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Optimizing surface-engineered ultra-small gold nanoparticles for highly efficient miRNA delivery to enhance osteogenic differentiation of bone mesenchymal stromal cells

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Nano Research 2017年第1期10卷 49-63页

作者： Meng Yu Bo Lei Chuanbo Gao Jin Yan peter X. ma Frontier Institute of Science and Technology Xi'an Jiaotong University Xi'an 710054 China State Key Laboratory for manufacturing Systems Engineering Xi'an Jiaotong University Xi'an 710054 China State Key Laboratory for Mechanical Behavior of materials Xi'an Jiootong University Xi'an 710054 China Department of Biomedical Engineering University of Michigan Ann Arbor M148109-2009 USA macromolecular Science and Engineering Center University of Michigan Ann Arbor M148109-1055 USA Department of materials Science and Engineering University of Michigan Ann Arbor M148109-1078 USA

Regulation of osteogenic differentiation of bone mesenchymal stromal cells （BMSCs） plays a critical role in bone regeneration. As small non-coding RNAs, microRNAs （miRNAs） play an important role in stem cell differentiation through regulating target-mRNA expression. Unfortunately, highly efficient and safe delivery of miRNAs to BMSCs to regulate their osteogenic differentiation remains challenging. Conventional inorganic nanocrystals have shown increased toxicity owing to their larger size precluding renal clearance. Here, we developed novel, surface-engineered, ultra-small gold nanoparticles （USAuNPs, 〈10 nm） for use as highly efficient miR-5106-delivery systems to enable regulation of BMSC differentiation. We exploited the effects of AuNPs coated layer-by-layer with polyethylenimine （PEI） and liposomes （Lipo） to enhance miR-5106-delivery activity and subsequent BMSC differentiation capacity. The PEI- and Lipo-coated AuNPs （Au@PEI@Lipo） showed negligible cytotoxicity, good miRNA-5106-binding affinity, highly efficient delivery of miRNAs to BMSCs, and long-term miRNA expression （21 days）. Additionally, compared with commercial Lipofectamine 3000 and 25 kD PEI, the optimized Au@PEI@Lipo-miR-5106 nanocomplexes significantly enhanced BMSC differentiation into osteoblast-like cells through activation of the Sox9 transcription factor. Our findings reveal a promising strategy for the rational design of ultra-small inorganic nanoparticles as highly efficient miRNA-delivery platforms for tissue regeneration and disease therapy.

关键词： ultra-small goldnanoparticles surface engineering microRNA (miRNA)delivery bone mesenchymalstromal cells osteogenic differentiation

Biomimetic delivery of signals for bone tissue engineering

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Bone Research 2018年第3期6卷 205-216页

作者： Ming Dang Laura Saunders Xufeng Niu Yubo Fan peter X.ma macromolecular Science and Engineering Center University of Michigan Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education School of Biological Science and Medical Engineering Beihang University Beijing Advanced Innovation Center for Biomedical Engineering Beihang University Department of Biologic and materials Sciences University of Michigan Department of Biomedical Engineering University of Michigan Department of materials Science and Engineering University of Michigan

Bone tissue engineering is an exciting approach to directly repair bone defects or engineer bone tissue for *** play a pivotal role in providing a template and extracellular environment to support regenerative cells and promote tissue regeneration. A variety of signaling cues have been identified to regulate cellular activity, tissue development, and the healing process. Numerous studies and trials have shown the promise of tissue engineering, but successful translations of bone tissue engineering research into clinical applications have been limited, due in part to a lack of optimal delivery systems for these signals. Biomedical engineers are therefore highly motivated to develop biomimetic drug delivery systems, which benefit from mimicking signaling molecule release or presentation by the native extracellular matrix during development or the natural healing process. Engineered biomimetic drug delivery systems aim to provide control over the location, timing, and release kinetics of the signal molecules according to the drug's physiochemical properties and specific biological mechanisms. This article reviews biomimetic strategies in signaling delivery for bone tissue engineering, with a focus on delivery systems rather than specific molecules. Both fundamental considerations and specific design strategies are discussed with examples of recent research progress, demonstrating the significance and potential of biomimetic delivery systems for bone tissue engineering.

关键词： exciting approach therefore highly motivated

Hybrid polymer biomaterials for bone tissue regeneration

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Frontiers of Medicine 2019年第2期13卷 189-201页

作者： Bo Lei Baolin Guo Kunal J.Rambhia peter X.ma Frontier Institute of Science and Technology Xi’an Jiaotong UniversityXi’an 710054China Department of Biomedical Engineering University of MichiganAnn ArborMI 48109USA Department of Biologic and materials Sciences University of MichiganAnn ArborMI 48109USA macromolecular Science and Engineering Center University of MichiganAnn ArborMI 48109USA Department of material Science and Engineering University of MichiganAnn ArborMI 48109USA

Native tissues possess unparalleled physiochemical and biological functions, which can be attributed to their hybrid polymer composition and intrinsic bioactivity. However, there are also various concerns or limitations over the use of natural materials derived from animals or cadavers, including the potential immunogenicity, pathogen transmission, batch to batch consistence and mismatch in properties for various applications. Therefore, there is an increasing interest in developing degradable hybrid polymer biomaterials with controlled properties for highly efficient biomedical applications. There have been efforts to mimic the extracellular protein structure such as nanofibrous and composite scaffolds, to functionalize scaffold surface for improved cellular interaction, to incorporate controlled biomolecule release capacity to impart biological signaling, and to vary physical properties of scaffolds to regulate cellular behavior. In this review, we highlight the design and synthesis of degradable hybrid polymer biomaterials and focus on recent developments in osteoconductive, elastomeric, photoluminescent and electroactive hybrid polymers. The review further exemplifies their applications for bone tissue regeneration.

关键词： hybrid polymer bone regeneration tissue engineering biomaterials

Functionalized scaffolds to enhance tissue regeneration

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Regenerative Biomaterials 2015年第1期2卷 47-57页

作者： Baolin Guo Bo Lei Peng Li peter X.ma Center for Biomedical Engineering and Regenerative Medicine Frontier Institute of Science and TechnologyXi’an Jiaotong UniversityXi’an 710049China Department of Biomedical Engineering University of Michigan Department of Biologic and materials Sciences University of Michigan1011North University AvenueRoom 2209 macromolecular Science and Engineering Center University of Michigan Department of materials Science and Engineering University of MichiganAnn ArborMI 48109USA

Tissue engineering scaffolds play a vital role in regenerative *** not only provides a temporary 3-dimensional support during tissue repair,but also regulates the cell behavior,such as cell adhesion,proliferation and *** this review,we summarize the development and trends of functional scaffolding biomaterials including electrically conducting hydrogels and nanocomposites of hydroxyapatite(HA)and bioactive glasses(BGs)with various biodegradable ***,the progress on the fabrication of biomimetic nanofibrous scaffolds from conducting polymers and composites of HA and BG via electrospinning,deposition and thermally induced phase separation is ***,bioactive molecules and surface properties of scaffolds are very important during tissue *** molecule-releasing scaffolds and antimicrobial surface coatings for biomedical implants and scaffolds are also reviewed.

关键词： biomaterials scaffolds electrically conductive polymers bioactive nanocomposites bone tissue engineering molecule-releasing scaffolds antimicrobial coatings

CHIP regulates bone mass by targeting multiple TRAF family members in bone marrow stromal cells

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Bone Research 2018年第2期6卷 145-154页

作者： Tingyu Wang Shan Li Dan Yi Guang-Qian Zhou Zhijie Chang peter X.ma Guozhi Xiao Di Chen Department of Pharmacy Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Department of Orthopedic Surgery Rush University Medical Center Department of Medical Cell Biology and Genetics Shenzhen Key Laboratory and the Center for Anti-Ageing and Regenerative Medicine Shenzhen University Medical School State Key Laboratory of Biomembrane and Membrane Biotechnology Tsinghua University School of Medicine Department of Biologic and materials Science University of Michigan

Carboxyl terminus of Hsp70-interacting protein（CHIP or STUB1） is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated that Chip deficient mice display bone loss phenotype due to increased osteoclast formation through enhancing TRAF6 activity in osteoclasts. In this study we provide novel evidence about the function of CHIP. We found that osteoblast differentiation and bone formation were also decreased in Chip KO mice. In bone marrow stromal（BMS） cells derived from Chip^-/- mice, expression of a panel of osteoblast marker genes was significantly decreased. ALP activity and mineralized bone matrix formation were also reduced in Chip-deficient BMS cells. We also found that in addition to the regulation of TRAF6, CHIP also inhibits TNFα-induced NF-κB signaling through promoting TRAF2 and TRAF5 degradation. Specific deletion of Chip in BMS cells downregulated expression of osteoblast marker genes which could be reversed by the addition of NF-κB inhibitor. These results demonstrate that the osteopenic phenotype observed in Chip^-/- mice was due to the combination of increased osteoclast formation and decreased osteoblast differentiation. Taken together, our findings indicate a significant role of CHIP in bone remodeling.

关键词： CHIP regulates bone mass targeting multiple TRAF family members marrow stromal cells

Multiple-sized Scaffold Design and Biologic Delivery

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Multiple-sized Scaffold Design and Biologic Delivery

Biomimetic polymer scaffolds for regeneration

2009年全国高分子学术论文报告会

作者： peter X ma University of Michigan Dental School Ann ArborMI 48109-1078 USA

＜正＞Regenerative medicine is an exciting field that aims at creating regenerative alternatives to harvested tissues for ***（synthetic temporary extracellular-matrices）provide three-dimensional environments for stem cells and anatomical templates for tissue *** fulfill these functions,we design biodegradable polymer scaffolds with structural features on multiple size *** mimic advantageous characteristics of the natural extracellular matrix,we

关键词： Scaffold biodegradable polymer tissue engineering regenerative medicine nanomaterials

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Biomimetic polymer scaffolds for regeneration

QTL analysis of soft scald in two apple populations

2007年全国高分子学术论文报告会

作者： peter X.ma

＜正＞Department of Biologic and materials Sciences,Department of Biomedical Engineering,macromolecular Science and Engineering Center,The University of Michigan,Ann Arbor,Michigan 48109-1078,USA（email:mapx@***）

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Horticulture Research 2016年第1期3卷 117-123页

作者： Kendra A McClure Kyle M Gardner peter ma Toivonen Cheryl R Hampson Jun Song Charles F Forney John DeLong Istvan Rajcan Sean Myles Department of Plant and Animal Sciences Faculty of AgricultureDalhousie UniversityTruroB2N 5E3Nova ScotiaCanada Department of Plant Agriculture Crop Science BuildingUniversity of GuelphGuelphN1G 2W1OntarioCanada Agriculture and Agri-Food Canada Fredericton Research and Development CentreFrederictonE3B 4Z7New BrunswickCanada Agriculture and Agri-Food Canada Summerland Research and Development CentreSummerlandV0H 1Z0British ColumbiaCanada Agriculture and Agri-Food Canada Kentville Research and Development CentreKentvilleB4N 1J5Nova ScotiaCanada

The apple(malus×domestica Borkh.)is one of the world’s most widely grown and valuable fruit *** demand for apples year round,storability has emerged as an important consideration for apple breeding *** scald is a cold storage-related disorder that results in sunken,darkened tissue on the fruit *** breeders are keen to generate new cultivars that do not suffer from soft scald and can thus be marketed year *** breeding approaches are protracted and labor intensive,and therefore marker-assisted selection(maS)is a valuable tool for *** advance maS for storage disorders in apple,we used genotyping-by-sequencing(GBS)to generate high-density genetic maps in two F1 apple populations,which were then used for quantitative trait locus(QTL)mapping of soft *** total,900 million DNA sequence reads were generated,but after several data filtering steps,only 2%of reads were ultimately used to create two genetic maps that included 1918 and 2818 single-nucleotide *** QTL associated with soft scald were identified in one of the bi-parental populations originating from parent 11W-12-11,an advanced breeding *** study demonstrates the utility of next-generation DNA sequencing technologies for QTL mapping in F1 populations,and provides a basis for the advancement of maS to improve storability of apples.

关键词： breeding cultivar apple

Primary graft dysfunction following lung transplantation:From pathogenesis to future frontiers

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World Journal of Transplantation 2023年第3期13卷 58-85页

作者： Sanjeet Singh Avtaar Singh Sudeep Das De Ahmed Al-Adhami Ramesh Singh peter ma Hopkins PhilipAlan Curry Department of Cardiothoracic Surgery Royal Infirmary of EdinburghEdinburgh EH164SAUnited Kingdom Institute of Cardiovascular and Medical Sciences University of GlasgowGlasgow G128QQUnited Kingdom Heart and Lung Transplant Unit Wythenshawe HospitalManchester M239NJUnited Kingdom Department of Heart and Lung Transplant Royal Papworth HospitalCambridge CB20AYUnited Kingdom Mechanical Circulatory Support Inova Health SystemFalls ChurchVA 22042United States Queensland Lung Transplant Service Prince Charles HospitalBrisbaneQLD 4032Australia Department of Cardiothoracic Surgery Golden Jubilee National HospitalGlasgow G814DYUnited Kingdom

Lung transplantation is the treatment of choice for patients with end-stage lung ***,just under 5000 lung transplants are performed worldwide ***,a major scourge leading to 90-d and 1-year mortality remains primary graft *** is a spectrum of lung injury ranging from mild to severe depending on the level of hypoxaemia and lung injury *** review aims to provide an in-depth analysis of the epidemiology,pathophysiology,risk factors,outcomes,and future frontiers involved in mitigating primary graft *** current diagnostic criteria are examined alongside changes from the previous *** also highlight the issues surrounding chronic lung allograft dysfunction and identify the novel therapies available for ex-vivo lung *** primary graft dysfunction remains a significant contributor to 90-d and 1-year mortality,ongoing research and development abreast with current technological advancements have shed some light on the issue in pursuit of future diagnostic and therapeutic tools.

关键词： Primary graft dysfunction Lung transplantation Pathophysiology Risk factors Extracorporeal membranous oxygenation