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1.
Nano Lett ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32379455

RESUMO

The lymphatic system provides a major route for the dissemination of many diseases such as tumor metastasis and virus infection. At present, treating these diseases remains a knotty task due to the difficulty of delivering sufficient drugs into lymphatics. After subcutaneous (SC) injection, the transferring of drugs to lymphatic vessels is significantly attenuated by physiological barriers in the interstitial space. Moreover, SC injection represents a highly challenging administration route for biological drugs, as it increases the risk of undesirable immune responses. Here, we demonstrate a simple and effective strategy to address this dilemma by conjugating protein therapeutics with zwitterionic poly(carboxy betaine) (PCB) polymers. PCB conjugation to l-asparaginase (ASP), a highly immunogenic enzyme drug, manifests to significantly promote the diffusion of ASP into the lymphatic system while mitigating its immunogenicity. This platform will facilitate the development of new therapies against diverse lymph-related diseases by enabling safe and efficient lymphatic drug delivery.

2.
Acta Biomater ; 109: 51-60, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32251778

RESUMO

The shelf-life of human platelets preserved in vitro for therapeutic transfusion is limited because of bacterial contamination and platelet storage lesion (PSL). The PSL is the predominant factor and limiting unfavorable interactions between the platelets and the non-biocompatible storage bag surfaces is the key to alleviate PSL. Here we describe a surface modification method for biocompatible platelet storage bags that dramatically extends platelet shelf-life beyond the current US Food and Drug Administration (FDA) standards of 5 days. The surface coating of the bags can be achieved through a simple yet effective dip-coating and light-irradiation method using a biocompatible polymer. The biocompatible polymers with tunable functional groups can be routinely fabricated at any scale and impart super-hydrophilicity and non-fouling capability on commercial hydrophobic platelet storage bags. As critical parameters reflecting the platelets quality, the activation level and binding affinity with von Willebrand factor (VWF) of the platelets stored in the biocompatible platelet bags at 8 days are comparable with those in the commercial bags at 5 days. This technique also demonstrates promise for a wide range of medical and engineering applications requiring biocompatible surfaces. STATEMENT OF SIGNIFICANCE: Current standard platelet preservation techniques agitate platelets at room temperature (20-24 °C) inside a hydrophobic (e.g., polyvinyl chloride (PVC)) storage bag, thereby allowing preservation of platelets only for 5 days. A key factor leading to quality loss is the unfavorable interaction between the platelets and the non-biocompatible storage bag surfaces. Here, a surface modification method for biocompatible platelet storage bags has been created to dramatically extend platelet shelf-life beyond the current FDA standards of 5 days. The surface coating of the bags can be achieved via a simple yet effective dip-coating and light-irradiation method using a carboxybetaine polymer. This technique is also applicable to many other applications requiring biocompatible surfaces.

3.
J Control Release ; 322: 170-176, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32200000

RESUMO

Pulmonary delivery of protein drugs into the systemic circulation is highly desirable as the lung provides a large absorption surface area and a more favorable environment for biologics compared to other delivery routes. However, pulmonary systemic delivery of proteins presents several challenges such as poor protein stability and limited bioavailability, especially for large proteins (molecular weight > 50 kDa), which exhibit an average bioavailability of 1% to 5% when delivered via the pulmonary route. Here, we demonstrated that with the conjugation of zwitterionic poly(carboxybetaine) (pCB) polymer, the bioavailability of organophosphate hydrolase (OPH) was significantly increased from 5% to 53%. OPH conjugated with pCB delivered through intubation-assisted intratracheal instillation (IAIS) into the lung exhibited improved pharmacokinetic properties and prophylactic efficacy against organophosphate poisoning, showing its application potential. Zwitterionic polymer conjugation provides the possibility for a favorable, non-invasive delivery of biological therapeutics into the systemic circulation.

4.
Langmuir ; 36(8): 2030-2036, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32091913

RESUMO

Albumin molecules are extensively used as biocompatible coatings, and poly(ethylene glycol) (PEG) materials are widely used for antifouling. PEG materials have excellent antifouling property because of their strong surface hydration. Our previous research indicates that hydration at the PEG/bovine serum albumin solution interface is stronger than that at the PEG/water interface. This research shows that this observation is general for different types of albumin molecules. Different albumins including bovine, porcine, rat, rabbit, and sheep serum albumins were studied in this research. It was found that the hydration at the PEG methacrylate (pOEGMA)/albumin solution interface is always stronger than that at the pOEGMA/water interface. Here, we define "strong interfacial hydration" as "ordered strongly hydrogen-bonded interfacial water". We believe that such a strong hydration is because of the strong hydration on the albumin surface, leading to its biocompatible property. All of the albumin molecules demonstrated stronger hydration on the pOEGMA surface compared to other protein molecules such as lysozyme and fibrinogen. The strong hydration on albumin molecules is related to the high surface coverage of glutamic acid and lysine with similar amounts.

5.
Nat Med ; 25(10): 1566-1575, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31591594

RESUMO

The ability to expand hematopoietic stem and progenitor cells (HSPCs) ex vivo is critical to fully realize the potential of HSPC-based therapies. In particular, the application of clinically effective therapies, such as cord blood transplantation, has been impeded because of limited HSPC availability. Here, using 3D culture of human HSPCs in a degradable zwitterionic hydrogel, we achieved substantial expansion of phenotypically primitive CD34+ cord blood and bone-marrow-derived HSPCs. This culture system led to a 73-fold increase in long-term hematopoietic stem cell (LT-HSC) frequency, as demonstrated by limiting dilution assays, and the expanded HSPCs were capable of hematopoietic reconstitution for at least 24 weeks in immunocompromised mice. Both the zwitterionic characteristics of the hydrogel and the 3D format were important for HSPC self-renewal. Mechanistically, the impact of 3D zwitterionic hydrogel culture on mitigating HSPC differentiation and promoting self-renewal might result from an inhibition of excessive reactive oxygen species (ROS) production via suppression of O2-related metabolism. HSPC expansion using zwitterionic hydrogels has the potential to facilitate the clinical application of hematopoietic-stem-cell therapies.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Terapia Baseada em Transplante de Células e Tecidos , Células-Tronco Hematopoéticas/citologia , Hidrogéis/farmacologia , Animais , Antígenos CD34/metabolismo , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Técnicas de Cultura de Células , Proliferação de Células/efeitos dos fármacos , Técnicas de Cocultura , Sangue Fetal/citologia , Sangue Fetal/metabolismo , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Humanos , Camundongos , Espécies Reativas de Oxigênio/metabolismo
6.
Sci Adv ; 5(6): eaaw9562, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31214655

RESUMO

Materials that resist nonspecific protein adsorption are needed for many applications. However, few are able to achieve ultralow fouling in complex biological milieu. Zwitterionic polymers emerge as a class of highly effective ultralow fouling materials due to their superhydrophilicity, outperforming other hydrophilic materials such as poly(ethylene glycol). Unfortunately, there are only three major classes of zwitterionic materials based on poly(phosphorylcholine), poly(sulfobetaine), and poly(carboxybetaine) currently available. Inspired by trimethylamine N-oxide (TMAO), a zwitterionic osmolyte and the most effective protein stabilizer, we here report TMAO-derived zwitterionic polymers (PTMAO) as a new class of ultralow fouling biomaterials. The nonfouling properties of PTMAO were demonstrated under highly challenging conditions. The mechanism accounting for the extraordinary hydration of PTMAO was elucidated by molecular dynamics simulations. The discovery of PTMAO polymers demonstrates the power of molecular understanding in the design of new biomimetic materials and provides the biomaterials community with another class of nonfouling zwitterionic materials.

7.
Sci Transl Med ; 11(473)2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-30602537

RESUMO

Nerve agents are a class of organophosphorus compounds (OPs) that blocks communication between nerves and organs. Because of their acute neurotoxicity, it is extremely difficult to rescue the victims after exposure. Numerous efforts have been devoted to search for an effective prophylactic nerve agent bioscavenger to prevent the deleterious effects of these compounds. However, low scavenging efficiency, unfavorable pharmacokinetics, and immunological problems have hampered the development of effective drugs. Here, we report the development and testing of a nanoparticle-based nerve agent bioscavenger (nanoscavenger) that showed long-term protection against OP intoxication in rodents. The nanoscavenger, which catalytically breaks down toxic OP compounds, showed a good pharmacokinetic profile and negligible immune response in a rat model of OP intoxication. In vivo administration of the nanoscavenger before or after OP exposure in animal models demonstrated protective and therapeutic efficacy. In a guinea pig model, a single prophylactic administration of the nanoscavenger effectively prevented lethality after multiple sarin exposures over a 1-week period. Our results suggest that the prophylactic administration of the nanoscavenger might be effective in preventing the toxic effects of OP exposure in humans.


Assuntos
Nanopartículas/química , Agentes Neurotóxicos/toxicidade , Substâncias Protetoras/farmacologia , Administração Intravenosa , Animais , Feminino , Cobaias , Masculino , Nanopartículas/administração & dosagem , Paraoxon/toxicidade , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacocinética , Ratos Sprague-Dawley , Sarina/toxicidade , Análise de Sobrevida , Fatores de Tempo , Distribuição Tecidual
8.
Langmuir ; 35(5): 1544-1551, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30265550

RESUMO

Here, we report a simple yet effective surface-modification approach to imparting hydrophobic surfaces with superhydrophilicity using ultralow fouling/functionalizable carboxybetaine (CB) copolymers via a dip-coating technique. A new series of CB random copolymers with varying amphiphilicities were synthesized and coated on hydrophobic polypropylene (PP) and polystyrene (PS) surfaces. The nonfouling capability of each coating was screened by an enzyme-linked immunosorbent assay (ELISA) and further comprehensively assessed against 100% human serum by a Micro BCA protein assay kit. The random copolymer containing ∼30 mol % CB units showed superhydrophilicity with the highest air contact angle of more than 165° in DI water and the best nonfouling capability against 100% human blood serum. Surfaces of a 96-well plate coated with the optimal CB random copolymer had a significantly better nonfouling capability than those of a commercial 96-well plate with an ultralow attachment surface. The adhesion of mouse embryonic fibroblast cells (NIH3T3) was completely inhibited on surfaces coated with CB random copolymers. Furthermore, the optimal nonfouling CB copolymer surface was functionalized with an antigen via covalent bonding where its specific interactions with its antibody were verified. Thus, this CB random copolymer is capable of imparting both ultralow fouling and functionalizable capabilities to hydrophobic surfaces for blood-contacting devices.


Assuntos
Resinas Acrílicas/química , Incrustação Biológica/prevenção & controle , Compostos de Amônio Quaternário/química , Resinas Acrílicas/síntese química , Resinas Acrílicas/metabolismo , Adsorção , Animais , Proteínas Sanguíneas/metabolismo , Humanos , Camundongos , Células NIH 3T3 , Polipropilenos/química , Poliestirenos/química , Ligação Proteica , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/metabolismo
9.
Langmuir ; 35(5): 1864-1871, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30119608

RESUMO

We report the synthesis of a zwitterionic carboxybetaine disulfide cross-linker (CBX-SS) and biodegradable poly(carboxybetaine) (PCB) hydrogels and nanocages (NCs) made using this cross-linker. The structure of CBX-SS combines zwitterionic carboxybetaine to confer nonfouling properties and a disulfide linkage to facilitate degradation. The physical, mechanical, and fouling characteristics of PCB hydrogels cross-linked with CBX-SS were investigated. Then, the degradation characteristics of CBX-SS-cross-linked hydrogels were evaluated through their weight loss and release of an encapsulated protein in a reducing environment. Furthermore, CBX-SS was applied to prepare degradable PCB NCs. Results show that encapsulating the highly immunogenic enzyme uricase in degradable PCB NCs eliminates or prevents an in vivo immune response to both the protein and polymer.

10.
ACS Nano ; 12(12): 12004-12014, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30412375

RESUMO

The undesirable immune response poses a life-threatening challenge to human health. It not only deteriorates the therapeutic performance of biologic drugs but also contributes to various diseases such as allergies and autoimmune diseases. Inspired by the role of chromatin in the maintenance of natural immune tolerance, here we report a DNA-protein polymeric nanocomplex that can mimic the tolerogenic function of chromatin and induce an immune tolerance to its protein cargos. We first proved that the chromatin-mimetic nanomedicine loaded with keyhole limpet hemocyanin (KLH), a highly immunogenic model protein, could elicit a durable antigen-specific immune tolerance to KLH lasting for at least five weeks in mice. Following the proof-of-concept study, we demonstrated that this nanomedicine could be applied to improve the safety and efficacy of a biologic drug, PEGylated uricase, by attenuating the relevant antibody (Ab) responses. Moreover, we also demonstrated that prophylactic treatments with this nanomedicine could tolerize the immune system with the allergen of ovalbumin (OVA) and thus inhibit the occurrence of airway inflammation in an OVA-induced allergic asthma murine model. Collectively, our work illustrates a nature-inspired concept of immune tolerance induction and establishes a useful tool to specifically suppress unwanted immune responses for therapeutic purposes.


Assuntos
Asma/imunologia , Cromatina/imunologia , Hemocianinas/imunologia , Tolerância Imunológica/imunologia , Nanomedicina , Animais , Asma/induzido quimicamente , Cromatina/química , Modelos Animais de Doenças , Hemocianinas/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina
11.
Adv Mater ; 30(39): e1803087, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30066374

RESUMO

Injectable and malleable hydrogels that combine excellent biocompatibility, physiological stability, and ease of use are highly desirable for biomedical applications. Here, a simple and scalable strategy is reported to make injectable and malleable zwitterionic polycarboxybetaine hydrogels, which are superhydrophilic, nonimmunogenic, and completely devoid of nonspecific interactions. When zwitterionic microgels are reconstructed, the combination of covalent crosslinking inside each microgel and supramolecular interactions between them gives the resulting zwitterionic injectable pellet (ZIP) constructs supportive moduli and tunable viscoelasticity. ZIP constructs can be lyophilized to a sterile powder that fully recovers its strength and elasticity upon rehydration, simplifying storage and formulation. The lyophilized powder can be reconstituted with any aqueous suspension of cells or therapeutics, and rapidly and spontaneously self-heals into a homogeneous composite construct. This versatile and highly biocompatible platform material shows great promise for many applications, including as an injectable cell culture scaffold that promotes multipotent stem cell expansion and provides oxidative stress protection.


Assuntos
Hidrogéis/química , Elasticidade , Viscosidade , Cicatrização
12.
Langmuir ; 34(22): 6538-6545, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29733605

RESUMO

Interfacial water structure on a polymer surface in water (or surface hydration) is related to the antifouling activity of the polymer. Zwitterionic polymer materials exhibit excellent antifouling activity due to their strong surface hydration. It was proposed to replace zwitterionic polymers using mixed charged polymers because it is much easier to prepare mixed charged polymer samples with much lower costs. In this study, using sum frequency generation (SFG) vibrational spectroscopy, we investigated interfacial water structures on mixed charged polymer surfaces in water and how such structures change while being exposed to salt solutions and protein solutions. The 1:1 mixed charged polymer exhibits excellent antifouling property whereas other mixed charged polymers with different ratios of the positive/negative charges do not. It was found that on the 1:1 mixed charged polymer surface, SFG water signal is dominated by the contribution of the strongly hydrogen bonded water molecules, indicating strong hydration of the polymer surface. The responses of the 1:1 mixed charged polymer surface to salt solutions are similar to those of zwitterionic polymers. Interestingly, exposure to high concentrations of salt solutions leads to stronger hydration of the 1:1 mixed charged polymer surface after replacing the salt solution with water. Protein molecules do not substantially perturb the interfacial water structure on the 1:1 mixed charged polymer surface and do not adsorb to the surface, showing that this mixed charged polymer is an excellent antifouling material.

13.
Angew Chem Int Ed Engl ; 57(26): 7743-7747, 2018 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-29707870

RESUMO

The commonly used "stealth material" poly(ethylene glycol) (PEG) effectively promotes the pharmacokinetics of therapeutic cargos while reducing their immune response. However, recent studies have suggested that PEG could induce adverse reactions, including the emergence of anti-PEG antibodies and tissue histologic changes. An alternative stealth material with no or less immunogenicity and organ toxicity is thus urgently needed. We designed a polypeptide with high zwitterion density (PepCB) as a stealth material for therapeutics. Neither tissue histological changes in liver, kidney, or spleen, nor abnormal behavior, sickness or death was induced by the synthesized polymer after high-dosage administration for three months in rats. When conjugated to a therapeutic protein uricase, the uricase-PepCB bioconjugate showed significantly improved pharmacokinetics and immunological properties compared with uricase-PEG conjugates.


Assuntos
Sistemas de Liberação de Medicamentos , Peptídeos/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Meia-Vida , Interações Hidrofóbicas e Hidrofílicas , Íons , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Peptídeos/efeitos adversos , Peptídeos/química , Peptídeos/imunologia , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Baço/patologia , Urato Oxidase/administração & dosagem , Urato Oxidase/imunologia , Urato Oxidase/farmacocinética
14.
Adv Mater ; 30(14): e1705728, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29457278

RESUMO

For biotherapeutics that require multiple administrations to fully cure diseases, the induction of undesirable immune response is one common cause for the failure of their treatment. Covalent binding of hydrophilic polymers to proteins is commonly employed to mitigate potential immune responses. However, while this technique is proved to partially reduce the antibodies (Abs) reactive to proteins, it may induce Abs toward their associated polymers and thus result in the loss of efficacy. Zwitterionic poly(carboxybetaine) (PCB) is recently shown to improve the immunologic properties of proteins without inducing any antipolymer Abs against itself. However, it is unclear if the improved immunologic profiles can translate to better clinical outcomes since improved immunogenicity cannot directly reflect amelioration in efficacy. Here, a PCB nanocage (PCB NC) is developed, which can physically encase proteins while keeping their structure intact. PCB NC encapsulation of uricase, a highly immunogenic enzyme, is demonstrated to eradicate all the immune responses. To bridge the gap between immunogenicity and efficacy studies, the therapeutic performance of PCB NC uricase is evaluated and compared with its PEGylated counterpart in a clinical-mimicking gouty rat model to determine any loss of efficacy evoked after five administrations.


Assuntos
Produtos Biológicos/química , Animais , Anticorpos , Preparações Farmacêuticas , Polímeros , Proteínas , Ratos
15.
Anal Chem ; 89(20): 10999-11004, 2017 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-28921971

RESUMO

Cellulose paper is an ideal diagnostic platform for low-cost, easily disposable and lightweight implementation, but requires surface modification to achieve detection with high sensitivity and specificity in complex media. In this work, a polymer-catechol conjugate containing a superhydrophilic nonfouling poly(carboxylbetaine) (pCB) and four surface-binding l-3,4-dihydroxyphenylalanine (DOPA) groups, pCB-(DOPA)4, were applied onto a paper-based sensor surface via a simple "graft-to" immersion process to render the surface with both nonfouling and protein functionalizable properties. This dip-coating technique is effective, convenient and robust as compared to the "graft-from" techniques reported previously with similar nonfouling properties. The coated paper sensor showed both increased analyte diffusion rate and improved sensitivity of glucose detection in human blood serum. The capability of pCB-(DOPA)4-modified paper sensor for specific antigen-antibody detection was demonstrated via the covalent immobilization of bovine serum albumin antibody (anti-BSA) and fibrinogen antibody (anti-Fg) onto the pCB-coated surface via simple 1-ethyl-3-(3-(dimethylamino)propyl)-carbodiimide and N-hydroxysuccinimide (EDC/NHS) chemistry.


Assuntos
Técnicas Biossensoriais/métodos , Di-Hidroxifenilalanina/química , Papel , Polímeros/química , Animais , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , Reações Antígeno-Anticorpo , Glicemia/análise , Bovinos , Fibrinogênio/imunologia , Humanos , Imunoensaio , Soroalbumina Bovina/imunologia , Succinimidas/química
16.
Langmuir ; 33(42): 11264-11269, 2017 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-28850239

RESUMO

The development of nonfouling zwitterionic materials has a wide range of biomedical and engineering applications. This work delineates the design and synthesis of a new zwitterionic material based on a naturally occurring compatible solute, ectoine, which is known to possess additional protective properties that stabilize even whole cells against ultraviolet radiation or cytotoxins. These properties and applications of ectoine inspire us to design a functional monomer containing the natural zwitterion moiety of ectoine imparting nonfouling properties and the methacrylate moiety for polymerization. The synthesis route designed for the ectoine methacrylate monomer is simple with a high yield, which is characterized by nuclear magnetic resonance spectroscopy and mass spectrometry. After monomer synthesis, we have prepared a poly(ectoine) hydrogel via thermal polymerization. The equilibrium water content, degree of cross-linking, mechanical strength, and nonfouling properties are determined for polyectoine hydrogels with different cross-linking conditions. Poly(ectoine) hydrogels are shown to have highly hydrated and excellent nonfouling properties and can be considered to be a promising biomaterial.


Assuntos
Diamino Aminoácidos/síntese química , Adsorção , Hidrogéis , Raios Ultravioleta
17.
Anal Chem ; 89(16): 8217-8222, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28727918

RESUMO

Pre-existing and induced anti-poly(ethylene glycol) (PEG) antibodies (abs) have been shown to be related with limitation of therapeutic efficacy and reduction in tolerance of several therapeutic agents. However, the current methods to detect anti-PEG abs are tedious and usually lack quantification. A facile, rapid, sensitive, and reliable technique to detect anti-PEG abs is highly desired in both research and clinic settings. In this work, we have presented a surface plasmon resonance (SPR) biosensor technique for the detection of anti-PEG abs and compared three PEG surface chemistries. Methoxy-PEG (mPEG) 5k was found to have the best performance. The detection of anti-PEG abs directly from diluted blood serum was achieved within 40 min. Detection sensitivity is as good as or better than enzyme-linked immunosorbent assay (ELISA). Furthermore, different antibody isotypes can be quantitatively differentiated by adopting secondary antibodies. A pilot study has been performed to analyze clinical blood samples using this technology, demonstrating its potential as a convenient and powerful method to prescreen and monitor anti-PEG abs in the patients before or after they receive treatment with PEG-containing drugs.


Assuntos
Anticorpos/sangue , Técnicas Biossensoriais/métodos , Polietilenoglicóis/metabolismo , Ressonância de Plasmônio de Superfície/métodos , Animais , Anticorpos/imunologia , Humanos , Limite de Detecção , Metacrilatos/química , Projetos Piloto , Polietilenoglicóis/química , Ratos , Ressonância de Plasmônio de Superfície/instrumentação
18.
Adv Mater ; 29(31)2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28620970

RESUMO

Medical devices face nonspecific biofouling from proteins, cells, and microorganisms, which significantly contributes to complications and device failure. Imparting these devices with nonfouling capabilities remains a major challenge, particularly for those made from elastomeric polymers. Current strategies, including surface coating and copolymerization/physical blending, necessitate compromise among nonfouling properties, durability, and mechanical strength. Here, a new strategy is reported to achieve both high bulk mechanical strength and excellent surface nonfouling properties, which are typically contradictory, in one material. This is realized through a nonfouling polymeric elastomer based on zwitterionic polycarboxybetaine derivatives. By hiding both charged moieties of the zwitterionic compounds with hydrocarbon ester and tertiary amine groups, the bulk polymer itself is elastomeric and hydrophobic while its superhydrophilic surface properties are restored upon hydrolysis. This coating-free nonfouling elastomer is a highly promising biomaterial for biomedical and engineering applications.

19.
Biointerphases ; 12(2): 02C411, 2017 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-28511543

RESUMO

Terminal sterilization of hydrogel-based biomaterials is crucial for their clinically relevant applications. The authors synthesized nonfouling zwitterionic hydrogels consisting of carboxybetaine (CB) acrylamide monomer and a carboxybetaine dimethacrylate crosslinker. The mechanical and biological stability of nonfouling hydrogels were investigated using three main terminal sterilization techniques, i.e., steam autoclave, ethylene oxide gas, and gamma irradiation. It was found that CB hydrogels are very stable at high temperature and pressure and in oxidative gas environments without changing their stress, modulus, and nonfouling properties. Gamma irradiation of CB hydrogels in dry state showed high mechanical and nonfouling stability by avoiding the adverse effect of the free radicals resulted from water inside the hydrogel network. The CB hydrogels can be dehydrated and hydrated back and forward reversibly in several cycles without any loss in mechanical properties, which is desirable for hydrogel storage, handling, and sterilization. The CB hydrogel tubes are easily prepared using a simple procedure, and they are uniformly transparent and tough after swelling. Furthermore, the good mechanical properties of the CB hydrogel tubes and their resistance to red blood cells indicate great potential of this nonfouling material for medical applications.


Assuntos
Acrilamidas/química , Dessecação , Óxido de Etileno/química , Raios gama , Hidrogéis/química , Esterilização , Radicais Livres/química
20.
ACS Appl Mater Interfaces ; 9(11): 9255-9259, 2017 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-28252277

RESUMO

We achieved ultralow fouling on target surfaces by controlled polymerization of carboxybetaine under ambient conditions. The polymerization process for grafting polymer films onto the surfaces was carried out in air and did not require any deoxygenation step or specialized equipment. This method allows one to conveniently introduce a nonfouling polymer network onto large substrates.

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