tethered with a cytochrome-c binding aptamer, which can be applied to evaluate the elevated intracellular cytochrome-c levels via in situ hybridization (FISH) analysis and fluorescence resonance energy transfer (FRET). The results showed that DNA-NTs were enriched within the tumor cells via anti-EGFR targeting with a pH-responsive controlled release of TW-37. In this way, it initiated the triple inhibition of "BH3, Bcl-2, Bcl-xL, and Mcl-1". The triple inhibition of these proteins caused Bax/Bak oligomerization, leading to the perforation of the mitochondrial membrane. This led to the elevation of intracellular cytochrome-c levels, which reacted with the cytochrome-c binding aptamer to produce FRET signals. In this way, we successfully targeted 2D/3D clusters of FaDu tumor cells and achieved the tumor-specific and pH-triggered release of TW-37, causing tumor cell apoptosis. This pilot study suggests that anti-EGFR functionalized, TW-37 loaded, and cytochrome-c binding aptamer tethered DNA-NTs might be the hallmark for early tumor diagnosis and therapy.

Disrupting biofilm and eradicating bacteria by Ag-Fe3O4@MoS2 MNPs nanocomposite carrying enzyme and antibiotics.

In this study, novel multilayered magnetic nanoparticles (ML-MNPs) loaded with DNase and/or vancomycin (Vanc) were fabricated for eliminating multispecies biofilms. Iron-oxide MNPs (IO-core) (500-800 nm) were synthesized via co-precipitation; further, the IO-core was coated with heavy-metal-based layers (Ag and MoS2 NPs) using solvent evaporation. DNase and Vanc were loaded onto the outermost layer of the ML-MNP formed by nanoporous MoS2 NPs through physical deposition and adsorption. The biofilms of S. mutans or E. faecalis (or both) were formed in a brain-heart-infusion broth (BHI) for 3 days, followed by treatment with ML-MNPs for 24 h. The results revealed that coatings of Ag (200 nm) and ultrasmall MoS2 (20 nm) were assembled as outer layers of ML-MNPs successfully, and they formed Ag-Fe3O4@MoS2 MNPs (3-5 µm). The DNase-Vanc-loaded MNPs caused nanochannels digging and resulted in the enhanced penetration of MNPs towards the bottom layers of biofilm, which resulted in a decrease in the thickness of the 72-h biofilm from 48 to 58 µm to 0-4 µm. The sustained release of Vanc caused a synergistic bacterial killing up to 96%-100%. The heavy-metal-based layers of MNPs act as nanozymes to interfere with bacterial metabolism and proliferation, which adversely affects biofilm integrity. Further, loading DNase/Vanc onto the nanoporous-MoS2-layer of ML-MNPs promoted nanochannel creation through the biofilm. Therefore, DNase-and Vanc-loaded ML-MNPs exhibited potent effects on biofilm disruption and bacterial killing.

Nanoscale packing of DNA tiles into DNA macromolecular lattices.

Nanoscale double-crossovers (DX), antiparallel (A), and even half-turns-perimeter (E) DNA tiles (DAE-tiles) with rectangular shapes can be packed into large arrays of micrometer-scale lattices. But the features and mechanical strength of DNA assembly made from differently shaped large-sized DAE DNA tiles and the effects of various geometries on the final DNA assembly are yet to be explored. Herein, we focused on examining DNA lattices synthesized from DX bi-triangular, DNA tiles (T) with concave and convex regions along the perimeter of the tiles. The bi-triangular DNA tiles "T(A) and T(B)" were synthesized by self-assembling the freshly prepared short circular scaffold (S) strands "S(A) and S(B)", each of 106 nucleotides (NT) lengths. The tiles "T(A) and T(B)" were then coupled together to get assembled via sticky ends. It resulted in the polymerization of DNA tiles into large-sized DNA lattices with giant micrometer-scale dimensions to form the "T(A) + T(B)" assembly. These DNA macro-frameworks were visualized "in the air" under atomic force microscopy (AFM) employing tapping mode. We have characterized how curvature in DNA tiles may undergo transitions and transformations to adjust the overall torque, strain, twists, and the topology of the final self-assembly array of DNA tiles. According to our results, our large-span DX tiles assembly "T(A) + T(B)" despite the complicated curvatures and mechanics, was successfully packed into giant DNA lattices of the width of 30-500 nm and lengths of 500 nm to over 10 µm. Conclusively, the micrometer-scale "T(A) + T(B)" framework assembly was rigid, stable, stiff, and exhibited enough tensile strength to form monocrystalline lattices.

Recent Developments in Plasmonic Nanostructures for Metal Enhanced Fluorescence-Based Biosensing.

Metal-enhanced fluorescence (MEF) is a unique phenomenon of surface plasmons, where light interacts with the metallic nanostructures and produces electromagnetic fields to enhance the sensitivity of fluorescence-based detection. In particular, this enhancement in sensing capacity is of importance to many research areas, including medical diagnostics, forensic science, and biotechnology. The article covers the basic mechanism of MEF and recent developments in plasmonic nanostructures fabrication for efficient fluorescence signal enhancement that are critically reviewed. The implications of current fluorescence-based technologies for biosensors are summarized, which are in practice to detect different analytes relevant to food control, medical diagnostics, and forensic science. Furthermore, characteristics of existing fabrication methods have been compared on the basis of their resolution, design flexibility, and throughput. The future projections emphasize exploring the potential of non-conventional materials and hybrid fabrication techniques to further enhance the sensitivity of MEF-based biosensors.

Flexible sensor matrix film-based wearable plantar pressure force measurement and analysis system.

Plantar pressure force data derived from gait and posture are commonly used as health indicators for foot diagnosis, injury prevention, and rehabilitation. This study developed a wearable plantar pressure force measurement and analysis (WPPFMA) system based on a flexible sensor matrix film to monitor plantar pressure force in real time. The developed system comprised a flexible sensor matrix film embedded in the insole of the shoe, a wearable data acquisition (DAQ) device with a Bluetooth module, and dedicated software with an intuitive graphical user interface for displaying the plantar pressure force data from receivers by using a terminal unit (laptop or smart-phone). The flexible sensor matrix film integrated 16 piezoresistive cell sensors to detect pressure force at different anatomical zones of the plantar and under different body positions. The signals from the flexible sensor matrix film were collected using the DAQ module embedded in the shoe and transmitted to the receivers through Bluetooth. The real-time display and analysis software can monitor, visualize, and record the detailed plantar pressure force data, such as average pressure force, maximum pressure force, and pressure force distributions and variations over time. The outcomes of the trials in which the system was worn revealed the applicability of the developed WPPFMA system for monitoring plantar pressure force under static and dynamic wearing conditions. The plantar pressure force data derived from this system provide valuable insights for personal foot care, gait analysis, and clinical diagnosis.

Collagen formation observed from healing calvarial defects with principal component analysis of Raman scattering.

Bone healing is a complex process involving molecular changes. Bone matrix consists of collagen proteins that serve as the framework and minerals, calcium and phosphate, are deposited into the matrix accordingly. Raman spectroscopy is a promising technique to study bone mineral and matrix environments simultaneously. We studied the bone composition using 785 nm excitation during healing of subcritical calvarial defects without disrupting the fracture. Calvarial defects (in vivo) were created using a 1 mm burr drill on the parietal bones of Sprague-Dawley rats (n = 12). After 7 days, subjects were sacrificed and an additional defect (control) was created. Principal component analysis was utilized for the analysis of Raman spectra and helped in classifying normal and healing bone. Principal component 1 (PC1) shows that the major variation between in vivo and control defects and normal bone surface is at 958 cm-1 (ν1 phosphate band). PC2 shows a major variation at 1448 cm-1 (CH2 deformation). PC2 score distinguishes in vivo defects from normal surface and control defects. The decrease in crystallinity and mineral to matrix ratio at the healing site as revealed by Raman confirms the new bone formation. Scanning electron and optical microscopy show the formation of newly generated matrix by means of bony bridges of collagens. The surface roughness increases by 23% from control to in vivo defects, as revealed by optical profiler. Histology shows the decreased depth of in vivo defects and new blood vessels formation. Overall, the new collagen formation shows the scaffolding of the bone is growing during healing.