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Heparin-functionalized polymer graft surface eluting MK2 inhibitory peptide to improve hemocompatibility and anti-neointimal activity.
Lee Y, Le Thi P, Seon GM, Ryu SB, Brophy CM, Kim Y, Park JC, Park KD, Cheung-Flynn J, Sung HJ
(2017) J Control Release 266: 321-330
MeSH Terms: Animals, Anticoagulants, Cell Movement, Cell Proliferation, Heparin, Humans, Myocytes, Smooth Muscle, Neointima, Peptides, Platelet Adhesiveness, Polyesters, Rats, Sprague-Dawley, Saphenous Vein, Thrombosis
Show Abstract · Added May 22, 2018
The leading cause of synthetic graft failure includes thrombotic occlusion and intimal hyperplasia at the site of vascular anastomosis. Herein, we report a co-immobilization strategy of heparin and potent anti-neointimal drug (Mitogen Activated Protein Kinase II inhibitory peptide; MK2i) by using a tyrosinase-catalyzed oxidative reaction for preventing thrombotic occlusion and neointimal formation of synthetic vascular grafts. The binding of heparin-tyramine polymer (HT) onto the polycarprolactone (PCL) surface enhanced blood compatibility with significantly reduced protein absorption (64.7% decrease) and platelet adhesion (85.6% decrease) compared to bare PCL surface. When loading MK2i, 1) the HT depot surface gained high MK2i-loading efficiency through charge-charge interaction, and 2) this depot platform enabled long-term, controlled release over 4weeks (92-272μg/mL of MK2i). The released MK2i showed significant inhibitory effects on VSMC migration through down-regulated phosphorylation of target proteins (HSP27 and CREB) associated with intimal hyperplasia. In addition, it was found that the released MK2i infiltrated into the tissue with a cumulative manner in ex vivo human saphenous vein (HSV) model. This present study demonstrates that enzymatically HT-coated surface modification is an effective strategy to induce long-term MK2i release as well as hemocompatibility, thereby improving anti-neointimal activity of synthetic vascular grafts.
Copyright © 2017 Elsevier B.V. All rights reserved.
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1 Members
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14 MeSH Terms
Remodeling of injectable, low-viscosity polymer/ceramic bone grafts in a sheep femoral defect model.
Talley AD, McEnery MA, Kalpakci KN, Zienkiewicz KJ, Shimko DA, Guelcher SA
(2017) J Biomed Mater Res B Appl Biomater 105: 2333-2343
MeSH Terms: Animals, Bone Remodeling, Bone Substitutes, Ceramics, Femur, Polyesters, Polyurethanes, Sheep
Show Abstract · Added March 25, 2018
Ceramic/polymer composite bone grafts offer the potential advantage of combining the osteoconductivity of ceramic component with the ductility of polymeric component, resulting in a graft that meets many of the desired properties for bone void fillers (BVF). However, the relative contributions of the polymer and ceramic components to bone healing are not well understood. In this study, we compared remodeling of low-viscosity (LV) ceramic/poly(ester urethane) composites to a ceramic BVF control in a sheep femoral condyle plug defect model. LV composites incorporating either ceramic (LV/CM) or allograft bone (LV/A) particles were evaluated. We hypothesized that LV/CM composites which have the advantageous handling properties of injectability, flowability, and settability would heal comparably to the CM control, which was evaluated for up to 2 years to study its long-term degradation properties. Remodeling of LV/CM was comparable to that observed for the CM control, as evidenced by new bone formation on the surface of the ceramic particles. At early time points (4 months), LV/CM composites healed similar to the ceramic clinical control, while LV/A components showed more variable healing due to osteoclast-mediated resorption of the allograft particles. At longer time points (12-15 months), healing of LV/CM composites was more variable due to the nonhomogeneous distribution and lower concentration of the ceramic particles compared to the ceramic clinical control. Resorption of the ceramic particles was almost complete at 2 years. This study highlights the importance of optimizing the loading and distribution of ceramic particles in polymer/ceramic composites to maximize bone healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2333-2343, 2017.
© 2016 Wiley Periodicals, Inc.
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8 MeSH Terms
Fiber/collagen composites for ligament tissue engineering: influence of elastic moduli of sparse aligned fibers on mesenchymal stem cells.
Thayer PS, Verbridge SS, Dahlgren LA, Kakar S, Guelcher SA, Goldstein AS
(2016) J Biomed Mater Res A 104: 1894-901
MeSH Terms: Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Shape, Collagen, DNA, Elastic Modulus, Ligaments, Male, Mesenchymal Stem Cells, Polyesters, Polyurethanes, RNA, Messenger, Rats, Sprague-Dawley, Stress, Mechanical, Tissue Engineering
Show Abstract · Added March 25, 2018
Electrospun microfibers are attractive for the engineering of oriented tissues because they present instructive topographic and mechanical cues to cells. However, high-density microfiber networks are too cell-impermeable for most tissue applications. Alternatively, the distribution of sparse microfibers within a three-dimensional hydrogel could present instructive cues to guide cell organization while not inhibiting cell behavior. In this study, thin (∼5 fibers thick) layers of aligned microfibers (0.7 μm) were embedded within collagen hydrogels containing mesenchymal stem cells (MSCs), cultured for up to 14 days, and assayed for expression of ligament markers and imaged for cell organization. These microfibers were generated through the electrospinning of polycaprolactone (PCL), poly(ester-urethane) (PEUR), or a 75/25 PEUR/PCL blend to produce microfiber networks with elastic moduli of 31, 15, and 5.6 MPa, respectively. MSCs in composites containing 5.6 MPa fibers exhibited increased expression of the ligament marker scleraxis and the contractile phenotype marker α-smooth muscle actin versus the stiffer fiber composites. Additionally, cells within the 5.6 MPa microfiber composites were more oriented compared to cells within the 15 and 31 MPa microfiber composites. Together, these data indicate that the mechanical properties of microfiber/collagen composites can be tuned for the engineering of ligament and other target tissues. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1894-1901, 2016.
© 2016 Wiley Periodicals, Inc.
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15 MeSH Terms
Novel behavior of the chromatographic separation of linear and cyclic polymers.
Montenegro-Burke JR, Bennett JM, McLean JA, Hercules DM
(2016) Anal Bioanal Chem 408: 677-81
MeSH Terms: Chromatography, Gel, Mass Spectrometry, Molecular Structure, Polyesters, Polyurethanes
Show Abstract · Added December 17, 2018
In various polymerization processes, the formation of a wide variety of chains, not only in length but also in chemical composition, broadly complicates comprehensive polymer characterization. In this communication, we compare different stationary and mobile phases for the analysis of complex polymer mixtures via size-exclusion chromatography-mass spectrometry (SEC-MS). To the best of our knowledge, we report novel chromatographic effects for the separation of linear and cyclic oligomers for polyesters (PE) and polyurethanes (PUR). A complete separation for the different structures was achieved for both polymer types with a single-solvent system (acetonitrile, ACN) and without extensive optimization. Additionally, cyclic species were found to show an inverse elution profile compared to their linear counterparts, suggesting distinct physical properties between species.
1 Communities
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MeSH Terms
Common gynecological challenges in adolescents with sickle cell disease.
Stimpson SJ, Rebele EC, DeBaun MR
(2016) Expert Rev Hematol 9: 187-96
MeSH Terms: Adolescent, Age Factors, Anemia, Iron-Deficiency, Anemia, Sickle Cell, Bone Density, Female, Genital Diseases, Female, Genotype, Gonadal Hormones, Hemoglobin, Sickle, Humans, Male, Menarche, Menorrhagia, Menstrual Cycle, Menstruation, Pain, Polyesters, Polystyrenes, Progesterone, Sex Factors, Vascular Diseases
Show Abstract · Added April 7, 2016
Sickle cell anemia is one of the most common genetic blood disorders worldwide. Individuals with sickle cell disease (SCD) experience clinical manifestations such as chronic anemia, developmental delay, vaso-occlusive pain, acute chest syndrome, and neurological complications. Adolescent girls with SCD face unique gynecological challenges including delayed puberty marked by a later onset in menarche, vaso-occlusive pain associated with their menstrual cycle, and underdiagnosed abnormal uterine bleeding. This review focuses on these challenges with particular emphasis on delayed menarche and vaso-occlusive pain episodes associated with menstruation, in addition to the evaluation and initial management of heavy menstrual bleeding for adolescents with SCD. We highlight research opportunities in this neglected area to help enhance the comprehensive care model for this population.
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22 MeSH Terms
Dual drug delivery of tamoxifen and quercetin: Regulated metabolism for anticancer treatment with nanosponges.
Lockhart JN, Stevens DM, Beezer DB, Kravitz A, Harth E
(2015) J Control Release 220: 751-7
MeSH Terms: Animals, Antineoplastic Combined Chemotherapy Protocols, Biological Availability, Biotransformation, Breast Neoplasms, Cell Line, Tumor, Cell Survival, Chemistry, Pharmaceutical, Cross-Linking Reagents, Cytochrome P-450 CYP3A, Delayed-Action Preparations, Dose-Response Relationship, Drug, Drug Carriers, Drug Stability, Female, Gastric Juice, Glucuronosyltransferase, Intestinal Secretions, Kinetics, Mice, Nanomedicine, Nanoparticles, Particle Size, Polyesters, Quercetin, Solubility, Tamoxifen
Show Abstract · Added February 15, 2016
We report the synthesis and encapsulation of polyester nanosponge particles (NPs) co-loaded with tamoxifen (TAM) and quercetin (QT) to investigate the loading, release and in vitro metabolism of a dual drug formulation. The NPs are made in two variations, 4% and 8% crosslinking densities, to evaluate the effects on metabolism and release kinetics. The NP-4% formulation with a particle size of 89.3 ± 14.8 nm was found to have loading percentages of 6.91 ± 0.13% TAM and 7.72 ± 0.15% QT after targeting 10% (w/w) each. The NP-8% formulation with a particle size of 91.5 ± 9.8 nm was found to have loading percentages of 7.26 ± 0.10% TAM and 7.80 ± 0.12% QT. The stability of the formulation was established in simulated gastrointestinal fluids, and the metabolism of TAM was shown to be reduced 2-fold and 3-fold for NP-4%s and NP-8%s, respectively, while QT metabolism was reduced 3 and 4-fold. The implications for improved bioavailability of the NP formulations were supported by cytotoxicity results that showed a similar efficacy to free dual drug formulations and even enhanced anti-cancer effects in the recovery condition. This work demonstrates the suitability of the nanosponges not only as a dual release drug delivery system but also enabling a regulated metabolism through the capacity of a nanonetwork. The variation in crosslinking enables a dual release with tailored release kinetics and suggests improved bioavailability aided by a reduced metabolism.
Copyright © 2015 Elsevier B.V. All rights reserved.
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27 MeSH Terms
Combinatorial polymer matrices enhance in vitro maturation of human induced pluripotent stem cell-derived cardiomyocytes.
Chun YW, Balikov DA, Feaster TK, Williams CH, Sheng CC, Lee JB, Boire TC, Neely MD, Bellan LM, Ess KC, Bowman AB, Sung HJ, Hong CC
(2015) Biomaterials 67: 52-64
MeSH Terms: Biomechanical Phenomena, Cell Differentiation, Cell Line, Gene Expression Regulation, Humans, Induced Pluripotent Stem Cells, Mitochondria, Myocardial Contraction, Myocytes, Cardiac, Myosin Light Chains, Polyesters, Polyethylene Glycols, Protein Isoforms, Real-Time Polymerase Chain Reaction, Reproducibility of Results, Sequence Analysis, RNA, Troponin I
Show Abstract · Added August 4, 2015
Cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CMs) hold great promise for modeling human heart diseases. However, iPSC-CMs studied to date resemble immature embryonic myocytes and therefore do not adequately recapitulate native adult cardiomyocyte phenotypes. Since extracellular matrix plays an essential role in heart development and maturation in vivo, we sought to develop a synthetic culture matrix that could enhance functional maturation of iPSC-CMs in vitro. In this study, we employed a library of combinatorial polymers comprising of three functional subunits - poly-ε-caprolacton (PCL), polyethylene glycol (PEG), and carboxylated PCL (cPCL) - as synthetic substrates for culturing human iPSC-CMs. Of these, iPSC-CMs cultured on 4%PEG-96%PCL (each % indicates the corresponding molar ratio) exhibit the greatest contractility and mitochondrial function. These functional enhancements are associated with increased expression of cardiac myosin light chain-2v, cardiac troponin I and integrin alpha-7. Importantly, iPSC-CMs cultured on 4%PEG-96%PCL demonstrate troponin I (TnI) isoform switch from the fetal slow skeletal TnI (ssTnI) to the postnatal cardiac TnI (cTnI), the first report of such transition in vitro. Finally, culturing iPSC-CMs on 4%PEG-96%PCL also significantly increased expression of genes encoding intermediate filaments known to transduce integrin-mediated mechanical signals to the myofilaments. In summary, our study demonstrates that synthetic culture matrices engineered from combinatorial polymers can be utilized to promote in vitro maturation of human iPSC-CMs through the engagement of critical matrix-integrin interactions.
Published by Elsevier Ltd.
1 Communities
5 Members
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17 MeSH Terms
A new paradigm for treatment of glaucoma.
Galloway RL, Delisi M, Harth EM, Mawn LA
(2014) Conf Proc IEEE Eng Med Biol Soc 2014: 6147-50
MeSH Terms: Animals, Blindness, Delayed-Action Preparations, Endoscopy, Equipment Design, Glaucoma, Humans, Magnetic Resonance Imaging, Nanoparticles, Nanostructures, Nanotechnology, Neuroprotective Agents, Phantoms, Imaging, Polyesters, Skull, Swine
Show Abstract · Added February 15, 2016
Glaucoma is the leading irreversible cause of blindness in the world. We are developing a new image-guidance system to deliver a neuroprotective drug in a controlled release nanosponge. The system consists of a magnetically tracked image-guidance system, the nanosponge material and the drug. We have characterized the performance of each aspect in phantoms, animals and ex-vivo human tissue.
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16 MeSH Terms
Uncoupling angiogenesis and inflammation in peripheral artery disease with therapeutic peptide-loaded microgels.
Zachman AL, Wang X, Tucker-Schwartz JM, Fitzpatrick ST, Lee SH, Guelcher SA, Skala MC, Sung HJ
(2014) Biomaterials 35: 9635-48
MeSH Terms: Angiogenesis Inducing Agents, Animals, Anti-Inflammatory Agents, Cell Line, Drug Carriers, Human Umbilical Vein Endothelial Cells, Inflammation, Injections, Matrix Metalloproteinase 9, Matrix Metalloproteinase Inhibitors, Mice, Neovascularization, Physiologic, Oligopeptides, Peripheral Arterial Disease, Polyesters, Tumor Necrosis Factor-alpha
Show Abstract · Added October 30, 2014
Peripheral artery disease (PAD) is characterized by vessel occlusion and ischemia in the limbs. Treatment for PAD with surgical interventions has been showing limited success. Moreover, recent clinical trials with treatment of angiogenic growth factors proved ineffective as increased angiogenesis triggered severe inflammation in a proportionally coupled fashion. Hence, the overarching goal of this research was to address this issue by developing a biomaterial system that enables controlled, dual delivery of pro-angiogenic C16 and anti-inflammatory Ac-SDKP peptides in a minimally-invasive way. To achieve the goal, a peptide-loaded injectable microgel system was developed and tested in a mouse model of PAD. When delivered through multiple, low volume injections, the combination of C16 and Ac-SDKP peptides promoted angiogenesis, muscle regeneration, and perfusion recovery, while minimizing detrimental inflammation. Additionally, this peptide combination regulated inflammatory TNF-α pathways independently of MMP-9 mediated pathways of angiogenesis in vitro, suggesting a potential mechanism by which angiogenic and inflammatory responses can be uncoupled in the context of PAD. This study demonstrates a translatable potential of the dual peptide-loaded injectable microgel system for PAD treatment.
Copyright © 2014 Elsevier Ltd. All rights reserved.
1 Communities
3 Members
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16 MeSH Terms
Tunable delivery of siRNA from a biodegradable scaffold to promote angiogenesis in vivo.
Nelson CE, Kim AJ, Adolph EJ, Gupta MK, Yu F, Hocking KM, Davidson JM, Guelcher SA, Duvall CL
(2014) Adv Mater 26: 607-14, 506
MeSH Terms: Animals, Drug Carriers, Gene Silencing, Mice, Neovascularization, Physiologic, Polyesters, RNA, Small Interfering, Tissue Scaffolds, Urethane
Added May 19, 2014
2 Communities
2 Members
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9 MeSH Terms