Publications by authors named "Hae-Won Kim"

506 Publications

CRISPR-Cas12a-regulated DNA adsorption and metallization on MXenes as enhanced enzyme mimics for sensitive colorimetric detection of hepatitis B virus DNA.

J Colloid Interface Sci 2022 Jan 10;613:406-414. Epub 2022 Jan 10.

Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou 510630, China. Electronic address:

Hepatitis B virus (HBV) infection is closely associated with the high risk of evolving into human hepatitis diseases including chronic hepatitis, liver fibrosis and cirrhosis, as well as hepatoma. Although various methods have been developed for HBV DNA detection, most of them either rely on expensive instruments or laborious procedures involving professional personnel. In this study, we for the first time established the CRISPR-Cas12a based colorimetric biosensor for target HBV detection by utilizing probe DNA regulation of the catalytic behaviors of Mxene-probe DNA-Ag/Pt nanohybrids. In the presence of HBV target, the Cas12a trans-cleavage activity could be efficiently activated to degrade the DNA probes, which led to the inhibition of DNA metallization and enzyme activity enhancer DNA adsorbed on Mxene, resulting in significantly reduced catalytic activity. The Mxene-probe DNA-Ag/Pt nanohybrids exhibited excellent sensitivity and specificity with subpicomolar detection limits, as well as good accuracy and stability for the determination of target HBV DNA in human serum samples. Moreover, this colorimetric sensing strategy could be integrated with the smartphone platform to allow the visible sensitive detection of target DNA. Taken together, the proposed colorimetric method provides a novel approach for HBV DNA diagnosis, especially suitable for the high endemic, developing countries with limited instrumental and medical supports.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2022.01.038DOI Listing
January 2022

TLR4 downregulation by the RNA-binding protein PUM1 alleviates cellular aging and osteoarthritis.

Cell Death Differ 2022 Jan 16. Epub 2022 Jan 16.

Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, 03722, South Korea.

Dysfunction of mRNA or RNA-binding proteins (RBPs) causes cellular aging and age-related degenerative diseases; however, information regarding the mechanism through which RBP-mediated posttranscriptional regulation affects cellular aging and related disease processes is limited. In this study, PUM1 was found to be associated with the self-renewal capacity and aging process of human mesenchymal stem cells (MSC). PUM1 interacted with the 3'-untranslated region of Toll-like receptor 4 (TLR4) to suppress TLR4 mRNA translation and regulate the activity of nuclear factor-κB (NF-κB), a master regulator of the aging process in MSCs. PUM1 overexpression protected MSCs against HO-induced cellular senescence by suppressing TLR4-mediated NF-κB activity. TLR4-mediated NF-κB activation is a key regulator in osteoarthritis (OA) pathogenesis. PUM1 overexpression enhanced the chondrogenic potential of MSCs even under the influence of inflammation-inducing factors, such as lipopolysaccharide (LPS) or interleukin-1β (IL-1β), whereas the chondrogenic potential was reduced following the PUM1 knockdown-mediated TLR4 activation. PUM1 levels decreased under inflammatory conditions in vitro and during OA progression in human and mouse disease models. PUM1 knockdown in human chondrocytes promoted chondrogenic phenotype loss, whereas PUM1 overexpression protected the cells from inflammation-mediated disruption of the chondrogenic phenotype. Gene therapy using a lentiviral vector encoding mouse PUM1 showed promise in preserving articular cartilage integrity in OA mouse models. In conclusion, PUM1 is a novel suppressor of MSC aging, and the PUM1-TLR4 regulatory axis represents a potential therapeutic target for OA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41418-021-00925-6DOI Listing
January 2022

Leveraging cellular mechano-responsiveness for cancer therapy.

Trends Mol Med 2021 Dec 29. Epub 2021 Dec 29.

Institute of Tissue Regeneration Engineering, Dankook University, Cheonan, Republic of Korea; Department of Nanobiomedical Science, Dankook University, Cheonan, Republic of Korea; Mechanobiology Dental Medicine Research Center, Dankook University, Cheonan, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Center, Dankook University, Cheonan, Republic of Korea. Electronic address:

Cells sense the biophysical properties of the tumor microenvironment (TME) and adopt these signals in their development, progression, and metastatic dissemination. Recent work highlights the mechano-responsiveness of cells in tumors and the underlying mechanisms. Furthermore, approaches to mechano-modulating diverse types of cell have emerged aiming to inhibit tumor growth and metastasis. These include targeting mechanosensitive machineries in cancer cells to induce apoptosis, intervening matrix stiffening incurred by cancer-associated fibroblasts (CAFs) in both primary and metastatic tumor sites, and modulating matrix mechanics to improve immune cell therapeutic efficacy. This review is envisaged to help scientists and clinicians in cancer research to advance understanding of the cellular mechano-responsiveness in TME, and to harness these concepts for cancer mechanotherapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molmed.2021.11.006DOI Listing
December 2021

Investigating the mechanophysical and biological characteristics of therapeutic dental cement incorporating copper doped bioglass nanoparticles.

Dent Mater 2021 Dec 18. Epub 2021 Dec 18.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan, Chungcheongnam-do 31116, Republic of Korea; Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, 119 Dandae-ro, Cheonan, Chungcheongnam-do 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan, Chungcheongnam-do 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, 119 Dandae-ro, Cheonan, Chungcheongnam-do 31116, Republic of Korea. Electronic address:

Objective: This study was investigated the mechanophysical properties of zinc phosphate cement (ZPC) with or without the copper doped bioglass nanoparticles (Cu-BGn) and their biological effect on dental pulp human cells and bacteria.

Materials And Methods: Cu-BGn were synthesized and characterized firstly and then, the experimental (Cu-ZPC) and control (ZPC) samples were fabricated with similar sizes and/or dimensions (diameter: 4 mm and height: 6 mm) based on the International Organization of Standards (ISO). Specifically, various concentrations of Cu-BGn were tested, and Cu-BGn concentration was optimized at 2.5 wt% based on the film thickness and overall setting time. Next, we evaluated the mechanophysical properties such as compressive strength, elastic modulus, hardness, and surface roughness. Furthermore, the biological behaviors including cell viability and odontoblastic differentiation by using dental pulp human cells as well as antibacterial properties were investigated on the Cu-ZPC. All data were analyzed statistically using SPSS® Statistics 20 (IBM®, USA). p < 0.05 (*) was considered significant, and 'NS' represents nonsignificant.

Results: Cu-BGn was obtained via a sol-gel method and added onto the ZPC for fabricating a Cu-ZPC composite and for comparison, the Cu-free-ZPC was used as a control. The film thickness (≤ 25 µm) and overall setting time (2.5-8 min) were investigated and the mechanophysical properties showed no significance ('NS') between Cu-ZPC and bare ZPC. However, cell viability and odontoblastic differentiation, alkaline phosphate (ALP) activity and alizarin red S (ARS) staining were highly stimulated in the extracts from the Cu-ZPC group compared to the ZPC group. Additionally, the antibacterial test showed that the Cu-ZPC extracts were more effective than the ZPC extracts (p < 0.05).

Significance: Cu-ZPC showed adequate mechanophysical properties (compressive strength, hardness, and surface roughness) and enhanced odontoblastic differentiation as well as antibacterial properties compared to the ZPC-only group. Based on the findings, the fabricated Cu-ZPC might have the potential for use in the field of dental medicine and clinical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dental.2021.12.019DOI Listing
December 2021

Freeform 3D printing of vascularized tissues: Challenges and strategies.

J Tissue Eng 2021 Jan-Dec;12:20417314211057236. Epub 2021 Nov 29.

Department of Biomedical and Chemical Engineering (BMCE), The Catholic University of Korea, Bucheon, Republic of Korea.

In recent years, freeform three-dimensional (3D) printing has led to significant advances in the fabrication of artificial tissues with vascularized structures. This technique utilizes a supporting matrix that holds the extruded printing ink and ensures shape maintenance of the printed 3D constructs within the prescribed spatial precision. Since the printing nozzle can be translated omnidirectionally within the supporting matrix, freeform 3D printing is potentially applicable for the fabrication of complex 3D objects, incorporating curved, and irregular shaped vascular networks. To optimize freeform 3D printing quality and performance, the rheological properties of the printing ink and supporting matrix, and the material matching between them are of paramount importance. In this review, we shall compare conventional 3D printing and freeform 3D printing technologies for the fabrication of vascular constructs, and critically discuss their working principles and their advantages and disadvantages. We also provide the detailed material information of emerging printing inks and supporting matrices in recent freeform 3D printing studies. The accompanying challenges are further discussed, aiming to guide freeform 3D printing by the effective design and selection of the most appropriate materials/processes for the development of full-scale functional vascularized artificial tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/20417314211057236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8638074PMC
November 2021

A Study on Myogenesis by Regulation of Reactive Oxygen Species and Cytotoxic Activity by Selenium Nanoparticles.

Antioxidants (Basel) 2021 Oct 29;10(11). Epub 2021 Oct 29.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Chungcheongnam-do, Korea.

Reactive oxygen species (ROS) are continuously produced by skeletal muscle during contractile activity and even at rest. However, the ROS generated from excessive exercise or traumatic damage may produce more ROS than can be neutralized by an antioxidant capacity, which can be harmful to muscle function. In particular, selenium is a known antioxidant that regulates physiological functions such as cell differentiation and anti-inflammatory function. In this study, we developed nano-sized antioxidative biomaterials using selenium to investigate the protective and differentiation effects against C2C12 myoblasts in an HO-induced oxidative stress environment. The selenium nanoparticles (SeNPs) were produced with a size of 35.6 ± 4.3 nm and showed antioxidant effects according to the 3,3',5,5'-tetramethylbenzidine assay. Then, SeNPs were treated to C2C12 cells with or without HO. Our results showed that SeNPs reduced C2C12 apoptosis and intracellular ROS levels. Additionally, SeNPs effectively up-regulated in the presence of HO, , , , and myosin heavy chain, which are well known to increase during myoblast differentiation as assayed by qRT-PCR, immunocytochemistry-staining, western blotting. These results demonstrate that SeNPs can accelerate differentiation with its protective effects from the ROS environment and can be applied to the treatment of skeletal muscle in a cellular redox environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox10111727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615179PMC
October 2021

Robust response of pulmonary pleomorphic carcinoma to pembrolizumab and sequential radiotherapy: A case report.

Respirol Case Rep 2021 Dec 10;9(12):e0875. Epub 2021 Nov 10.

Division of Pulmonary Disease and Critical Care Medicine, Department of Internal Medicine, Dongsan Hospital Keimyung University School of Medicine Daegu South Korea.

Pulmonary pleomorphic carcinoma (PPC) is a rare type of non-small cell lung cancer (NSCLC) with a more aggressive clinical course and a worse outcome than other types of NSCLC. Pembrolizumab, a monoclonal antibody targeting programmed cell death-1 (PD-1), has been approved as the first-line treatment for advanced NSCLC with robust PD-L1 expression in at least 50% of tumour cells, without epidermal growth factor receptor gene (EGFR) mutations or anaplastic lymphoma kinase gene (ALK) rearrangement. Here, we report the case of an 81-year-old man with multiple comorbidities who was diagnosed with PPC and showed a robust response to pembrolizumab followed by radiation therapy without adverse effects. In the absence of randomized clinical trials for PPCs, our case report demonstrates the potential application of pembrolizumab and radiation therapy for the treatment of PPCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/rcr2.875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580814PMC
December 2021

Carbon nanomaterials as emerging nanotherapeutic platforms to tackle the rising tide of cancer - A review.

Bioorg Med Chem 2021 12 10;51:116493. Epub 2021 Nov 10.

Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Guangzhou University, Guangzhou 510006, China; Institute of Environmental Research at Greater Bay Area, Ministry of Education, Guangzhou University, Guangzhou 510006, China. Electronic address:

Cancer has become one of the main reasons for human death in recent years. Around 18 million new cancer cases and approximately 9.6 million deaths from cancer reported in 2018, and the annual number of cancer cases will have increased to 22 million in the next two decades. These alarming facts have rekindled researchers' attention to develop and apply different approaches for cancer therapy. Unfortunately, most of the applied methods for cancer therapy not only have adverse side effects like toxicity and damage of healthy cells but also have a short lifetime. To this end, introducing innovative and effective methods for cancer therapy is vital and necessary. Among different potential materials, carbon nanomaterials can cope with the rising threats of cancer. Due to unique physicochemical properties of different carbon nanomaterials including carbon, fullerene, carbon dots, graphite, single-walled carbon nanotube and multi-walled carbon nanotubes, they exhibit possibilities to address the drawbacks for cancer therapy. Carbon nanomaterials are prodigious materials due to their ability in drug delivery or remedial of small molecules. Functionalization of carbon nanomaterials can improve the cancer therapy process and decrement the side effects. These exceptional traits make carbon nanomaterials as versatile and prevalent materials for application in cancer therapy. This article spotlights the recent findings in cancer therapy using carbon nanomaterials (2015-till now). Different types of carbon nanomaterials and their utilization in cancer therapy were highlighted. The plausible mechanisms for the action of carbon nanomaterials in cancer therapy were elucidated and the advantages and disadvantages of each material were also illustrated. Finally, the current problems and future challenges for cancer therapy based on carbon nanomaterials were discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2021.116493DOI Listing
December 2021

Faster Region-Based Convolutional Neural Network in the Classification of Different Parkinsonism Patterns of the Striatum on Maximum Intensity Projection Images of [F]FP-CIT Positron Emission Tomography.

Diagnostics (Basel) 2021 Aug 28;11(9). Epub 2021 Aug 28.

Department of Radiology, Daegu Catholic University Medical Center, Daegu Catholic University School of Medicine, Daegu 42472, Korea.

The aim of this study was to compare the performance of a deep-learning convolutional neural network (Faster R-CNN) model to detect imaging findings suggestive of idiopathic Parkinson's disease (PD) based on [F]FP-CIT PET maximum intensity projection (MIP) images versus that of nuclear medicine (NM) physicians. The anteroposterior MIP images of the [F]FP-CIT PET scan of 527 patients were classified as having PD (139 images) or non-PD (388 images) patterns according to the final diagnosis. Non-PD patterns were classified as overall-normal (ONL, 365 images) and vascular parkinsonism with definite defects or prominently decreased dopamine transporter binding (dVP, 23 images) patterns. Faster R-CNN was trained on 120 PD, 320 ONL, and 16 dVP pattern images and tested on the 19 PD, 45 ONL, and seven dVP patterns images. The performance of the Faster R-CNN and three NM physicians was assessed using receiver operating characteristics curve analysis. The difference in performance was assessed using Cochran's Q test, and the inter-rater reliability was calculated. Faster R-CNN showed high accuracy in differentiating PD from non-PD patterns and also from dVP patterns, with results comparable to those of NM physicians. There were no significant differences in the area under the curve and performance. The inter-rater reliability among Faster R-CNN and NM physicians showed substantial to almost perfect agreement. The deep-learning model accurately differentiated PD from non-PD patterns on MIP images of [F]FP-CIT PET, and its performance was comparable to that of NM physicians.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics11091557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467049PMC
August 2021

Multifunctional GelMA platforms with nanomaterials for advanced tissue therapeutics.

Bioact Mater 2022 Feb 6;8:267-295. Epub 2021 Jul 6.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea.

Polymeric hydrogels are fascinating platforms as 3D scaffolds for tissue repair and delivery systems of therapeutic molecules and cells. Among others, methacrylated gelatin (GelMA) has become a representative hydrogel formulation, finding various biomedical applications. Recent efforts on GelMA-based hydrogels have been devoted to combining them with bioactive and functional nanomaterials, aiming to provide enhanced physicochemical and biological properties to GelMA. The benefits of this approach are multiple: i) reinforcing mechanical properties, ii) modulating viscoelastic property to allow 3D printability of bio-inks, iii) rendering electrical/magnetic property to produce electro-/magneto-active hydrogels for the repair of specific tissues (e.g., muscle, nerve), iv) providing stimuli-responsiveness to actively deliver therapeutic molecules, and v) endowing therapeutic capacity in tissue repair process (e.g., antioxidant effects). The nanomaterial-combined GelMA systems have shown significantly enhanced and extraordinary behaviors in various tissues (bone, skin, cardiac, and nerve) that are rarely observable with GelMA. Here we systematically review these recent efforts in nanomaterials-combined GelMA hydrogels that are considered as next-generation multifunctional platforms for tissue therapeutics. The approaches used in GelMA can also apply to other existing polymeric hydrogel systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioactmat.2021.06.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424393PMC
February 2022

Genetic association of FKBP5 with trait resilience in Korean male patients with alcohol use disorder.

Sci Rep 2021 09 16;11(1):18454. Epub 2021 Sep 16.

Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

The FKBP5 gene is known to have an important role in alcohol use disorder (AUD) in response to stress and has been reported to affect stress responses by interacting with childhood trauma. This study investigated the effects of the FKBP5 polymorphism rs1360780 and childhood trauma on trait resilience in male patients with AUD. In addition, allele-specific associations between FKBP5 DNA methylation and resilience were examined. In total, 297 men with AUD were assessed for alcohol use severity, childhood trauma, resilience, and impulsivity. Genotyping for FKBP5 rs1360780 and DNA methylation were analyzed. The effects of the rs1360780 single nucleotide polymorphism (SNP) and clinical variables on resilience were tested using linear regression analysis. Possible associations between FKBP5 DNA methylation and resilience were tested with partial correlation analysis. The rs1360780 risk allele, a low education level, and high impulsivity were associated with diminished resilience, whereas no significant main or interaction effect of childhood trauma with the SNP rs1360780 genotype on resilience was shown. No significant association between FKBP5 DNA methylation and resilience was found. The present study demonstrated the involvement of the rs1360780 risk allele in trait resilience in men with AUD, suggesting that the genetic vulnerability of FKBP5 may influence resilience related to AUD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-98032-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445975PMC
September 2021

Risk of psychiatric diseases among patients with psoriasis in Korea: A 12-year nationwide population-based cohort study.

J Dermatol 2021 Nov 30;48(11):1763-1771. Epub 2021 Aug 30.

Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, South Korea.

The association between psoriasis and risk of psychiatric diseases has not been thoroughly evaluated in a large longitudinal cohort of the Asian population. We conducted a nationwide cohort study encompassing more than 1.6 million Koreans with a 12-year follow-up period. Patients were considered to be in the psoriasis cohort if they had an incident diagnostic code for psoriasis and included patients were followed up until they developed any psychiatric disease. In adjusted models, psoriasis patients (n = 10 868) were at an 18% increased risk for depression (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.09-1.26), 16% for anxiety disorders (HR, 1.16; 95% CI, 1.08-1.26), and 21% for somatoform disorders (HR, 1.21; 95% CI, 1.08-1.34) compared with the referent cohort (n = 1 620 055). Patients with moderate-to-severe psoriasis had a higher risk of developing depression and somatoform disorders than patient with mild disease (depression, HR, 1.28; 95% CI, 1.07-1.54 vs HR, 1.17; 95% CI, 1.07-1.27; somatoform disorders, HR, 1.60; 95% CI, 1.26-2.03 vs HR, 1.13; 95% CI, 1.00-1.28). Our results highlight the burden of psychiatric diseases in patients with psoriasis in Korea and suggest that appropriate medical support for possible mental illness is warranted in Asian psoriatic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1346-8138.16115DOI Listing
November 2021

Combined Beneficial Effect of Genistein and Atorvastatin on Adipogenesis in 3T3-L1 Adipocytes.

Biomolecules 2021 07 18;11(7). Epub 2021 Jul 18.

College of Korean Medicine, Gachon University, Seongnam 13120, Korea.

Genistein (4,5,7-trihydroxyisoflavone) is abundant in various dietary vegetables, especially soybeans, and is known to have not only an estrogenic effect but also an antiadipogenic effect. Atorvastatin (dihydroxy monocarboxylic acid) is a statin used to prevent heart disease. Although genistein and atorvastatin have been reported to possess antiadipogenic effects, their combined effects are still unclear. The aim of the current study was to explore whether the combination of genistein and atorvastatin at low concentrations significantly suppresses adipogenesis in a murine preadipocyte cell line (3T3-L1) compared to treatment with genistein or atorvastatin alone. Our results showed that cotreatment with 50 µM genistein and 50 nM atorvastatin significantly suppressed preadipocyte differentiation, whereas when each compound was used alone, there was no inhibitory effect. Additionally, cotreatment with genistein and atorvastatin significantly downregulated adipogenic marker proteins, including mitogen-activated protein kinases (MAPKs), peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), glucocorticoid receptor (GR), and CCAAT/enhancer-binding protein β (C/EBPβ). This is the first evidence of the combined antiadipogenic effects of genistein and atorvastatin. Although additional experiments are required, combinational treatment with genistein and atorvastatin may be an alternative treatment for menopause-associated lipid metabolic disorders and obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom11071052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301876PMC
July 2021

Selenium Nanoparticles as Candidates for Antibacterial Substitutes and Supplements against Multidrug-Resistant Bacteria.

Biomolecules 2021 07 14;11(7). Epub 2021 Jul 14.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Korea.

In recent years, multidrug-resistant (MDR) bacteria have increased rapidly, representing a major threat to human health. This problem has created an urgent need to identify alternatives for the treatment of MDR bacteria. The aim of this study was to identify the antibacterial activity of selenium nanoparticles (SeNPs) and selenium nanowires (SeNWs) against MDR bacteria and assess the potential synergistic effects when combined with a conventional antibiotic (linezolid). SeNPs and SeNWs were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), zeta potential, and UV-visible analysis. The antibacterial effects of SeNPs and SeNWs were confirmed by the macro-dilution minimum inhibitory concentration (MIC) test. SeNPs showed MIC values against methicillin-sensitive (MSSA), methicillin-resistant (MRSA), vancomycin-resistant (VRSA), and vancomycin-resistant enterococci (VRE) at concentrations of 20, 80, 320, and >320 μg/mL, respectively. On the other hand, SeNWs showed a MIC value of >320 μg/mL against all tested bacteria. Therefore, MSSA, MRSA, and VRSA were selected for the bacteria to be tested, and SeNPs were selected as the antimicrobial agent for the following experiments. In the time-kill assay, SeNPs at a concentration of 4X MIC (80 and 320 μg/mL) showed bactericidal effects against MSSA and MRSA, respectively. At a concentration of 2X MIC (40 and 160 μg/mL), SeNPs showed bacteriostatic effects against MSSA and bactericidal effects against MRSA, respectively. In the synergy test, SeNPs showed a synergistic effect with linezolid (LZD) through protein degradation against MSSA and MRSA. In conclusion, these results suggest that SeNPs can be candidates for antibacterial substitutes and supplements against MDR bacteria for topical use, such as dressings. However, for use in clinical situations, additional experiments such as toxicity and synergistic mechanism tests of SeNPs are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biom11071028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301847PMC
July 2021

Mechanistic Pathways for the Molecular Step Growth of Calcium Oxalate Monohydrate Crystal Revealed by In Situ Liquid-Phase Atomic Force Microscopy.

ACS Appl Mater Interfaces 2021 Aug 30;13(31):37873-37882. Epub 2021 Jul 30.

The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.

Calcium oxalate monohydrate (COM) crystal is the most common crystalline component of human kidney stones. The molecular-scale inhibitory mechanisms of COM crystal growth by urinary biomolecules such as citrate and osteopontin adsorbed onto the crystal surface are now well understood. However, the pathways by which dissolved calcium and oxalate ions are incorporated into the molecular step of the COM crystal surface, leading to COM crystal growth-a prerequisite to be elucidated for developing effective therapeutics to inhibit COM stones-remain unknown. Here, using in situ liquid-phase atomic microscopy along with a step kinetic model, we reveal the pathways of the calcium and oxalate ions into the COM molecular step via the growth speed analysis of the molecular steps with respect to their step width at the nanoscale. Our results show that, primarily, the ions are adsorbed onto the terrace of the crystal surface from the solution-the rate-controlling stage for the molecular step growth, i.e., COM crystal growth-and then diffuse over it and are eventually incorporated into the steps. This primary pathway of the ions is unaffected by the model peptide D-Asp adsorbed on the COM crystal surface, suggesting that urinary biomolecules will not alter the pathway. These new findings rendering an essential understanding of the fundamental growth mechanism of COM crystal at the nanoscale provide crucial insights beneficial to the development of effective therapeutics for COM kidney stones.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c09245DOI Listing
August 2021

Dual actions of osteoclastic-inhibition and osteogenic-stimulation through strontium-releasing bioactive nanoscale cement imply biomaterial-enabled osteoporosis therapy.

Biomaterials 2021 09 15;276:121025. Epub 2021 Jul 15.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; Department of Regenerative Dental Medicine, School of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; Cell & Matter Institute, Dankook University, Cheonan, 31116, Republic of Korea; Mechanobiology Dental Medicine Research Center, Cheonan, 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea. Electronic address:

Repair of defective hard-tissues in osteoporotic patients faces significantly challenges with limited therapeutic options. Although biomedical cements are considered promising materials for healthy bone repair, their uses for healing osteoporotic fracture are clinically limited. Herein, strontium-releasing-nanoscale cement was introduced to provide dual therapeutic-actions (pro-osteogenesis and anti-osteoclastogenesis), eventually for the regeneration of osteoporotic bone defect. The Sr-nanocement hardened from the Sr-doped nanoscale-glass particles was shown to release multiple ions including silicate, calcium and strontium at doses therapeutically relevant over time. When the Sr-nanocement was treated to pre-osteoblastic cells, the osteogenic mRNA level (Runx2, Opn, Bsp, Ocn), alkaline phosphatase activity, calcium deposition, and target luciferase reporter were stimulated with respect to the case with Sr-free-nanocement. When treated to pre-osteoclastic cells, the Sr-nanocement substantially reduced the osteoclastogenesis, such as osteoclastic mRNA level (Casr, Nfatc1, c-fos, Acp, Ctsk, Mmp-9), tartrate-resistant acid trap activity, and bone resorption capacity. In particular, the osteoclastic inhibition resulted in part from the interactive effect of osteoblasts which were activated by the Sr-nanocement, i.e., blockage of RANKL (receptor activator of nuclear factor-κB ligand) binding by enhanced osteoprotegerin and the deactivated Nfatc1. The Sr-nanocement, administered to an ovariectomized tibia defect (osteoporotic model) in rats, exhibited profound bone regenerative potential in cortical and surrounding trabecular area, including increased bone volume and density, enhanced production of osteopromotive proteins, and more populated osteoblasts, together with reduced signs of osteoclastic bone resorption. These results demonstrate that Sr-nanocement, with its dual effects of osteoclastic inhibition and osteogenic-stimulation, can be considered an effective nanotherapeutic implantable biomaterial platform for the treatment of osteoporotic bone defects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2021.121025DOI Listing
September 2021

Alterations of cellular aging markers in obsessive- compulsive disorder: mitochondrial DNA copy number and telomere length.

J Psychiatry Neurosci 2021 Jul 22;46(4):E451-E458. Epub 2021 Jul 22.

From the Department of Psychiatry and Institute of Behavioural Science in Medicine, Yonsei University College of Medicine, Seoul, South Korea (Kang, S.-T. Kim, S.-J. Kim); the Department of Psychiatry, CHA Bundang Medical Centre, CHA University, Seongnam, Republic of Korea (Park); the Department of Biochemistry and Biophysics, UCSF School of Medicine, San Francisco, CA, USA (Lin); and the Department of Medical Education, Yonsei University College of Medicine, Seoul, South Korea (H.-W. Kim).

Background: The present study examined whether mitochondrial DNA copy number (mtDNAcn) and telomere length - key markers of cellular aging - were altered in male and female participants with obsessive-compulsive disorder (OCD) compared to healthy controls. We also tested for associations between these alterations and OCD-related clinical features and inflammatory index.

Methods: A total of 235 patients with OCD (38.7% female) and 234 healthy controls (41.5% female) were included. We quantified whole-blood mtDNAcn and leukocyte telomere length using quantitative polymerase chain reaction. We also calculated the neutrophil-to-lymphocyte ratio from complete blood cell counts.

Results: Multivariate analysis of covariance showed that OCD status had a significant overall effect on cellular aging markers in men (Wilks λ = 0.889, F2,275 = 17.13, p < 0.001) and women (Wilks λ = 0.742, F2,182 = 31.61, p < 0.001) after controlling for age, body mass index and childhood trauma. In post-hoc comparisons, men with OCD had lower mtDNAcn than controls (p < 0.001), but we found no between-group difference for telomere length (p = 0.55). Women with OCD had a significantly lower mtDNAcn (p < 0.001) and shortened telomere length (p = 0.023) compared to controls. Moreover, the lower mtDNAcn shown in the OCD group was significantly correlated with an increase in systemic inflammation for both sexes, as measured by neutrophil-to-lymphocyte ratio.

Limitations: The present cross-sectional design did not allow us to infer a causal relationship between OCD disease status and cellular aging markers.

Conclusion: The present study is, to our knowledge, the first to demonstrate alterations in mtDNAcn and telomere shortening in OCD. These results suggest that aging-associated molecular mechanisms may be important in the pathophysiology of OCD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1503/jpn.200238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519490PMC
July 2021

Research Models of the Nanoparticle-Mediated Drug Delivery across the Blood-Brain Barrier.

Tissue Eng Regen Med 2021 Dec 28;18(6):917-930. Epub 2021 Jun 28.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea.

Brain diseases and damages come in many forms such as neurodegenerative diseases, tumors, and stroke. Millions of people currently suffer from neurological diseases worldwide. While Challenges of current diagnosis and treatment for neurological diseases are the drug delivery to the central nervous system. The Blood-Brain Barrier (BBB) limits the drug from reaching the targeted site thus showing poor effects. Nanoparticles that have advantage of the assembly at the nanoscale of available biomaterials can provide a delivery platform with potential to raising brain levels of either imaging therapeutic drugs or imaging. Therefore, successful modeling of the BBB is another crucial factor for the development of nanodrugs. In this review, we analyze the in vitro and in vivo findings achieved in various models, and outlook future development of nanodrugs for the successful treatment of brain diseases and damages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13770-021-00356-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599764PMC
December 2021

Antioxidant cerium ions-containing mesoporous bioactive glass ultrasmall nanoparticles: Structural, physico-chemical, catalase-mimic and biological properties.

Colloids Surf B Biointerfaces 2021 Oct 18;206:111932. Epub 2021 Jun 18.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobimedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea; Cell & Matter Institute, Dankook University, Cheonan, 31116, Republic of Korea. Electronic address:

The multifunctional biological properties of Ce ions including antioxidant, anti-inflammatory, antibacterial and anti-cancer effects are very encouraging for development of Ce-containing biomaterials with therapeutic properties. Herein, novel Ce/Ce ions containing mesoporous bioactive glass ultrasmall nanoparticles (Ce-BGn) were prepared by a facile one-pot ultrasound-assisted sol-gel method. Interestingly, CeO incorporation exerted a significant influence on the particle size and textural properties of mesoporous BGn (SiO - CaO binary glass system). Ce-BGn exhibited ultrasmall nanoparticle size (< 30 nm), mesoporous texture (pore size up to 2.82 nm and pore volume up to 0.191 cm/g) and large specific surface area ca. 132.9 m/g. Notably, in situ formation of CeO nanospheres (3-6 nm) was detected at the surface and in the amorphous glass matrix of mesoporous Ce-BGn. Importantly, X-ray photoelectron spectroscopy (XPS) revealed the presence of 72.57 % Ce and 27.43 % Ce at the surface of mesoporous Ce-BGn with Ce/Ce ratio = 2.66. Furthermore, mesoporous Ce-BGn exhibited high catalase-mimic activity and showed sustained release of Ce (2.5-32 ppm), Ca (85-327 ppm) and Si (54-200 ppm) ions within 4 weeks along with excellent bone-like hydroxyapatite formation. Finally, the in vitro biological behavior of mesoporous Ce-BGn in cell cultures of human skin fibroblasts (HSF) revealed that mesoporous Ce-BGn (with concentrations up to 300 μg/mL) possess good cyto-biocompatibility. Taken together, novel ultrasmall mesoporous Ce-BGn showed remarkable catalase-mimic activity via surface containing Ce/Ce ions which can scavenge ROS (Ce↔ Ce) and decompose HO molecules into HO and O. In addition to that, Ce-BGn demonstrated sustained release of bioactive ions (Ce, Ca and Si), excellent bone-like hydroxyapatite formation and good cyto-biocompatibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.colsurfb.2021.111932DOI Listing
October 2021

Electricity auto-generating skin patch promotes wound healing process by activation of mechanosensitive ion channels.

Biomaterials 2021 08 9;275:120948. Epub 2021 Jun 9.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, 31116, Republic of Korea; Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, 31116, Republic of Korea; Department of Biomaterials Science, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; Department of Regenerative Dental Medicine, College of Dentistry, Dankook University, Cheonan, 31116, Republic of Korea; Cell & Matter Institute, Dankook University, Cheonan, 31116, Republic of Korea; Mechanobiology Dental Medicine Research Center, Cheonan, 31116, Republic of Korea; UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, Republic of Korea. Electronic address:

Electricity constitutes a natural biophysical component that preserves tissue homeostasis and modulates many biological processes, including the repair of damaged tissues. Wound healing involves intricate cellular events, such as inflammation, angiogenesis, matrix synthesis, and epithelialization whereby multiple cell types sense the environmental cues to rebuild the structure and functions. Here, we report that electricity auto-generating glucose-responsive enzymatic-biofuel-cell (EBC) skin patch stimulates the wound healing process. Rat wounded-skin model and in vitro cell cultures showed that EBC accelerated wound healing by modulating inflammation while stimulating angiogenesis, fibroblast fuctionality and matrix synthesis. Of note, EBC-activated cellular bahaviors were linked to the signalings involved with calcium influx, which predominantly dependent on the mechanosensitive ion channels, primarily Piezo1. Inhibition of Piezo1-receptor impaired the EBC-induced key functions of both fibroblasts and endothelial cells in the wound healing. This study highlights the significant roles of electricity played in wound healing through activated mechanosensitive ion channels and the calcium influx, and suggests the possibility of the electricity auto-generating EBC-based skin patch for use as a wound healing device.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2021.120948DOI Listing
August 2021

Prognostic value of metabolic parameters on F-fluorodeoxyglucose positron tomography/computed tomography in classical rectal adenocarcinoma.

Sci Rep 2021 06 21;11(1):12947. Epub 2021 Jun 21.

Department of Nuclear Medicine, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, 1035, Dalgubeol-daero, Dalseo-gu, Daegu, Republic of Korea.

We aimed to investigate the prognostic value of the metabolic parameters of F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in classical rectal adenocarcinoma (CRAC). We retrospectively reviewed 149 patients with CRAC who underwent preoperative F-FDG PET/CT at initial diagnosis followed by curative surgical resection. F-FDG PET/CT metabolic parameters including maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) for disease-free survival (DFS) and overall survival (OS) were evaluated for prognostic significance by univariate and multivariate analyses, along with conventional risk factors including pathologic T (pT) stage, lymph node (LN) metastasis, lymphovascular invasion (LVI), perineural invasion (PNI), and preoperative carcinoembryonic antigen (CEA) level. On univariate analysis, high pT stage, positive LN metastasis, LVI, PNI, MTV, and TLG were significant prognostic factors affecting DFS (all P < 0.05), while CEA level, high pT stage, positive LN metastasis, LVI, PNI, MTV, and TLG affected OS (all P < 0.05). On multivariate analysis, positive LN metastasis, LVI, MTV, and TLG were independent prognostic factors affecting DFS (all P < 0.05), while CEA level, positive LN metastasis, and MTV affected OS (all P < 0.05). Thus, the volume-based metabolic parameters from preoperative F-FDG PET/CT scans are independent prognostic factors in patients with CRAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-92118-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217562PMC
June 2021

Spatiotemporal control of CRISPR/Cas9 gene editing.

Signal Transduct Target Ther 2021 06 20;6(1):238. Epub 2021 Jun 20.

Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) gene editing technology, as a revolutionary breakthrough in genetic engineering, offers a promising platform to improve the treatment of various genetic and infectious diseases because of its simple design and powerful ability to edit different loci simultaneously. However, failure to conduct precise gene editing in specific tissues or cells within a certain time may result in undesirable consequences, such as serious off-target effects, representing a critical challenge for the clinical translation of the technology. Recently, some emerging strategies using genetic regulation, chemical and physical strategies to regulate the activity of CRISPR/Cas9 have shown promising results in the improvement of spatiotemporal controllability. Herein, in this review, we first summarize the latest progress of these advanced strategies involving cell-specific promoters, small-molecule activation and inhibition, bioresponsive delivery carriers, and optical/thermal/ultrasonic/magnetic activation. Next, we highlight the advantages and disadvantages of various strategies and discuss their obstacles and limitations in clinical translation. Finally, we propose viewpoints on directions that can be explored to further improve the spatiotemporal operability of CRISPR/Cas9.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41392-021-00645-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214627PMC
June 2021

The eggshell membrane: A potential biomaterial for corneal wound healing.

J Biomater Appl 2021 11 18;36(5):912-929. Epub 2021 Jun 18.

School of Clinical and Pharmaceutical Sciences, University of Hertfordshire, Hatfield, UK.

The eggshell membrane (ESM) is an abundant resource with innate complex structure and composition provided by nature. With at least 60 million tonnes of hen eggs produced globally per annum, utilisation of this waste resource is highly attractive in positively impacting sustainability worldwide. Given the morphology and mechanical properties of this membrane, it has great potential as a biomaterials for wound dressing. However, to date, no studies have demonstrated nor reported this application. As such, the objective of this investigation was to identify and optimise a reproducible extraction protocol of the ESM and to assess the physical, chemical, mechanical and biological properties of the substrate with a view to use as a wound dressing. ESM samples were isolated by either manual peeling (ESM-strip) or via extraction using acetic acid [ESM-A0.5] or ethylenediaminetetraacetic acid, EDTA [ESM-E0.9]. Energy dispersive X-ray spectroscopy (EDS) confirmed that there were no traces of calcium residues from the extraction process. Fourier transform infrared (FTIR) spectroscopy revealed that the extraction method (acetic acid and EDTA) did not alter the chemical structures of the ESM and also clarified the composition of the fibrous proteins of the ESM. Scanning electron microscopy (SEM) analyses revealed a three-layer composite structure of the ESM: an inner layer as continuous, dense and non-fibrous (limiting membrane), a middle layer with a network of fibres (inner shell membrane) and the outer layer (outer shell membrane) of larger fibres. Material properties including optical transparency, porosity, fluid absorption/uptake, thermal stability, mechanical profiling of the ESM samples were performed and demonstrated suitable profiles for translational applications. Biological studies using SV40 immortalised corneal epithelial cells (ihCEC) and corneal mesenchymal stromal cells (C-MSC) demonstrated excellent biocompatibility. Taken together, these results document the development of a novel sustainable biomaterial that may be used for ophthalmic wounds and/or other biomedical therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/08853282211024040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606947PMC
November 2021

Scaffold-mediated CRISPR-Cas9 delivery system for acute myeloid leukemia therapy.

Sci Adv 2021 May 19;7(21). Epub 2021 May 19.

Department of Biomedical Engineering, Columbia University, New York, NY, USA.

Leukemia stem cells (LSCs) sustain the disease and contribute to relapse in acute myeloid leukemia (AML). Therapies that ablate LSCs may increase the chance of eliminating this cancer in patients. To this end, we used a bioreducible lipidoid-encapsulated Cas9/single guide RNA (sgRNA) ribonucleoprotein [lipidoid nanoparticle (LNP)-Cas9 RNP] to target the critical gene interleukin-1 receptor accessory protein () in human LSCs. To enhance LSC targeting, we loaded LNP-Cas9 RNP and the chemokine CXCL12α onto mesenchymal stem cell membrane-coated nanofibril (MSCM-NF) scaffolds mimicking the bone marrow microenvironment. In vitro, CXCL12α release induced migration of LSCs to the scaffolds, and LNP-Cas9 RNP induced efficient gene editing. knockout reduced LSC colony-forming capacity and leukemic burden. Scaffold-based delivery increased the retention time of LNP-Cas9 in the bone marrow cavity. Overall, sustained local delivery of Cas9/IL1RAP sgRNA via CXCL12α-loaded LNP/MSCM-NF scaffolds provides an effective strategy for attenuating LSC growth to improve AML therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abg3217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133753PMC
May 2021

Status of Four Trace Elements in Elderly Patients with Online Hemodiafiltration.

Clin Lab 2021 Jun;67(6)

Background: Essential trace elements play key roles in multiple biological systems, and hemodialysis patients are at risk for deficiency of essential trace elements. The aim of the study was to assess the essential element status in end stage renal disease patients undergoing online hemodiafiltration (online HDF) in outpatient dialysis clinic.

Methods: A total of 28 Korean patients with regular online HDF were included. Blood samples were collected before and after one HDF session, and serum concentrations of zinc, copper, selenium, and manganese were simulta-neously measured by inductively coupled plasma mass spectrometry.

Results: Selenium, zinc, copper deficiencies were observed in 71.4%, 35.8%, and 21.4%, compared with the reference range. No patients revealed manganese deficiency. After the HDF, the post-HDF level significantly increased in all trace elements, compared with the pre-HDF (11.2% for selenium, 10.7% for copper, and 6.6% for zinc). However, 50% patients were still deficient for selenium at the post-HDF.

Conclusions: Our data suggest that the patients undergoing online HDF are at an increased risk of trace element deficiency, especially for selenium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7754/Clin.Lab.2020.201026DOI Listing
June 2021

Three dimensional porous scaffolds derived from collagen, elastin and fibrin proteins orchestrate adipose tissue regeneration.

J Tissue Eng 2021 Jan-Dec;12:20417314211019238. Epub 2021 May 27.

Regenerative Biomaterials Group, The RAFT Institute and The Griffin Institute, Northwick Park & Saint Mark's Hospital, London, UK.

Current gold standard to treat soft tissue injuries caused by trauma and pathological condition are autografts and off the shelf fillers, but they have inherent weaknesses like donor site morbidity, immuno-compatibility and graft failure. To overcome these limitations, tissue-engineered polymers are seeded with stem cells to improve the potential to restore tissue function. However, their interaction with native tissue is poorly understood so far. To study these interactions and improve outcomes, we have fabricated scaffolds from natural polymers (collagen, fibrin and elastin) by custom-designed processes and their material properties such as surface morphology, swelling, wettability and chemical cross-linking ability were characterised. By using 3D scaffolds, we comprehensive assessed survival, proliferation and phenotype of adipose-derived stem cells in vitro. In vivo, scaffolds were seeded with adipose-derived stem cells and implanted in a rodent model, with X-ray microtomography, histology and immunohistochemistry as read-outs. Collagen-based materials showed higher cell adhesion and proliferation in vitro as well as higher adipogenic properties in vivo. In contrast, fibrin demonstrated poor cellular and adipogenesis properties but higher angiogenesis. Elastin formed the most porous scaffold, with cells displaying a non-aggregated morphology in vitro while in vivo elastin was the most degraded scaffold. These findings of how polymers present in the natural polymers mimicking ECM and seeded with stem cells affect adipogenesis in vitro and in vivo can open avenues to design 3D grafts for soft tissue repair.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/20417314211019238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165536PMC
May 2021

Emerging biogenesis technologies of extracellular vesicles for tissue regenerative therapeutics.

J Tissue Eng 2021 Jan-Dec;12:20417314211019015. Epub 2021 May 25.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Chungcheongnam-do, Cheonan, Republic of Korea.

Extracellular vesicles (EVs), including exosomes, carry the genetic packages of RNA, DNA, and proteins and are heavily involved in cell-cell communications and intracellular signalings. Therefore, EVs are spotlighted as therapeutic mediators for the treatment of injured and dysfunctional tissues as well as biomarkers for the detection of disease status and progress. Several key issues in EVs, including payload content and bioactivity, targeting and bio-imaging ability, and mass-production, need to be improved to enable effective therapeutics and clinical translation. For this, significant efforts have been made recently, including genetic modification, biomolecular and chemical treatment, application of physical/mechanical cues, and 3D cultures. Here we communicate those recent technological advances made mainly in the biogenesis process of EVs or at post-collection stages, which ultimately aimed to improve the therapeutic efficacy in tissue healing and disease curing and the possibility of clinical translation. This communication will help tissue engineers and biomaterial scientists design and produce EVs optimally for tissue regenerative therapeutics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/20417314211019015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155774PMC
May 2021

Mussel Inspired Chemistry and Bacteria Derived Polymers for Oral Mucosal Adhesion and Drug Delivery.

Front Bioeng Biotechnol 2021 5;9:663764. Epub 2021 May 5.

Division of Biomaterials and Tissue Engineering, Royal Free Hospital, Eastman Dental Institute, University College London, London, United Kingdom.

Ulceration of the oral mucosa is common, can arise at any age and as a consequence of the pain lessens enjoyment and quality of life. Current treatment options often involve the use of topical corticosteroids with poor drug delivery systems and inadequate contact time. In order to achieve local controlled delivery to the lesion with optimal adhesion, we utilized a simple polydopamine chemistry technique inspired by mussels to replicate their adhesive functionality. This was coupled with production of a group of naturally produced polymers, known as polyhydroxyalkanoates (PHA) as the delivery system. Initial work focused on the synthesis of PHA using CH50; once synthesized and extracted from the bacteria, the PHAs were solvent processed into films. Polydopamine coating was subsequently achieved by immersing the solvent cast film in a polymerized dopamine solution. Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy confirmed functionalization of the PHA films via the presence of amine groups. Further characterization of the samples was carried out via surface energy measurements and Scanning Electron Microscopy (SEM) micrographs for surface topography. An adhesion test via reverse compression testing directly assessed adhesive properties and revealed an increase in polydopamine coated samples. To further identify the effect of surface coating, LIVE/DEAD imaging and Alamar Blue metabolic activity evaluated attachment and proliferation of fibroblasts on the biofilm surfaces, with higher cell growth in favor of the coated samples. Finally, biocompatibility was investigated in a rat model where the polydopamine coated PHA showed less inflammatory response over time compared to uncoated samples with sign of neovascularization. In conclusion, this simple mussel inspired polydopamine chemistry introduces a step change in bio-surface functionalization and holds great promise for the treatment of oral conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fbioe.2021.663764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133231PMC
May 2021

Dysfunctional Metacognitive Beliefs in Patients With Obsessive-Compulsive Disorder and Pattern of Their Changes Following a 3-Month Treatment.

Front Psychiatry 2021 22;12:628985. Epub 2021 Apr 22.

Department of Psychiatry, Yonsei University College of Medicine, Seoul, South Korea.

Metacognitions are considered to be crucial factors for the development and maintenance of pathologic anxiety. The present case-control study aimed to examine how metacognitive beliefs are associated with the diagnostic status and subtypes of obsessive-compulsive disorder (OCD). In addition, we examined the pattern of changes in metacognitive beliefs after a 3-month pharmacological treatment in patients with OCD. A total of 562 cases with OCD and 236 healthy controls were assessed with the Metacognitions Questionnaire (MCQ) and various measures of OC symptom severity. Multivariate analyses of variance (MANOVAs) with covariates were conducted to explore the relationship between subdimensions of metacognitive beliefs and OCD disease status. In addition, for the OCD patients, Pearson's correlation was performed between baseline MCQ subdimensions and Obsessive-Compulsive Inventory-Revised-Korean subscales (OCI-R-K). Finally, in a subset of drug-free OCD patients ( = 144), the MCQ was reassessed after 3 months of treatment and patterns of changes in subdimensions of the MCQ were examined. Patients with OCD scored significantly higher on the four dimensions of the MCQ. There were significant associations between all MCQ subdimensions and OCI-R-K subscales. In the repeated-measure MANOVA, a significant group (non-responders vs. responders)-by-time interaction effect was found only for the negative beliefs about the uncontrollability and danger of worry (NB) subdimension ( = 10.75; η = 0.072; = 0.001). The presence of dysfunctional metacognitive beliefs in OCD subjects and their association with OCD characteristics suggest that dysfunctional metacognitions may play a crucial role in the pathophysiology of OCD. Improvement of metacognitive beliefs in the NB dimension may be a clinically meaningful correlate of good treatment response in the pharmacological treatment of OCD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2021.628985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100225PMC
April 2021

Ceria-Incorporated Biopolymer for Preventing Fungal Adhesion.

ACS Biomater Sci Eng 2021 05 4;7(5):1808-1816. Epub 2020 Dec 4.

Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, South Korea.

Although biopolymers are widely used in biomedical fields, the issue of poor antimicrobial properties remains unsolved, leading to a potential increase in infections. Here, ceria nanoparticles (CNPs) were incorporated into a representative biopolymer, poly(methyl methacrylate) (PMMA), for drug-free antimicrobial properties. After characterizing the CNPs and surface/mechanical properties of the CNP-PMMA nanocomposite, antiadhesive effects against , the most common fungal species responsible for fungal infections, were determined using metabolic activity assays, and the underlying microbial antiadhesive mechanism was revealed. Hydrothermally fabricated CNPs showed a size of ∼20 nm with a zeta potential of 12 ± 2.3 mV and showed catalytic properties as a ROS modulator. Successful incorporation of CNPs into PMMA up to 2 wt % was confirmed by EDS analysis. The surface roughness and mechanical properties such as flexural strength and modulus were relatively unchanged up to 2 wt %. In contrast, the surface energy increased, and the Vickers hardness decreased in the 2 wt % PMMA compared with the control. A drop of up to 90% of adherent was observed in CNP-incorporated PMMA, which was confirmed and quantified via fungus staining images. The antiadhesive mechanism was revealed from the direct antimicrobial effects of CNP via the upregulation of the intracellular ROS level. Taken together, the antimicrobial-adhesive properties of the CNP-PMMA nanocomposite suggest the potential usefulness of CNP as a promising drug-free antimicrobial ingredient for biopolymers, which could lead to the prevention of microbial-induced complications in clinical settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsbiomaterials.0c01039DOI Listing
May 2021
-->