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Identification of a pro-angiogenic functional role for FSP1-positive fibroblast subtype in wound healing.
Saraswati S, Marrow SMW, Watch LA, Young PP
(2019) Nat Commun 10: 3027
MeSH Terms: Actins, Animals, Bone Marrow Transplantation, Calcium-Binding Proteins, Cell Differentiation, Disease Models, Animal, Fibroblasts, Fibrosis, Green Fluorescent Proteins, Human Umbilical Vein Endothelial Cells, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myocardial Infarction, Myocardium, Neovascularization, Physiologic, S100 Calcium-Binding Protein A4, Transplantation Chimera, Wound Healing
Show Abstract · Added March 24, 2020
Fibrosis accompanying wound healing can drive the failure of many different organs. Activated fibroblasts are the principal determinants of post-injury pathological fibrosis along with physiological repair, making them a difficult therapeutic target. Although activated fibroblasts are phenotypically heterogeneous, they are not recognized as distinct functional entities. Using mice that express GFP under the FSP1 or αSMA promoter, we characterized two non-overlapping fibroblast subtypes from mouse hearts after myocardial infarction. Here, we report the identification of FSP1-GFP cells as a non-pericyte, non-hematopoietic fibroblast subpopulation with a predominant pro-angiogenic role, characterized by in vitro phenotypic/cellular/ultrastructural studies and in vivo granulation tissue formation assays combined with transcriptomics and proteomics. This work identifies a fibroblast subtype that is functionally distinct from the pro-fibrotic αSMA-expressing myofibroblast subtype. Our study has the potential to shift our focus towards viewing fibroblasts as molecularly and functionally heterogeneous and provides a paradigm to approach treatment for organ fibrosis.
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Substrate stiffness heterogeneities disrupt endothelial barrier integrity in a micropillar model of heterogeneous vascular stiffening.
VanderBurgh JA, Hotchkiss H, Potharazu A, Taufalele PV, Reinhart-King CA
(2018) Integr Biol (Camb) 10: 734-746
MeSH Terms: Adherens Junctions, Animals, Aorta, Atherosclerosis, Cattle, Cell Adhesion, Cell Communication, Cell Movement, Dimethylpolysiloxanes, Endothelial Cells, Endothelium, Vascular, Focal Adhesions, Human Umbilical Vein Endothelial Cells, Humans, Leukocytes, Materials Testing, Neutrophils, Phenotype, Tunica Intima, Vascular Stiffness, Vinculin
Show Abstract · Added April 10, 2019
Intimal stiffening has been linked with increased vascular permeability and leukocyte transmigration, hallmarks of atherosclerosis. However, recent evidence indicates age-related intimal stiffening is not uniform but rather characterized by increased point-to-point heterogeneity in subendothelial matrix stiffness, the impact of which is much less understood. To investigate the impact of spatially heterogeneous matrix rigidity on endothelial monolayer integrity, we develop a micropillar model to introduce closely-spaced, step-changes in substrate rigidity and compare endothelial monolayer phenotype to rigidity-matched, uniformly stiff and compliant substrates. We found equivalent disruption of adherens junctions within monolayers on step-rigidity and uniformly stiff substrates relative to uniformly compliant substrates. Similarly, monolayers cultured on step-rigidity substrates exhibited equivalent percentages of leukocyte transmigration to monolayers on rigidity-matched, uniformly stiff substrates. Adherens junction tension and focal adhesion density, but not size, increased within monolayers on step-rigidity and uniformly stiff substrates compared to more compliant substrates suggesting that elevated tension is disrupting adherens junction integrity. Leukocyte transmigration frequency and time, focal adhesion size, and focal adhesion density did not differ between stiff and compliant sub-regions of step-rigidity substrates. Overall, our results suggest that endothelial monolayers exposed to mechanically heterogeneous substrates adopt the phenotype associated with the stiffer matrix, indicating that spatial heterogeneities in intimal stiffness observed with age could disrupt endothelial barrier integrity and contribute to atherogenesis.
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21 MeSH Terms
Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
Evangelou E, Warren HR, Mosen-Ansorena D, Mifsud B, Pazoki R, Gao H, Ntritsos G, Dimou N, Cabrera CP, Karaman I, Ng FL, Evangelou M, Witkowska K, Tzanis E, Hellwege JN, Giri A, Velez Edwards DR, Sun YV, Cho K, Gaziano JM, Wilson PWF, Tsao PS, Kovesdy CP, Esko T, Mägi R, Milani L, Almgren P, Boutin T, Debette S, Ding J, Giulianini F, Holliday EG, Jackson AU, Li-Gao R, Lin WY, Luan J, Mangino M, Oldmeadow C, Prins BP, Qian Y, Sargurupremraj M, Shah N, Surendran P, Thériault S, Verweij N, Willems SM, Zhao JH, Amouyel P, Connell J, de Mutsert R, Doney ASF, Farrall M, Menni C, Morris AD, Noordam R, Paré G, Poulter NR, Shields DC, Stanton A, Thom S, Abecasis G, Amin N, Arking DE, Ayers KL, Barbieri CM, Batini C, Bis JC, Blake T, Bochud M, Boehnke M, Boerwinkle E, Boomsma DI, Bottinger EP, Braund PS, Brumat M, Campbell A, Campbell H, Chakravarti A, Chambers JC, Chauhan G, Ciullo M, Cocca M, Collins F, Cordell HJ, Davies G, de Borst MH, de Geus EJ, Deary IJ, Deelen J, Del Greco M F, Demirkale CY, Dörr M, Ehret GB, Elosua R, Enroth S, Erzurumluoglu AM, Ferreira T, Frånberg M, Franco OH, Gandin I, Gasparini P, Giedraitis V, Gieger C, Girotto G, Goel A, Gow AJ, Gudnason V, Guo X, Gyllensten U, Hamsten A, Harris TB, Harris SE, Hartman CA, Havulinna AS, Hicks AA, Hofer E, Hofman A, Hottenga JJ, Huffman JE, Hwang SJ, Ingelsson E, James A, Jansen R, Jarvelin MR, Joehanes R, Johansson Å, Johnson AD, Joshi PK, Jousilahti P, Jukema JW, Jula A, Kähönen M, Kathiresan S, Keavney BD, Khaw KT, Knekt P, Knight J, Kolcic I, Kooner JS, Koskinen S, Kristiansson K, Kutalik Z, Laan M, Larson M, Launer LJ, Lehne B, Lehtimäki T, Liewald DCM, Lin L, Lind L, Lindgren CM, Liu Y, Loos RJF, Lopez LM, Lu Y, Lyytikäinen LP, Mahajan A, Mamasoula C, Marrugat J, Marten J, Milaneschi Y, Morgan A, Morris AP, Morrison AC, Munson PJ, Nalls MA, Nandakumar P, Nelson CP, Niiranen T, Nolte IM, Nutile T, Oldehinkel AJ, Oostra BA, O'Reilly PF, Org E, Padmanabhan S, Palmas W, Palotie A, Pattie A, Penninx BWJH, Perola M, Peters A, Polasek O, Pramstaller PP, Nguyen QT, Raitakari OT, Ren M, Rettig R, Rice K, Ridker PM, Ried JS, Riese H, Ripatti S, Robino A, Rose LM, Rotter JI, Rudan I, Ruggiero D, Saba Y, Sala CF, Salomaa V, Samani NJ, Sarin AP, Schmidt R, Schmidt H, Shrine N, Siscovick D, Smith AV, Snieder H, Sõber S, Sorice R, Starr JM, Stott DJ, Strachan DP, Strawbridge RJ, Sundström J, Swertz MA, Taylor KD, Teumer A, Tobin MD, Tomaszewski M, Toniolo D, Traglia M, Trompet S, Tuomilehto J, Tzourio C, Uitterlinden AG, Vaez A, van der Most PJ, van Duijn CM, Vergnaud AC, Verwoert GC, Vitart V, Völker U, Vollenweider P, Vuckovic D, Watkins H, Wild SH, Willemsen G, Wilson JF, Wright AF, Yao J, Zemunik T, Zhang W, Attia JR, Butterworth AS, Chasman DI, Conen D, Cucca F, Danesh J, Hayward C, Howson JMM, Laakso M, Lakatta EG, Langenberg C, Melander O, Mook-Kanamori DO, Palmer CNA, Risch L, Scott RA, Scott RJ, Sever P, Spector TD, van der Harst P, Wareham NJ, Zeggini E, Levy D, Munroe PB, Newton-Cheh C, Brown MJ, Metspalu A, Hung AM, O'Donnell CJ, Edwards TL, Psaty BM, Tzoulaki I, Barnes MR, Wain LV, Elliott P, Caulfield MJ, Million Veteran Program
(2018) Nat Genet 50: 1412-1425
MeSH Terms: Adult, Aged, Aged, 80 and over, Blood Pressure, Cardiovascular Diseases, Cells, Cultured, Female, Genetic Loci, Genetic Predisposition to Disease, Genetic Testing, Genetics, Population, Genome-Wide Association Study, Human Umbilical Vein Endothelial Cells, Humans, Hypertension, Life Style, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors
Show Abstract · Added March 3, 2020
High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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Matrix stiffness regulates vascular integrity through focal adhesion kinase activity.
Wang W, Lollis EM, Bordeleau F, Reinhart-King CA
(2019) FASEB J 33: 1199-1208
MeSH Terms: Adherens Junctions, Animals, Antigens, CD, Cadherins, Capillary Permeability, Chick Embryo, Endothelium, Vascular, Enzyme Activation, Extracellular Matrix, Female, Focal Adhesion Protein-Tyrosine Kinases, Human Umbilical Vein Endothelial Cells, Humans, Mice, Mice, Transgenic, Phosphorylation, Protein Transport, Tyrosine, src-Family Kinases
Show Abstract · Added April 10, 2019
Tumor vasculature is known to be more permeable than the vasculature found in healthy tissue, which in turn can lead to a more aggressive tumor phenotype and impair drug delivery into tumors. While the stiffening of the stroma surrounding solid tumors has been reported to increase vascular permeability, the mechanism of this process remains unclear. Here, we utilize an in vitro model of tumor stiffening, ex ovo culture, and a mouse model to investigate the molecular mechanism by which matrix stiffening alters endothelial barrier function. Our data indicate that the increased endothelial permeability caused by heightened matrix stiffness can be prevented by pharmaceutical inhibition of focal adhesion kinase (FAK) both in vitro and ex ovo. Matrix stiffness-mediated FAK activation determines Src localization to cell-cell junctions, which then induces increased vascular endothelial cadherin phosphorylation both in vitro and in vivo. Endothelial cells in stiff tumors have more activated Src and higher levels of phosphorylated vascular endothelial cadherin at adherens junctions compared to endothelial cells in more compliant tumors. Altogether, our data indicate that matrix stiffness regulates endothelial barrier integrity through FAK activity, providing one mechanism by which extracellular matrix stiffness regulates endothelial barrier function. Additionally, our work also provides further evidence that FAK is a promising potential target for cancer therapy because FAK plays a critical role in the regulation of endothelial barrier integrity.-Wang, W., Lollis, E. M., Bordeleau, F., Reinhart-King, C. A. Matrix stiffness regulates vascular integrity through focal adhesion kinase activity.
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19 MeSH Terms
Ascorbic acid attenuates endothelial permeability triggered by cell-free hemoglobin.
Kuck JL, Bastarache JA, Shaver CM, Fessel JP, Dikalov SI, May JM, Ware LB
(2018) Biochem Biophys Res Commun 495: 433-437
MeSH Terms: Antioxidants, Ascorbic Acid, Capillary Permeability, Endothelium, Vascular, Hemoglobins, Human Umbilical Vein Endothelial Cells, Humans, Sepsis
Show Abstract · Added March 14, 2018
BACKGROUND - Increased endothelial permeability is central to shock and organ dysfunction in sepsis but therapeutics targeted to known mediators of increased endothelial permeability have been unsuccessful in patient studies. We previously reported that cell-free hemoglobin (CFH) is elevated in the majority of patients with sepsis and is associated with organ dysfunction, poor clinical outcomes and elevated markers of oxidant injury. Others have shown that Vitamin C (ascorbate) may have endothelial protective effects in sepsis. In this study, we tested the hypothesis that high levels of CFH, as seen in the circulation of patients with sepsis, disrupt endothelial barrier integrity.
METHODS - Human umbilical vein endothelial cells (HUVEC) were grown to confluence and treated with CFH with or without ascorbate. Monolayer permeability was measured by Electric Cell-substrate Impedance Sensing (ECIS) or transfer of C-inulin. Viability was measured by trypan blue exclusion. Intracellular ascorbate was measured by HPLC.
RESULTS - CFH increased permeability in a dose- and time-dependent manner with 1 mg/ml of CFH increasing inulin transfer by 50% without affecting cell viability. CFH (1 mg/ml) also caused a dramatic reduction in intracellular ascorbate in the same time frame (1.4 mM without CFH, 0.23 mM 18 h after 1 mg/ml CFH, p < 0.05). Pre-treatment of HUVECs with ascorbate attenuated CFH induced permeability.
CONCLUSIONS - CFH increases endothelial permeability in part through depletion of intracellular ascorbate. Supplementation of ascorbate can attenuate increases in permeability mediated by CFH suggesting a possible therapeutic approach in sepsis.
Copyright © 2017 Elsevier Inc. All rights reserved.
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8 MeSH Terms
The Dihydroxy Metabolite of the Teratogen Thalidomide Causes Oxidative DNA Damage.
Wani TH, Chakrabarty A, Shibata N, Yamazaki H, Guengerich FP, Chowdhury G
(2017) Chem Res Toxicol 30: 1622-1628
MeSH Terms: Catalase, DNA Cleavage, DNA Damage, Free Radical Scavengers, HEK293 Cells, Hep G2 Cells, Human Umbilical Vein Endothelial Cells, Humans, Microscopy, Fluorescence, Plasmids, Poly(ADP-ribose) Polymerases, Reactive Oxygen Species, Teratogens, Thalidomide
Show Abstract · Added March 14, 2018
Thalidomide [α-(N-phthalimido)glutarimide] (1) is a sedative and antiemetic drug originally introduced into the clinic in the 1950s for the treatment of morning sickness. Although marketed as entirely safe, more than 10 000 babies were born with severe birth defects. Thalidomide was banned and subsequently approved for the treatment of multiple myeloma and complications associated with leprosy. Although known for more than 5 decades, the mechanism of teratogenicity remains to be conclusively understood. Various theories have been proposed in the literature including DNA damage and ROS and inhibition of angiogenesis and cereblon. All of the theories have their merits and limitations. Although the recently proposed cereblon theory has gained wide acceptance, it fails to explain the metabolism and low-dose requirement reported by a number of groups. Recently, we have provided convincing structural evidence in support of the presence of arene oxide and the quinone-reactive intermediates. However, the ability of these reactive intermediates to impart toxicity/teratogenicity needs investigation. Herein we report that the oxidative metabolite of thalidomide, dihydroxythalidomide, is responsible for generating ROS and causing DNA damage. We show, using cell lines, the formation of comet (DNA damage) and ROS. Using DNA-cleavage assays, we also show that catalase, radical scavengers, and desferal are capable of inhibiting DNA damage. A mechanism of teratogenicity is proposed that not only explains the DNA-damaging property but also the metabolism, low concentration, and species-specificity requirements of thalidomide.
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14 MeSH Terms
Matrix stiffening promotes a tumor vasculature phenotype.
Bordeleau F, Mason BN, Lollis EM, Mazzola M, Zanotelli MR, Somasegar S, Califano JP, Montague C, LaValley DJ, Huynh J, Mencia-Trinchant N, Negrón Abril YL, Hassane DC, Bonassar LJ, Butcher JT, Weiss RS, Reinhart-King CA
(2017) Proc Natl Acad Sci U S A 114: 492-497
MeSH Terms: Animals, Biomechanical Phenomena, Cattle, Cells, Cultured, Chick Embryo, Collagen, Extracellular Matrix, Female, Human Umbilical Vein Endothelial Cells, Humans, Mammary Neoplasms, Experimental, Matrix Metalloproteinases, Mice, Microvessels, Neoplasm Invasiveness, Neovascularization, Pathologic, Phenotype, Tumor Microenvironment, Vascular Stiffness
Show Abstract · Added April 10, 2019
Tumor microvasculature tends to be malformed, more permeable, and more tortuous than vessels in healthy tissue, effects that have been largely attributed to up-regulated VEGF expression. However, tumor tissue tends to stiffen during solid tumor progression, and tissue stiffness is known to alter cell behaviors including proliferation, migration, and cell-cell adhesion, which are all requisite for angiogenesis. Using in vitro, in vivo, and ex ovo models, we investigated the effects of matrix stiffness on vessel growth and integrity during angiogenesis. Our data indicate that angiogenic outgrowth, invasion, and neovessel branching increase with matrix cross-linking. These effects are caused by increased matrix stiffness independent of matrix density, because increased matrix density results in decreased angiogenesis. Notably, matrix stiffness up-regulates matrix metalloproteinase (MMP) activity, and inhibiting MMPs significantly reduces angiogenic outgrowth in stiffer cross-linked gels. To investigate the functional significance of altered endothelial cell behavior in response to matrix stiffness, we measured endothelial cell barrier function on substrates mimicking the stiffness of healthy and tumor tissue. Our data indicate that barrier function is impaired and the localization of vascular endothelial cadherin is altered as function of matrix stiffness. These results demonstrate that matrix stiffness, separately from matrix density, can alter vascular growth and integrity, mimicking the changes that exist in tumor vasculature. These data suggest that therapeutically targeting tumor stiffness or the endothelial cell response to tumor stiffening may help restore vessel structure, minimize metastasis, and aid in drug delivery.
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Potentiation and tolerance of toll-like receptor priming in human endothelial cells.
Koch SR, Lamb FS, Hellman J, Sherwood ER, Stark RJ
(2017) Transl Res 180: 53-67.e4
MeSH Terms: Endothelial Cells, Extracellular Signal-Regulated MAP Kinases, Human Umbilical Vein Endothelial Cells, Humans, Immune Tolerance, Interferon Regulatory Factor-7, Interferons, Interleukin-6, Lipopeptides, Lipopolysaccharides, Nuclear Pore Complex Proteins, Phosphorylation, Poly I-C, RNA-Binding Proteins, Toll-Like Receptors, Up-Regulation
Show Abstract · Added August 28, 2016
Repeated challenge of lipopolysaccharide (LPS) alters the response to subsequent LPS exposures via modulation of toll-like receptor 4 (TLR4). Whether activation of other TLRs can modulate TLR4 responses, and vice versa, remains unclear. Specifically with regards to endothelial cells, a key component of innate immunity, the impact of TLR cross-modulation is unknown. We postulated that TLR2 priming (via Pam3Csk4) would inhibit TLR4-mediated responses while TLR3 priming (via Poly I:C) would enhance subsequent TLR4-inflammatory signaling. We studied human umbilical vein endothelial cells (HUVECs) and neonatal human dermal microvascular endothelial cells (HMVECs). Cells were primed with a combination of Poly I:C (10 μg/ml), Pam3Csk4 (10 μg/ml), or LPS (100 ng/ml), then washed and allowed to rest. They were then rechallenged with either Poly I:C, Pam3Csk4 or LPS. Endothelial cells showed significant tolerance to repeated LPS challenge. Priming with Pam3Csk4 also reduced the response to secondary LPS challenge in both cell types, despite a reduced proinflammatory response to Pam3Csk4 in HMVECs compared to HUVECs. Poly I:C priming enhanced inflammatory and interferon producing signals upon Poly I:C or LPS rechallenge, respectively. Poly I:C priming induced interferon regulatory factor 7, leading to enhancement of interferon production. Finally, both Poly I:C and LPS priming induced significant changes in receptor-interacting serine/threonine-protein kinase 1 activity. Pharmacological inhibition of receptor-interacting serine/threonine-protein kinase 1 or interferon regulatory factor 7 reduced the potentiated phenotype of TLR3 priming on TLR4 rechallenge. These results demonstrate that in human endothelial cells, prior activation of TLRs can have a significant impact on subsequent exposures and may contribute to the severity of the host response.
Copyright © 2016 Elsevier Inc. All rights reserved.
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16 MeSH Terms
Endothelial cell tolerance to lipopolysaccharide challenge is induced by monophosphoryl lipid A.
Stark RJ, Choi H, Koch SR, Fensterheim BA, Lamb FS, Sherwood ER
(2016) Clin Sci (Lond) 130: 451-61
MeSH Terms: Adaptor Proteins, Vesicular Transport, Adjuvants, Immunologic, Extracellular Signal-Regulated MAP Kinases, Human Umbilical Vein Endothelial Cells, Humans, Immune Tolerance, Interleukin-1 Receptor-Associated Kinases, Lipid A, Lipopolysaccharides, Myeloid Differentiation Factor 88, Phosphorylation
Show Abstract · Added December 17, 2015
Prior exposure to lipopolysaccharide (LPS) produces a reduced or "tolerant" inflammatory response to subsequent challenges with LPS, however the potent pro-inflammatory effects of LPS limit its clinical benefit. The adjuvant monophosphoryl lipid A (MPLA) is a weak toll-like receptor 4 (TLR4) agonist that induces negligible inflammation but retains potent immunomodulatory properties. We postulated that pre-treatment with MPLA would inhibit the inflammatory response of endothelial cells to secondary LPS challenge. Human umbilical vein endothelial cells (HUVECs), were exposed to MPLA (10 μg/ml), LPS (100 ng/ml) or vehicle control. HUVECs were then washed and maintained in culture for 24 h before being challenged with LPS (100 ng/ml). Supernatants were collected and examined for cytokine production in the presence or absence of siRNA inhibitors of critical TLR4 signalling proteins. Pre-treatment with MPLA attenuated interleukin (IL)-6 production to secondary LPS challenge to a similar degree as LPS. The application of myeloid differentiation primary response gene 88 (MyD88) siRNA dramatically reduced MPLA-induced tolerance while TIR-domain-containing adapter-inducing interferon-β (TRIF) siRNA had no effect. The tolerant phenotype in endothelial cells was associated with reduced IκB kinase (IKK), p38 and c-Jun N-terminal kinase (JNK) phosphorylation and enhanced IL-1 receptor associated kinase-M (IRAK-M) expression for LPS-primed HUVECs, but less so in MPLA primed cells. Instead, MPLA-primed HUVECs demonstrated enhanced p-extracellular-signal-regulated kinase (ERK) phosphorylation. In contrast with leucocytes in which tolerance is largely TRIF-dependent, MyD88 signalling mediated endotoxin tolerance in endothelial cells. Most importantly, MPLA, a vaccine adjuvant with a wide therapeutic window, induced tolerance to LPS in endothelial cells.
© 2016 Authors; published by Portland Press Limited.
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Pendant allyl crosslinking as a tunable shape memory actuator for vascular applications.
Boire TC, Gupta MK, Zachman AL, Lee SH, Balikov DA, Kim K, Bellan LM, Sung HJ
(2015) Acta Biomater 24: 53-63
MeSH Terms: Animals, Blood Vessel Prosthesis, Blood Vessel Prosthesis Implantation, Cross-Linking Reagents, Disease Models, Animal, Hindlimb, Human Umbilical Vein Endothelial Cells, Humans, Ischemia, Materials Testing, Mice, Polystyrenes
Show Abstract · Added March 18, 2020
UNLABELLED - Thermo-responsive shape memory polymers (SMPs) can be programmed to fit into small-bore incisions and recover their functional shape upon deployment in the body. This property is of significant interest for developing the next generation of minimally-invasive medical devices. To be used in such applications, SMPs should exhibit adequate mechanical strengths that minimize adverse compliance mismatch-induced host responses (e.g. thrombosis, hyperplasia), be biodegradable, and demonstrate switch-like shape recovery near body temperature with favorable biocompatibility. Combinatorial approaches are essential in optimizing SMP material properties for a particular application. In this study, a new class of thermo-responsive SMPs with pendant, photocrosslinkable allyl groups, x%poly(ε-caprolactone)-co-y%(α-allyl carboxylate ε-caprolactone) (x%PCL-y%ACPCL), are created in a robust, facile manner with readily tunable material properties. Thermomechanical and shape memory properties can be drastically altered through subtle changes in allyl composition. Molecular weight and gel content can also be altered in this combinatorial format to fine-tune material properties. Materials exhibit highly elastic, switch-like shape recovery near 37°C. Endothelial compatibility is comparable to tissue culture polystyrene (TCPS) and 100%PCL in vitro and vascular compatibility is demonstrated in vivo in a murine model of hindlimb ischemia, indicating promising suitability for vascular applications.
STATEMENT OF SIGNIFICANCE - With the ongoing thrust to make surgeries minimally-invasive, it is prudent to develop new biomaterials that are highly compatible and effective in this workflow. Thermo-responsive shape memory polymers (SMPs) have great potential for minimally-invasive applications because SMP medical devices (e.g. stents, grafts) can fit into small-bore minimally-invasive surgical devices and recover their functional shape when deployed in the body. To realize their potential, it is imperative to devise combinatorial approaches that enable optimization of mechanical, SM, and cellular responses for a particular application. In this study, a new class of thermo-responsive SMPs is created in a robust, facile manner with readily tunable material properties. Materials exhibit excellent, switch-like shape recovery near body temperature and promising biocompatibility for minimally-invasive vascular applications.
Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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