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Circulating tumor cells (CTCs) are cells that have been shed from tumors and circulate in the bloodstream. These cells can also be responsible for further metastases and the spread of cancer. Taking a closer look and analyzing CTCs through what has come to be known as "liquid biopsy" has immense potential to further researchers' understanding of cancer biology. However, CTCs are very sparse and are therefore difficult to detect and capture. To combat this issue, researchers have attempted to create devices, assays, and further techniques to successfully isolate CTCs for analysis. In this work, new and existing biosensing techniques for CTC isolation, detection, and release/detachment are discussed and compared to evaluate their efficacy, specificity, and cost. Here, we specifically aim to evaluate and identify the potential success of these techniques and devices in point-of-care (POC) settings. [ABSTRACT FROM AUTHOR]

Osteosarcoma is a malignant tumor of bone that leads to poor mortality and morbidity. Management of this cancer through conventional methods involves invasive treatment options that place patients at an increased risk of adverse events. The use of hydrogels to target osteosarcoma has shown promising results both in vitro and in vivo to eradicate tumor cells while promoting bone regeneration. The loading of hydrogels with chemotherapeutic drugs provides a route for site-specific targeted therapy for osteosarcoma. Current studies demonstrate tumor regression in vivo and lysis of tumor cells in vitro when exposed to doped hydrogel scaffolds. Additionally, novel stimuli-responsive hydrogels are able to react with the tissue microenvironment to facilitate the controlled release of anti-tumor drugs and with biomechanical properties that can be modulated. This narrative review of the current literature discusses both in vitro and in vivo studies of different hydrogels, including stimuli-responsive, designed to treat bone osteosarcoma. Future applications to address patient treatment for this bone cancer are also discussed. [ABSTRACT FROM AUTHOR]

The generation of biomaterials via 3D printing is an emerging biotechnology with novel methods that seeks to enhance bone regeneration. Alginate and collagen are two commonly used biomaterials for bone tissue engineering and have demonstrated biocompatibility. Strontium (Sr) and Calcium phosphate (CaP) are vital elements of bone and their incorporation in composite materials has shown promising results for skeletal repair. In this study, we investigated strontium calcium polyphosphate (SCPP) doped 3D printed alginate/collagen hydrogels loaded with MC3T3-E1 osteoblasts. These cell-laden scaffolds were crosslinked with different concentrations of 1% SCPP to evaluate the effect of strontium ions on cell behavior and the biomaterial properties of the scaffolds. Through scanning electron microscopy and Raman spectroscopy, we showed that the scaffolds had a granular surface topography with the banding pattern of alginate around 1100 cm−1 and of collagen around 1430 cm−1. Our results revealed that 2 mg/mL of SCPP induced the greatest scaffold degradation after 7 days and least amount of swelling after 24 h. Exposure of osteoblasts to SCPP induced severe cytotoxic effects after 1 mg/mL. pH analysis demonstrated acidity in the presence of SCPP at a pH between 2 and 4 at 0.1, 0.3, 0.5, and 1 mg/mL, which can be buffered with cell culture medium. However, when the SCPP was added to the scaffolds, the overall pH increased indicating intrinsic activity of the scaffold to buffer the SCPP. Moreover, cell viability was observed for up to 21 days in scaffolds with early mineralization at 0.3, 0.5, and 1 mg/mL of SCPP. Overall, low doses of SCPP proved to be a potential additive in biomaterial approaches for bone tissue engineering; however, the cytotoxic effects due to its pH must be monitored closely. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) is a global epidemic; however, many individuals are able to obtain treatment and manage their condition. Progression to acquired immunodeficiency syndrome (AIDS) occurs during late-stage HIV infection, which compromises the immune system, making it susceptible to infections. While there is no cure, antiretroviral therapy can be used provided that detection occurs, preferably during the early phase. However, the detection of HIV is expensive and resource-intensive when tested with conventional methods, such as flow cytometry, polymerase chain reaction (PCR), or enzyme-linked immunosorbent assays (ELISA). Improving disease detection in resource-constrained areas requires equipment that is affordable, portable, and can deliver rapid results. Microfluidic devices have transformed many benchtop techniques to on-chip detection for portable and rapid point-of-care (POC) testing. These devices are cost-effective, sensitive, and rapid and can be used in areas lacking resources. Moreover, their functionality can rival their benchtop counterparts, making them efficient for disease detection. In this review, we discuss the limitations of currently used conventional HIV diagnostic assays and provide an overview of potential microfluidic technologies that can improve HIV testing in POC settings. [ABSTRACT FROM AUTHOR]

Silicon oxynitride (Si-O-N) is a new biomaterial in which its O/N ratio is tunable for variable Si release and its subsequent endocytotic incorporation into native hydroxyapatite for enhanced bone healing. However, the effect of nitrogen and hydrogen bonding on the formation and structure of hydroxyapatite is unclear. This study aims to uncover the roles of H and N in tuning Si-O-N surface bioactivity for hydroxyapatite formation. Conformal Si-O-N films were fabricated by plasma-enhanced chemical vapor deposition (PECVD) onto Ti/Si substrates. Fourier transform infrared spectroscopy (FTIR) and Rutherford backscattering spectrometry (RBS) analysis indicated increased Si-H and N-H bonding with increased N content. Surface energy decreased with increased N content. X-ray absorbance near edge structure (XANES) analysis showed tetrahedral coordination in O-rich films and trigonal coordination in N-rich films. O-rich films exhibited a 1:1 ratio of 2p3/2 to 2p1/2 electron absorbance, while this ratio was 1.73:1 for N-rich films. Both Si and N had a reduced partial charge for both O- and N-rich films, whereas O maintained its partial charge for either film. O-rich films were found to exhibit random bonding SizOxNy, while N-rich films exhibited random mixing: [Si-Si]-[Si-O]-[Si-N]. Thus, hydrogen bonding limits random nitrogen bonding in Si-O-N films via surface Si-H and N-H bonding. Moreover, increased nitrogen content reduces the partial charge of constituent elements and changes the bonding structure from random bonding to random mixing. [ABSTRACT FROM AUTHOR]

Cancer treatment, care, and outcomes are much more effective if started at early stages of the disease. The presence of malignant cancer cells in human samples such as blood or biopsied tissue can be used to reduce overtreatment and underdiagnosis as well as for prognosis monitoring. Reliable quantification of metastatic tumor cells (MTCs) and non-metastatic tumor cells (NMTCs) from human samples can help in cancer staging as well. We report a simple, fast, and reliable approach to identify and quantify metastatic and non-metastatic cancer cells from whole biological samples in a point-of-care manner. The metastatic (MDA MB-231) and non-metastatic (MCF7) breast cancer cells were pushed through a solid-state micropore made in a 200 nm thin SiO2 membrane while measuring current across the micropore. The cells generated very distinctive translocation profiles. The translocation differences stemmed from their peculiar mechanophysical properties. The detection efficiency of the device for each type of tumor cells was ~75%. MTCs showed faster translocation (36%) and 34% less pore blockage than NMTCs. The micropore approach is simple, exact, and quantitative for metastatic cell detection in a lab-on-a chip setting, without the need for any preprocessing of the sample. [ABSTRACT FROM AUTHOR]

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are widely used for controlled delivery of bioactive agents in therapeutic applications. These nanoparticles show bioavailability, better encapsulation, controlled release, biocompatibility, and in vivo biodegradability. This paper reports a novel approach to synthesize porous PLGA nanoparticles and their use as controlled release vehicles. Bovine serum albumin (BSA) loaded PLGA nanoparticles (porous and nonporous) were synthesized using water-in-oil-in-water double emulsion method. Specifically, PLGA nanoparticles were prepared using chloroform and polyvinyl alcohol, and freeze drying was employed for the phase separation to obtain the nanoparticles. The porous nanoparticles were prepared through the salt-leaching process where sodium bicarbonate was used as an extractable porogen. In vitro drug release behavior of porous and nonporous nanoparticles was monitored over a period of 30 days. A much more enhanced BSA release was observed in case of porous polymeric nanoparticles when compared to nonporous nanoparticles. The characterization was done using laser scattering, zeta potential analysis, and scanning electron microscopy. The drug loading efficiencies for BSA in porous and nonporous PLGA nanoparticles were 65.50% and 77.59%, respectively. Over a period of 30 days, the cumulative BSA released from PLGA porous and nonporous nanoparticles were measured to be 87.41% and 59.91%, respectively. The synthesis of porous nanoparticles with this novel, rapid, and inexpensive method opens a new horizon of using a wide range of cheap and easily-accessible water-soluble salts that can be extracted through leaching process to introduce porous morphology on the nanoparticle surfaces. The porous nanoparticles can have useful applications in controlled drug delivery systems. [ABSTRACT FROM PUBLISHER]

Plants and photosynthetic bacteria hold protein molecular complexes that can efficiently harvest photons. This article presents fundamental studies to harness photochemical activities of photosynthetically active protoplast extracted from Arabidopsis plants. The conversion of photonic energy into electrical energy was characterized in the presence and absence of light. The photoinduced reactions of photosynthesis were measured using a patch clamp measurement system at a constant voltage. The optical characterization was also performed on the extracted protoplast. It showed absorption bands at a number of wavelengths. The current-voltage measurements done on protoplast extracts showed two orders of magnitude increase in current from dark to light conditions. The absorbance measurements showed very large bandwidth for extracted protoplasts. The analysis of the optical data measurements showed that protein complexes obtained from photosynthetic cells overcame the limitation of traditional organic solar cells that cannot absorb light in the visible-near infrared spectrum. The demonstration of electrical power scavenging from the protoplast of the plant can open avenues for bio-- inspired and bio-derived power with better quantum electrical efficiency. [ABSTRACT FROM AUTHOR]

Curcumin and bovine serum albumin (BSA) were used as model drugs and loaded into micro- and nanoparticles of biodegradable poly(lactic-co-glycolic acid) (PLGA). The PLGA was incorporated into hydrophilic and biocompatible gelatin scaffolds to design a controlled drug release system. The gelatin scaffolds were cross-linked using glutaraldehyde. The controlled delivery of drugs from biologically active PLGA micro- and nanoparticles was measured and these showed consistent release for 30 days. Curcumin- and BSA-loaded PLGA micro/nanoparticles-based gelatin scaffolds define a novel approach to embed multiple drug molecules to overcome multidrug resistance as well as depict a new type of biocompatible and biodegradable implant. Such scaffold constructs can be used for breast implants after lumpectomy to not only overcome cosmetic issues, but also to provide sustained drug release during healing process. In one type of construct, only BSA-loaded microparticles were mixed with gelatin, while in the other type of construct, both BSA- and curcumin-loaded PLGA microparticles were embedded. BSA- and curcumin-loaded nanoparticles were also embedded into gelatin constructs to see the effects of particle size on drug release. After 30 days, cumulative BSA release from PLGA micro- and nanoparticles embedded in gelatin scaffold were measured to be 69.87% and 86.11%, respectively. The cumulative release of curcumin was measured to be 53.11% and 60.42% from curcumin-loaded PLGA micro- and nanoparticles, respectively. A statistically significant difference was seen in cumulative drug release from these scaffolds (p value < 0.05). [ABSTRACT FROM PUBLISHER]

Bioprinting stem cells into three-dimensional (3D) scaffolds has emerged as a new avenue for regenerative medicine, bone tissue engineering, and biosensor manufacturing in recent years. Mesenchymal stem cells, such as adipose-derived and bone-marrow-derived stem cells, are capable of multipotent differentiation in a 3D culture. The use of different printing methods results in varying effects on the bioprinted stem cells with the appearance of no general adverse effects. Specifically, extrusion, inkjet, and laser-assisted bioprinting are three methods that impact stem cell viability, proliferation, and differentiation potential. Each printing method confers advantages and disadvantages that directly influence cellular behavior. Additionally, the acquisition of 3D bioprinters has become more prominent with innovative technology and affordability. With accessible technology, custom 3D bioprinters with capabilities to print high-performance bioinks are used for biosensor fabrication. Such 3D printed biosensors are used to control conductivity and electrical transmission in physiological environments. Once printed, the scaffolds containing the aforementioned stem cells have a significant impact on cellular behavior and differentiation. Natural polymer hydrogels and natural composites can impact osteogenic differentiation with some inducing chondrogenesis. Further studies have shown enhanced osteogenesis using cell-laden scaffolds in vivo. Furthermore, selective use of biomaterials can directly influence cell fate and the quantity of osteogenesis. This review evaluates the impact of extrusion, inkjet, and laser-assisted bioprinting on adipose-derived and bone-marrow-derived stem cells along with the effect of incorporating these stem cells into natural and composite biomaterials. [ABSTRACT FROM AUTHOR]

Cell adhesion, morphology and growth are influenced by surface topography at nano and micrometer scales. Nano-textured surfaces are prepared using photolithography, plasma etching and long polymer chemical etching which are cost prohibitive and require specialized equipment. This article demonstrates a simple approach to synthesize nano-textured scaffolds from chicken eggshells. Varieties of pattern are made on the eggshells like micro-needle forests and nanopores, giving very uniform nano-textures to the surfaces. The surfaces are characterized for chemical composition and crystal phase. The novel patterns are transferred to PDMS surfaces and the nano-textured PDMS surfaces are used to study the effect of texturing on human fibroblast cell growth and attachment. The effects of surface topographies, along with laminin coating on cell cultures, are also studied. We find an exciting phenomenon that the initial seeding density of the fibroblast cells affects the influence of the nano-texturing on cell growth. These nano-textured surfaces give 16 times more fibroblast growth when compared to flat PDMS surfaces. The novel nano-textured patterns also double the laminin adsorption on PDMS. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) is a cell surface protein overexpressed in cancerous cells. It is known to be the most common oncogene. EGFR concentration also increases in the serum of cancer patients. The detection of small changes in the concentration of EGFR can be critical for early diagnosis, resulting in better treatment and improved survival rate of cancer patients. This article reports an RNA aptamer based approach to selectively capture EGFR protein and an electrical scheme for its detection. Pairs of gold electrodes with nanometer separation were made through confluence of focused ion beam scratching and electromigration. The aptamer was hybridized to a single stranded DNA molecule, which in turn was immobilized on the SiO2 surface between the gold nanoelectrodes. The selectivity of the aptamer was demonstrated by using control chips with mutated non-selective aptamer and with no aptamer. Surface functionalization was characterized by optical detection and two orders of magnitude increase in direct current (DC) was measured when selective capture of EGFR occurred. This represents an electronic biosensor for the detection of proteins of interest for medical applications. [ABSTRACT FROM AUTHOR]

Solid-state nanopores have emerged as sensors for single molecules and these have been employed to examine the biophysical properties of an increasingly large variety of biomolecules. Herein we describe a novel and facile approach to precisely adjust the pore size, while simultaneously controlling the surface chemical composition of the solid-state nanopores. Specifically, nanopores fabricated using standard ion beam technology are shrunk to the requisite molecular dimensions via the deposition of highly conformal pulsed plasma generated thin polymeric films. The plasma treatment process provides accurate control of the pore size as the conformal film deposition depends linearly on the deposition time. Simultaneously, the pore and channel chemical compositions are controlled by appropriate selection of the gaseous monomer and plasma conditions employed in the deposition of the polymer films. The controlled pore shrinkage is characterized with high resolution AFM, and the film chemistry of the plasma generated polymers is analyzed with FTIR and XPS. The stability and practical utility of this new approach is demonstrated by successful single molecule sensing of double-stranded DNA. The process offers a viable new advance in the fabrication of tailored nanopores, in terms of both the pore size and surface composition, for usage in a wide range of emerging applications. [ABSTRACT FROM AUTHOR]

The generation of biomaterials via 3D printing is an emerging biotechnology with novel methods that seeks to enhance bone regeneration. Alginate and collagen are two commonly used biomaterials for bone tissue engineering and have demonstrated biocompatibility. Strontium (Sr) and Calcium phosphate (CaP) are vital elements of bone and their incorporation in composite materials has shown promising results for skeletal repair. In this study, we investigated strontium calcium polyphosphate (SCPP) doped 3D printed alginate/collagen hydrogels loaded with MC3T3-E1 osteoblasts. These cell-laden scaffolds were crosslinked with different concentrations of 1% SCPP to evaluate the effect of strontium ions on cell behavior and the biomaterial properties of the scaffolds. Through scanning electron microscopy and Raman spectroscopy, we showed that the scaffolds had a granular surface topography with the banding pattern of alginate around 1100 cm -1 and of collagen around 1430 cm -1 . Our results revealed that 2 mg/mL of SCPP induced the greatest scaffold degradation after 7 days and least amount of swelling after 24 h. Exposure of osteoblasts to SCPP induced severe cytotoxic effects after 1 mg/mL. pH analysis demonstrated acidity in the presence of SCPP at a pH between 2 and 4 at 0.1, 0.3, 0.5, and 1 mg/mL, which can be buffered with cell culture medium. However, when the SCPP was added to the scaffolds, the overall pH increased indicating intrinsic activity of the scaffold to buffer the SCPP. Moreover, cell viability was observed for up to 21 days in scaffolds with early mineralization at 0.3, 0.5, and 1 mg/mL of SCPP. Overall, low doses of SCPP proved to be a potential additive in biomaterial approaches for bone tissue engineering; however, the cytotoxic effects due to its pH must be monitored closely.

Treatment for critical size defects (CSDs) in bone often use bone grafts to act as a scaffold to help complete healing. Biological scaffolds require bone extraction from the individual or an outside donor while synthetic grafts mostly suffer from poor degradation kinetics and decreased bioactivity. In this study, we investigated a 3D printed scaffold derived from a novel composite bioink composed of alginate and collagen augmented with varying doses from 2 m g/ m L to 20 m g/ m L of 1% strontium-calcium polyphosphate (SCPP) to control biodegradability and fluid uptake. Scaffolds with increased SCPP concentrations showed higher particle density, lesser swelling ratio and greater biodegradability indicating that these critically important properties for bone healing are fine-tunable and highly dependent on SCPP dosing. Clinical Relevance- The dosing of 1% SCPP into porous alginate/collagen scaffolds provides adjustable long-term degradation and material properties suitable for potential in vivo CSD applications.

Fracture healing is a complex biological process. Severe bone loss and ischemia from traumatic fractures lead to inflammation and accumulation of damaging reactive oxygen species (ROS). Fixative devices that not only provide mechanical support but also stimulate antioxidants such as superoxide dismutase (SOD1) and influence signaling pathways for extracellular matrix (ECM) mineralization, are critical for normal healing of such fractures. In this study, we report a novel biomaterial, silicon oxynitrophosphide (SiONP) that provides sustained release of ionic silicon (Si +4 ) and phosphorous (P) over few weeks under physiological conditions. Anti-oxidant role of Si +4 and augmented ECM mineralization by P ions lead to enhanced osteogenesis coupled with quick revascularization for rapid bone regeneration. Plasma enhanced chemical vapor deposition (PECVD) provided a conformal, well adherent and highly reproducible surface chemistry overlaid onto nanofabricated bioinspired surfaces. The Nitrogen to P and O content ratio was observed to change the dissolution rate and the release kinetics of the overlaid film. The SiONP films with optimal release kinetics promoted anti-oxidant expression via enhanced SOD1, which downstream upregulated other osteogenic markers with MC3T3-E1 cells. These surfaces also promoted angiogenesis evident by formation of thicker tubules by Human umbilical vein endothelial cells (HUVEC). In-vivo evaluation using a rat critical-sized calvarial defect model showed rapid bone-regeneration for these nanofabricated biomaterials as compared to control groups, and opens new horizon for future clinical trials of new antioxidant materials on biomedical devices that can reduce healing time, lower medical care cost, and increase the quality of newly formed bone in critical size defects.

Structurally unstable fracture sites require metal fixative devices, which have long healing times due to their lack of osteoinductivity. Bioactive glass coatings lack in interfacial bonding, delaminate, and have reduced bioactivity due to the high temperatures used for their fabrication. Here, we test the hypothesis that low-temperature PECVD amorphous silica can enhance adhesion to the underlying metal surface and that N incorporation enhances osteogenesis and rapid biomineralization. A model Ti/TiO2-SiOx interface was formed by first depositing Ti onto Si wafers, followed by surface patterning, thermal annealing to form TiO2, and depositing SiOx/Si(ON)x overlays. TEM micrographs showed conformal SiOx layers on Ti/TiO2 overlays while XPS data revealed the formation of an elemental Ti-O-Si interface. Nanoscratch testing verified strong SiOx bonding with the underlying TiO2 layers. In vitro studies showed that the surface properties changed significantly to reveal the formation of hydroxycarbonate apatite within 6 h, and Si(ON)x surface chemistry induced osteogenic gene expression of human periosteal cells and led to a rapid "bone-like" biomineral formation within 4 weeks. XANES data revealed that the incorporation of N increased the surface HA bioactivity by increasing the carbonate to phosphate ratio. In conclusion, silicon oxynitride overlays on bone-implant systems enhance osteogenesis and biomineralization via surface nitrogen incorporation.

Solid-state micropores can provide direct information of ex vivo or in vitro cell populations. Micropores are used to detect and discriminate cancer cells based on the translocation behavior through micropores. The approach provides rapid detection of cell types based on their size and mechano-physical properties like elasticity, viscosity and stiffness. Use of a single micropore device enables detection of tumor cells from whole blood efficiently, at 70% CTC detection efficiency. The CTCs show characteristic electrical signals which easily distinguish these from other cell types. The approach provides a gentle and inexpensive instrument that can be used for specific blood analysis in a lab-on-a-chip setting. The device does not require any preprocessing of the blood sample, particles/beads attachment, surface functionalization or fluorescent tags and provides quantitative and objective detection of cancer cells.