Publications by authors named "Liping Tang"

165 Publications

A small molecule that induces translational readthrough of CFTR nonsense mutations by eRF1 depletion.

Nat Commun 2021 07 16;12(1):4358. Epub 2021 Jul 16.

Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham (UAB), Birmingham, AL, USA.

Premature termination codons (PTCs) prevent translation of a full-length protein and trigger nonsense-mediated mRNA decay (NMD). Nonsense suppression (also termed readthrough) therapy restores protein function by selectively suppressing translation termination at PTCs. Poor efficacy of current readthrough agents prompted us to search for better compounds. An NMD-sensitive NanoLuc readthrough reporter was used to screen 771,345 compounds. Among the 180 compounds identified with readthrough activity, SRI-37240 and its more potent derivative SRI-41315, induce a prolonged pause at stop codons and suppress PTCs associated with cystic fibrosis in immortalized and primary human bronchial epithelial cells, restoring CFTR expression and function. SRI-41315 suppresses PTCs by reducing the abundance of the termination factor eRF1. SRI-41315 also potentiates aminoglycoside-mediated readthrough, leading to synergistic increases in CFTR activity. Combining readthrough agents that target distinct components of the translation machinery is a promising treatment strategy for diseases caused by PTCs.
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http://dx.doi.org/10.1038/s41467-021-24575-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285393PMC
July 2021

Recommendations for proficiency testing criteria for hemoglobin A based on the Shanghai Center for Clinical Laboratory's study.

Clin Chem Lab Med 2021 Jul 6. Epub 2021 Jul 6.

Shanghai Center for Clinical Laboratory, Shanghai, P. R. China.

Objectives: The US Centers for Medicare & Medicaid Services proposed in 2019 that glycated hemoglobin A (HbA) be a CLIA'88 regulated analyte. People who commented expressed concerns that the proposed acceptance limit (AL, HbA in NGSP unit) ±10% for proficiency testing (PT) would be unable to maintain already improved analytical performance and guarantee the clinical utility of HbA testing. Assessing impact of various ALs on PT performance is needed to provide scientific evidence for adopting an appropriate AL.

Methods: Ten patient EDTA-whole blood specimens were distributed to 318 and 336 laboratories in the 2018 and 2019 PT events organized by Shanghai Center for Clinical Laboratory (SCCL). HbA concentrations were measured by participants using various methodologies commonly used in the USA and China. Targets were determined using secondary reference measurement procedures (SRM) at SCCL. "Failed Results" were those outside the SRM-defined target ± AL (5% through 10%). Laboratories with Failed Results ≥2 out of five samples per PT event obtained Event Unsatisfactory Status.

Results: HbA target values ranged 33.3 mmol/mol (5.2 NGSP%) -102.2 mmol/mol (11.5 NGSP%) for 2018 event, and 33.3 mmol/mol (5.2 NGSP%) -84.7 mmol/mol (9.9 NGSP%) for 2019 event. Overall Laboratory Event Unsatisfactory Rates were 11.3-12.2%, 4.8-5.3%, 0.9-3.1%, 0.6-2.2%, 0.6-1.4% and 0.6-1.4%, at AL of ±5, ±6, ±7, ±8, ±9 and ±10%, respectively.

Conclusions: The AL (in NGSP unit) of ±6% or ±7% for PT evaluation of HbA results would be appropriate, with satisfactory event scores for about 95% of participant laboratories in a PT event.
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http://dx.doi.org/10.1515/cclm-2020-1311DOI Listing
July 2021

Click chemistry-based pre-targeting cell delivery for cartilage regeneration.

Regen Biomater 2021 Jun 2;8(3):rbab018. Epub 2021 May 2.

Department of Bioengineering, University of Texas at Arlington, PO Box 19138, Arlington, TX 76019, USA.

A fraction of the OA patient population is affected by post-traumatic osteoarthritis (PTOA) following acute joint injuries. Stopping or reversing the progression of PTOA following joint injury could improve long-term functional outcomes, reduced disability, and medical costs. To more effectively treat articular cartilage injury, we have developed a novel cell-based therapy that involves the pre-targeting of apoptotic chondrocytes and the delivery of healthy, metabolically active chondrocytes using click chemistry. Specifically, a pre-targeting agent was prepared via conjugating apoptotic binding peptide (ApoPep-1) and -cyclooctene (TCO) onto polyethylene glycol (PEG) polymer carrier. The pre-targeting agent would be introduced to injured areas of articular cartilage, leading to the accumulation of TCO groups on the injured areas from actively binding to apoptotic chondrocytes. Subsequently, methyltetrazine (Tz)-bearing chondrocytes would be immobilized on the surface of TCO-coated injured cartilage via Tz-TCO click chemistry reaction. Using an human cartilage explant PTOA model, the effectiveness of this new approach was evaluated. Our studies show that this novel approach (Tz-TCO click chemistry) significantly enhanced the immobilization of healthy and metabolically active chondrocytes to the areas of apoptotic chondrocytes. Histological analyses demonstrated that this treatment regimen would significantly reduce the area of cartilage degeneration and enhance ECM regeneration. The results support that Tz-TCO click chemistry-mediated cell delivery approach has great potential in clinical applications for targeting and treatment of cartilage injury.
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http://dx.doi.org/10.1093/rb/rbab018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240595PMC
June 2021

Toujie Quwen granule used with conventional western therapy for coronavirus disease 2019: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jun;100(24):e26370

Academician Workstation, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China.

Background: Coronavirus disease 2019 (COVID-19) is an epidemic infectious disease resulted from 2019 novel coronavirus (2019-nCoV). Up till now, COVID-19 has swept globally. Currently, due to many high-profiled benefits, clinical studies on Toujie Quwen granule (TJQW) have been increasing. The aim of the study is to assess the efficacy and safety of TJQW used with conventional western therapy for COVID-19.

Methods: Relevant randomized controlled trials (RCTs) were searched in Chinese and English databases, and the search time is January 2020 to May 2021. English databases include PubMed, Embase, Web of Science, and the Cochrane Library. Chinese databases include CNKI, WF, VIP, and CBM. The international clinical trial registration platform and the Chinese clinical trial registration platform of controlled trials will be searched by us from January 2020 to May 2021. According to the inclusion and exclusion criteria, screening literature, extraction data will be conducted by 2 researchers independently. Statistical analysis will be conducted using the RevMan 5.3.5 software. After screening the literature based on the inclusion and exclusion criteria, The Recommendation, Assessment, Development, and Evaluation (GRADE) system will be used to evaluate the quality of each result.

Results: This study will provide the evidence for TJQW to be used with conventional western therapy for COVID-19.

Conclusion: The efficacy and safety of TJQW used with conventional western therapy for COVID-19 will be assessed.

Inplasy Registration Number: INPLASY202150038.
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http://dx.doi.org/10.1097/MD.0000000000026370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213269PMC
June 2021

A non-contact device for fast screening of wound infections.

Exp Dermatol 2021 Jun 5. Epub 2021 Jun 5.

Progenitec Inc, Arlington, TX, USA.

Screening for wound infection relies on the expertise of the provider. Clinical diagnosis of infections based on wound swab/biopsy results often takes a few days and may not assess the full wound. There is a need for a non-invasive tool that can quickly and accurately diagnose wound infection. Leukocyte esterase strips are used to identify various infectious diseases. However, it is not clear whether infected wounds also have elevated leukocyte esterase activities as compared with non-infected wounds. To achieve the objective, a device was developed to detect elevated leukocyte esterase activities in wounds by measuring wound exudates adsorbed onto wound dressings in 3 minutes. The efficacy of the device in assessing leukocyte esterase activities across various chronic wounds was tested. Such measurements were unaffected by the type of underlying wound dressing. By correlating the device outputs with clinical adjudication of infection, we found that this device had high positive predictive values for diagnosing wound infection in a wide variety of chronic wounds. In addition, a positive device output increases the probability of detecting infected wounds, while the negative device output reduces the probability of detecting infected wounds. This rapid non-contact and disposable diagnostic tool may serve as a rapid and accurate indication of infection in the chronic wound.
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http://dx.doi.org/10.1111/exd.14399DOI Listing
June 2021

Moxibustion for stable chronic obstructive pulmonary disease: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Apr;100(17):e25713

Institute of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Jiangxi, China.

Background: There is no optimal treatment to alleviate the decline of lung function in the stable phase of chronic obstructive pulmonary disease (COPD). The effectiveness of moxibustion as an adjunctive treatment for COPD in the stable phase has been reported clinically, but the conclusions on efficacy and safety have not been unified. This study will systematically evaluate the efficacy and safety of moxibustion on the treatment of COPD in the stable phase, providing clinical-based evidence.

Methods: We will systematically search 7 literature databases and 2 clinical trial registration platforms. The searching time will be conducted from the establishment of databases to March 31, 2021, regardless of language. We will include the randomized controlled trial (RCT) evaluation of moxibustion combined with basic therapy vs basic therapy alone for the treatment of stable COPD. We will assess the risk of bias for individual RCTs using the Cochrane Handbook 5.1.0 evaluation tool. The primary outcome is forced expiratory volume in 1 second/forced vital capacity. The secondary outcomes include forced expiratory volume in 1 second, forced vital capacity, six-minute walking distance, COPD assessment test score, maximum ventilation, response to treatment, and incidence of adverse events. We will collect the effective data of individual RCT through systematic analysis of the random effect model. Heterogeneity will be tested by Cochran Q test and I-squared statistics. Two subgroup analyses will be performed to explore the sources of heterogeneity based on clinical experience. Excluding RCTs with a high risk of bias, fixed-effect model will be used for sensitivity analysis to test the robustness of the meta-analysis results. The publication bias will be assessed by funnel plot and Egger test.

Results: This study will provide systematic evidence on the efficacy and safety of moxibustion on the treatment of patients with stable COPD through strict quality assessment and reasonable data synthesis. We hope that the results will be submitted to a peer-reviewed journal for publication.

Conclusion: This systematic review will provide the best current evidence for the adjuvant treatment of stable COPD with moxibustion.

Inplasy Registration Number: INPLASY202140047.
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http://dx.doi.org/10.1097/MD.0000000000025713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084073PMC
April 2021

Epigenetic identification of mitogen-activated protein kinase 10 as a functional tumor suppressor and clinical significance for hepatocellular carcinoma.

PeerJ 2021 2;9:e10810. Epub 2021 Feb 2.

Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.

Background: Mitogen-activated protein kinase 10 () is a member of the c-jun N-terminal kinases () subgroup in the MAPK superfamily, and was proposed as a tumor suppressor inactivated epigenetically. Its role in hepatocellular carcinoma (HCC) has not yet been illustrated. We aimed to investigate the expression and epigenetic regulation of as well as its clinical significance in HCC.

Results: was expressed in almost all the normal tissues including liver, while we found that the protein expression of MAPK10 was significantly downregulated in clinical samples of HCC patients compared with these levels in adjacent normal tissues (29/46, < 0.0001). Clinical significance of MAPK10 expression was then assessed in a cohort of 59 HCC cases, which indicated its negative expression was significantly correlated with advanced tumor stage ( = 0.001), more microsatellite nodules ( = 0.025), higher serum AFP ( = 0.001) and shorter overall survival time of HCC patients. Methylation was further detected in 58% of the HCC cell lines we tested and in 66% of primary HCC tissues by methylation-specific PCR (MSP), which was proved to be correlated with the silenced or downregulated expression of . To get the mechanisms more clear, the transcriptional silencing of was reversed by pharmacological demethylation, and ectopic expression of in silenced HCC cell lines significantly inhibited the colony formation ability, induced apoptosis, or enhanced the chemosensitivity of HCC cells to 5-fluorouracil.

Conclusion: appears to be a functional tumor suppressor gene frequently methylated in HCC, which could be a valuable biomarker or a new diagnosis and therapy target in a clinical setting.
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http://dx.doi.org/10.7717/peerj.10810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863782PMC
February 2021

Can Corporate Social Responsibility Promote Employees' Taking Charge? The Mediating Role of Thriving at Work and the Moderating Role of Task Significance.

Front Psychol 2020 28;11:613676. Epub 2021 Jan 28.

Business School, Central South University, Changsha, China.

There is growing evidence to suggest that employees' perceptions of their employer's corporate social responsibility (CSR) positively influences their attitude and behavior. An increasing number of scholars have called for further explorations of the microfoundations of CSR. To that end, this study takes the conservation of resources perspective to examine relationships and the perception of CSR by employees, considering areas such as thriving at work, task significance, and employees taking charge. By analyzing 444 questionnaires completed by employees in China and using the conditional process analysis to test a hypothesis, results showed that the association between employees' CSR perception and taking charge is significantly and positively correlated, with thriving at work mediating the connection. We also found that task significance negatively moderates the mediating effect between CSR and taking charge, such that the lower the level of task significance of a job, the more positive the effect of CSR on taking charge via thriving at work. These findings have theoretical implications for micro-level CSR research and managerial implications for entrepreneurs.
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http://dx.doi.org/10.3389/fpsyg.2020.613676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875869PMC
January 2021

Imaging of Actively Proliferating Bacterial Infections by Targeting the Bacterial Metabolic Footprint with d-[5-C]-Glutamine.

ACS Infect Dis 2021 02 21;7(2):347-361. Epub 2021 Jan 21.

Since most d-amino acids (DAAs) are utilized by bacterial cells but not by mammalian eukaryotic hosts, recently DAA-based molecular imaging strategies have been extensively explored for noninvasively differentiating bacterial infections from the host's inflammatory responses. Given glutamine's pivotal role in bacterial survival, cell growth, biofilm formation, and even virulence, here we report a new positron emission tomography (PET) imaging approach using d-5-[C]glutamine (d-[5-C]-Gln) for potential clinical assessment of bacterial infection through a comparative study with its l-isomer counterpart, l-[5-C]-Gln. In both control and infected mice, l-[5-C]-Gln had substantially higher uptake levels than d-[5-C]-Gln in most organs except the kidneys, showing the expected higher use of l-[5-C]-Gln by mammalian tissues and more efficient renal excretion of d-[5-C]-Gln. Importantly, our work demonstrates that PET imaging with d-[5-C]-Gln is capable of detecting infections induced by both () and methicillin-resistant (MRSA) in a dual-infection murine myositis model with significantly higher infection-to-background contrast than with l-[5-C]-Gln (in , 1.64; in MRSA, 2.62, = 0.0004). This can be attributed to the fact that d-[5-C]-Gln is utilized by bacteria while being more efficiently cleared from the host tissues. We confirmed the bacterial infection imaging specificity of d-[5-C]-Gln by comparing its uptake in active bacterial infections versus sterile inflammation and with 2-deoxy-2-[F]fluoroglucose ([F]FDG). These results together demonstrate the translational potential of PET imaging with d-[5-C]-Gln for the noninvasive detection of bacterial infectious diseases in humans.
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http://dx.doi.org/10.1021/acsinfecdis.0c00617DOI Listing
February 2021

PLZF and PLZF-MAPK10 can predict the prognosis of postoperative patients with hepatocellular carcinoma.

Int J Clin Exp Pathol 2020 1;13(12):3158-3166. Epub 2020 Dec 1.

Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University Chongqing, China.

Objective: The current study aimed to explore the expression level of promyelocytic leukaemia zinc finger (PLZF) in hepatocellular carcinoma tissues and to investigate the value of detecting the expression levels of PLZF and mitogen-activated protein kinase 10 (MAPK10) on predicting prognosis.

Methods: This study selected data from 53 patients with HCC who had undergone hepatectomy in our hospital. The expressions of PLZF and MAPK10 in tumor tissues and normal tissues were compared and related clinical factors were analyzed. The clinical data including patient's gender, age, hepatitis B virus infection (HBV), alpha-fetoprotein levels (AFP), tumor size, TNM stage (AJCC), cirrhosis, portal vein tumor thrombus (PVTT), bile duct tumor thrombus (BDTT), and OS (Overall survival) was collected.

Results: We found that PLZF expression was significantly down-regulated in HCC samples compared with that in adjacent non-tumor tissues (P=0.001). The expression level of PLZF was correlated with patients' gender (P=0.046), tumor stage (P=0.039), and OS (P=0.015). Moreover, the expression level of PLZF-MAPK10 (P-M protein) was correlated with gender (P=0.000) and tumor stage (P=0.045). Multivariate analyses showed that microsatellite nodules, PLZF, and P-M protein were independent risk factors of HCC prognosis. Postoperative patients with a normal expression level of PLZF and MAPK10 have a longer overall survival than those with abnormal levels (P=0.039).

Conclusion: PLZF expression was significantly down-regulated in HCC tissues and itself and PLZF-MAPK10 were both independent prognostic factors for the OS of patients with HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791377PMC
December 2020

An in vitro system to investigate IOL: Lens capsule interaction.

Exp Eye Res 2021 02 7;203:108430. Epub 2021 Jan 7.

Department of Bioengineering, University of Texas at Arlington, Arlington, TX, 76019, USA. Electronic address:

Posterior capsule opacification (PCO) is the most common complication associated with intraocular lens (IOL) implantation. Unfortunately, current in vitro models cannot be used to assess the potential of PCO due to their failure to simulate the posterior curvature of the lens capsule (LC) and IOL, a factor known to affect PCO pathogenesis in clinic. To overcome such a challenge, a new system to study IOL: LC interaction and potentially predict PCO was developed in this effort. It is believed that the interactions between an IOL and the lens capsule may influence the extent of PCO formation. Specifically, strong adhesion force between an IOL and the LC may impede lens epithelial cell migration and proliferation and thus reduce PCO formation. To assess the adhesion force between an IOL and LC, a new in vitro model was established with simulated LC and a custom-designed micro-force tester. A method to fabricate simulated LCs was developed by imprinting IOLs onto molten gelatin to create simulated three dimensional (3D) LCs with curvature resembling the bag-like structure that collapses on the IOL post implantation. By pushing the LC mold vertically downward, while measuring the change in position of the bending bar with respect to its start position, the adhesion force between the IOLs and LCs was measured. An in vitro system that can measure the adhesion force reproducibly between an IOL and LC with a resolution of ~1 μN was established in this study. During system optimization, the 10% high molecular weight gelatin produced the best LC with the highest IOL: LC adhesion force with all test lenses that were fabricated from acrylic foldable, polymethylmethacrylate (PMMA) and silicone materials. Test IOLs exerted different adhesion force with the 3D simulated LCs in the following sequence: acrylic foldable IOL > silicone IOL > PMMA IOL. These results are in good agreement with the clinical observations associated with PCO performance of IOLs made of the same materials. This novel in vitro system can provide valuable insight on the IOL: LC interplay and its relationship to clinical PCO outcomes.
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http://dx.doi.org/10.1016/j.exer.2020.108430DOI Listing
February 2021

Enhanced Endothelial Cell Delivery for Repairing Injured Endothelium via Pretargeting Approach and Bioorthogonal Chemistry.

ACS Biomater Sci Eng 2020 12 10;6(12):6831-6841. Epub 2020 Nov 10.

Department of Bioengineering, University of Texas at Arlington, P.O. Box 19138, Arlington, Texas 76010, United States.

Arterial wall injury often leads to endothelium cell activation, endothelial detachment, and atherosclerosis plaque formation. While abundant research efforts have been placed on treating the end stages of the disease, no cure has been developed to repair injured and denude endothelium often occurred at an early stage of atherosclerosis. Here, a pretargeting cell delivery strategy using combined injured endothelial targeting nanoparticles and bioorthogonal click chemistry approach was developed to deliver endothelial cells to replenish the injured endothelium via a two-step process. First, nanoparticles bearing glycoprotein 1b α (Gp1bα) proteins and tetrazine (Tz) were fabricated to provide a homogeneous nanoparticle coating on an injured arterial wall via the interactions between Gp1bα and von Willebrand factor (vWF), a ligand that is present on denuded endothelium. Second, transplanted endothelium cells bearing transcyclooctene (TCO) would be quickly immobilized on the surfaces of nanoparticles via TCO:Tz reactions. binding studies under both static and flow conditions confirmed that our novel Tz-labeled Gp1bα-conjugated poly(lactic--glycolic acid) (PLGA) nanoparticles can successfully pretargeted toward the injured site and support rapid adhesion of endothelial cells from the circulation. results also confirm that such an approach is highly efficient in mediating the local delivery of endothelial cells at the sites of arterial injury. The results support that this pretargeting cell delivery approach may be used for repairing injured endothelium at its early stage.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00957DOI Listing
December 2020

Optimizing Anisotropic Polyurethane Scaffolds to Mechanically Match with Native Myocardium.

ACS Biomater Sci Eng 2020 05 6;6(5):2757-2769. Epub 2020 Apr 6.

Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USA.

Biodegradable cardiac patch is desirable to possess mechanical properties mimicking native myocardium for heart infarction treatment. We fabricated a series of anisotropic and biodegradable polyurethane porous scaffolds via thermally induced phase separation (TIPS) and tailored their mechanical properties by using various polyurethanes with different soft segments and varying polymer concentrations. The uniaxial mechanical properties, suture retention strength, ball-burst strength, and biaxial mechanical properties of the anisotropic porous scaffolds were optimized to mechanically match native myocardium. The optimal anisotropic scaffold had a ball burst strength (20.7 ± 1.5 N) comparable to that of native porcine myocardium (20.4 ± 6.0 N) and showed anisotropic behavior close to biaxial stretching behavior of the native porcine myocardium. Furthermore, the optimized porous scaffold was combined with a porcine myocardium-derived hydrogel to form a biohybrid scaffold. The biohybrid scaffold showed morphologies similar to the decellularized porcine myocardial matrix. This combination did not affect the mechanical properties of the synthetic scaffold alone. After rat subcutaneous implantation, the biohybrid scaffolds showed minimal immune response and exhibited higher cell penetration than the polyurethane scaffold alone. This biohybrid scaffold with biomimetic mechanics and good tissue compatibility would have great potential to be applied as a biodegradable acellular cardiac patch for myocardial infarction treatment.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725265PMC
May 2020

Combined Tumor Environment Triggered Self-Assembling Peptide Nanofibers and Inducible Multivalent Ligand Display for Cancer Cell Targeting with Enhanced Sensitivity and Specificity.

Small 2020 09 18;16(38):e2002780. Epub 2020 Aug 18.

Department of Chemistry & Biochemistry, The University of Texas at Arlington, Arlington, TX, 76019, USA.

Many new technologies, such as cancer microenvironment-induced nanoparticle targeting and multivalent ligand approach for cell surface receptors, are developed for active targeting in cancer therapy. While the principle of each technology is well illustrated, most systems suffer from low targeting specificity and sensitivity. To fill the gap, this work demonstrates a successful attempt to combine both technologies to simultaneously improve cancer cell targeting sensitivity and specificity. Specifically, the main component is a targeting ligand conjugated self-assembling monomer precursor (SAM-P), which, at the tumor site, undergoes tumor-triggered cleavage to release the active form of self-assembling monomer capable of forming supramolecular nanostructures. Biophysical characterization confirms the chemical and physical transformation of SAM-P from unimers or oligomers with low ligand valency to supramolecular assemblies with high ligand valency under a tumor-mimicking reductive microenvironment. The in vitro fluorescence assay shows the importance of supramolecular morphology in mediating ligand-receptor interactions and targeting sensitivity. Enhanced targeting specificity and sensitivity can be achieved via tumor-triggered supramolecular assembly and induces multivalent ligand presentation toward cell surface receptors, respectively. The results support this combined tumor microenvironment-induced cell targeting and multivalent ligand display approach, and have great potential for use as cell-specific molecular imaging and therapeutic agents with high sensitivity and specificity.
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http://dx.doi.org/10.1002/smll.202002780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283777PMC
September 2020

A pretargeting nanoplatform for imaging and enhancing anti-inflammatory drug delivery.

Bioact Mater 2020 Dec 15;5(4):1102-1112. Epub 2020 Jul 15.

Department of Bioengineering, University of Texas at Arlington, Engineering Research Building, Room 226, Box 19138, Arlington, TX, 76010, USA.

This work details a newly developed "sandwich" nanoplatform via neutravidin-biotin system for the detection and treatment of inflammation. First, biotinylated- and folate-conjugated optical imaging micelles targeted activated macrophages via folate/folate receptor interactions. Second, multivalent neutravidin proteins in an optimal concentration accumulated on the biotinylated macrophages. Finally, biotinylated anti-inflammatory drug-loaded micelles delivered drugs effectively at the inflammatory sites via a highly specific neutravidin-biotin affinity. Both and studies have shown that the "sandwich" pretargeting platform was able to diagnose inflammation by targeting activated macrophages as well as improve the therapeutic efficacy by amplifying the drug delivery to the inflamed tissue. The overall results support that our new pretargeting platform has the potential for inflammatory disease diagnosis and treatment.
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http://dx.doi.org/10.1016/j.bioactmat.2020.06.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365982PMC
December 2020

Development of 3D Lymph Node Mimetic for Studying Prostate Cancer Metastasis.

Adv Biosyst 2019 09 24;3(9):e1900019. Epub 2019 Jul 24.

Bioengineering Department, University of Texas Southwestern Medical Center and The University of Texas at Arlington, Arlington, TX, 76019, USA.

Lymph node (LN) metastasis causes poor prognosis for patients with prostate cancer (PCa). Although LN-cells and cellular responses play a pivotal role in cancer metastasis, the interplay between LN-cells and PCa cells is undetermined due to the small size and widespread distribution of LNs. To identify factors responsible for LN metastasis, a 3D cell culture biosystem is fabricated to simulate LN responses during metastasis. First, it is determined that LN explants previously exposed to high metastatic PCa release substantially more chemotactic factors to promote metastatic PCa migration than those exposed to low-metastatic PCa. Furthermore, T-lymphocytes are found to produce chemotactic factors in LNs, among which, CXCL12, CCL21, and IL-10 are identified to have the most chemotactic effect. To mimic the LN microenvironment, Cytodex beads are seeded with T cells to produce a LN-mimetic biosystem in both static and flow conditions. As expected, the flow condition permits prolonged cellular responses. Interestingly, when PCa cells with varying metastatic potentials are introduced into the system, it produces PCa-specific chemokines accordingly. These results support that the LN mimetic helps in analyzing the processes underlying metastasized LNs and for testing various treatments to reduce cancer LN metastasis.
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http://dx.doi.org/10.1002/adbi.201900019DOI Listing
September 2019

Ivacaftor Reverses Airway Mucus Abnormalities in a Rat Model Harboring a Humanized G551D-CFTR.

Am J Respir Crit Care Med 2020 11;202(9):1271-1282

Department of Medicine.

Animal models have been highly informative for understanding the characteristics, onset, and progression of cystic fibrosis (CF) lung disease. In particular, the CFTR rat has revealed insights into the airway mucus defect characteristic of CF but does not replicate a human-relevant CFTR (cystic fibrosis transmembrane conductance regulator) variant. We hypothesized that a rat expressing a humanized version of CFTR and harboring the ivacaftor-sensitive variant G551D could be used to test the impact of CFTR modulators on pathophysiologic development and correction. In this study, we describe a humanized-CFTR rat expressing the G551D variant obtained by zinc finger nuclease editing of a human complementary DNA superexon, spanning exon 2-27, with a 5' insertion site into the rat gene just beyond intron 1. This targeted insertion takes advantage of the endogenous rat promoter, resulting in appropriate expression compared with wild-type animals. The bioelectric phenotype of the epithelia recapitulates the expected absence of CFTR activity, which was restored with ivacaftor. Large airway defects, including depleted airway surface liquid and periciliary layers, delayed mucus transport rates, and increased mucus viscosity, were normalized after the administration of ivacaftor. This model is useful to understand the mechanisms of disease and the extent of pathology reversal with CFTR modulators.
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http://dx.doi.org/10.1164/rccm.202002-0369OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605185PMC
November 2020

Diagnostics for Wound Infections.

Adv Wound Care (New Rochelle) 2021 06 7;10(6):317-327. Epub 2020 Jul 7.

Department of Bioengineering, The University of Texas at Arlington, Arlington, Texas, USA.

Infections can significantly delay the healing process in chronic wounds, placing an enormous economic burden on health care resources. Identification of infection biomarkers and imaging modalities to observe and quantify them has seen progress over the years. Traditionally, clinicians determine the presence of infection through visual observation of wounds and confirm their diagnosis through wound culture. Many laboratory markers, including C-reactive protein, procalcitonin, presepsin, and bacterial protease activity, have been quantified to assist diagnosis of infection. Moreover, imaging modalities like plain radiography, computed tomography, magnetic resonance imaging, ultrasound imaging, spatial frequency domain imaging, thermography, autofluorescence imaging, and biosensors have emerged for real-time wound infection diagnosis and showed their unique advantages in deeper wound infection diagnosis. While traditional diagnostic approaches provide valuable information, they are time-consuming and depend on clinicians' experiences. There is a need for noninvasive wound infection diagnostics that are highly specific, rapid, and accurate, and do not require extensive training. While innovative diagnostics utilizing various imaging instrumentation are being developed, new biomarkers have been investigated as potential indicators for wound infection. Products may be developed to either qualitatively or quantitatively measure these biomarkers. This review summarizes and compares all available diagnostics for wound infection, including those currently used in clinics and still under development. This review could serve as a valuable resource for clinicians treating wound infections as well as patients and wound care providers who would like to be informed of the recent developments.
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http://dx.doi.org/10.1089/wound.2019.1103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082727PMC
June 2021

Injectable Click Chemistry-based Bioadhesives for Accelerated Wound Closure.

Acta Biomater 2020 07 30;110:95-104. Epub 2020 Apr 30.

Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USA. Electronic address:

Tissue adhesives play a vital role in surgical processes as a substitute for sutures in wound closure. However, several existing tissue adhesives suffer from cell toxicity, weak tissue-adhesive strength, and high cost. In this study, by taking advantage of the fast and specific inverse-demand Diels-Alder cycloaddition reaction, a series of bioadhesives were produced by employing copper-free click chemistry pair trans-cyclooctene (TCO) /tetrazine (Tz) in chitosan. The gelation time of the bioadhesives can be optimized to be less than 2 minutes, which meets the need for surgical wound closure in practice. By adding 4-arm polyethylene glycol propionaldehyde (PEG-PALD) as a co-crosslinker, the adhesive strength of the bioadhesives was optimized to be 2.3 times higher than that of the conventional fibrin glue. Moreover, by adjusting the amount of the co-crosslinker, the swelling ratio and pore size of the chitosan bioadhesives can be tuned to fit the need of drug encapsulation and cell seeding. The chitosan bioadhesives possess no significant in vitro cytotoxicity. Using a mice skin incision wound model, we found that the chitosan bioadhesives were able to close the wound faster and promote wound healing process than the fibrin glue. In conclusion, our results support that the innovative click-chemistry based bioadhesives have been developed with improved physical and biological properties for surgical wound closures. STATEMENT OF SIGNIFICANCE: The manuscript describes a new group of click chemistry-based chitosan bioadhesives fabricated by reacting copper-free click chemistry pair trans-cyclooctene/tetrazine with co-crosslinker PEG-PALD. The new bioadhesives possess the properties of simple preparation, injectability, fast gelation, a minimal cytotoxicity, strong adhesive strength to tissue, and enhanced wound healing responses. This innovative strategy may draw interests of readers from the field of biomaterials, drug delivery, surgical device, and translational medicine.
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http://dx.doi.org/10.1016/j.actbio.2020.04.004DOI Listing
July 2020

A Device to Predict Short-Term Healing Outcome of Chronic Wounds.

Adv Wound Care (New Rochelle) 2020 06 27;9(6):312-324. Epub 2019 Dec 27.

Department of Bioengineering, University of Texas at Arlington, Arlington, Texas.

While myriads of studies have suggested that a survey of wound pH environment could indicate wound healing activities, it is not clear whether wound alkalinity can be used as a prognostic indicator of nonhealing wounds. Currently available systems cannot reliably assess the pH environment across wounds, which is the objective of this study. A disposable device, DETEC pH, was developed and characterized on its ability to map wound alkalinity by pressing a freshly recovered wound dressing against its test surface. By comparing the wound's alkalinity and size reduction rates (∼7 days) following pH measurement, we assessed the capability of wound alkalinity to prognosticate subsequent short-term wound size reduction rates. The device had high accuracy and specificity in determining the alkalinity of simulated wound fluids soaked onto wound dressing. The type of wound dressing type had an insignificant effect on its detection sensitivity. Upon testing discarded wound dressings from human patients, the device quickly determined alkaline and acidic wounds. Finally, statistical analyses of wound size reduction rates in wounds with various alkalinities confirmed that wound alkalinity has a strong influence on, at least, short-term wound healing activity. Without directly contacting the patient, this device provides a quick assessment of wound alkalinity to prognosticate immediate and short-term wound healing activities. DETEC pH may serve as a prognosis device for wound care specialists during routine wound assessment to predict wound healing progress. This information can assist the decision-making process in a clinical setting and augur well for chronic wound treatment. DETEC pH can also be used as an aid for home health care nurses or health care providers to screen nonhealing wounds outside clinics.
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http://dx.doi.org/10.1089/wound.2019.1064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155926PMC
June 2020

Imaging in Chronic Wound Diagnostics.

Adv Wound Care (New Rochelle) 2020 05 19;9(5):245-263. Epub 2020 Mar 19.

Department of Bioengineering, University of Texas at Arlington, Arlington, Texas.

Chronic wounds affect millions of patients worldwide, placing a huge burden on health care resources. Although significant progress has been made in the development of wound treatments, very few advances have been made in wound diagnosis. Standard imaging methods like computed tomography, single-photon emission computed tomography, magnetic resonance imaging, terahertz imaging, and ultrasound imaging have been widely employed in wound diagnostics. A number of noninvasive optical imaging modalities like optical coherence tomography, near-infrared spectroscopy, laser Doppler imaging, spatial frequency domain imaging, digital camera imaging, and thermal and fluorescence imaging have emerged over the years. While standard diagnostic wound imaging modalities provide valuable information, they cannot account for dynamic changes in the wound environment. In addition, they lack the capability to predict the healing outcome. Thus, there remains a pressing need for more efficient methods that can not only indicate the current state of the wound but also help determine whether the wound is on track to heal normally. Many imaging probes have been fabricated and shown to provide real-time assessment of tissue microenvironment and inflammatory responses . These probes have been demonstrated to noninvasively detect various changes in the wound environment, which include tissue pH, reactive oxygen species, fibrin deposition, matrix metalloproteinase production, and macrophage accumulation. This review summarizes the creation of these probes and their potential implications in wound monitoring.
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http://dx.doi.org/10.1089/wound.2019.0967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099416PMC
May 2020

Gut Microbiomes of Endangered Przewalski's Horse Populations in Short- and Long-Term Captivity: Implication for Species Reintroduction Based on the Soft-Release Strategy.

Front Microbiol 2020 12;11:363. Epub 2020 Mar 12.

School of Nature Conservation, Beijing Forestry University, Beijing, China.

Captivity maybe the only choice for survival of many endangered vertebrates, and understanding its broad effects is important for animal management and conservation, including breeding endangered species for subsequent release. Extreme environmental changes during captivity may influence survival ability in the wild. Captivity decreases gut bacterial diversity in a wide range of animals. However, most studies directly compare animals living in captivity with those in the wild, and there is a lack of understanding of effects of gradient shift in lifestyle during species reintroduction based on the soft-release strategy, which involves a confinement period in a field enclosure. Here, we used 16S rRNA amplicon sequencing to analyze gut microbiomes of 11 captive and 12 semi-wild Przewalski's horses (PH; ) under the same captivity environment, using fecal samples. A subset of samples with abundant extracted DNA (including 3 captive and 3 semi-wild individuals) was selected for whole-genome shotgun sequencing. We found that community diversity did not differ between the semi-wild PH and captive PH, but the semi-wild PH had significantly higher bacterial richness than those in captivity. Relative abundances of all dominant phyla were similar across the semi-wild or captive horses, while those of the non-dominant phyla Tenericutes and Proteobacteria were significantly higher in semi-wild PH than in captive PH. Beta diversity results indicated that bacterial communities of captives and semi-wild horses were clearly separated distinct when considering only composition. Functional profiling of the microbiomes revealed that the semi-wild and captive gut microbiomes were largely similar. However, semi-wild horse microbiomes had higher abundance of bacterial genes related to core metabolic processes, such as carbohydrates, amino acids, and nucleic acid metabolism. The study revealed that semi-wild PH could retain specific non-dominant bacteria and harbor a more diverse microbiome than the captive counterpart, and thus have higher metabolic potential to utilize the complex plants efficiently. These results indicate that change in host lifestyle may play a role in microbiome differentiation in the process of reintroduction, suggesting that a short period of time in captivity is acceptable for PH from the perspective of maintaining the richness of intestinal bacterial flora to some extent.
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http://dx.doi.org/10.3389/fmicb.2020.00363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081077PMC
March 2020

The antilymphatic metastatic effect of hyaluronic acid in a mouse model of oral squamous cell carcinoma.

Cancer Biol Ther 2020 06 18;21(6):541-548. Epub 2020 Mar 18.

Division of Oral Pathology, Beijing Institute of Dental Research, Beijing Stomatological Hospital & School of Stomatology, Capital Medical University, Beijing, China.

: Lymphatic metastasis is the main cause of low patient survival in cases of oral squamous cell carcinoma (OSCC). Several animal models have been established to uncover the mechanism that regulates lymph node metastasis of OSCC cells. Unfortunately, these models often take a long time to establish. The prolonged tumor burden can lead to animal cachexia, which may ultimately affect the experimental outcome. To overcome the disadvantages of these models, we established an orthotopic metastatic animal model of OSCC that showed quick lymph node metastasis potential.: DiR dye-labeled CAL27 cells were injected into tongue tissues of BALB/c nude mice, and the cells metastasized to lymph nodes on day 3. Metastasis was monitored using an in vivo imaging system and confirmed by histological observation. Using this model, we investigated the role of hyaluronic acid (HA) on the cervical metastasis of OSCC cells. Surprisingly, we found that the presence of HA significantly reduced the incidence of metastasis to cervical lymph nodes compared with the control group. Further analysis revealed that the presence of exogenous HA promoted mesenchymal-epithelial transition (MET) in primary tumors while reducing the metastatic potential of OSCC.: Our findings confirmed the establishment of a fast and reliable lymphatic metastatic mouse model of OSCC that can be used for investigating metastatic mechanisms and analyzing various antimetastasis strategies. An equally important discovery is the antimetastatic property of HA, which could provide a potential therapeutic strategy for OSCC.
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http://dx.doi.org/10.1080/15384047.2020.1736737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515457PMC
June 2020

Chemokine releasing particle implants for trapping circulating prostate cancer cells.

Sci Rep 2020 03 10;10(1):4433. Epub 2020 Mar 10.

Department of Bioengineering, the University of Texas at Arlington, Arlington, Texas, 76019, USA.

Prostate cancer (PCa) is the most prevalent cancer in U.S. men and many other countries. Although primary PCa can be controlled with surgery or radiation, treatment options of preventing metastatic PCa are still limited. To develop a new treatment of eradicating metastatic PCa, we have created an injectable cancer trap that can actively recruit cancer cells in bloodstream. The cancer trap is composed of hyaluronic acid microparticles that have good cell and tissue compatibility and can extend the release of chemokines to 4 days in vitro. We find that erythropoietin (EPO) and stromal derived factor-1α can attract PCa in vitro. Animal results show that EPO-releasing cancer trap attracted large number of circulating PCa and significantly reduced cancer spreading to other organs compared with controls. These results support that cancer trap may serve as a unique device to sequester circulating PCa cells and subsequently reduce distant metastasis.
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http://dx.doi.org/10.1038/s41598-020-60696-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064596PMC
March 2020

Quantum dot light-emitting diodes with an Al-doped ZnO anode.

Nanotechnology 2020 Apr 5;31(25):255203. Epub 2020 Mar 5.

Key Lab for Special Functional Materials, Ministry of Education, National & Local Joint Engineering Research Center for High-efficiency Display and Lighting Technology, School of Materials Science and Engineering, and Collaborative Innovation Center of Nano Functional Materials and Applications, Henan University, Kaifeng 475004, People's Republic of China.

A study of hybrid ZnCdSeS/ZnS quantum dot light-emitting diodes (QLEDs) device fabricated with indium tin oxide-free transparent electrodes is presented. Al-doped zinc oxide (AZO) prepared by magnetron sputtering is adopted in anode transparent electrodes for green QLEDs with different sputtering pressures. A Kelvin probe force microscopy measurement showed that AZO has a work function of approximately 5.0 eV. The AZO/poly(ethylene-dioxythiophene)/polystyrenesulfonate (PEDOT:PSS) interface can be adjusted by the sputtering pressures, which was confirmed by hole-only devices. AZO films with low surface roughness can form a good AZO/PEDOT:PSS interface, which can increase the holes' injection, and result in an improved charge balance. The maximum current efficiency, luminance, and external quantum efficiency of the optimized QLED devices under a sputtering pressure of 1 mTorr can achieve values of 50.75 cd A, 102 500 cd m, and 12.94%, respectively.
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http://dx.doi.org/10.1088/1361-6528/ab7cebDOI Listing
April 2020

Erratum: Dual target gene therapy to EML4-ALK NSCLC by a gold nanoshell-based system: Erratum.

Theranostics 2020;10(5):2402-2404. Epub 2020 Jan 18.

Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, 24th Tong Jia street, Nanjing 210009, Jiangsu Province, China.

[This corrects the article DOI: 10.7150/thno.24469.].
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http://dx.doi.org/10.7150/thno.43075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019152PMC
January 2020

Recruitment of endogenous progenitor cells by erythropoietin loaded particles for in situ cartilage regeneration.

Bioact Mater 2020 Mar 6;5(1):142-152. Epub 2020 Feb 6.

Bioengineering Department, University of Texas Southwestern Medical Center, The University of Texas at Arlington, Arlington, TX, 76019, USA.

Cartilage injury affects millions of people throughout the world, and at this time there is no cure. While transplantation of stem cells has shown some success in the treatment of injured cartilage, such treatment is limited by limited cell sources and safety concerns. To overcome these drawbacks, a microscaffolds system was developed capable of targeting, reducing the inflammatory response and recruiting endogenous progenitor cells to cartilage-defect. Erythropoietin (EPO)-loaded-hyaluronic acid (HA) microscaffolds (HA + EPO) were fabricated and characterized. HA-microscaffolds showed good cell-compatibility and could target chondrocytes via CD44 receptors. HA + EPO was designed to slowly release EPO while recruiting progenitor cells. Finally, the ability of HA + EPO to repair cartilage-defects was assessed using a rabbit model of full-thickness cartilage-defect. Our results showed that the intra-articular administration of EPO, HA, and EPO + HA reduced the number of inflammatory cells inside the synovial-fluid, while EPO + HA had the greatest anti-inflammatory effects. Furthermore, among all groups, EPO + HA achieved the greatest progenitor cell recruitment and subsequent chondrogenesis. The results of this work support that, by targeting and localizing the release of growth-factors, HA + EPO can reduce inflammatory responses and promote progenitor cells responses. This new platform represents an alternative treatment to stem-cell transplantation for the treatment of cartilage injury.
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http://dx.doi.org/10.1016/j.bioactmat.2020.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011041PMC
March 2020

Tracking and Imaging of Transplanted Stem Cells in Animals.

Methods Mol Biol 2020 ;2150:45-56

Department of Bioengineering, The University of Texas at Arlington, Arlington, TX, USA.

The shortage of organ donors has contributed to the rapid development of cell-based therapy in which stem cells are transplanted and administered to repair or regenerate damaged tissues or organs. The common sources of stem cells are embryonic, mesenchymal, stromal, and induced pluripotent cells. Despite the popularity of stem cell therapy, evaluation of the therapeutic efficiency of transplanted stem cells and their tracking in vivo remains a major challenge. Current imaging modalities such as magnetic resonance imaging, radionuclide imaging, and positron emission tomography have certain limitations such as toxicity, shorter circulation time, and higher cost. Here, we describe near-infrared imaging methods to track and monitor stem cell recruitment to the site of injury.
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http://dx.doi.org/10.1007/7651_2019_275DOI Listing
March 2021

A near-infrared fluorescent pH sensing film for wound milieu pH monitoring.

Exp Dermatol 2020 01 17;29(1):107-111. Epub 2019 Oct 17.

Department of Bioengineering, University of Texas at Arlington, Arlington, TX, USA.

Studies have shown that wound pH is a potentially influential factor in the healing process. Due to the flaws of traditional pH measurement approaches, wound pH measurement has not become part of current standard of care. A near-infrared pH-sensitive ratiometric film was created and characterized for measuring wound pH. This film was fabricated by physically absorbing poly (N-isopropyl Acrylamide) nanoparticles conjugated with pH-sensitive (CypHer5E) and pH-insensitive (Cy7) fluorescent dyes into 2-hydroxyethyl methacrylate hydrogel film. The pH pattern on wounds can be indirectly measured by pressing freshly discarded wound dressing on top of the pH-sensitive film and imaging it. In vitro tests show that the film can accurately and rapidly detect a wide range of pH (from pH 4 to 8) in wound milieu. Further, patient studies showed that, by measuring pH on wound contact side of discarded wound gauze, the pH and its non-homogeneous distribution on wounds can be indirectly determined. By comparing patients with different wound conditions, we find that near-infrared pH sensing film can be used to measure wound exudate pH with high accuracy and efficiency. In addition, wound pH determination can provide an accurate assessment of wound healing activity in real time.
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http://dx.doi.org/10.1111/exd.14046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989363PMC
January 2020

Design and evaluation of an imager for assessing wound inflammatory responses and bioburden in a pig model.

J Biomed Opt 2019 09;25(3):1-9

University of Texas at Arlington, Department of Bioengineering, Arlington, Texas, United States.

Our work details the development and characterization of a portable luminescence imaging device for detecting inflammatory responses and infection in skin wounds. The device includes a CCD camera and close-up lens integrated into a customizable 3D printed imaging chamber to create a portable light-tight imager for luminescence imaging. The chamber has an adjustable light portal that permits ample ambient light for white light imaging. This imager was used to quantify in real time the extent of two-dimensional reactive oxygen species (ROS) activity distribution using a porcine wound infection model. The imager was used to successfully visualize ROS-associated luminescent activities and . Using a pig full-thickness cutaneous wound model, we further demonstrate that this portable imager can detect the change of ROS activities and their relationship with vasculature in the wound environment. Finally, by analyzing ROS intensity and distribution, an imaging method was developed to distinguish infected from uninfected wounds. We discovered a distinct ROS pattern between bacteria-infected and control wounds corresponding to the microvasculature. The results presented demonstrate that this portable luminescence imager is capable of imaging ROS activities in cutaneous wounds in a large animal model, indicating suitability for future clinical applications.
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http://dx.doi.org/10.1117/1.JBO.25.3.032002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739619PMC
September 2019
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