Nanocomposites comprising of biopolymers and calcium phosphate cements (CaP) are promising due to their biocompatibility, non-toxicity, biodegradability and suitable mechanical properties for biomedical applications. In here, a new composite material was synthesized with carboxymethylcellulose (CMC) and gelatin (GEL) as the liquid phase and CaP based powder as the solid phase. In this study, the effect of addition of different wt% of GEL including 0, 5, 10, 20 in the liquid phase was investigated on the physical properties of the nanocomposites. Physico-chemical characteristics of materials were determined by using Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and mechanical tests. Swelling analysis was performed after 1, 8, 16, 24 and 48 hours and degradation of samples was studied after 7 and 14 days. FTIR results showed that there was physical interaction between CMC and GEL with H bonding which was evident from the peak at 3288cm-1. Disruption in GEL structure was observed from the band at 1600-1400 cm-1 Disruption of GEL structure may increase the interaction between CMC and GEL molecules. After mixing of solid and liquid phases, negative charged COO- groups on CMC and Ca2+ molecules from CaP start to interact with each other. This produces attraction sites for PO43- molecules. This lead to accumulation of hydroxyapatite-like structures. A homogenous and porous microstructure was observed by using SEM in all samples. Mechanical tests showed that GEL improved the strength of the samples up to 20 wt% of GEL. The addition of 20 wt% of GEL decreased the mechanical properties. The compressive strength values were found up to approximately 6 MPa. Swelling results revealed that increasing in GEL concentration cause decrease in swelling until the 16th hour, after that 10wt% GEL samples had the lowest swelling which was approximately 28%. Finally, degradation studies indicated that the highest degradation rate was for 10% GEL incorporated samples. Addition of further GEL also reduced the degradation rate. Overall, the addition of GEL improved physical properties of the samples for potential biomedical applications.

Near infrared (NIR) optical imaging has demonstrated significant potential as an effective modality for cancer molecular imaging. Among various NIR probes currently under investigation, upconversion nanophosphors (UCNPs) possess great promise due to their anti-Stokes emission and sequential photon absorption which result in superior detection sensitivity and a simple imaging setup, respectively. Here we investigated the utility of this imaging modality to detect tumor cells expressing the epidermal growth factor receptor (EGFR) using affibody functionalized nanophosphors and a custom built imaging system. Initially, aqueous dispersible NaYF4: Tm+3, Yb+3 UCNPs were synthesized and their photophysical properties were characterized. Then, their luminescence response as a function of concentration and their depth resolving capability in a tissue-simulating phantom were examined. Finally, we demonstrated the use of bioconjugated UCNPs for imaging EGFR-expressing tumors both in vitro and in vivo. Our data suggests that NIR imaging with UCNPs may be useful for noninvasive imaging of tumors.

Neural electrodes have been widely used to monitor neural signals and/or deliver electrical stimulation in the brain. Currently, biodegradable and biocompatible materials have been actively investigated to create temporary electrodes that could degrade after serving their functions for neural recording and stimulation from days to months. The new class of biodegradable electrodes eliminate the necessity of secondary surgery for electrode removal. In this study, we created biodegradable, biocompatible, and implantable magnesium (Mg)-based microelectrodes for in vivo neural recording for the first time. Specifically, conductive poly-3,4-ethylenedioxythiophene (PEDOT) was first deposited onto Mg microwire substrates by electrochemical deposition, and a biodegradable insulating polymer was subsequently sprayed onto the surface of electrodes. The tip of electrodes was designed to be conductive for neural recording and stimulation, while the rest of electrodes was insulated with a polymer that is biocompatible with neural tissue. The impedance of Mg-based microelectrodes and their performance during neural recording in the auditory cortex of a mouse were studied. The results first demonstrated the capability of Mg-based microelectrodes for in vivo recording of multi-unit stimulus-evoked activity in the brain.

Technological advances in synthesis and preparation of aerogels have resulted in formulations that have the mechanical integrity (while retaining flexibility) to be utilized in a broad range of applications and have overcome the initial brittleness that this class of materials was once known for. Both structural and functional aerogels show a drop in performance when subjected to certain cyclic thermal or impact loading due to the wear and formation of cracks, which reduces their lifespan. Here we present the proof-of-concept of a computational toolset that connects the change in thermal profile to structural failure and degradation. In combination with an appropriate finite element (FEM) solver, we have developed a genetic algorithm that can reconstruct the size and shape of the defective region in silica aerogels given the temperatures from a sensor grid. Results show that a heatmap can be used as the foundation for reconstructing faults and defects in thermally insulating materials. Furthermore, the model developed in this study can be expanded to accommodate other material types. Experimental setup can used to benchmark and refine the computational toolset.

Liquid phase analysis dominates the field of blood diagnostics and requires drawing blood volumes of several ml for each test. To achieve acceptable accuracy, each single liquid blood test requires ∼7 mL per blood sample, and repeated blood tests are often needed. Frequent testing ca result in Hospital Acquired Anemia for infants, chronically ill, and critically ill patients. Blood testing methods that can be utilized with small amounts of blood are a critical need to save lives. Theranos claimed to have developed novel methods requiring only a few nL of blood. However, Theranos’ techniques led to errors that exceeded beyond the medically acceptable threshold of 10%. This work investigates solid state blood analysis using low volumes of several µL. The most common blood tests used as first line for diagnostics and monitoring patients’ status, always include blood electrolytes, iron, and in some cases, heavy metals.

The present work investigates the formation of rapidly solidified Homogeneous Thin Solid Films (HTSFs) formed from blood drops, in order to make them suitable for solid state analysis in vacuo and in air. The solidification of ∼5 micro-liter (µL)-sized blood droplets into HTSFs is studied with two goals: achieve reproducible HTSFs optimized for producing accurate analysis, and successfully measure the potential accuracy of measurements made on HTSFs for blood electrolytes Na, K, Mg, Ca, and Cl and heavy metals such as Fe.

The blood volumes selected for this work are in the µL range, one thousandth volumes drawn for current liquid phase analysis. Balanced Saline Solution (BSS) is used as an initial liquid for testing solidification uniformity and a potential calibration material. Next, canine and human blood are studied on two types of HemaDropTM coatings for solidification: super-hydrophilic and hyper-hydrophilic. HTSF formation from BSS and blood drops are compared on both coated and uncoated surfaces.

Three solid state analytical methods are investigated in parallel to probe composition at different depths and test each for reproducibility and accuracy: Ion Beam Analysis (IBA), X-ray Fluorescence (XRF), and X-ray Photoelectron Spectroscopy (XPS). The results show that using solid films of blood yields composition, which can be reproducibly measured by IBA, XPS and XRF to varying degrees. XPS’s depth of analysis, limited to ∼5 nm, probes a small fraction of the HTSF, but provides insights into the range of thickness for homogeneous compositions in HTSFs. Statistical and error analysis help establish whether measurements taken in sets of three typically used in lab fall below the medically accepted error threshold (<10%) for each technique and element detected. Measurements are repeated and taken at various locations and on different HTSFs to establish reproducibility. XRF is of particular interest, because it is fast, accurate, portable and can be conducted in air, making it ideal for areas with limited resources.

Defined chemical reactions in a physiological environment are a prerequisite for the in situ synthesis of implant materials potentially serving as matrix for drug delivery systems, tissue fillers or surgical glues. ‘Click’ reactions like thiol Michael-type reactions have been successfully employed as bioorthogonal reaction. However, due to the individual stereo-electronic and physical properties of specific substrates, an exact understanding their chemical reactivity is required if they are to be used for in-situ biomaterial synthesis. The chiral (S)-2-mercapto-carboxylic acid analogues of L-phenylalanine (SH-Phe) and L-leucine (SH-Leu) which are subunits of certain collagenase sensitive synthetic peptides, were explored for their potential for in-situ biomaterial formation via the thiol Michael-type reaction.

In model reactions were investigated the kinetics, the specificity and influence of stereochemistry of this reaction. We could show that only reactions involving SH-Leu yielded the expected thiol-Michael product. The inability of SH-Phe to react was attributed to the steric hindrance of the bulky phenyl group. In aqueous media, successful reaction using SH-Leu is thought to proceed via the sodium salt formed in-situ by the addition of NaOH solution, which was intented to aid the solubility of the mercapto-acid in water. Fast reaction rates and complete acrylate/maleimide conversion were only realized at pH 7.2 or higher suggesting the possible use of SH-Leu under physiological conditions for thiol Michael-type reactions. This method of in-situ formed alkali salts could be used as a fast approach to screen mercapto-acids for thio Michael-type reactions without the synthesis of their corresponding esters.

We present a new class of bioinspired nanomaterials that are stabilized by a combination of covalent and hydrogen bonds. Prior work by others has shown that cyclic peptides can self-assemble to form supramolecular assemblies through backbone-backbone hydrogen bonding. To improve upon this molecular architecture, we develop a synthesis route to polymerize cyclic peptides and form a linear polymer chain that can transition between a rigid nanorod and an unfolded conformation. For a cyclic peptide polymer containing amine-terminated side chains on each ring, we demonstrate self-assembly can be triggered in aqueous solutions by varying the pH. We measure the elastic modulus of the rigid nanorods to be ca. 50 GPa, which is comparable to our molecular dynamics (MD) prediction (ca. 64 GPa). Our results highlight the uniqueness of our molecular architecture, namely their exemplary toughness (up to 3 GJ m-3), in comparison to other cyclic peptide-based assemblies. Finally, we demonstrate amphiphilic cyclic β-peptides are capable of inhibiting the growth of gram-negative and gram-positive bacteria.

A novel Fluorescence Resonance Energy Transfer (FRET) based ‘Turn-ON’ biosensor has been developed using fluorescent ZnO/APTMS-FITC (ZFA) nanoflakes as sensing probe. In this biosensor, Lactate Dehydrogenase (LDH) is used for the detection of L-lactate, a diagnostic marker for abnormal physiological conditions like muscular dystrophy, myocardial infraction, abnormal tissue formation and tissue damage. Lactate Dehydrogeanse (LDH) catalyses the conversion of L-Lactate to L-Pyruvate, in presence of β-NAD reducing to β-NADH. We tried to explore this mechanism with FRET based system for highly sensitive detection of L-Lactate. The fluorescence of these nanoflakes can be reversibly quenched in the presence of β-NAD.

Sintered tape-cast yttria-stabilized zirconia (YSZ) was evaluated for its elemental composition, crystal structure, and imaged with atomic force microscopy (AFM) and scanning electron microscopy (SEM). Human bone marrow stem cells (hBMSC) were cultured on the ceramic and differentiated into the osteoblast lineage; alkaline phosphatase (ALP) activity was tracked as a differentiation marker. The YSZ was composed of purely tetragonal grains with a median equivalent circular diameter of 283 nm. Zirconium, yttrium, oxygen, and adventitious carbon was detected on the substrate with no other elements in significant quantities detected. YSZ samples had an RMS roughness value of 27 nm, elastic modulus of 206 ± 14 GPa, and hardness of 14 ± 2 GPa. hBMSC were observed to attach and proliferate on the YSZ surfaces and had significantly increased ALP versus the undifferentiated control cultured on glass. This method for producing a YSZ ceramic yields a typical material of this type and supports attachment and differentiation of hBMSC; thus, making it useful as a bone implant material.

There is growing evidence that minimizing the mechanical mismatch between neural implants and brain tissue mitigates inflammatory, biological responses at the interface under long-term implant conditions. The goal of this study is to develop a brain-like soft, conductive neural interface and use an improvised, penetrating microindentation technique reported by us earlier to quantitatively assess the (a) elastic modulus of the neural interface after implantation, (b) mechanical stresses during penetration of the probe, and (c) periodic stresses at steady-state due to tissue micromotion around the probe. We fabricated poly- dimethylsiloxane (PDMS) matrices with multi-walled carbon nanotubes (MWCNTs) using two distinct but carefully calibrated cross-linking ratios, resulting in hard (elastic modulus∼484 kPa) or soft, brain-like (elastic modulus∼5.7 kPa) matrices, the latter being at least 2 orders of magnitude softer than soft neural interfaces reported so far. Subsequent loading of the hard and soft silicone based matrices with (100% w/w) low-molecular weight PDMS siloxanes resulted in further decrease in the elastic modulus of both matrices. Carbon probes with soft PDMS coating show significantly less maximum axial forces (-587 ± 51.5 µN) imposed on the brain than hard PDMS coated probes (-1,253 ± 252 µN) during and after insertion. Steady-state, physiological micromotion related stresses were also significantly less for soft- PDMS coated probes (55.5 ± 17.4 Pa) compared to hard-PDMS coated probes (141.0 ± 21.7 Pa). The penetrating microindentation technique is valuable to quantitatively assess the mechanical properties of neural interfaces in both acute and chronic conditions.