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Nanofiber matrix formulations for the delivery of Exendin-4 for tendon regeneration: In vitro and in vivo assessment

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Bioactive materials 2023年第7期25卷 42-60页

作者： Sama Abdulmalik Jack Gallo Jonathan Nip Sara Katebifar michael Arul Amir Lebaschi Lucas N.munch jenna m.bartly Shilpa Choudhary Ivo Kalajzic Yeshavanth Kumar Banasavadi-Siddegowdae Syam P.Nukavarapu Sangamesh G.Kumbar Department of Orthopedic Surgery University of Connecticut HealthFarmingtonCTUSA Department of Biomedical Engineering University of ConnecticutStorrsCTUSA Department of materials Science and Engineering University of ConnecticutStorrsCTUSA Department of Physiology and Neurobiology University of ConnecticutStorrsCTUSA Department of Immunology Center on AgingUniversity of Connecticut HealthFarmingtonCTUSA Department of Reconstructive Sciences University of Connecticut HealthFarmingtonCTUSA Surgical Neurology Branch National Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesdaMDUSA

Tendon and ligament injuries are the most common musculoskeletal injuries,which not only impact the quality of life but result in a massive economic *** interventions for tendon/ligament injuries utilize biological and/or engineered grafts to reconstruct damaged tissue,but these have *** matrices confer superior physicochemical properties over biological grafts but lack desirable bioactivity to promote tissue *** incorporating drugs can enhance bioactivity,large matrix surface areas and hydrophobicity can lead to uncontrolled burst release and/or incomplete release due to *** overcome these limitations,we evaluated the delivery of a peptide growth factor(exendin-4;Ex-4)using an enhanced nanofiber matrix in a tendon injury *** overcome drug surface binding due to matrix hydrophobicity of poly(caprolactone)(PCL)-which would be expected to enhance cell-material interactions-we blended PCL and cellulose acetate(CA)and electrospun nanofiber matrices with fiber diameters ranging from 600 to 1000 *** avoid burst release and protect the drug,we encapsulated Ex-4 in the open lumen of halloysite nanotubes(HNTs),sealed the HNT tube endings with a polymer blend,and mixed Ex-4-loaded HNTs into the polymer mixture before *** reduced burst release from~75%to~40%,but did not alter matrix morphology,fiber diameter,or tensile *** evaluated the bioactivity of the Ex-4 nanofiber formulation by culturing human mesenchymal stem cells(hmSCs)on matrix surfaces for 21 days and measuring tenogenic differentiation,compared with nanofiber matrices in basal media ***,we observed that Ex-4 nanofiber matrices accelerated the hmSC proliferation rate and elevated levels of sulfated glycosaminoglycan,tendon-related genes(Scx,mkx,and Tnmd),and ECm-related genes(Col-Ⅰ,Col-Ⅲ,and Dcn),compared to *** then assessed the safety and efficacy of Ex-4 nanofiber matrices in a full-thickness rat Achilles tendon

关键词： Nanofiber matrix formulation Protein delivery Soft tissue regeneration Halloysite nanotubes

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Viscoelastic analysis of single-component and composite PEG and alginate hydrogels

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Acta mechanica Sinica 2014年第1期30卷 7-14页

作者： jenna m.Shapiro michelle L.Oyen Cambridge University Engineering Department CambridgeUK Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health

Hydrogels, three-dimensional hydrophilic polymer networks, are appealing candidate materials for study- ing the cellular microenvironment as their substantial water content helps to better mimic soft tissue. However, hydrogels can lack mechanical stiffness, strength, and tough- ness. Composite hydrogel systems have been shown to improve upon mechanical properties compared to their single- component counterparts. Poly （ethylene glycol） dimethacrylate （PEGDmA） and alginate are polymers that have been used to form hydrogels for biological applications. Single- component and composite PEGDmA and alginate systems were fabricated with a range of total polymer concentrations. Bulk gels were mechanically characterized using spherical indentation testing and a viscoelastic analysis framework. An increase in shear modulus with increasing polymer con- centration was demonstrated for all systems. Alginate hydro- gels were shown to have a smaller viscoelastic ratio than the PEGDmA gels, indicating more extensive relaxation over time. Composite alginate and PEGDmA hydrogels exhib- ited a combination of the mechanical properties of the con- stituents, as well as a qualitative increase in toughness. Additionally, multiple hydrogel systems were produced that had similar shear moduli, but different viscoelastic behaviors. Accurate measurement of the mechanical properties of hydrogels is necessary in order to determine what parameters are key in modeling the cellular microenvironment.

关键词： Hydrogel Viscoelastic Indentation Nanoin-dentation Composite

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Oxidation state specific analysis of arsenic species in tissues of wild-type and arsenic(+3 oxidation state)methyltransferase-knockout mice

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Journal of Environmental Sciences 2016年第11期28卷 104-112页

作者： jenna m.Currier Christelle Douillet Zuzana Drobná miroslav Styblo Curriculum in Toxicology University of North Carolina at Chapel Hill Department of Nutrition Gillings School of Global Public Health University of North Carolina at Chapel Hill

Arsenic methyltransferase（As3mt） catalyzes the conversion of inorganic arsenic（i As） to its methylated metabolites, including toxic methylarsonite（mAs~Ⅲ） and dimethylarsinite（DmAs~Ⅲ）. Knockout（KO） of As3 mt was shown to reduce the capacity to methylate i As in mice. However, no data are available on the oxidation states of As species in tissues of these mice. Here, we compare the oxidation states of As species in tissues of male C57BL/6 As3mt-KO and wild-type（WT） mice exposed to arsenite（iA s~Ⅲ） in drinking water. WT mice were exposed to50 mg/L As and As3mt-KO mice that cannot tolerate 50 mg/L As were exposed to 0, 15, 20, 25 or30 mg/L As. iA s~Ⅲaccounted for 53% to 74% of total As in liver, pancreas, adipose, lung, heart, and kidney of As3mt-KO mice; tri- and pentavalent methylated arsenicals did not exceed 10% of total As. Tissues of WT mice retained iA s and methylated arsenicals： iA s~Ⅲ, mAs~Ⅲand DmAs~Ⅲ represented 55%‐68% of the total As in the liver, pancreas, and brain. High levels of methylated species, particularly mAs~Ⅲ, were found in the intestine of WT, but not As3mt-KO mice,suggesting that intestinal bacteria are not a major source of methylated As. Blood of WT mice contained significantly higher levels of As than blood of As3mt-KO mice. This study is the first to determine oxidation states of As species in tissues of As3mt-KO mice. Results will help to design studies using WT and As3mt-KO mice to examine the role of iA s methylation in adverse effects of iA s exposure.

关键词： Arsenic speciation analysis Hydride generation-cryotrapping-atomic absorption spectrometry Arsenic(+ 3 oxidation state) methyltransferase As3mt knockout mice

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Decision making for managing Community Flood Risks:Perspectives of United States Floodplain managers

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International Journal of Disaster Risk Science 2021年第5期12卷 649-660页

作者： jenna Tyler Abdul-Akeem Sadiq Douglas S.Noonan Rebecca m.Entress School of Public Administration University of Central FloridaOrlandoFL 32801USA O'Neill School of Public and Environmental Affairs Indiana University–Purdue University IndianapolisIN 46202USA

To reduce flood losses,floodplain managers make decisions on how to effectively manage their community’s flood *** there is a growing body of research that examines how individuals and households make decisions to manage their flood risks,far less attention has been directed at understanding the decision-making processes for flood management at the community *** study aimed to narrow this research gap by examining floodplain managers’perceptions of the quality of their community’s flood management decision-making *** gathered from interviews with 200 floodplain managers in the United States indicate that most floodplain managers perceive their community’s flood management decision-making processes to be *** results also indicate that communities participating in the Federal Emergency management Agency’s Community Rating System,as well as communities with a higher level of concern for flooding and a lower poverty rate,are significantly more likely to report better flood management decision-making processes.

关键词： Community flood risk management Decision making Floodplain managers United States

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mixing and matching SmXL proteins to fine-tune strigolactone responses

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molecular Plant 2024年第8期17卷 1167-1169页

作者： jenna E.Hountalas Shelley Lumba Department of Cell&Systems Biology University of Toronto25 Willcocks StreetTorontoON M5S 3B2Canada Centre for the Analysis of Genome Evolution and Function University of Toronto25 Willcocks StreetTorontoON M5S 3B2Canada

A common mechanism in plant hormone signaling is hormonedependent degradation of downstream *** the case of strigolactone(SL)signaling,one group of SUPPRESSOR OF mORE AXILLARY BRANCHES 2(mAX2)1-LIKE(SmXL)proteins undergoes hormone-dependent degradation,while another does not.A recent publication in molecular Plant by Li et al.(2024)illustrates that mixing and matching a SmXL resistant to SL degradation with a SmXL sensitive to SL degradation finely tunes SL *** phenomenon could reflect a naturally occurring negative transdominance,which is a dominantnegative effect arising not from a mutant allele of the same gene but rather from a different gene altogether(Veitia,2007).This trans-acting protein attenuates SL-dependent degradation of the SmXL *** findings have exciting implications for how different SmXL combinations could result in a gradient of SL responses.

关键词： complex. matching degradation

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Advances in targeted nanotherapeutics： From bioconjugation to biomimicry

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Nano Research 2018年第10期11卷 4999-5016页

作者： Danielle m. Valcourt jenna Harris Rachel S. Riley megan Dang Jianxin Wang Emily S. Day 161 Colburn L ab Department of Biomedical Engineering University of Delaware Newark DE 19716 USA 201 DuPont Hall Department of Materials Science & Engineering University o f Delaware Newark DE 79716 USA 4701 Ogletown Stanton Road Helen F. Graham Cancer Center & Research Institute Newark DE 19713 USA

Since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles （NPs） that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-target effects seen with conventional treatments like chemotherapy. Initial endeavors focused on the bioconjugation of targeting agents to NPs, and more recently, researchers have begun to develop biomimetic NP platforms that can avoid immune recognition to maximally accumulate in tumors. In this review, we describe the advantages and limitations of each of these targeting strategies. First, we review developments in bioconjugation strategies, where NPs are coated with biomolecules such as antibodies, aptamers, peptides, and small molecules to enable cell-specific binding. While bioconjugated NPs offer many exciting features and have improved pharmacokinetics and biodistribution relative to unmodified NPs, they are still recognized by the body as ＂foreign＂, resulting in their clearance by the mononuclear phagocytic system （mPS）. To overcome this limitation, researchers have recently begun to investigate biomimetic approaches that can hide NPs from immune recognition and reduce clearance by the mPS. These biomimetic NPs fall into two distinct categories： synthetic NPs that present naturally occurring structures, and NPs that are completely disguised by natural structures. Overall bioconjugated and biomimetic NPs have substantial potential to improve upon conventional treatments by reducing off-target effects through site-specific delivery. and they show great promise for future standards of care. Here, we provide a summary of each strategy, discuss considerations for their design moving forward, and highlight their potential clinical impact on cancer therapy.

关键词： targeting nanoparticles cancer biomimicry bioconjugation delivery

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Lions, hyenas and mobs （oh my!）

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Current Zoology 2017年第3期63卷 313-322页

作者： Kenna D.S. LEHmANN Tracy m. mONTGOmERY Sarah m. mACLACHLAN jenna m. PARKERC livia S. SPAGNUOLO Kelsey J. VANDEWETERING Patrick S. BILLS Kay E. HOLEKAmP Department of Integrative Biology Michigan State University 288 Farm Lane Room 203 East Lansing MI 48824 USA Ecology Evolutionary Biology and Behavior Michigan State University 293 Farm Lane Room 103 East Lansing MI 48824 USA Department of Fish Wildlife and Conservation Biology Colorado State University 1474 Campus Delivery Fort Collins CO 80523 USA Conservation Ecology and Environmental Informatics School of Natural Resources and Environment University of Michigan 440 Church St. Ann Arbor MI 48109 USA Institute for Cyber Enabled Research Michigan State University Biomedical & Physical Sciences Building 567 Wilson Road Room 1440 East Lansing MI 48824 USA

Understanding the factors that facilitate the emergence of cooperation among organisms is central to the study of social evolution. Spotted hyenas Crocuta crocuta frequently cooperate to mob lions Panthera leo, approaching the lions as a tightknit group while vocalizing loudly in an attempt to overwhelm them and drive them away. Whereas cooperative mobbing behavior has been well documented in birds and some mammals, to our knowledge it has never been described during interactions between 2 apex predators. Using a 27-year dataset, we characterize lion-hyena encoun- ters, assess rates of mobbing behavior observed during these interactions, and inquire whether mobbing results in successful acquisition of food. Lions and hyenas interacted most often at fresh kills, especially as prey size and the number of hyenas present increased. Possession of food at the beginning of an interaction positively affected retention of that food by each predator species. The presence of male lions increased the probability of an interspecific interaction but decreased the likelihood of hyenas obtaining or retaining possession of the food. Hyena mobbing rates were highest at fresh kills, but lower when adult male lions were present. The occurrence of mobbing was predicted by an increase in the number of hyenas present. Whether or not mobbing resulted in acquisition of food from lions was predicted by an increase in the number of mobs formed by the hyenas present, suggesting that cooperation among hyenas enhances their fitness.

关键词： competition cooperation hyena lion mobbing sociality.

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Biopolymer-nanotube nerve guidance conduit drug delivery for peripheral nerve regeneration:In vivo structural and functional assessment

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Bioactive materials 2021年第9期6卷 2881-2893页

作者： Ohan S.manoukian Swetha Rudraiah michael R.Arul jenna m.Bartley Jiana T.Baker Xiaojun Yu Sangamesh G.Kumbar Department of Biomedical Engineering University of ConnecticutStorrsCTUSA Department of Orthopedic Surgery University of Connecticut HealthFarmingtonCTUSA Department of Pharmaceutical Sciences University of Saint JosephHartfordCTUSA Department of Immunology Center on AgingUniversity of Connecticut HealthFarmingtonCTUSA Department of Biomedical Engineering Stevens Institute of TechnologyHobokenNJUSA

Peripheral nerve injuries account for roughly 3%of all trauma patients with over 900,000 repair procedures annually in the *** all extremity peripheral nerve injuries,51%require nerve repair with a transected *** current gold-standard treatment for peripheral nerve injuries,autograft repair,has several *** constructs are currently only suitable for short gaps or small diameter ***,we investigate novel nerve guidance conduits with aligned microchannel porosity that deliver sustained-release of neurogenic 4-aminopyridine(4-AP)for peripheral nerve regeneration in a critical-size(15 mm)rat sciatic nerve transection *** results of functional walking track analysis,morphometric evaluations of myelin development,and histological assessments of various markers confirmed the equivalency of our drug-conduit with autograft *** nerves showed formation of thick myelin,presence of S100 and neurofilament markers,and promising functional *** conduit’s aligned microchannel architecture may play a vital role in physically guiding axons for distal target reinnervation,while the sustained release of 4-AP may increase nerve conduction,and in turn synaptic neurotransmitter release and upregulation of critical Schwann cell neurotrophic ***,our nerve construct design facilitates efficient and efficacious peripheral nerve regeneration via a drug delivery system that is feasible for clinical applications.

关键词： Peripheral nerve regeneration Nerve guidance conduit Sciatic nerve transection Small-molecule drug delivery Neurotrophic factor Functional recovery

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Transcriptome landscape of the early Brassica napus seed

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Journal of Integrative Plant Biology 2019年第5期61卷 639-650页

作者： Dylan J.Ziegler Deirdre Khan jenna L.Kalichuk michael G.Becker mark F.Belmonte University of manitoba

Brassica napus L.(canola) is one of the world’s most economically important oilseeds. Despite our growing knowledge of Brassica genetics, we still know little about the genes and gene regulatory networks underlying early seed development. In this work, we use laser microdissection coupled with RNA sequencing to profile gene activity of both the maternal and filial subregions of the globular seed. We find subregions of the chalazal end including the chalazal endosperm, chalazal proliferating tissue, and chalazal seed coat, have unique transcriptome profiles associated with hormone biosynthesis and polysaccharide metabolism. We confirm that the chalazal seed coat is uniquely enriched for sucrose biosynthesis and transport, and that the chalazal endosperm may function as an important regulator of the maternal region through brassinosteroid synthesis. The chalazal proliferating tissue,a poorly understood subregion, was specifically enriched in transcripts associated with megasporogenesis and trehalose biosynthesis, suggesting this ephemeral structure plays an important role in both sporophytic development and carbon nutrient balance, respectively. Finally, compartmentalization of transcription factors and their regulatory circuits has uncovered previously unknown roles for the chalazal pole in early seed development.

关键词： Brassica napus L.(canola) understood subregion

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microstructural abnormalities are evident by histology but not HR-pQCT at the periosteal cortex of the human tibia under CVD and T2D conditions

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medicine in Novel Technology and Devices 2021年第2期10卷 33-40页

作者： Barbara Garita jenna maligro Saghi Sadoughi Po Hung Wu Ellen Liebenberg Andrew Horvai Thomas m.Link Galateia J.Kazakia Department of Radiology and Biomedical Imaging University of CaliforniaSan Francisco185 Berry St Suite 350San FranciscoCA94107USA Department of Orthopaedic Surgery University of CaliforniaSan Francisco513 Parnassus AvenueSan FranciscoCA94143USA Department of Pathology University of CaliforniaSan Francisco18254th StSan FranciscoCA94143USA

Cortical bone microstructure deficits may increase fracture risk in individuals with cardiovascular disease and *** resolution peripheral quantitative computed tomography(HR-pQCT)enables in vivo microstructure characterization but is limited in its ability to visualize important biological *** conducted histological analyses and HR-pQCT imaging of distal tibia bone samples from 6 donors with cardiovascular disease(CVD)and type 2 diabetes mellitus(T2D).Histology but not HR-pQCT identified previously undocumented morphopathological deficits that may contribute to cortical bone *** observations may provide guidance for improved HR-pQCT microstructural characterization as well as insight into mechanisms of cortical bone degradation.

关键词： Cortical bone porosity Type 2 diabetes HR-pQCT

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