Ultrathin Parylene C-based sensitivity-gain nanoplasmonic sensor integrated on VCSEL for Aß42 detection.

As Alzheimer's disease prevalence continues to rise, there is an increasing demand for efficient on-chip biosensors capable of early biomarker detection. This study presents a novel biosensor chip leveraging vertical cavity surface emitting laser (VCSEL) technology, with Parylene C serving as the antibody coupling layer and utilizing a streamlined one-step antibody modification method. Integration of Parylene C enhances chip sensitivity from 34.28 µW/RIU to 40.32 µW/RIU. Moreover, post-testing removal of Parylene C enables chip reusability without significant alteration of results. The sensor demonstrates effective detection of Aß42, an Alzheimer's biomarker, exhibiting a linear range of 1-200 ng/mL and a detection limit of 0.26 ng/mL. These findings underscore the reusability and reliability of the ultrathin Parylene C-based VCSEL biosensor chip, highlighting its potential for point-of-care Alzheimer's disease diagnosis.

PEGylated Self-Assembled Nano-Bacitracin A: Probing the Antibacterial Mechanism and Real-Time Tracing of Target Delivery in Vivo.

Although nano-self-assemblies of hydrophobic-modified bacitracin A with poly(d,l-lactic- co-glycolic acid) (PLGA) (nano-BAPLGA) have demonstrated promising antibacterial activities, the application of nano-BAPLGA was severely compromised by low water solubility. In this study, a series of PEGylated PLGA copolymers were selected to conjugate with the N-terminus of bacitracin A to construct PEGylated self-assembled nano-BAs and to further develop nano-self-assemblies of bacitracin A with strong antibacterial potency and high solubility. Compared with nano-BAPLGA, all PEGylated nano-BAs, except nano-BA5k, exhibited strong antibacterial efficiency against both Gram-positive and Gram-negative bacteria by inducing loss of cytoplasmic membrane potential, membrane permeabilization, and leakage of calcein from artificial cell membranes. Studies elucidating the underlying mechanism of PEGylated nano-BAs against Gram-negative bacteria indicated that the strong hydrophobic and van der Waals interactions between PLGA and lipopolysaccharide (LPS) could bind, neutralize, and disassociate LPS, facilitating cellular uptake of the nanoparticles, which could destabilize the membrane, resulting in cell death. Moreover, PEGylated nano-BAs (nano-BA12k) with a longer PLGA block were expected to occupy a higher local density of BA mass on the surface and result in stronger hydrophobic and van der Waals interactions with LPS, which were responsible for the enhanced antibacterial activity against Gram-positive and emerging antibacterial activity against Gram-negative bacteria, respectively. In vivo imaging verified that PEGylated nano-BAs exhibited higher inflammatory tissue distribution and longer circulation time than nano-BAPLGA. Therefore, although PEGylation did not affect antibacterial activity, it is necessary for target delivery and resistance to clearance of the observed PEGylated nano-BAs. In vivo, nano-BA12k also showed the highest therapeutic index against infection burden in a mouse thigh infection model among the tested formulations, which showed good correlation with the in vitro results. In conclusion, nano-BA12k showed high efficacy in the treatment of invasive infections. This new approach of constructing nanoantibiotics by modification of commercially available antibiotics with PEGylated copolymers is safe, cost-effective, and environmentally friendly.

Enhanced osteointegration of poly(methylmethacrylate) bone cements by incorporating strontium-containing borate bioactive glass.

Although poly(methylmethacrylate) (PMMA) cements are widely used in orthopaedics, they have numerous drawbacks. This study aimed to improve their bioactivity and osseointegration by incorporating strontium-containing borate bioactive glass (SrBG) as the reinforcement phase and bioactive filler of PMMA cement. The prepared SrBG/PMMA composite cements showed significantly decreased polymerization temperature when compared with PMMA and retained properties of appropriate setting time and high mechanical strength. The bioactivity of SrBG/PMMA composite cements was confirmed in vitro, evidenced by ion release (Ca, P, B and Sr) from SrBG particles. The cellular responses of MC3T3-E1 cells in vitro demonstrated that SrBG incorporation could promote adhesion, migration, proliferation and collagen secretion of cells. Furthermore, our in vivo investigation revealed that SrBG/PMMA composite cements presented better osseointegration than PMMA bone cement. SrBG in the composite cement could stimulate new-bone formation around the interface between the composite cement and host bone at eight and 12 weeks post-implantation, whereas PMMA bone cement only stimulated development of an intervening connective tissue layer. Consequently, the SrBG/PMMA composite cement may be a better alternative to PMMA cement in clinical applications and has promising orthopaedic applications by minimal invasive surgery.

Evaluation of an injectable bioactive borate glass cement to heal bone defects in a rabbit femoral condyle model.

There is a need for synthetic biomaterials to heal bone defects using minimal invasive surgery. In the present study, an injectable cement composed of bioactive borate glass particles and a chitosan bonding solution was developed and evaluated for its capacity to heal bone defects in a rabbit femoral condyle model. The injectability and setting time of the cement in vitro decreased but the compressive strength increased (8±2MPa to 31±2MPa) as the ratio of glass particles to chitosan solution increased (from 1.0gml-1 to 2.5gml-1). Upon immersing the cement in phosphate-buffered saline, the glass particles reacted and converted to hydroxyapatite, imparting bioactivity to the cement. Osteoblastic MC3T3-E1 cells showed enhanced proliferation and alkaline phosphatase activity when incubated in media containing the soluble ionic product of the cement. The bioactive glass cement showed a better capacity to stimulate bone formation in rabbit femoral condyle defects at 12weeks postimplantation when compared to a commercial calcium sulfate cement. The injectable bioactive borate glass cement developed in this study could provide a promising biomaterial to heal bone defects by minimal invasive surgery.

Systemic tumor-targeted gene delivery by anti-transferrin receptor scFv-immunoliposomes.

An ideal therapeutic for cancer would be one that selectively targets to tumor cells, is nontoxic to normal cells, and that could be systemically delivered, thereby reaching metastases as well as primary tumor. Immunoliposomes directed by monoclonal antibody or its fragments are promising vehicles for tumor-targeted drug delivery. However, there is currently very limited data on gene delivery using these vehicles. We have recently described a cationic immunoliposome system directed by a lipid-tagged, single-chain antibody Fv fragment (scFv) against the human transferrin receptor (TfR) that shows promising efficacy for systemic p53 tumor suppressor gene therapy in a human breast cancer metastasis model. However, the extremely low yield of this lipid-tagged scFv limited further downstream development and studies. Here we report a different expression strategy for the anti-TfR scFv, which produces high levels of protein without any tags, and a different approach for complexing the targeting scFv to the liposomes. This approach entails covalently conjugating the scFv to the liposome via a cysteine at the 3'-end of the protein and a maleimide group on the liposome. Our results show that this conjugation does not impair the immunological activity or targeting ability of the scFv. The scFv-cys targets the cationic liposome-DNA complex (lipoplex) to tumor cells and enhances the transfection efficiencies both in vitro and in vivo in a variety of human tumor models. This scFv-immunoliposome can deliver the complexed gene systemically to tumors in vivo, where it is efficiently expressed. In comparison with the whole antibody or transferrin molecule itself, the scFv has a much smaller size for better penetration into solid tumors. It is also a recombinant protein rather than a blood product; thus, large scale production and strict quality control are feasible. This new approach provides a promising system for tumor-targeted gene delivery that may have potential for systemic gene therapy of various human cancers.

Preparation of chitosan/silk fibroin blending membrane fixed with alginate dialdehyde for wound dressing.

The objective of this work was to prepare chitosan/silk fibroin (CS/SF) blending membranes crosslinked with alginate dialdehyde (ADA) as wound dressings and to evaluate the physical properties and biocompatibility of the membranes. The morphology of membrane was observed by scanning electron microscopy (SEM) which showed that the well consistency of these two compositions. Further, the stability, water absorption and water vapor permeability of the ADA fixed CS/SF membranes could meet the needs of wound dressing. Furthermore, the biocompatibility of ADA fixed membranes was investigated by MTT assays and SEM in vitro, and the membranes were found to promote the cell attachment and proliferation. These results suggest that ADA fixed CS/SF blending membranes with a suitable ratio could be a promising candidate for wound healing applications.

In vitro cytocompatibility evaluation of alginate dialdehyde for biological tissue fixation.

Biological tissues must be chemically fixed before they can be implanted in humans, due to the immediate degradation and presence of antigenicity of naturally derived tissues. To provide a crosslinking reagent which is cytocompatible and may prepare biocompatible fixed tissues, a novel crosslinking agent, alginate dialdehyde (ADA), was employed to fix biological tissues by our group. The study was to evaluate the cytocompatibility of ADA for biological tissue fixation. Glutaraldehyde and genipin counterparts were used as controls. The result suggested that the cytotoxicity of ADA was significantly lower than that of glutaraldehyde and genipin. Additionally, in the evaluation of cytotoxicity of fixed tissue itself and the residues, as well as the cell adhesion property, ADA-fixed tissue was significantly superior to its glutaraldehyde counterpart and comparable to its genipin counterpart. The results obtained in this study demonstrate that ADA is a cytocompatible crosslinking reagent for biological tissue fixation.

In vitro enzymatic degradation of a biological tissue fixed by alginate dialdehyde.

Biological tissues must be chemically fixed before they can be implanted in humans as tissue engineering scaffolds. To provide an ideal tissue engineering scaffold material, which is biodegradable and cytocompatible, a novel crosslinking agent, alginate dialdehyde (ADA), was employed to fix biological tissues by our group. The study mainly investigated the enzymatic degradation of ADA fixed biological tissues in vitro. Glutaraldehyde, the most commonly used crosslinking agent for biological tissue fixation, was employed as a control. The results suggested that, the ADA fixation could enhance the resistance against enzymatic degradation of biological tissues effectively. Meanwhile, compared to glutaraldehyde-fixed tissues, the ADA-fixed tissues could also degrade gradually over time. Moreover, the ADA crosslinking reagent itself had a stimulatory effect on cell proliferation when at an appropriate concentration. The results obtained in this study demonstrate that ADA fixation might provide a successful example of the biodegradable scaffold materials in tissue engineering.