Blood Compatibility Of Polymers Research Articles

Hydrolyzable and biocompatible aliphatic polycarbonates with ether-functionalized side chains attached via amide linkers

Investigating polymer degradation mechanisms enables the establishment of controlled degradation techniques for the development of sustainable and recyclable materials. Hydration can play a crucial role in controlling the hydrolysis of polymers. Here, ether-functionalized aliphatic polycarbonates (APCs) susceptible to nonenzymatic hydrolysis were developed for application as biocompatible biomaterials. Among these polymers, those grafted with 2-methoxyethyl and 3-methoxypropyl side chains via an amide group were highly wettable, strongly interacted with water, and experienced almost complete hydrolysis in phosphate-buffered saline over 30 days, which was attributed to the hydrogen bonding between water and the amide/methoxy groups. In an alkaline medium, all amide-linked APCs were completely hydrolyzed within 30 days, regardless of the side-chain structure. In contrast, the nonamide-linked APCs and a representative aliphatic polycarbonate, poly(trimethylene carbonate), were minimally degraded in the buffer and experienced <31% degradation under alkaline conditions. The APC with the 3-methoxypropyl side chain exhibited platelet adhesion properties comparable to those of ether-functionalized APCs previously reported as blood-compatible polymers. Thus, our results demonstrate the effects of an amide linker on the hydration and hydrolytic properties of APCs and can help establish new design concepts for degradable polymers.

Enrichment of Cancer Cells Based on Antibody-Free Selective Cell Adhesion.

Blood-compatible and cell-adhering polymer materials are extremely useful for regenerative medicine and disease diagnosis. (Meth)acryl polymers with high hydrophilicity have been widely used in industries, and attempts to apply these polymers in the medical field are frequently reported. We focused on crosslinked polymer films prepared using bifunctional monomers, which are widely used as coating materials, and attempted to alter the cell adhesion behavior while maintaining blood compatibility by changing the chemical structure of the crosslinker. Four bifunctional monomers were studied, three of which were found to be blood-compatible polymers and to suppress platelet adhesion. The adhesion behavior of cancer cells to polymer films varied; moreover, the cancer model cells MCF-7 [EpCAM(+)] and MDA-MB-231 [EpCAM (-)], with different expression levels of epithelial cell adhesion molecule (EpCAM), showed distinct adhesion behavior for each material. We suggest that a combination of these materials has the potential to selectively capture and enrich highly metastatic cancer cells.

Observing the repulsion layers on blood-compatible polymer-grafted interfaces by frequency modulation atomic force microscopy

Blood-compatible materials that do not promote reactions in contact with human blood are required to support emerging medical technologies. The interfaces of poly(2-methoxyethyl acrylate) (PMEA), a blood-compatible polymer, and its analogues were investigated by frequency modulation atomic force microscopy (FM-AFM). The grafted polymers exhibited phase separation into polymer-rich and water-rich domains. Thin repulsive layers of hydrated polymer chains were observed in the water-rich domains of the blood-compatible polymers; on the other hand, such layers were not observed for the non-blood-compatible polymers. We report for the first time that FM-AFM enables characteristic repulsive layers composed of hydrated polymer chains in water-rich domains to be observed, which is a significant design factor for blood-compatible polymers.

Hydration Mechanism in Blood-Compatible Polymers Undergoing Phase Separation.

Interactions involving intermediate water are crucial for the design of novel blood-compatible materials. Herein, we use a combination of atomic force microscopy, quartz crystal microbalance measurements, and soft X-ray emission spectroscopy to investigate the local hydrogen-bonded configuration of water on blood-compatible poly(2-methoxyethyl acrylate) and non-blood-compatible poly(n-butyl acrylate) grafted on a gold substrate. We find that the initially incorporated water induces polymer-dependent phase separation, facilitating further water uptake. For the blood-compatible polymer, tetrahedrally coordinated water coexists with water adsorbed on C═O groups in low-density regions of the grafted polymer surface, providing a scaffold for the formation of intermediate water. The amount of intermediate water is determined by the type of functional groups, local polymer configuration, and polymer morphology. Thus, blood compatibility is governed by the complex water/polymer interactions.

Poly(tertiary amide acrylate) Copolymers Inspired by Poly(2-oxazoline)s: Their Blood Compatibility and Hydration States.

Modifying the side chain of poly(meth)acrylate with moieties originating from biocompatible polymers can be an effective method for developing novel blood-compatible polymers. Inspired by biocompatible poly(2-methyl-2-oxazoline) (PMeOx) and poly(2-ethyl-2-oxazoline) (PEtOx), four water-soluble poly(tertiary amide acylate) analogues bearing a pendant tertiary amide were synthesized. The results of hemolysis and cell viability tests showed that all the poly(tertiary amide acylate) analogues were compatible with red blood cells, HeLa cells, and normal human dermal fibroblasts as PMeOx or PEtOx. Among the four poly(tertiary amide acylate) analogues, poly[2-(N-methylpropionamido)ethyl acrylate] (PPEA) and poly[2-(N-ethylacetamido)ethyl acrylate] (PEAE) showed thermosensitivity in aqueous solution; especially, PPEA (10 mg mL-1) exhibited a lower critical solution temperature of 37 °C. Water-insoluble copolymers were prepared to investigate the possibility of applying these synthesized polymers as blood-compatible coatings. The poly[n-butyl methacrylate70-co-2-(N-methylacetamido)ethyl methacrylate30] (coPAEM) coatings significantly suppressed plasma protein adsorption, denaturation degree of adsorbed fibrinogen, and platelet adhesion. Intermediate water (IW), whose content can generally indicate the blood compatibility of polymers, was found in all hydrated homopolymers and copolymers by differential scanning calorimetry. The present work demonstrated that the tertiary amide moiety in the side chain of poly(meth)acrylate was an effective contributor to blood compatibility and IW.

Effect of interfacial structure based on grafting density of poly(2-methoxyethyl acrylate) on blood compatibility

An excellent blood-compatible polymer, poly(2-methoxyethyl acrylate) (PMEA), exhibits nanometer-scale phase-separated structures at the interface with water or phosphate-buffered saline (PBS), and fibrinogen adsorption is suppressed, especially on the water-rich region. To understand the correlation between the interfacial structure based on the grafting density of PMEA and blood compatibility, grafted PMEA (gPMEA) surfaces with controlled density were prepared by immobilizing thiol-terminated PMEA on a gold substrate. The amount of adsorbed fibrinogen and the number of adhered platelets on gPMEAs decreased first with the increasing grafting density (σ), but increased after showed minimum at σ of approximately 0.11 chains/nm2. The interfacial structures of the gPMEA/PBS interface changed with grafting density, and the maximum area of water-rich region was obtained at σ = 0.11. The water contact angle at σ = 0.11 is smaller than that at the other grafting density. These results revealed that hydration to the polymer is very effective to suppress the platelet adhesion and water-rich region shows excellent blood compatibility on gPMEA surfaces. This work clearly indicated that the density of PMEA affects the interfacial structure and plays an important role in the blood compatibility of the material.

Control of interfacial structures and anti-platelet adhesion property of blood-compatible random copolymers

Fibrinogen adsorption behavior on the blood-compatible polymer, poly(2-methoxyethyl acrylate) (PMEA), non-blood-compatible polymer, poly(n-butyl acrylate) (PBA), and random copolymers of both were examined. Adsorption and denaturation of fibrinogen on the polymers increased as the ratio of PBA increased. The incremental change corresponded to the amount of intermediate water included in the hydrated polymers. The composition of PBA altered the features of the phase-separated structures observed on the polymer/phosphate-buffered saline interfaces. Microscopically, the denaturation of fibrinogen was observed as the formation of fibrous networks on the interfaces by atomic force microscopy. Fibrinogen adsorption and denaturation were enhanced on the water-rich domains in the phase-separated structures on the non-blood-compatible polymers. This suggested that the excellent blood compatibility of PMEA is caused by the constrained adsorption and denaturation of fibrinogen in water-rich domains, possibly due to the high content of intermediate water in this region. This work provides essential scientific foundations for the design and fabrication of highly functional biomaterials.

Controlling the Hydration Structure with a Small Amount of Fluorine To Produce Blood Compatible Fluorinated Poly(2-methoxyethyl acrylate).

Poly(2-methoxyethyl acrylate) (PMEA) shows excellent blood compatibility because of the existence of intermediate water. Various modifications of PMEA by changing its main or side chain's chemical structure allowed tuning of the water content and the blood compatibility of numerous novel polymers. Here, we exploit a possibility of manipulating the surface hydration structure of PMEA by incorporation of small amounts of hydrophobic fluorine groups in MEA polymers using atom-transfer radical polymerization and the (macro) initiator concept. Two kinds of fluorinated MEA polymers with similar molecular weights and the same 5.5 mol % of fluorine content were synthesized using the bromoester of 2,2,3,3,4,4,5,5,6,6,7,7,8,8-pentadecafluoro-1-octanol (F15) and poly(2,2,2-trifluoroethyl methacrylate) (PTFEMA) as (macro) initiators, appearing liquid and solid at room temperature, respectively. The fibrinogen adsorption of the two varieties of fluorinated MEA polymers was different, which could not be explained only by the bulk hydration structure. Both polymers show a nanostructured morphology in the hydrated state with different sizes of the features. The measured elastic modulus of the domains appearing in atomic force microscopy and the intermediate water content shed light on the distinct mechanism of blood compatibility. Contact angle measurements reveal the surface hydration dynamics-while in the hydrated state, F15- b-PMEA reorients easily to the surface exposing its PMEA part to the water, the small solid PTFEMA block with high glass-transition temperature suppresses the movement of PTFEMA- b-PMEA and its reconstruction on the surface. These findings illustrate that in order to make a better blood compatible polymer, the chains containing sufficient intermediate water need to be mobile and efficiently oriented to the water surface.

Design and development of metallic biomaterials with biological and mechanical biocompatibility.

In the present article, the recent trends in the research and development of metallic biomaterials are discussed with focus on the results obtained by the author's group. The design of biocompatible metallic biomaterials possessing excellent biological and mechanical properties, including titanium alloys with low Young's modulus, is reviewed with focus on Young's modulus, fatigue strength, and peculiar behavior. The evaluation of biological compatibility including cell viability and living tissue compatibility using animal models and surface modifications using bioactive ceramic and blood-compatible polymers are summarized. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 944-954, 2019.

Effect of the Molecular Weight of Poly(2-methoxyethyl acrylate) on Interfacial Structure and Blood Compatibility.

The blood-compatible polymer poly(2-methoxyethyl acrylate) (PMEA) is composed of nanometer-scale interfacial structures because of the phase separation of the polymer and water at the PMEA/phosphate-buffered saline (PBS) interface. We synthesized PMEA with four different molecular weights (19, 30, 44, and 183 kg/mol) to investigate the effect of the molecular weight on the interfacial structures and blood compatibility. The amounts of intermediate water and fibrinogen adsorption were not affected by the molecular weight of PMEA. In contrast, the degree of denaturation of adsorbed fibrinogen molecules and platelet adhesion increased as the molecular weight increased. Atomic force microscopy observation revealed that the domain size of the microphase separation structures observed at the PMEA/PBS interfaces drastically (nearly 3 times in the mean area of a domain) changed with the molecular weight. PMEA with a lower molecular weight showed a smaller polymer-rich domain size, as expected on the basis of the microphase separation of polymer-rich and water-rich domains. The small domain size suppressed the aggregation and denaturation of adsorbed fibrinogen molecules because only a few fibrinogen molecules were adsorbed on a domain. Increasing the domain size enhanced the denaturation of adsorbed fibrinogen molecules. Controlling the interfacial structures is crucial for ensuring the blood compatibility of polymer interfaces.

Analysis of Interaction Between Interfacial Structure and Fibrinogen at Blood-Compatible Polymer/Water Interface.

The correlation between the interfacial structure and protein adsorption at a polymer/water interface was investigated. Poly(2-methoxyethyl acrylate)(PMEA), which is one of the best blood compatible polymers available, was employed. Nanometer-scale structures generated through the phase separation of polymer and water were observed at the PMEA/phosphate buffered saline interface. The interaction between the interfacial structures and fibrinogen (FNG) was measured using atomic force microscopy. Attraction was observed in the polymer-rich domains as well as in the non-blood compatible polymer. In contrast, no attractive interactions were observed, and only a repulsion occurred in the water-rich domains. The non-adsorption of FNG into the water rich domains was also clarified through topographic and phase image analyses. Furthermore, the FNG molecules adsorbed on the surface of PMEA were easily desorbed, even in the polymer-rich domains. Water molecules in the water-rich domains are anticipated to be the dominant factor in preventing FNG adsorption and thrombogenesis on a PMEA interface.

Synthesis and Thrombogenicity Evaluation of Poly(3-methoxypropionic acid vinyl ester): A Candidate for Blood-Compatible Polymers.

A poly(vinyl acetate) derivative, poly(3-methoxypropionic acid vinyl ester) (PMePVE), was synthesized to develop a new candidate for blood compatible polymers. The monomer MePVE was synthesized by a simple two-step reaction, and then the MePVE was polymerized via free radical polymerization to obtain PMePVE. Human platelet adhesion tests were performed to evaluate the thrombogenicity, and the platelet adhesion was suppressed on the PMePVE-coated substrate. To determine the expression of the nonthrombogenicity of the PMePVE, the plasma protein adsorption and a conformationally altered state of fibrinogen were analyzed by a microBCA assay and enzyme-linked immunosorbent assay. The adsorption and denaturation of the plasma proteins were inhibited on the PMePVE; thus, PMePVE exhibited blood compatibility. A distinctive hydration water structure in the nonthrombogenic polymer, intermediate water (IW), was observed in the hydrated PMePVE by differential scanning calorimetry analysis. The nonthrombogenicity of PMePVE is considered to be brought about by the presence of IW.

Interfacial Structures and Fibrinogen Adsorption at Blood-Compatible Polymer/Water Interfaces.

The interfacial structures of a blood-compatible polymer, poly(2-methoxyethyl acrylate) (PMEA), and several analogues were investigated by atomic force microscopy (AFM). The blood-compatible polymers exhibited nanometer-scale protrusions that spontaneously and homogeneously formed at polymer/water and polymer/phosphate-buffered saline interfaces. AFM observation also revealed that fibrinogen adsorption occurred locally on the protrusions rather than uniformly at the interface, with the regions adjacent to the protrusions apparently preventing the adsorption of fibrinogen. The formation of these interfacial structures may be due to in-plane microphase separation of polymer and water at the interface.

Biocompatibility and hemocompatibility evaluation of polyether urethanes synthesized using DBU organocatalyst

Biomaterials must fulfill some requirements before moving into in vivo application. In vitro test is usually conducted as a preliminary screening evaluation. Although most of the studies are focused in the cytotoxicity, interactions between blood elements and the biomaterials or hemocompatibility must also be considered. Aliphatic polyurethanes have been always considered ideal candidates for in-vivo application due to their versatility. However, the utilization of metal catalyst to promote the polymerization have limited their use. Recently, some organocatalysts have shown to be competitive to tin based catalyst for the preparation of polyurethanes and have relaunched their use in biomedicine. In the present study we carried out the organocatalyzed polymerization of 5 commercially available isocyanates, hexamethylene diisocyanate, isophorone diisocyanate, trans-1,4-cyclohexylene diisocyanate, 4,4′-methylenebis(cyclohexyl isocyanate) and l-lysine diisocyanate to analyze the cytotoxicity and hemocompatibility of the resultant polymers as a function of the employed diisocyanate. The diisocyanates were polymerized with hydroxy end-capped oligomeric poly (tetramethylene glycol) (PT2K) as the long chain diol and 1,3-propanediol as the short chain diol. We demonstrated that from selected diisocyanates, lysine diisocyanate based polyurethanes possessed lower cytotoxicity and better hemocompatibility than the other polyurethanes. In comparison with a well known blood compatible polymer such as poly(2-methoxyethyl acrylate), the lysine diisocyanate based polyurethanes showed remarkable values in terms of cytotoxicity and platelet adhesion, but major levels of protein adsorption.

Blood-compatible poly (2-methoxyethyl acrylate) for the adhesion and proliferation of lung cancer cells toward the isolation and analysis of circulating tumor cells

Circulating tumor cells have received attention for their role in cancer diagnosis and the decision on which chemotherapeutic course to take. For these purposes, the isolation of circulating tumor cells has been important. Previously, we reported that non-blood cells can adhere on blood-compatible polymer substrates, such as poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate). In this study, we examined whether blood-compatible poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) allow the adhesion and growth of A549 lung cancer cells for isolating circulating tumor cells by adhesion-mediated manner to diagnose metastatic cancer and to decide on the chemotherapeutic course. A549 cells can adhere on poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates via an integrin-dependent mechanism after 1 h of incubation, suggesting that blood-compatible poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates possess the ability to capture circulating tumor cells selectively from peripheral blood. After 1 day of culture, A549 cells started to spread on poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates. A549 can also grow on poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates. Additionally, the chemoresistance of A549 cells against 5-fluorouracil on poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates was similar to that on the conventional cell culture substrate, tissue culture polystyrene. These results indicate that circulating tumor cells can be cultured on poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates after they are isolated from peripheral blood, and poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates can be used as circulating tumor cell culture substrates for screening anti-cancer drugs. Therefore, poly(2-methoxyethyl acrylate) and poly(tetrahydrofurfuryl acrylate) substrates might be able to be applied to the development of a new device for a circulating tumor cell–based diagnosis of metastatic cancer and a personalized medicine approach regarding the decision of which chemotherapeutic course should be taken.

Hemocompatible poly(trimethylene carbonate) derivatives for potential application to biodegradable artificial blood vessels

Event Abstract Back to Event Hemocompatible poly(trimethylene carbonate) derivatives for potential application to biodegradable artificial blood vessels Kazuki Fukushima1*, Shunya Takaoka1*, Shunsuke Shishido1*, Yuto Inoue1*, Takayuki Ota1* and Masaru Tanaka1, 2* 1 Yamagata University, Department of Polymer Science and Engineering, Japan 2 Kyushu University, Institute for Materials Chemistry and Engineering, Japan Introduction: Poly(trimethylene carbonate) (PTMC) attratcs increasing attention as a degradable polymeric platform for biomedical applications, due to the softness and its unique degradation behavior unlike biodegradable polyesters.[1] In addition, PTMC analogs with a functional side chain (PMTC) now afford many functionalized implantable biomaterials.[2] Recent progress in organocatalysis allows controlled polymerization of MTCs, monomers of PMTC, enabling formation of complex architecture and multi-functionalization.[3] One of the critical features as biomaterials used in the body involves hemocompatibility. So far, few biodegradable polymers have presented sufficient blood compatibility. Then, we focused on a blood compatible polymer, poly(2-methoxyethyl acrylate) (PMEA). According to Tanaka et al., the ether side chain plays a significant role in hydration and formation of ‘intermediate water’ that is recognized to contribute to suppression of protein and platelet adsorption.[4] Thus, we have produced poly(2-methoxyethyl 2-methyltrimethylene carbonate carboxylate) (PMEMTC), demonstrating decent hemocompatibility and enzymatic degradability. However, as for the vascular regeneration application, adhesion of endothelial cells (ECs) is also important. Poly(tetrahydrofurfuryl acrylate) (PTHFA) is another blood compatible polymer and effective in ECs attachment and proliferation. Thus, we designed new analogs of PMEMTC with cyclic ether moiety at the side chain to install both hemocompatibility and EC adhesion property. Furthermore, we also developed a new facile synthetic route to MTC-type monomers through an ammonium salt intermediate TEA-MTC (Figure 1). Results and Discussion: PTHFMTC and PTHPEMTC were successfully prepared as a consequence of the relatively controlled ROP, allowing for Mn and molar mass distribution, 11,000 (1.12) and 9,400 (1.14), respectively. All carbonate polymers used in this study were hydrophobic. Interestingly, contact angles were 61° for PTHFMTC and 58° for PTHPEMTC, which are comparable to that of PMEMTC, despite more hydrocarbons installed. Figure 2 represents the comparison of adherent human platelets on the polymer surfaces after treatment at 37°C for 1 h. A few platelets adhered on PTHFMTC and PMEMTC. The numbers of adherent platelets are slightly higher than that on PMEA, but significantly lower than that on PTMC. Then, we investigated water structure of hydrated water bound by polymer structure. On the cooling DSC chart of the hydrated polymers, crystallization exotherms were observed around -40°C for both PMEMTC and PTHFMTC (Figure 3). These crystalized water peaks should not be asigned as free or bulk water, exhibiting the exotherm above -20°C, according to our recent report.[5] Thus, we currently believe that this type of water also is attributed to suppression of platelet adhesion. Further studies are ongoing. The results of EC adhesion test will also be discussed. Preliminarily, human umbilical vein endothelial cells (HUVECs) were found to reasonably adhere on PMEMTC at 1 and 3 days after incubation. Conclusion: These (potentially) biodegradable polycarbonates with ether side chain can be applicable for both a coating of blood contacting devices and a candidate scaffold for vascular regeneration.

Blood-compatible polymers for hepatocyte adhesive culture with the maintenance of hepatic functions toward bioartificial liver support development

Event Abstract Back to Event Blood-compatible polymers for hepatocyte adhesive culture with the maintenance of hepatic functions toward bioartificial liver support development Takashi Hoshiba1, 2, Takayuki Otaki1 and Masaru Tanaka1 1 Yamagata University, Frontier Center for Organic Materials, Japan 2 National Institute for Materials Science, International Center for Materials Nanoarchitectonics, Japan Bioartificial liver support has been focused on the therapy of severe liver failures. There are two problems in its development; 1) thrombus forms when blood contacts conventional polymer substrates and 2) hepatocytes lose hepatic functions rapidly in vitro. It is well-known that hepatic functions are maintained at high level when hepatocytes formed round shape. We have previously reported that poly(2-methoxyethyl acrylate) (PMEA) and poly(tetrahydrofurfuryl acrylate) (PTHFA) were blood compatible, although normal tissue cells can adhere on these polymers. Moreover, adhered cells exhibited round and spreading shapes on PMEA and PTHFA, respectively. It is expected that these blood-compatible polymers are able to control liver functions via the regulation of cell shape. Here, we investigated the adhesion and shapes of human hepatocyte model, HepG2, on PMEA and PTHFA to assess the possibility to apply these polymers as the substrates for bioartificial liver support. Polymer-coated substrates were prepared by spin coating on polyethylene terephthalate (PET) disks. Adherent HepG2 were counted under an optical microscope after crystal violet staining. Focal adhesions were visualized after 1 day by immunofluorescent staining. The expression levels of hepatic genes, HNF4A and ALB, were measured by real time PCR analyses. HepG2 adhered on PMEA and PTHFA as well as PET, indicating that hepatocytes can adhere on PMEA and PTHFA, although these polymers are blood compatible. To compare the shape of adhered HepG2, projected cell areas were measured after 1 day of culture. The projected cell areas were in the order of PTHFA > PET > PMEA. This result indicated that HepG2 kept round on PMEA, while the cells spread on PTHFA and PET. Additionally, HepG2 on PMEA expressed the highest hepatic genes among the polymers examined. These results indicated that hepatocytes on PMEA kept round shape and expressed high hepatic functions. To assess the reason why HepG2 exhibited round shape and expressed high hepatic genes, we focused on integrin signaling and Hippo signaling pathways. Generally, the cells adhered on polymeric substrates via the interaction between integrin and adsorbed proteins. Surprisingly, HepG2 adhered on PMEA via both integrin-dependent and –independent manners and integrin signaling was weakened compared with the cells on PTHFA and PET. Integrin signaling promotes cell spreading. It seemed that weakened integrin signaling suppressed HepG2 spreading on PMEA. Moreover, YAP was located in nucleus on PTHFA but not PMEA. It has been reported that nuclear localization of YAP inhibits the expression of hepatic genes. Therefore, it seemed that nuclear localization of YAP on PTHFA inhibited the expression of hepatic genes. Conclusively, PMEA is expected to be a new biomaterial to achieve the development of bioartificial liver support. Keywords: protein, Biocompatibility, Polymeric material, hemocompatiblility Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Biomaterials in constructing tissue substitutes Citation: Hoshiba T, Otaki T and Tanaka M (2016). Blood-compatible polymers for hepatocyte adhesive culture with the maintenance of hepatic functions toward bioartificial liver support development. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00646 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Takashi Hoshiba Takayuki Otaki Masaru Tanaka Google Takashi Hoshiba Takayuki Otaki Masaru Tanaka Google Scholar Takashi Hoshiba Takayuki Otaki Masaru Tanaka PubMed Takashi Hoshiba Takayuki Otaki Masaru Tanaka Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

In situ nano-objects via RAFT aqueous dispersion polymerization of 2-methoxyethyl acrylate using poly(ethylene oxide) macromolecular chain transfer agent as steric stabilizer

Poly(ethylene oxide)-poly(2-methoxyethyl acrylate) diblock copolymers (PEO-b-PMEA) are synthesized by RAFT aqueous dispersion polymerization of MEA using poly(ethylene oxide) macromolecular chain transfer agent as a reactive steric stabilizer. Both segments are well-known to be bio- and blood-compatible polymers. This formulation enables the production of various particle morphologies such as spheres, worms, and vesicles from the same block copolymer in water. The synthesis starts when both the reactive steric stabilizer and MEA monomer are dissolved in water; however, the growing polymer is not water-soluble and begins to form nano-objects. In the case of the synthesis of PEO113-b-MEA300 diblock copolymers, the nano-objects change from spheres into larger aggregates of worms when the solids concentration in the polymerization increases from 5 to 15 wt% at full monomer conversion. The morphology finally turns into vesicles as the solids concentration increases to 20 wt%. The final block copolymer morphology at full monomer conversion is dictated by not only degree of polymerization of MEA but also the solids concentration in the polymerization mixture.

Blood-Compatible Polymer for Hepatocyte Culture with High Hepatocyte-Specific Functions toward Bioartificial Liver Development.

The development of bioartificial liver (BAL) is expected because of the shortage of donor liver for transplantation. The substrates for BAL require the following criteria: (a) blood compatibility, (b) hepatocyte adhesiveness, and (c) the ability to maintain hepatocyte-specific functions. Here, we examined blood-compatible poly(2-methoxyethyl acrylate) (PMEA) and poly(tetrahydrofurfuryl acrylate) (PTHFA) (PTHFA) as the substrates for BAL. HepG2, a human hepatocyte model, could adhere on PMEA and PTHFA substrates. The spreading of HepG2 cells was suppressed on PMEA substrates because integrin contribution to cell adhesion on PMEA substrate was low and integrin signaling was not sufficiently activated. Hepatocyte-specific gene expression in HepG2 cells increased on PMEA substrate, whereas the expression decreased on PTHFA substrates due to the nuclear localization of Yes-associated protein (YAP). These results indicate that blood-compatible PMEA is suitable for BAL substrate. Also, PMEA is expected to be used to regulate cell functions for blood-contacting tissue engineering.

Effect of local chain dynamics on a bioinert interface.

Although many kinds of synthetic polymers have been investigated to construct blood-compatible materials, only a few have achieved success. To establish molecular designs for blood-compatible polymers, the chain structure and dynamics at the water interface must be understood using solid evidence as the first bench mark. Here we show that polymer dynamics at the water interface impacts on structure of the interfacial water, resulting in a change in protein adsorption and of platelet adhesion. As a particular material, a blend composed of poly(2-methoxyethyl acrylate) (PMEA) and poly(methyl methacrylate) was used. PMEA was segregated to the water interface. While the local conformation of PMEA at the water interface was insensitive to its molecular weight, the local dynamics became faster with decreasing molecular weight, resulting in a disturbance of the network structure of waters at the interface. This leads to the extreme suppression of protein adsorption and platelet adhesion.