Responsive cell–material interfaces

Major design aspects for novel biomaterials are driven by the desire to mimic more varied and complex properties of a natural cellular environment with man-made materials. The development of stimulus responsive materials makes considerable contributions to the effort to incorporate dynamic and reversible elements into a biomaterial. This is particularly challenging for cell–material interactions that occur at an interface (biointerfaces); however, the design of responsive biointerfaces also presents opportunities in a variety of applications in biomedical research and regenerative medicine. This review will identify the requirements imposed on a responsive biointerface and use recent examples to demonstrate how some of these requirements have been met. Finally, the next steps in the development of more complex biomaterial interfaces, including multiple stimuli-responsive surfaces, surfaces of 3D objects and interactive biointerfaces will be discussed

Zwitterionic materials for biomedical applications

La resposta del nostre cos als biomaterials suposa una gran obstacle per la efectivitat de múltiples teràpies basades en biomaterials. Accionats per la absorció inespecífica de biomolècules a la superfície del material, barreres com el sistema immune o les superfícies mucoses eliminen els materials del cos, evitant que arribin al seu destí i realitzin la seva funció. Els materials zwitteriònics han emergit en els últims anys com a materials antiadherents prometedors per a superar les mencionades barreres. Tot i que molts sistemes han utilitzat els materials zwitteriònics com a recobriments, les seves propietats úniques de superhidrofilicitat i versatilitat química suggereixen múltiples beneficis en utilitzar-los com a material principal. Aquí, dos sistemes diferents basats en materials zwitteriònics són presentats. En primer lloc una plataforma de alliberament de fàrmac antiadherent basat en copolímers de bloc amfifílics (CBA) és desenvolupada. Els CBAs zwitteriònics són sintetitzats i optimitzats perquè s’auto-organitzin en nanopartícules zwitteriòniques. Les propietats antiadherents d’aquestes nanopartícules es demostren, al igual que el seu potencial per a esdevenir un sistema d’alliberament de fàrmac oral. Seguidament, el sistema s’utilitza com a portador per a fàrmacs contra la malària i el càncer. Les nanopartícules mostren internalització en eritròcits infectats per Plasmòdium, i nanopartícules carregades amb curcumina demostren la seva eficàcia contra la malària in vitro. S’observa absorció oral de polímer i curcumina in vivo utilitzant un model de ratolí, indicant el potencial del sistema per a esdevenir una teràpia oral contra la malària. Quan s’optimitza el sistema per la teràpia contra el càncer, nanopartícules carregades de Paclitaxel exhibeixen activitat anti-cancerígena en models in vitro de cèl·lules canceroses. En segon lloc, microrobots zwitteriònics no-immunogènics que poden evitar el reconeixement per el sistema immune són introduïts. Es desenvolupa una fotoresistència zwitteriònica per a la microimpressió de microrobots zwitteriònics a través de la polimerització de dos fotons amb una ample funcionalització: propietats mecàniques variables, anti-bioadhesió i propietats no-immunogèniques, funcionalització per a la actuació magnètica, encapsulació de biomolècules i modificació superficial per a l’alliberament de fàrmac. Els robots invisibles eviten que els macròfags del sistema immune els detectin després d’una inspecció exhaustiva (de més de 90 hores), fet que no s’ha aconseguit fins el moment en cap sistema microrobòtic. Aquests materials zwitteriònics versàtils eliminen un dels grans obstacles en el desenvolupament de microrobots biocompatibles, i serviran com una caixa d’eines de materials no-immunogènics per a crear robots biomèdics i altres dispositius per a la bioenginyeria i per a aplicacions biomèdiques.La respuesta de nuestro cuerpo a los biomateriales supone un gran obstáculo para la efectividad de múltiples terapias basadas en los biomateriales. Accionados por la absorción de biomoléculas en la superficie del material, barreras como el sistema inmune o las superficies mucosas eliminan los materiales del cuerpo, evitando que lleguen a su destino y realicen su función. Los materiales zwitteriónicos han emergido en los últimos años como materiales antiadherentes prometedores para superar las barreras mencionadas. Aunque muchos sistemas utilizan materiales zwitteriónicos como recubrimientos, sus propiedades únicas de superhidrofilicidad i versatilidad química sugieren múltiples beneficios en utilizarlos como material principal. Aquí, dos sistemas basados en materiales zwitteriónicos son presentados. En primer lugar, una plataforma para la liberación de fármaco antiadherente basada en copolímeros de bloque amfifílicos (CBA) es desarrollada. Los CBA zwitteriónicos son sintetizados y optimizados para que se auto-organicen en nanopartículas zwitteriónicas. Las propiedades antiadherentes de estas nanopartículas son probadas, al igual que su potencial para convertirse en un sistema oral de liberación de fármaco. Seguidamente, el sistema se utiliza como portador para fármacos animalarios y anticancerígenos. Las nanopartículas muestran internalización en eritrocitos infectados por Plasmodio, y nanopartículas cargadas con curcumina demuestran su eficacia contra la malaria in vitro. Se observa la absorción oral de polímero y curcumina in vivo utilizando un modelo de ratón, indicando el potencial del sistema para convertirse en una terapia oral contra malaria. Cuando se optimiza el sistema para la terapia contra el cáncer, las nanopartículas cargadas con Paclitaxel exhiben actividad anticancerígena en modelos in vitro de células cancerosas. En segundo lugar, microrobots zwitteriónicos no-inmunológicos que pueden evitar el reconocimiento por parte del sistema inmune son introducidos. Se desarrolla una fotoresisténcia zwitteriónica para la microimpresión de microrobots zwitteriónicos a través de la polimerización de dos fotones con una amplia funcionalización: propiedades mecánicas variables, anti-bioadhesión i propiedades no-inmunogénicas, funcionalización para la actuación magnética, encapsulación de biomoléculas i modificación superficial para la liberación de fármaco. Los robots invisibles evitan que los macrófagos del sistema inmune innato los detecten después de una inspección exhaustiva (de más de 90 horas), hecho que no se ha conseguido hasta la fecha por ningún sistema microrobótico. Estos materiales zwitteriónicos versátiles eliminan uno de los grandes obstáculos en el desarrollo de microrobots biocompatibles, y servirán como una caja de herramientas de materiales no-inmunogénicos para crear robots biomédicos y otros dispositivos para la bioingeniería y para las aplicaciones biomédicas.Body response to biomaterials suppose a major roadblock for the effectiveness of multiple biomaterial-based therapies. Triggered by unspecific absorption of biomolecules in the material surface, barriers such as immune system or mucosal surfaces clear foreign materials from the body, preventing them to reach their target and perform their function. Zwitterionic materials have emerged in the last years as promising antifouling materials to overcome the mentioned barriers. Although many systems have used zwitterionic materials as coatings, the unique properties of superhydrophilicity and chemical versatility suggest multiple benefits of using zwitterionic polymers as bulk materials. Here, two different systems based on zwitterionic materials are presented. In first place, an antifouling drug delivery platform based on zwitterionic amphiphilic polymers (ABC) is developed. Zwitterionic ABCs are synthetized and optimized to self-assemble in zwitterionic nanoparticles. The antifouling properties of zwitterionic nanoparticles are proved, together with their potential to become an oral drug delivery system. Next, the system is used as a drug carrier for antimalarial and anticancer drugs. Nanoparticles show internalization in Plasmodium infected erythrocytes, and curcumin-loaded nanoparticles prove their antimalarial efficacy in vitro. Oral absorption of polymer and curcumin is also observed in vivo using mice model, indicating the potential of this system to become oral therapy against malaria. When optimizing the system for anticancer therapy, Paclitaxel-loaded nanoparticles exhibit anticancer activity in in vitro cancer cell models. Second, non‐immunogenic stealth zwitterionic microrobots that avoid recognition from immune cells are introduced. Zwitterionic photoresist are developed for the 3D microprinting of zwitterionic hydrogel microrobots through 2-photon polymerization with ample functionalization: tunable mechanical properties, anti-biofouling and non-immunogenic properties, functionalization for magnetic actuation, encapsulation of biomolecules, and surface functionalization for drug delivery. Stealth microrobots avoid detection by macrophage cells of the innate immune system after exhaustive inspection (> 90 h), which has not been achieved in any microrobotic platform to date. These versatile zwitterionic materials eliminate a major roadblock in the development of biocompatible microrobots, and will serve as a toolbox of non-immunogenic materials for medical microrobot and other device technologies for bioengineering and biomedical applications

Natural-based hydrogels for tissue engineering applications

In the field of tissue engineering and regenerative medicine, hydrogels are used as biomaterials to support cell attachment and promote tissue regeneration due to their unique biomimetic characteristics. The use of natural-origin materials significantly influenced the origin and progress of the field due to their ability to mimic the native tissuesâ extracellular matrix and biocompatibility. However, the majority of these natural materials failed to provide satisfactory cues to guide cell differentiation toward the formation of new tissues. In addition, the integration of technological advances, such as 3D printing, microfluidics and nanotechnology, in tissue engineering has obsoleted the first generation of natural-origin hydrogels. During the last decade, a new generation of hydrogels has emerged to meet the specific tissue necessities, to be used with state-of-the-art techniques and to capitalize the intrinsic characteristics of natural-based materials. In this review, we briefly examine important hydrogel crosslinking mechanisms. Then, the latest developments in engineering natural-based hydrogels are investigated and major applications in the field of tissue engineering and regenerative medicine are highlighted. Finally, the current limitations, future challenges and opportunities in this field are discussed to encourage realistic developments for the clinical translation of tissue engineering strategies.Authors acknowledge financial support from the European Union Framework Programme for Research and Innovation Horizon 2020 under European Research Council grant agreement No. 772817; FCT (Fundação para a Ciência e a Tecnologia) for individual fellowship CEECIND/01375/2017 (MGF); FCT for project PTDC/NAN-MAT/30595/2017; Xunta de Galicia for postdoctoral fellowship ED481B-2019-025 (AP); Norwegian Research Council (NFR) for project No. 287953

Protein and Polysaccharide-Based Magnetic Composite Materials for Medical Applications.

The combination of protein and polysaccharides with magnetic materials has been implemented in biomedical applications for decades. Proteins such as silk, collagen, and elastin and polysaccharides such as chitosan, cellulose, and alginate have been heavily used in composite biomaterials. The wide diversity in the structure of the materials including their primary monomer/amino acid sequences allow for tunable properties. Various types of these composites are highly regarded due to their biocompatible, thermal, and mechanical properties while retaining their biological characteristics. This review provides information on protein and polysaccharide materials combined with magnetic elements in the biomedical space showcasing the materials used, fabrication methods, and their subsequent applications in biomedical research

BioMEMS

As technological advancements widen the scope of applications for biomicroelectromechanical systems (BioMEMS or biomicrosystems), the field continues to have an impact on many aspects of life science operations and functionalities. Because BioMEMS research and development require the input of experts who use different technical languages and come from varying disciplines and backgrounds, scientists and students can avoid potential difficulties in communication and understanding only if they possess a skill set and understanding that enables them to work at the interface of engineering and biosciences. Keeping this duality in mind throughout, BioMEMS: Science and Engineering Perspectives supports and expedites the multidisciplinary learning involved in the development of biomicrosystems. Divided into nine chapters, it starts with a balanced introduction of biological, engineering, application, and commercialization aspects of the field. With a focus on molecules of biological interest, the book explores the building blocks of cells and viruses, as well as molecules that form the self-assembled monolayers (SAMs), linkers, and hydrogels used for making different surfaces biocompatible through functionalization. The book also discusses: Different materials and platforms used to develop biomicrosystems Various biological entities and pathogens (in ascending order of complexity) The multidisciplinary aspects of engineering bioactive surfaces Engineering perspectives, including methods of manufacturing bioactive surfaces and devices Microfluidics modeling and experimentation Device level implementation of BioMEMS concepts for different applications. Because BioMEMS is an application-driven field, the book also highlights the concepts of lab-on-a-chip (LOC) and micro total analysis system (μTAS), along with their pertinence to the emerging point-of-care (POC) and point-of-need (PON) applications

Synthesis and Assembly of Anisotropic Ellipsoidal Particles.

We create complex non-close packed assemblies from ellipsoidal anisotropic particles using external electric fields in this dissertation. Spherical colloidal particles have long been self-assembled into close-packed 2-D and 3-D ordered structures, while external fields have been used to accelerate their self-assembly as well as to alter the free energy landscape to create novel field driven ordered structures. In the first part of the dissertation, we develop a direct current (DC) electric field assembly method that accelerates the self-assembly of charged colloidal particles. In the second part of the dissertation, we use alternating current (AC) electric fields to alter the free energy landscape and actuate the self-assembled colloidal assemblies created from anisotropic particles.PHDMacromolecular Science & EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/107255/1/aayushs_1.pd

BioMEMS

As technological advancements widen the scope of applications for biomicroelectromechanical systems (BioMEMS or biomicrosystems), the field continues to have an impact on many aspects of life science operations and functionalities. Because BioMEMS research and development require the input of experts who use different technical languages and come from varying disciplines and backgrounds, scientists and students can avoid potential difficulties in communication and understanding only if they possess a skill set and understanding that enables them to work at the interface of engineering and biosciences. Keeping this duality in mind throughout, BioMEMS: Science and Engineering Perspectives supports and expedites the multidisciplinary learning involved in the development of biomicrosystems. Divided into nine chapters, it starts with a balanced introduction of biological, engineering, application, and commercialization aspects of the field. With a focus on molecules of biological interest, the book explores the building blocks of cells and viruses, as well as molecules that form the self-assembled monolayers (SAMs), linkers, and hydrogels used for making different surfaces biocompatible through functionalization. The book also discusses: Different materials and platforms used to develop biomicrosystems Various biological entities and pathogens (in ascending order of complexity) The multidisciplinary aspects of engineering bioactive surfaces Engineering perspectives, including methods of manufacturing bioactive surfaces and devices Microfluidics modeling and experimentation Device level implementation of BioMEMS concepts for different applications. Because BioMEMS is an application-driven field, the book also highlights the concepts of lab-on-a-chip (LOC) and micro total analysis system (μTAS), along with their pertinence to the emerging point-of-care (POC) and point-of-need (PON) applications

Tailoring bombyx mori silk as multifuctional material for advanced applications.

288 p.Materials support human development. Among the available materials, polymers are nowadays essential and practically omnipresent because of their unrivalled properties. Unfortunately, polymers are synthesized from oil, and they tend to accumulate in nature, which represents a serious environmental impact.To minimize these damages, materials science suggests replacing synthetic polymers with bio-based materials. To promote the use of these more sustainable materials, the objective of the work has been to demonstrate the real applicability of bio-based materials, and more specifically Silk Fibroin (SF), a protein obtained from Bombyx mori (silkworm) cocoons. This protein displays unique physical-chemical properties that make it an interesting substrate for the development of new materials with advanced properties.Two main fields of application have been selected in this work for SF: i) electronics (active composites for sensors and actuators) and ii) porous structures for biomedicine, energy, and environment.For electronics, SF has been combined with i) carbon nanotubes (CNT) to obtain force sensors with piezoresistive responses (PR) of ~ 4 MPa-1 at pressures of 0.11 MPa; ii) with silver nanowires (SNW) to obtain PR of 26 GPa-1 when the pressure is between 0.2 and 0.4 MPa. Also, SF/SNW nanocomposites show optical transparency at SNW loads above 3%; iii) with cobalt ferrite nanoparticles (CFO) to obtain magnetic actuators with a magnetization value of ~ 10 emu·g¿1 and coercivity of almost 4 kOe, (20 wt. % CFO); and iv) with ionic liquids (IL) to obtain bending actuators with bending responses of ~ 0.5 by applying low voltages (3-5 V).SF has been processed also for the development of porous structures by i) electrospinning, to obtain scaffolds that when are combined with CFO particles, stimulate the bone cells development; ii) by salt leaching; to obtain Li-ion battery separators that lead to battery performance of 89,3 y 131,3 mAh·g¿1, for 2C and C/8 cycles respectively and iii) by gas foaming, gelation and freeze-drying, to obtain samples with porosity values above 94% and aqueous Cr adsorption capacities up to 3 mg/g.Bc Materials: Basque Center for materials applications & nanostructure

Electroactive poly(vinylidene fluoride) based materials: recent progress, challenges and opportunities

A poly(vinylidene fluoride) (PVDF) and its copolymers are polymers that, in specific crystalline phases, show high dielectric and piezoelectric values, excellent mechanical behavior and good thermal and chemical stability, suitable for many applications from the biomedical area to energy devices. This chapter introduces the main properties, processability and polymorphism of PVDF. Further, the recent advances in the applications based on those materials are presented and discussed. Thus, it shown the key role of PVDF and its copolymers as smart and multifunctional material, expanding the limits of polymer-based technologies.FCT (Fundação para a Ciência e Tecnologia) for financial support under the framework of Strategic Funding grants UID/FIS/04650/2019, and UID/QUI/0686/2019 and project PTDC/FIS-MAC/28157/2017, PTDC/BTMMAT/28237/2017, PTDC/EMD-EMD/28159/2017. The author also thanks the FCT for financial support under grant SFRH/BPD/112547/2015 (C.M.C.), SFRH/BPD/98109/2013 (V.F.C.), SFRH/BD/140698/2018 (R.B.P.), SFRH/BPD/96227/2013 (P.M.), SFRH/BPD/121526/2016 (D.M.C.), SFRH/BPD/97739/2013 (V. C.), SFRH/BPD/90870/2012 (C.R.). Financial support from the Spanish Ministry of Economy and Competitiveness (MINECO) through project MAT2016-76039-C4-3-R (AEI/FEDER, UE) (including FEDER financial support) and from the Basque Government Industry and Education Departments under the ELKARTEK, HAZITEK and PIBA (PIBA-2018-06)