Machine learning-assisted label-free colorectal cancer diagnosis using plasmonic needle-endoscopy system.

Early and accurate detection of colorectal cancer (CRC) is critical for improving patient outcomes. Existing diagnostic techniques are often invasive and carry risks of complications. Herein, we introduce a plasmonic gold nanopolyhedron (AuNH)-coated needle-based surface-enhanced Raman scattering (SERS) sensor, integrated with endoscopy, for direct mucus sampling and label-free detection of CRC. The thin and flexible stainless-steel needle is coated with polymerized dopamine, which serves as an adhesive layer and simultaneously initiates the nucleation of gold nanoparticle (AuNP) seeds on the needle surface. The AuNP seeds are further grown through a surface-directed reduction using Au ions-hydroxylamine hydrochloride solution, resulting in the formation of dense AuNHs. The formation mechanism of AuNHs and the layered structure of the plasmonic needle-based SERS (PNS) sensor are thoroughly analyzed. Furthermore, a strong field enhancement of the PNS sensor is observed, amplified around the edges of the polyhedral shapes and at nanogap sites between AuNHs. The feasibility of the PNS sensor combined with endoscopy system is further investigated using mouse models for direct colonic mucus sampling and verifying noninvasive label-free classification of CRC from normal controls. A logistic regression-based machine learning method is employed and successfully differentiates CRC and normal mice, achieving 100% sensitivity, 93.33% specificity, and 96.67% accuracy. Moreover, Raman profiling of metabolites and their correlations with Raman signals of mucus samples are analyzed using the Pearson correlation coefficient, offering insights for identifying potential cancer biomarkers. The developed PNS-assisted endoscopy technology is expected to advance the early screening and diagnosis approach of CRC in the future.

Ionic Liquid-Based Extraction of Fulvic-like Substances from Wood Sawdust: Reproducing Unique Biological Activities of Fulvic Acids Using Renewable Natural Sources.

Fulvic acids (FAs) have been commercially used in cosmetics and agronomy due to their unique biological activities, such as plant stimulation and anti-inflammatory effects. However, the extraction sources of FAs, such as peat, are currently limited. Consequently, new extraction methods using renewable resources need to be developed, while reproducing the biological functions. Here, ionic liquids (ILs) effectively extracted fulvic-like substances (FLSs) from wood sawdust. The overall molecular weight distributions of FLSs were similar to those of commercial FAs, and key organic groups (e.g., aromatic, phenolic, and methoxy groups) were also found to be shared between commercial FAs and FLSs. Detailed compositional analysis revealed by high-resolution mass spectrometry showed that the extracts contain both lignin-like and lipid-like molecules, while commercial FAs are biased toward lignin-like and carbohydrate-like molecules. FLSs generally showed better and similar performance in radical scavenging activity against ABTS+· and H2O2. Fibroblast proliferation and lettuce growth enhancements were also observed with the extract containing 1-ethyl-3-methylimidazolium acetate and triethylammonium hydrogen sulfate, respectively, which performed better than commercial FAs. Immunofluorescence staining of in vitro human follicle dermal papilla cells supports that coexpression of hair growth-related proteins can be accelerated with FLSs, and this effect was further evidenced by in vivo mouse model experiments. Finally, the reusability of ILs in the extraction process was confirmed by analyzing the structural features of FLSs from each recycling. Our findings indicate that ILs are useful for obtaining biologically functional fulvic analogs from renewable plant sources.

Cold-Responsive Hyaluronated Upconversion Nanoplatform for Transdermal Cryo-Photodynamic Cancer Therapy.

Cryotherapy leverages controlled freezing temperature interventions to engender a cascade of tumor-suppressing effects. However, its bottleneck lies in the standalone ineffectiveness. A promising strategy is using nanoparticle therapeutics to augment the efficacy of cryotherapy. Here, a cold-responsive nanoplatform composed of upconversion nanoparticles coated with silica - chlorin e6 - hyaluronic acid (UCNPs@SiO2-Ce6-HA) is designed. This nanoplatform is employed to integrate cryotherapy with photodynamic therapy (PDT) in order to improve skin cancer treatment efficacy in a synergistic manner. The cryotherapy appeared to enhance the upconversion brightness by suppressing the thermal quenching. The low-temperature treatment afforded a 2.45-fold enhancement in the luminescence of UCNPs and a 3.15-fold increase in the photodynamic efficacy of UCNPs@SiO2-Ce6-HA nanoplatforms. Ex vivo tests with porcine skins and the subsequent validation in mouse tumor tissues revealed the effective HA-mediated transdermal delivery of designed nanoplatforms to deep tumor tissues. After transdermal delivery, in vivo photodynamic therapy using the UCNPs@SiO2-Ce6-HA nanoplatforms resulted in the optimized efficacy of 79% in combination with cryotherapy. These findings underscore the Cryo-PDT as a truly promising integrated treatment paradigm and warrant further exploring the synergistic interplay between cryotherapy and PDT with bright upconversion to unlock their full potential in cancer therapy.

Biomedical Applications of CNT-Based Fibers.

Carbon nanotubes (CNTs) have been regarded as emerging materials in various applications. However, the range of biomedical applications is limited due to the aggregation and potential toxicity of powder-type CNTs. To overcome these issues, techniques to assemble them into various macroscopic structures, such as one-dimensional fibers, two-dimensional films, and three-dimensional aerogels, have been developed. Among them, carbon nanotube fiber (CNTF) is a one-dimensional aggregate of CNTs, which can be used to solve the potential toxicity problem of individual CNTs. Furthermore, since it has unique properties due to the one-dimensional nature of CNTs, CNTF has beneficial potential for biomedical applications. This review summarizes the biomedical applications using CNTF, such as the detection of biomolecules or signals for biosensors, strain sensors for wearable healthcare devices, and tissue engineering for regenerating human tissues. In addition, by considering the challenges and perspectives of CNTF for biomedical applications, the feasibility of CNTF in biomedical applications is discussed.

Nano/Micro Biosensors for Biomedical Applications.

Advances in nano/micro technologies in recent years have significantly improved biosensors in terms of their viability for biomedical purposes, from diagnostic to therapeutic applications, allowing for effective early detection and personalized treatment modalities [...].

Terbium-doped carbon dots (Tb-CDs) as a novel contrast agent for efficient X-ray attenuation.

Metal-doped carbon dots have attracted considerable attention in nanomedicine over the last decade owing to their high biocompatibility and great potential for bioimaging, photothermal therapy, and photodynamic therapy. In this study, we prepared, and for the first time, examined terbium-doped CDs (Tb-CDs) as a novel contrast agent for computed tomography. A detailed physicochemical analysis revealed that the prepared Tb-CDs have small sizes (∼2-3 nm), contain relatively high terbium concentration (∼13.3 wt%), and exhibit excellent aqueous colloidal stability. Furthermore, preliminary cell viability and CT measurements suggested that Tb-CDs exhibit negligible cytotoxicity toward L-929 cells and demonstrate high X-ray absorption performance (∼48.2 ± 3.9 HU L g-1). Based on these findings, the prepared Tb-CDs could serve as a promising contrast agent for efficient X-ray attenuation.

Recent Trends in Macromolecule-Based Approaches for Hair Loss Treatment.

Macromolecules are large, complex molecules composed of smaller subunits known as monomers. The four primary categories of macromolecules found in living organisms are carbohydrates, lipids, proteins, and nucleic acids; they also encompass a broad range of natural and synthetic polymers. Recent studies have shown that biologically active macromolecules can help regenerate hair, providing a potential solution for current hair regeneration therapies. This review examines the latest developments in the use of macromolecules for the treatment of hair loss. The fundamental principles of hair follicle (HF) morphogenesis, hair shaft (HS) development, hair cycle regulation, and alopecia have been introduced. Microneedle (MN) and nanoparticle (NP) delivery systems are innovative treatments for hair loss. Additionally, the application of macromolecule-based tissue-engineered scaffolds for the in vitro and in vivo neogenesis of HFs is discussed. Furthermore, a new research direction is explored wherein artificial skin platforms are adopted as a promising screening method for hair loss treatment drugs. Through these multifaceted approaches, promising aspects of macromolecules for future hair loss treatments are identified.

Molecularly imprinted polymers (MIPs): emerging biomaterials for cancer theragnostic applications.

Cancer is a disease caused by abnormal cell growth that spreads through other parts of the body and threatens life by destroying healthy tissues. Therefore, numerous techniques have been employed not only to diagnose and monitor the progress of cancer in a precise manner but also to develop appropriate therapeutic agents with enhanced efficacy and safety profiles. In this regard, molecularly imprinted polymers (MIPs), synthetic receptors that recognize targeted molecules with high affinity and selectivity, have been intensively investigated as one of the most attractive biomaterials for theragnostic approaches. This review describes diverse synthesis strategies to provide the rationale behind these synthetic antibodies and provides a selective overview of the recent progress in the in vitro and in vivo targeting of cancer biomarkers for diagnosis and therapeutic applications. Taken together, the topics discussed in this review provide concise guidelines for the development of novel MIP-based systems to diagnose cancer more precisely and promote successful treatment. Molecularly imprinted polymers (MIPs), synthetic receptors that recognize targeted molecules with high affinity and selectivity, have been intensively investigated as one of the most attractive biomaterials for cancer theragnostic approaches. This review describes diverse synthesis strategies to provide the rationale behind these synthetic antibodies and provides a selective overview of the recent progress in the in vitro and in vivo targeting of cancer biomarkers for diagnosis and therapeutic applications. The topics discussed in this review aim to provide concise guidelines for the development of novel MIP-based systems to diagnose cancer more precisely and promote successful treatment.

Plasmon Modulated Upconversion Biosensors.

Over the past two decades, lanthanide-based upconversion nanoparticles (UCNPs) have been fascinating scientists due to their ability to offer unprecedented prospects to upconvert tissue-penetrating near-infrared light into color-tailorable optical illumination inside biological matter. In particular, luminescent behavior UCNPs have been widely utilized for background-free biorecognition and biosensing. Currently, a paramount challenge exists on how to maximize NIR light harvesting and upconversion efficiencies for achieving faster response and better sensitivity without damaging the biological tissue upon laser assisted photoactivation. In this review, we offer the reader an overview of the recent updates about exciting achievements and challenges in the development of plasmon-modulated upconversion nanoformulations for biosensing application.

Marine plankton exoskeletone-derived hydroxyapatite/polycaprolactone composite 3D scaffold for bone tissue engineering.

3D porous scaffolds based on biodegradable polymers are one of the materials for bone tissue regeneration. In this study, a porous scaffold was prepared using a solvent casting/particulate leaching method that used polycaprolactone (PCL) and hydroxyapatite (OceanBone-HAp) extracted from a marine plankton exoskeleton to achieve excellent bone regeneration. In this study, the morphology and physicochemical properties of the PCL/OceanBone-HAp scaffolds were evaluated using scanning electron microscopy, X-ray diffraction, and porosity analysis. The results confirmed the porous structure of the scaffold and removal of the solvent and porogen particles. In vitro test results revealed superior cell adhesion, proliferation, and viability of PCL/OceanBone-HAp scaffolds compared to PCL scaffolds alone. The enhanced alkaline phosphatase activity and expression of bone morphogenetic protein 2, collagen type I α 1, osteocalcin, and bone sialoprotein in the PCL/OceanBone-HAp scaffolds were confirmed through ALP and real-time polymerase chain reaction assays. Moreover, in vivo experiments using a rabbit calvarial defect model showed that the PCL/OceanBone-HAp scaffold exhibited enhanced bone regeneration compared to the PCL scaffold. Therefore, the PCL/OceanBone-HAp scaffold is a promising scaffold for bone repair.

Enhanced Biocompatibility and Osteogenic Activity of Marine-Plankton-Derived Whitlockite Bone Granules through Bone Morphogenetic Protein 2 Incorporation.

Whitlockite (WH) is a calcium-phosphate-based Mg-containing ceramic with good mechanical properties, rapid resorption, and good osteogenicity. Recently, we successfully synthesized highly porous WH granules using a marine plankton exoskeleton (MP-WH). In the present study, we improved the osteoinductive activity of MP-WH granules by bone morphogenetic protein2 (BMP2) (MP-WH/BMP2). The surface morphology and composition of the fabricated MP-WH/BMP2 granules were characterized using scanning electron microscopy (SEM), X-ray diffraction, and Fourier transform infrared (FT-IR) spectroscopy. The biocompatibility and osteogenic effects were evaluated using human mesenchymal stem cells (hMSCs). BMP2 was absorbed on the surfaces of the MP-WH/BMP2 granules. Immobilized BMP2 was released at a moderate rate over 30 days. hMSCs seeded on MP-WH/BMP2 granules became biocompatible, with a better proliferation and adhesion for MP-WH/BMP2, compared with MP-WH. Bone-specific markers Runx2, type I collagen, osteocalcin, and osteopontin were significantly upregulated following BMP2 incorporation. Similar observations were made regarding the alkaline phosphatase activity. This study suggests that BMP2 incorporation improves the osteoinductive activity of marine-plankton-derived WH granules for bone tissue repair.

3D Printing of Skin Equivalents with Hair Follicle Structures and Epidermal-Papillary-Dermal Layers Using Gelatin/Hyaluronic Acid Hydrogels.

Recent advances in three-dimensional (3D) bioprinting technologies have enabled the fabrication of sophisticated live 3D tissue analogs. Despite the existing hydrogel-based bioinks, the development of advanced bioink materials that can accurately reproduce the composition of a native extracellular matrix and mimic the intrinsic properties of laden cells remains challenging. In this study, 3D printed skin equivalents incorporating hair follicle structures and epidermal/papillary dermal layers were fabricated using gelatin methacryloyl/hyaluronic acid methacryloyl (GelMA/HAMA) bioink. The composition of collagen and glycosaminoglycan in native skin was recapitulated by adjusting the combination of GelMA and HAMA. The GelMA/HAMA bioink exhibited excellent viscoelastic and physicochemical properties, 3D printability, cytocompatibility, and functionality to maintain hair-inductive potency while facilitating spontaneous hair pore development. The results indicate that GelMA/HAMA hydrogels are promising candidates as bioinks for the 3D printing of skin equivalents. Furthermore, they may serve as useful models for skin tissue engineering and regeneration.

Upconversion nanomaterials and delivery systems for smart photonic medicines and healthcare devices.

In the past decade, upconversion (UC) nanomaterials have been extensively investigated for the applications to photomedicines with their unique features including biocompatibility, near-infrared (NIR) to visible conversion, photostability, controllable emission bands, and facile multi-functionality. These characteristics of UC nanomaterials enable versatile light delivery for deep tissue biophotonic applications. Among various stimuli-responsive delivery systems, the light-responsive delivery process has been greatly advantageous to develop spatiotemporally controllable on-demand "smart" photonic medicines. UC nanomaterials are classified largely to two groups depending on the photon UC pathway and compositions: inorganic lanthanide-doped UC nanoparticles and organic triplet-triplet annihilation UC (TTA-UC) nanomaterials. Here, we review the current-state-of-art inorganic and organic UC nanomaterials for photo-medicinal applications including photothermal therapy (PTT), photodynamic therapy (PDT), photo-triggered chemo and gene therapy, multimodal immunotherapy, NIR mediated neuromodulations, and photochemical tissue bonding (PTB). We also discuss the future research direction of this field and the challenges for further clinical development.

Marine Plankton-Derived Whitlockite Powder-Based 3D-Printed Porous Scaffold for Bone Tissue Engineering.

Powder-based 3D printing is an excellent technique for the fabrication of complex structural shapes. The outstanding bone remodeling capacity of calcium phosphate bioceramics is a desirable characteristic for such fabrication. Whitlockite (WH) is a calcium phosphate-based ceramic that contains Mg ions and possesses good mechanical properties, rapid resorbability, and promotes osteogenesis. The aim of this study was to fabricate 3D-printed scaffolds using marine plankton-derived WH (MP-WH) powder. The surface morphology and composition of the fabricated scaffolds were characterized by scanning electron microscopy and X-ray diffraction. The biocompatibility and osteogenic effects were evaluated using human mesenchymal stem cells. We successfully obtained a 3D porous scaffold using MP-WH. The MP-WH 3D scaffold showed improved compressive strength compared to the tricalcium phosphate (TCP) 3D scaffold. The in vitro results showed that compared with TCP 3D scaffolds, MP-WH 3D scaffolds were biocompatible and enhanced cell proliferation and adhesion. In addition, alkaline phosphatase activity and real-time polymerase chain reaction assays demonstrated that osteoblast differentiation was improved on the MP-WH scaffold. These results suggest that marine plankton-derived WH is useful for fabricating 3D-printed scaffolds for bone tissue engineering applications.

Combinatorial wound healing therapy using adhesive nanofibrous membrane equipped with wearable LED patches for photobiomodulation.

Wound healing is the dynamic tissue regeneration process replacing devitalized and missing tissue layers. With the development of photomedicine techniques in wound healing, safe and noninvasive photobiomodulation therapy is receiving attention. Effective wound management in photobiomodulation is challenged, however, by limited control of the geometrical mismatches on the injured skin surface. Here, adhesive hyaluronic acid-based gelatin nanofibrous membranes integrated with multiple light-emitting diode (LED) arrays are developed as a skin-attachable patch. The nanofibrous wound dressing is expected to mimic the three-dimensional structure of the extracellular matrix, and its adhesiveness allows tight coupling between the wound sites and the flexible LED patch. Experimental results demonstrate that our medical device accelerates the initial wound healing process by the synergetic effects of the wound dressing and LED irradiation. Our proposed technology promises progress for wound healing management and other biomedical applications.

Role of Graphene Family Nanomaterials in Skin Wound Healing and Regeneration.

Owing to astonishing properties such as the large surface area to volume ratio, mechanical stability, antimicrobial property, and collagen crosslinking, graphene family nanomaterials (GFNs) have been widely used in various biomedical applications including tissue regeneration. Many review literatures are available to compile the role of GFNs in cardiac, bone, and neuronal tissue regeneration. However, the contribution of GFNs in skin wound healing and tissue regeneration was not yet discussed. In the present review, we have highlighted the properties of GFNs and their application in skin wound healing. In addition, we have included challenges and future directions of GFNs in skin tissue regeneration in the portion of conclusion and perspectives.

Graphene-Based Nanomaterials as Drug Delivery Carriers.

Graphene and graphene-based materials have been attracted in the past few years for biomedical applications due to their physicochemical and biological properties such as large surface area, chemical and mechanical stability, excellent conductivity, and good biocompatibility. Graphene-based materials not only surface modified graphene-based materials like graphene oxide (GO) or reduced graphene oxide (rGO) but also other structural forms like fullerene, carbon nanotubes, and graphite have been applied to advanced drug delivery systems. In this chapter, we review on the application of graphene-based materials in the drug delivery system with their physicochemical properties, methods for the preparation of graphene-based carriers, followed by analysis about their biodistribution and biosafety whether they are suitable as drug delivery carriers.

Graphene-Based Nanomaterials for Biomedical Imaging.

Graphene is sp2-hybridized carbon structure-based two-dimensional (2D) sheet. Graphene-based nanomaterials possess several features such as unique mechanical, electronic, thermal, and optical properties, high specific surface area, versatile surface functionalization, and biocompatibility, which attracted researcher's interests in various fields including biomedicine. In this chapter, we particularly focused on the biomedical imaging applications of graphene-based nanomaterials like graphene oxide (GO), reduced graphene oxide (rGO), graphene quantum dots (GQDs), graphene oxide quantum dots (GOQDs), and other derivatives, which utilize their outstanding optical properties. There are some biomedical imaging modalities using Graphene-based Nanomaterials, among which we will highlight fluorescence imaging, Raman imaging, magnetic resonance imaging, and photoacoustic imaging. We also discussed the brief perspectives and future application related to them.

Rotating Cylinder-Assisted Nanoimprint Lithography for Enhanced Chemisorbable Filtration Complemented by Molecularly Imprinted Polymers.

Rotating cylindrical stamp-based nanoimprint technique has many advantages, including the continuous fabrication of intriguing micro/nanostructures and rapid pattern transfer on a large scale. Despite these advantages, the previous nanoimprint lithography has rarely been used for producing sophisticated nanoscale patterns on a non-planar substrate that has many extended applications. Here, the simple integration of nanoimprinting process with a help of a transparent stamp wrapped on the cylindrical roll and UV optical source in the core to enable high-throughput pattern transfer, particularly on a fabric substrate is demonstrated. Moreover, as a functional resin material, this innovative strategy involves a synergistic approach on the synthesis of molecularly imprinted polymer, which are spatially organized free-standing perforated nanostructures such as nano/microscale lines, posts, and holes patterns on various woven or nonwoven blank substrates. The proposed materials can serve as a self-encoded filtration medium for selective separation of formaldehyde molecules. It is envisioned that the combinatorial fabrication process and attractive material paves the way for designing next-generation separation systems in use to capture industrial or household toxic substances.

Recent advances in transdermal drug delivery systems: a review.

Various non-invasive administrations have recently emerged as an alternative to conventional needle injections. A transdermal drug delivery system (TDDS) represents the most attractive method among these because of its low rejection rate, excellent ease of administration, and superb convenience and persistence among patients. TDDS could be applicable in not only pharmaceuticals but also in the skin care industry, including cosmetics. Because this method mainly involves local administration, it can prevent local buildup in drug concentration and nonspecific delivery to tissues not targeted by the drug. However, the physicochemical properties of the skin translate to multiple obstacles and restrictions in transdermal delivery, with numerous investigations conducted to overcome these bottlenecks. In this review, we describe the different types of available TDDS methods, along with a critical discussion of the specific advantages and disadvantages, characterization methods, and potential of each method. Progress in research on these alternative methods has established the high efficiency inherent to TDDS, which is expected to find applications in a wide range of fields.