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Recent advances on the systems metabolically engineered Pseudomonas species as versatile biosynthetic platforms for the production of polyhydroxyalkanoates

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Systems Microbiology and Biomanufacturing 2024年第2期4卷 473-499页

作者： Hye Min Song Seo Young Jo Haeyoung Lee Subeen Jeon Dohye Yun Chaerin Kim Jina Son Yu Jung Sohn Jong-Il Choi Si Jae Park Department of Chemical Engineering and Materials Science Graduate Program in System Health Science and EngineeringEwha Womans UniversitySeoul 03760Republic of Korea Department of Biotechnology and Bioengineering Chonnam National UniversityGwangju 61186Republic of Korea

Pseudomonas *** been considered one of the most promising microbial platform strains due to its versatile metabolism,enabling the valorization of waste materials into value-added chemical *** the native producer of polyhydroxyal-kanoates(PHAs),the biodegradable biopolyesters,it has been widely engineered by various metabolic engineering tools for the production of PHAs composed of short-chain-length and medium-chain-length monomers with adjustable composition from diverse carbon sources,ranging from pure sugars to crude oils and fatty *** review discusses the feasibility of Pseudomonas *** the industrial host strain and the recent advances regarding the systems metabolic engineering strategies for PHAs production in Pseudomonas sp.

关键词： Pseudomonas sp. Polyhydroxyalkanoates Systems metabolic engineering Synthetic biology Fermentation

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Mussel-inspired sulfated hyaluronan cryogel patch with antioxidant, anti-inflammatory, and drug-loading properties for multifunctional wound adhesives

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Bioactive Materials 2024年第10期40卷 582-596页

作者： Wonmoon Song Young Hwan Choi Young Gi Moon Changyub Lee M.Nivedhitha Sundaram Nathaniel S.Hwang School of Chemical and Biological Engineering Institute for Chemical ProcessesSeoul National UniversitySeoul08826Republic of Korea Interdisciplinary Program in Bioengineering Seoul National UniversitySeoul08826Republic of Korea Bio-MAX/N-Bio Institute Institute of BioEngineeringSeoul National UniversitySeoul08826Republic of Korea Division of Pediatric Cardiac Surgery Department of SurgeryJohns Hopkins School of MedicineBaltimoreMDUSA Institute of Engineering Research Seoul National UniversitySeoul08826Republic of Korea

Wounds, characterized by the disruption of the continuity of body tissues resulting from external trauma,manifest in diverse types and locations. Although numerous wound dressings are available for various woundscenarios, it remains challenging to find an integrative wound dressing capable of addressing diverse woundsituations. We focused on utilizing sulfated hyaluronan (sHA), known for its anti-inflammatory properties andcapacity to load cationic drugs. By conjugating catechol groups to sHA (sHA-CA), we achieved several advantagesin wound healing: 1) Fabrication of patches through crosslinking with catechol-modified high-molecularweighthyaluronan (HA(HMW)-CA), 2) Adhesiveness that enabled stable localization, 3) Radical scavenging thatcould synergize with the immunomodulation of sHA. The sHA-CA patches demonstrated therapeutic efficacy inthree distinct murine wound models: diabetic wound, hepatic hemorrhage, and post-surgical adhesion. Collectively,these findings underscore the potential of the sHA-CA patch as a promising candidate for the nextgenerationwound dressing.

关键词： Adhesive patch Anti-inflammation Sulfated hyaluronic acid Post-surgical adhesion Diabetic wound Hemostasis

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Modular, programmable RNA sensing using ADAR editing in living cells (vol 41, pg 482, 2023)

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NATURE BIOTECHNOLOGY 2023年第4期41卷 577-577页

作者： Kaseniit, K. Eerik Katz, Noa Kolber, Natalie S. Call, Connor C. Wengier, Diego L. Cody, Will B. Sattely, Elizabeth S. Gao, Xiaojing J. Department of Bioengineering Stanford University Stanford CA USA Department of Chemical Engineering Stanford University Stanford CA USA ChEM-H Chemistry/Biology Interface Training Program Stanford University Stanford CA USA Howard Hughes Medical Institute Stanford CA USA

With the increasing availability of single-cell transcriptomes, RNA signatures offer a promising basis for targeting living cells. Molecular RNA sensors would enable the study of and therapeutic interventions for specific cell types/states in diverse contexts, particularly in human patients and non-model organisms. Here we describe a modular, programmable system for live RNA sensing using adenosine deaminases acting on RNA (RADAR). We validate, and then expand, our basic design, characterize its performance, and analyze its compatibility with human and mouse transcriptomes. We identify strategies to boost output levels and improve the dynamic range. Additionally, we show that RADAR enables compact AND logic. In addition to responding to transcript levels, RADAR can distinguish disease-relevant sequence alterations of transcript identities, such as point mutations and fusions. Finally, we demonstrate that RADAR is a self-contained system with the potential to function in diverse organisms.

关键词： Gene targeting Molecular engineering in plants Nucleic-acid therapeutics Synthetic biology Translation

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Design considerations for piezocomposite materials for electrical stimulation in medical implants

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Journal of Medical engineering and Technology 2022年第5期46卷 402-414页

作者： Krech, Ember Haas, Evan Tideman, Grace Reinsch, Bonnie Friis, Elizabeth Bioengineering Graduate Program University of Kansas LawrenceKS United States Department of Mechanical Engineering University of Kansas LawrenceKS United States Department of Chemical Engineering University of Kansas LawrenceKS United States

Incidence of non-union following long bone fracture fixation and spinal fusion procedures is increasing, and very costly for patients and the medical system. Direct current (DC) electrical stimulation has shown success as an adjunct therapy to stimulate bone healing and increase surgery success rates, though drawbacks of current devices and implantable battery packs have limited widespread use. Energy harvesting utilising piezoelectric materials has been widely studied for powering devices without a battery, and a preclinical animal study has shown efficacy of a piezocomposite spinal fusion implant resulting in faster, more robust fusion. Most piezoelectric energy harvesters operate most effectively at high frequencies, limiting power generation from loads experienced by orthopaedic implants during human motion. This work characterises the efficient power generation capability of a novel composite piezoelectric material under simulated walking loads. Building on compliant layer adaptive composite stacks (CLACS), the power generation of mixed-mode CLACS (MMCLACS) is defined. Utilising poling direction to capitalise on in-plane strain generation due to compliant layer expansion, MMCLACS significantly increased power output compared to a standard piezo stack. The combination of radial and through-thickness poled piezoelectric elements within a stack to create MMCLACS significantly increases power generation under low-frequency dynamic loads. This technology can be adapted to a variety of architectures and assembled as a load-bearing energy harvester within current implants. MMCLACS integrated with implants would provide enough power to deliver bone healing electrical stimulation directly to the fusion site, decreasing non-union rates, and also could provide quantitative assessment of healing progression through load sensing. © 2022 Informa UK Limited, trading as Taylor & Francis Group.

关键词： Energy harvesting

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Zwitterionic peptides:Tunable next-generation stealth nanoparticle modifications

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Bioactive Materials 2023年第9期27卷 113-124页

作者： Clyde Overby Soomin Park Austin Summers Danielle S.W.Benoit Department of Biomedical Engineering University of Rochester RochesterNYUSA Center for Musculoskeletal Research University of RochesterRochesterNYUSA Department of Biology University of Rochester RochesterNYUSA Department of Biology Duquesne UniversityPAUSA Department of Chemical Engineering University of RochesterRochesterNYUSA Materials Science Program University of RochesterRochesterNYUSA Knight Campus for Accelerating Scientific Impact Department of BioengineeringUniversity of OregonEugeneORUSA

Adsorption of proteins to nanoparticles(NPs),a complex process that results in a protein corona,is controlled by NP surface properties that define NP interactions in *** to control adsorbed protein quantity through surface modification have led to improvements in circulation time or ***,current approaches have yet to be identified to control adsorbed protein identities within the ***,we report the development and characterization of diverse zwitterionic peptides(ZIPs)for NP anti-fouling surface functionalization with specific and controllable affinity for protein adsorption profiles defined by ZIP *** serum exposure of ZIP-conjugated NPs and proteomics analysis of the resulting corona,we determined that protein adsorption profiles depend not on the exact composition of the ZIPs but on the sequence and order of charges along the sequence(charge motif).These findings pave the way for developing tunable ZIPs to orchestrate specific ZIP-NP protein adsorption profiles as a function of ZIP charge motif to better control cell and tissue specificity and pharmacokinetics and provide new tools for investigating relationships between protein corona and biological ***,overall ZIP diversity enabled by the diversity of amino acids may ameliorate adaptive immune responses.

关键词： Nanoparticles Protein corona Surface functionalization Peptide design Cellular uptake

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Bioceramic-mediated chondrocyte hypertrophy promotes calcified cartilage formation for rabbit osteochondral defect repair

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Bioactive Materials 2024年第10期40卷 306-317页

作者： Rachel H.Koh Junhee Kim Jeong-Uk Kim Seunghyun L.Kim Arun Kumar Rajendran Seunghun SLee Heesoo Lee Joo Hyun Kim Ji Hoon Jeong Yongsung Hwang Jong Woo Bae Nathaniel S.Hwang School of Chemical and Biological Engineering Institute of Chemical ProcessesSeoul National UniversitySeoul08826South Korea Interdisciplinary Program in Bioengineering Seoul National UniversitySeoul08826South Korea Department of Biomedical Engineering Dongguk UniversitySeoul10326South Korea Soonchunhyang Institute of Medi-bio Science(SIMS) Soonchunhyang UniversityCheonan31151South Korea Department of Integrated Biomedical Science Soonchunhyang UniversityAsan31538South Korea Department of Orthopaedic Surgery Konkuk University Chungju HospitalKonkuk University School of MedicineChungju27376South Korea BioMAX Institute Seoul National UniversitySeoul08826South Korea

Osteochondral tissue is a highly specialized and complex tissue composed of articular cartilage and subchondral bone that are separated by a calcified cartilage *** or gradient scaffolds,often in conjunction with stem cells and growth factors,have been developed to mimic the respective layers for osteochondral defect *** this study,we designed a hyaline cartilage-hypertrophic cartilage bilayer graft(RGD/RGDW)with ***,we demonstrated that RGD peptide-modified chondroitin sulfate cryogel(RGD group)is chondro-conductive and capable of hyaline cartilage ***,we incorporated whitlockite(WH),a Mg^(2+)-containing calcium phosphate,into RGD cryogel(RGDW group)to induce chondrocyte hypertrophy and form collagen X-rich hypertrophic *** is the first study to use WH to produce hypertrophic ***-laden RGDW cryogel exhibited significantly upregulated expression of hypertrophy markers in vitro and formed ectopic hypertrophic cartilage in vivo,which mineralized into calcified cartilage in bone ***,RGD cryogel and RGDW cryogel were combined into bilayer(RGD/RGDW group)and implanted into rabbit osteochondral defect,where RGD layer supports hyaline cartilage regeneration and bioceramic-containing RGDW layer promotes calcified cartilage *** the RGD group(monolayer)formed hyaline-like neotissue that extends into the subchondral bone,the RGD/RGDW group(bilayer)regenerated hyaline cartilage tissue confined to its respective layer and promoted osseointegration for integrative defect repair.

关键词： Bioceramic Whitlockite Bilayer scaffold Chondrocyte hypertrophy Osteochondral defect repair

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Goldilocks Energy Minimum: Peptide-Based Reversible Aggregation and Biosensing (Vol 15, Pg 42293, 2023)

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ACS APPLIED MATERIALS & INTERFACES 2023年第41期15卷 48838-48838页

作者： Yim, Wonjun Retout, Maurice Chen, Amanda A. Ling, Chuxuan Amer, Lubna Jin, Zhicheng Chang, Yu-Ci Chavez, Saul Barrios, Karen Lam, Benjamin Li, Zhi Zhou, Jiajing Shi, Lingyan Pascal, Tod A. Jokerst, Jesse V. Materials Science and Engineering Program University of California San Diego La Jolla California 92093 United States Department of Nano and Chemical Engineering University of California San Diego La Jolla California 92093 United States Shu Chien-Gene Lay Department of Bioengineering University of California San Diego La Jolla California 92093 United States Department of Radiology University of California San Diego La Jolla California 92093 United States

Colorimetric biosensors based on gold nanoparticle (AuNP) aggregation are often challenged by matrix interference in biofluids, poor specificity, and limited utility with clinical samples. Here, we propose a peptide-driven nanoscale disassembly approach, where AuNP aggregates induced by electrostatic attractions are dissociated in response to proteolytic cleavage. Initially, citrate-coated AuNPs were assembled via a short cationic peptide (RRK) and characterized by experiments and simulations. The dissociation peptides were then used to reversibly dissociate the AuNP aggregates as a function of target protease detection, i.e., main protease (Mpro), a biomarker for severe acute respiratory syndrome coronavirus 2. The dissociation propensity depends on peptide length, hydrophilicity, charge, and ligand architecture. Finally, our dissociation strategy provides a rapid and distinct optical signal through Mpro cleavage with a detection limit of 12.3 nM in saliva. Our dissociation peptide effectively dissociates plasmonic assemblies in diverse matrices including 100% human saliva, urine, plasma, and seawater, as well as other types of plasmonic nanoparticles such as silver. Our peptide-enabled dissociation platform provides a simple, matrix-insensitive, and versatile method for protease sensing.

关键词： colorimetric biosensor DLVO theory reversible aggregation dissociation peptide matrix-insensitive SARS-CoV-19

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Nanoconfinement effect of nanoporous carbon electrodes for ionic liquid-based aluminum metal anode

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Journal of Energy Chemistry 2022年第11期31卷 121-127,I0005页

作者： Juhee Yoon Seongbak Moon Son Ha Hyung-Kyu Lim Hyoung-Joon Jin Young Soo Yun Program in Environmental and Polymer Engineering Inha UniversityIncheon 22212South Korea Department of Polymer Science and Engineering Inha UniversityIncheon 22212South Korea KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul 02841South Korea Division of Chemical Engineering and Bioengineering Kangwon National UniversityGangwon-do 24341South Korea Department of Integrative Energy Engineering Korea UniversitySeoul 02841South Korea

Rechargeable aluminum batteries(RABs),which use earth-abundant and high-volumetric-capacity metal anodes(8040 m Ah cm-3),have great potential as next-generation power sources because they use cheaper resources to deliver higher energies,compared to current lithium ion ***,the mechanism of charge delivery in the newly developed,ionic liquid-based electrolytic system for RABs differs from that in conventional organic ***,targeted research efforts are required to address the large overpotentials and cycling decay encountered in the ionic liquid-based electrolytic *** this study,a nanoporous carbon(NPC)electrode with well-developed nanopores is used to develop a high-performance aluminum *** negatively charged nanopores can provide quenched dynamics of electrolyte molecules in the aluminum deposition process,resulting in an increased collision *** fast chemical equilibrium of anionic species induced by the facilitated anionic collisions leads to more favorable reduction reactions that form aluminum *** nanoconfinement effect causes separated nucleation and growth of aluminum nanoparticles in the multiple confined nanopores,leading to higher coulombic efficiencies and more stable cycling performance compared with macroporous carbon black and 2D stainless steel electrodes.

关键词： Nanoconfinement effect Nanoporous carbon Ionic liquid electrolyte Metal anode Aluminum batteries Multivalent batteries

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Transferrin-Mediated Nanophotosensitizer to Enhance Phototherapy with Photoacoustic Imaging Under Hypoxia

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CCS Chemistry 2025年第4期7卷 1127-1141页

作者： Mengyao Yang Yunyoung Nah Donghyeon Oh Xingshu Li Heejeong Kim Sinyoung Park Junha Lim Aibing Chen Chulhong Kim Won Jong Kim Juyoung Yoon College of Chemical and Pharmaceutical Engineering Hebei University of Science and TechnologyShijiazhuang 050018 Department of Chemistry and Nanoscience Ewha Womans UniversitySeoul 03760 Department of Chemistry POSTECH-Catholic Biomedical Engineering InstitutePOSTECHPohang 37673 Department of Electrical Engineering Convergence IT EngineeringMechanical Engineeringand Medical Science and EngineeringMedical Device Innovation CenterPOSTECHPohang 37673 Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy College of ChemistryFuzhou UniversityFuzhou 350108 School of Interdisciplinary Bioscience and Bioengineering POSTECHPohang 37673 Graduate Program in Innovative Biomaterials Convergence Ewha Womans UniversitySeoul 03760

Various obstacles[poor tissue penetration,hypoxic tumor microenvironment,and reactive oxygen species(ROS)production quenching due to aggregation]obstruct imaging-guided high-efficiency phototherapy targeting ***,nanophthalocyanine(ZnPcN4-TF)is elaborately designed based on a synthetic phthalocyanine derivative(ZnPcN4)and nonimmunogenic transferrin(TF)through multiple noncovalent interactions for photoacoustic(PA)imaging-guided *** conjugating electron-rich amino groups effectively suppressed fluorescence and ROS generation due to the strong photoinduced electron transfer effect,ZnPcN4 became an ideal photothermal and PA imaging ***4-TF not only effectively targeted tumor sites and accumulated there,but also,surprisingly,facilitated the enhancement of ROS production via a type I process in an aggregate compared to ZnPcN4 itself,potentially due to accelerated electron ***,ZnPcN4-TF had a substantially more powerful photothermal effect than ZnPcN4 ***,this design effectively overcomes the obstacles to photodynamic therapy(aggregation-related ROS generation quenching in a hypoxic environment).Furthermore,PA imaging solves the tissue penetration challenge in optical *** study provides a broader base for designing novel photosensitizers to improve phototherapy under hypoxia.

关键词： photoacoustic imaging type I reactive oxygen species photothermal effect tumor accumulation self-assembly

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Advances in AAV capsid engineering: Integrating rational design, directed evolution and machine learning

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Molecular Therapy 2025年第5期33卷 1937-1945页

作者： Nisanov, Alan M. Rivera de Jesús, Julio A. Schaffer, David V. Department of Chemistry University of California Berkeley Berkeley 94720 CA United States Department of Chemical and Biomolecular Engineering University of California Berkeley Berkeley 94720 CA United States Department of Bioengineering University of California Berkeley Berkeley 94720 CA United States Graduate Program in Bioengineering University of California Berkeley San Francisco and University of California Berkeley 94720 CA United States Department of Neurological Surgery University of California San Francisco 94143 CA United States Department of Molecular and Cell Biology University of California Berkeley Berkeley 94720 CA United States

Adeno-associated virus (AAV) has emerged as a highly promising vector for human gene therapy due to its favorable safety profile, versatility, and ability to transduce a wide range of tissues. However, natural AAV serotypes have shortcomings, including suboptimal transduction efficiency, pre-existing immunity, and a lack of tissue specificity, that hinder their therapeutic potential. To address these challenges, significant efforts are being applied to engineer novel AAV capsids. Rational design leverages structural insights to enhance capsid properties, directed evolution enables unbiased selection of superior variants, and machine learning accelerates discovery by computational analysis of high-throughput screening results to enable predictive algorithms. These strategies have yielded novel capsids with improved transduction efficiency, reduced immunogenicity, and enhanced tissue targeting. Future advances that continue to integrate such multi-disciplinary approaches will further drive the clinical translation of AAV-based therapies. © 2025 The Authors

关键词： AAV directed evolution gene therapy high-throughput screening machine learning next generation sequencing NGS rational design

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