Biocompatible Substrate Research Articles

Cell Behavior of Primary Fibroblasts and Osteoblasts on Plasma-Treated Fluorinated Polymer Coated with Honeycomb Polystyrene.

The development of new biocompatible polymer substrates is still of interest to many research teams. We aimed to combine a plasma treatment of fluorinated ethylene propylene (FEP) substrate with a technique of improved phase separation. Plasma exposure served for substrate activation and modification of surface properties, such as roughness, chemistry, and wettability. The treated FEP substrate was applied for the growth of a honeycomb-like pattern from polystyrene solution. The properties of the pattern strongly depended on the primary plasma exposure of the FEP substrate. The physico-chemical properties such as changes of the surface chemistry, wettability, and morphology of the prepared pattern were determined. The cell response of primary fibroblasts and osteoblasts was studied on a honeycomb pattern. The prepared honeycomb-like pattern from polystyrene showed an increase in cell viability and a positive effect on cell adhesion and proliferation for both primary fibroblasts and osteoblasts.

Graphene-coated Si nanowires as substrates for surface-enhanced Raman scattering

Si nanowires always exhibited no Raman enhancement for application in surface-enhanced Raman scattering (SERS). Herein, surface modifications of Si nanowires, without the presence of noble metals, were carried out to develop biocompatible SERS substrates. The treatment of hydrogen plasma on as-prepared Si nanowires leads to no enhanced Raman signals for the absorbed R6G molecules. The coatings of nanocrystalline diamond and multilayer graphene enable Raman signals to be enhanced with a reduced fluorescent background. The graphene-coated sample exhibits a much lower fluorescent background than the diamond-coated sample at a high concentration of the dye molecules. For the sample with graphene-coated Si nanowires, the minimum detection limit is 10-7 mol/L, and the enhancement factor reaches above 104. Such stable Raman enhancement is attributed to the formation of hydrogen-terminated graphene and the presence of the nanowire structure, accelerating charger transfer between graphene and the dye molecules. Importantly, the Raman enhancement is independent of the number of graphene layers. The Raman signal remains stable after exposure to the atmosphere for one month. Therefore, a new nanostructure of Si nanowires with graphene coating is developed, which shows great potential in SERS applications.

Efficient cardiomyocyte differentiation of induced pluripotent stem cells on PLGA nanofibers enriched by platelet‐rich plasma

Regeneration and restoring the function of the myocardial‐infracted hearts have been one of the constant challenges in medicine. Recently, tissue engineering, using biocompatible substrates and stem cells, holds a real promise to solve these problems. Herein, poly(lactic‐co‐glycolic acid) (PLGA) nanofibers and platelet‐rich plasma (PRP) enriched PLGA nanofibers (PLGA‐PRP) were fabricated by electrospinning. Scanning electron microscopy (SEM) demonstrated that fiber diameters in PLGA scaffolds with and without PRP were in the range of 500 ± 280 nm and fibers were also bead free, smooth, in random orientation, and with interconnected pores. During culture of the human‐induced pluripotent stem cells (iPSCs) on the nanofibrous scaffold, further differentiation of the iPSCs to cardiomyocytes was detected in PLGA‐PRP nanofibers compared to the PLGA. This improvement in differentiation potential was evaluated at the morphological, molecular gene, and protein expression levels using SEM, real‐time reverse transcription‐polymerase chain reaction (RT‐PCR), and immunocytochemistry, respectively. The results obtained in this study highlighted the significance of natural growth factors present in the artificial scaffold applied in cardiac tissue engineering according to the improvements in cell‐biomaterial interactions. Taken together, our result indicated that PRP‐incorporated PLGA could be considered as a great potential candidate to use for engineering suitable myocardium replacement constructs.

Flexible CoFeB/Silk Films for Biocompatible RF/Microwave Applications.

Aiming to realize the integration of signal processing with the human body, wearable and implantable radio frequency (RF)/microwave devices are rapidly developed. However, the insufficiency in skin commonality and biocompatibility brings up challenges in making such devices. In this study, an ultra-flexible and biocompatible CoFeB/silk film is developed potentially for on-skin and implantable RF/microwave applications. Moreover, the CoFeB/silk films present controllable dissolvability in aqueous solutions and exhibit great potentials in applications for environmentally friendly disposable devices. A strain-tunable bandstop filter based on the CoFeB/silk film was fabricated, which exhibited a large frequency tunability of 3 GHz and ability in monitoring the finger-joints' motions. This concept and method of combining ferromagnetic materials with the biocompatible substrate offers a novel pathway for wearable/implantable applications.

Design and Optimization of Piezoresistive PEO/PEDOT:PSS Electrospun Nanofibers for Wearable Flex Sensors.

Flexible strain sensors are fundamental devices for application in human body monitoring in areas ranging from health care to soft robotics. Stretchable piezoelectric strain sensors received an ever-increasing interest to design novel, robust and low-cost sensing units for these sensors, with intrinsically conductive polymers (ICPs) as leading materials. We investigated a sensitive element based on crosslinked electrospun nanofibers (NFs) directly collected and thermal treated on a flexible and biocompatible substrate of polydimethylsiloxane (PDMS). The nanostructured active layer based on a blend of poly(ethylene oxide) (PEO) and poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS) as the ICP was optimized, especially in terms of the thermal treatment that promotes electrical conductivity through crosslinking of PEO and PSS, preserving the nanostructuration and optimizing the coupling between the sensitive layer and the substrate. We demonstrate that excellent properties can be obtained thanks to the nanostructured active materials. We analyzed the piezoresistive response of the sensor in both compression and traction modes, obtaining an increase in the electrical resistance up to 90%. The Gauge Factors (GFs) reflected the extraordinary piezoresistive behavior observed: 45.84 in traction and 208.55 in compression mode, which is much higher than the results presented in the literature for non-nanostructurated PEDOT.

One-Step Dip-Coating-Fabricated Core-Shell Silk Fibroin Rice Paper Fibrous Scaffolds for 3D Tumor Spheroid Formation.

Bioscaffolds are important substrates for supporting three-dimensional (3D) cell cultures. Silk fibroin (SF) is an attractive biomaterial in tissue engineering because of its good biocompatibility and mechanical properties. Electrospinning is one of the most often used approaches to fabricate SF fibrous scaffolds; yet, this technique still faces many challenges, such as low yield, residual organic solvents, limited extensibility of fibers, and a lack of spatial control over pore size. To circumvent these limitations, a core-shell SF on rice paper (SF@RP) fibrous scaffold was fabricated using a mild one-step dip-coating method. The cellulose fiber matrix of RP is the physical basis of the 3D scaffold, whereas the SF coating on the cellulose fiber controls the adhesion/spreading of the cells. The results indicated that by tuning the secondary structure of SF on the surface of a SF@RP scaffold, the cell behavior on SF@RP could be tuned. Tumor spheroids can be formed on SF@RP scaffolds with a dominant random secondary structure, in contrast to cells adhering and spreading on SF@RP scaffolds with a higher ratio of β-sheet secondary structures. Direct culturing of breast cancer MDA-MB-231 and MCF-7, lung cancer A549, prostate cancer DU145, and liver cancer HepG2 cells could spontaneously lead to corresponding tumor spheroids on SF@RP. In addition, the physiological characteristics of HepG2 tumor spheroids were investigated, and the results showed that compared with HepG2 monolayer cells, CYP3A4, CYP1A1, and albumin gene expression levels in HepG2 cell spheres formed on SF@RP scaffolds were significantly higher. Moreover, these spheroids showed higher drug resistance. In summary, these SF@RP scaffolds prepared by the dip-coating method are biocompatible substrates for cell culture, especially for tumor cell spheroid formation.

Printing Sensors on Biocompatible Substrates for Selective Detection of Glucose

This article presents development of organic electrochemical transistor (OECT) on a cellulose based biocompatible substrate for selective detection of glucose. The cost-effective manufacturing through drop on demand inkjet printing and blade casting techniques are adopted for the development of OECTs at ambient environment. The OECT is designed by printing carbon-based nanocomposite as the source, drain and gate electrodes, whereas for the channel layer, Poly (3, 4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS) is printed. Optical and physical characterizations were performed to investigate the printability, patterns' uniformity, repeatability, and adhesion of the printed structures onto the target substrate. The sensors are tested against specific enzyme i.e. glucose oxidase mixed in a PBS (phosphate buffer saline) solution. Transistor characteristics of the OECTs are determined to find the best coupling parameters for the device test. The optimal coupling parameters i.e. Vds at 0.8V and Vgs at 0.7V produced the transconductance i.e. 0.15 mS, in suitable ranges of the device test. Five different concentrations of glucose were tested in the electrolyte solution starting from the 1μM and at maximum 100mM, producing a prominent change in the current response i.e. 20% of its initial value. The distinctive current responses for each glucose concentration at an average response time of ~15 sec show very promising results for rapid glucose detection. The low-cost fabrication of these printed sensors on biocompatible substrates show favorable results towards deploying these sensors on human bodies for real-time glucose monitoring.

Single‐Material OECT‐Based Flexible Complementary Circuits Featuring Polyaniline in Both Conducting Channels

AbstractThe organic electrochemical transistor (OECT) with a conjugated polymer as the active material is the elementary unit of organic bioelectronic devices. Improved functionalities, such as low power consumption, can be achieved by building complementary circuits featuring two or more OECTs. Complementary circuits commonly combine both p‐ and n‐type transistors to reduce power draw. While p‐type OECTs are readily available, n‐type OECTs are less common mainly due to poor stability of the n‐type active channel material in aqueous electrolyte. Here, a complementary circuit is made using a pair of OECTs having polyaniline (PANI) as the channel material in both transistors. PANI, with a finite electrochemical window accessible at voltages lower than 1 V, exhibits a peak in current versus gate voltage when used as an active channel in an OECT. The current peak has two slopes, one n‐like and one p‐like, which correspond to different electrochemical regimes of the same underlying conjugated polymer. The electrochemistry enables the design of a complementary circuit using only PANI as the channel material. The PANI‐based circuit is shown to have excellent performance with gain of ≈7 and is transferred on a flexible biocompatible chitosan substrate with demonstrated operation in aqueous electrolyte.

SeedEZ™ Interdigitated Electrodes and Multifunctional Layered Biosensor Composites (MLBCs): A Paradigm Shift in the Development of In Vitro BioMicrosystems.

We have developed a new technology for the realization of composite biosensor systems, capable of measuring electrical and electrophysiological signals from electrogenic cells, using SeedEZ™ 3D cell culture-scaffold material. This represents a paradigm-shift for BioMEMS processing; 'Biology-Microfabrication' versus the standard 'Microfabrication-Biology' approach. An Interdigitated Electrode (IDE) developed on the 3D cell-scaffold was used to successfully monitor acute cardiomyocyte growth and controlled population decline. We have further characterized processability of the 3D scaffold, demonstrated long-term biocompatibility of the scaffold with various cell lines and developed a multifunctional layered biosensor composites (MLBCs) using SeedEZ™ and other biocompatible substrates for future multilayer sensor integration.

Extremely flexible and mechanically durable planar supercapacitors: High energy density and low-cost power source for E-skin electronics

The development of multifunctional devices on highly flexible and biocompatible substrates has received great attention in the field of wearable and healthcare technologies. To realize such a unique technology typically on a single platform, it is very crucial to adopt highly-flexible and embeddable energy storage devices with adequate efficiencies as power sources. In this direction, we introduce a versatile and scalable approach to fabricate planar and symmetric micro-supercapacitors, which can be mounted on any complicated surface. The micro-supercapacitors developed on highly flexible and ultrathin substrates by the angular spray of graphene-ink showed excellent performance with a maximum areal capacitance of ~8.38 mF/cm 2 and operating flexibility for a bending radius of 1.8 mm. The devices also displayed outstanding mechanical stability for 10,000 bending cycles with a high specific capacitance (~22 F/g) and power density (~1.13 kW/kg) typically at a scan rate of 100 mV/s. Further, the demonstrations on skin-mountable and wrappable characteristics of mSCs emphasized their adaptability as embeddable power sources for various epidermal and wearable devices. • Micro-supercapacitors fabricated using cost-effective spray method. • Device exhibits high energy density and excellent sustainability. • Extremely flexible micro-supercapacitor showed high mechanical durability and stability. • Our device developed on epidermal substrate showed integrability with human skin. • This micro-supercapacitors can greatly support for e-skin device as a power source.

Device for Cell Culture under Variable Mechanical Stress by Controlling Deformation on its Substrate

Mechanotransduction can enhance cell cultures when its substrate is subjected to dynamic strain. This paper presents the design and implementation of a device that applies variable mechanical stress on a flexible biocompatible substrate. An embedded system implements a closed-loop PID control that acts on a proportional valve, which regulates the negative pressure in a chamber, generated by a miniature vacuum pump. The top cover of the chamber is a membrane that stretches according to the generated vacuum and is used for cell culture. The elastic modulus of the produced membrane was 260 kPa, similar to soft biological tissue. The deformation of the membrane was quantified by image processing and a linear pressure-deformation relationship was achieved (r and gt; 0.99). The controller was designed based on the identified valve's dynamic and it allowed variable deformations on the membrane with an amplitude of 20 % and a frequency of 2 Hz, selected by the user. The implemented device is PC independent and has a cost, size and weight almost two orders of magnitude lower than a similar commercial version.

Fully Inkjet‐Printed, Ultrathin and Conformable Organic Photovoltaics as Power Source Based on Cross‐Linked PEDOT:PSS Electrodes

AbstractUltra‐lightweight solar cells have attracted enormous attention due to their ultra‐conformability, flexibility, and compatibility with applications including electronic skin or miniaturized electronics for biological applications. With the latest advancements in printing technologies, printing ultrathin electronics is becoming now a reality. This work offers an easy path to fabricate indium tin oxide (ITO)‐free ultra‐lightweight organic solar cells through inkjet‐printing while preserving high efficiencies. A method consisting of the modification of a poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) ink with a methoxysilane‐based cross‐linker (3‐glycidyloxypropyl)trimethoxysilane (GOPS)) is presented to chemically modify the structure of the electrode layer. Combined with plasma and solvent post‐treatments, this approach prevents shunts and ensures precise patterning of solar cells. By using poly(3‐hexylthiophene) along rhodanine‐benzothiadiazole‐coupled indacenodithiophene (P3HT:O‐IDTBR), the power conversion efficiency (PCE) of the fully printed solar cells is boosted up to 4.73% and fill factors approaching 65%. All inkjet‐printed ultrathin solar cells on a 1.7 µm thick biocompatible parylene substrate are fabricated with PCE reaching up to 3.6% and high power‐per‐weight values of 6.3 W g−1. After encapsulation, the cells retain their performance after being exposed for 6 h to aqueous environments such as water, seawater, or phosphate buffered saline, paving the way for their integration in more complex circuits for biological systems.

(Invited) Heterogeneous Electronics Packaging Innovations Based on Silicon Technology

Electronics Packaging refers to the electrical interconnection of heterogeneous dies using a hierarchy of packaging constructs. Today’s packaging is based on organic substrates called FR4 – glass reinforced epoxy laminate material with coarse pitches and solder-based connections. which have not shrunk over the last several decades. More recently however, packaging is undergoing materials and integration innovations that promise to usher in an era of package and board level scaling. These borrow extensively from silicon technology. We will address two such approaches: The Silicon Interconnect Fabric (Si IF), where we attempt to replace the PCB with a Silicon wafer that has fine wires and directly connects to heterogeneous dielets using solderless thermal compression bonding, to build large heterogeneous Systems on Wafers; and Flextratetm, a PDMS based flexible biocompatible substrate, that uses a fan-out wafer level processing approach to similar things. The talk will address the materials and processing challenges of these approaches.

Study of nitrogen implantation in Ti surface using plasma immersion ion implantation & deposition technique as biocompatible substrate for artificial membranes.

The present investigation reports the modification of Ti substrates by a plasma technique to enhance their physio-chemical properties as biocompatible substrates for the deposition of artificial membranes. For that purpose, nitrogen ions are implanted into Ti substrate using the plasma immersion ion implantation & deposition (PIII&D) technique in a capacitively coupled radio frequency plasma. The plasma was characterized using optical emission spectroscopy, together with radio frequency compensated Langmuir probe, while the ion current towards the substrate was measured during the implantation process using an opto-electronic device. X-ray photoelectron spectroscopy (XPS) was used for chemical analysis of the surface, confirming the presence of δ-TiN. The penetration depth of the nitrogen ions into the Ti substrate was measured using secondary ions mass spectroscopy (SIMS) while the morphological changes were observed using atomic force microscopy (AFM). A calorimetric assay was used to prove that the TiN samples maintain the biocompatibility of the untreated Ti surface with its native oxide layer. The ion implantation increases the load bearing ability of Ti surface by the formation of α-Ti(N) and δ-TiN phases on the sub-surface of Ti, and maintains the bio compatibility of Ti surface. After the plasma treatment a thin layer of chitosan (CH) was deposited in order to provide a moisturizing matrix for the artificial membrane of 1,2-dipalmitoyl-sn-3- phosphor glycerocholine (DPPC). The CH and subsequently the DPPC were deposited on the plasma deposited TiN substrate by using physical vapor deposition. The formation of artificial membranes was confirmed by AFM, measuring the topography at different temperatures and performing force curves.

Alteration of cell motility dynamics through collagen fiber density in photopolymerized polyethylene glycol hydrogels

Polyethylene glycol (PEG) hydrogels that have natural fibers mimicking extracellular matrix can be used as a model to understand the role of substrate properties on cell growth and migration. Due to the dependence of cell movement to adhesion, characterization of motility is needed to prepare biocompatible substrates. We demonstrated a method to encapsulate collagen into PEG hydrogel crosslinked via photopolymerization and studied the effect of fiber density on motility dynamics. Porous hydrogel immersed into collagen solution was coated with fibers after neutralizing solution. We provided a detailed study of cell instantaneous/average speed, total displacement, persistence and angular displacement. We found that cells demonstrated a biphasic motility where a maximum speed of 17.4 μm/h with a total distance of 215 μm and persistence of 0.43 were obtained at 1.2 mg/ml collagen. High occurrence of low angular displacement observed at intermediate fiber density suggests that cells tend to move forward along hydrogels. Increased anisotropy at low density was an indication of forward and backward movement. Finally, matrix deformation was determined in the absence of fluorescent beads by tracking fiber displacement at subpixel resolution. Our findings establish a method for preparation of collagen coated hydrogels and provide an insight into cell motility dynamics.

Standing surface acoustic wave-assisted fabrication of patterned microstructures for enhancing cell migration

Microfluidic device with patterned microstructures on the substrate surface was used to regulate cell adhesion, morphology, and functions in tissue engineering. We developed a microfluidic device which employing microscale patterned microstructures to achieve enhanced cell adhesion and migration. Biocompatible hydrogel substrates with micro-wavy and lattice-patterned microstructures were fabricated using standing surface acoustic waves and ultraviolet solidification. After seeding the L929 mouse fibroblast cells onto the patterned substrate of the microfluidic device, we determined that the viability and proliferation rate of cell migration can be greatly enhanced. Furthermore, L929 cells showed two types of gathering modes after 48 h of culturing. Cell growth was guided by the patterned substrate used in the microfluidic device and showed differences in the location distribution. Therefore, the developed microfluidic device with patterned microstructures can extend the application of in vitro cell culturing for future drug development and disease diagnosis.

Biopolymer Substrates in Buccal Drug Delivery: Current Status and Future Trend.

This paper provides a critical review of biopolymer-based substrates, especially the cellulose derivatives, for their application in buccal drug delivery. Drug delivery to the buccal mucous has the benefits of immobile muscle, abundant vascularization and rapid recovery, but not all the drugs can be administered through the buccal mucosa (e.g., macromolecular drugs), due to the low bioavailability caused by their large molecular size. This shortfall inspired the rapid development of drug-compounding technologies and the corresponding usage of biopolymer substrates. Cellulose derivatives have been extensively developed for drug manufacturing to facilitate its delivery. We engaged in structured research of cellulose-based drug compounding technologies. We summarized the characteristic cellulose derivatives which have been used as the biocompatible substrates in buccal delivery systems. The discussion of potential use of the rapidly-developed nanocellulose (NC) is also notable in this paper. Seventy-eight papers were referenced in this perspective paper with the majority (sixty-five) published later than 2010. Forty-seven papers defined the buccal drug delivery systems and their substrates. Fifteen papers outlined the properties and applications of cellulose derivatives. Nanocellulose was introduced as a leading edge of nanomaterial with sixteen papers highlighted its adaptability in drug compounding for buccal delivery. The findings of this perspective paper proposed the potential use of cellulose derivatives, the typical kind of biopolymers, in the buccal drug delivery system for promoting the bioavailability of macromolecular drugs. Nanocellulose (NC) in particular was proposed as an innovative bio-binder/carrier for the controlled-release of drugs in buccal system.

RETRACTED ARTICLE: A miniaturized circular maze shaped antenna for implantable health care applications

In this work, a novel miniaturized circular maze shaped implantable antenna has been proposed for medical applications to be operated in medical band. The biocompatible polyamide substrate (er = 4.3 and tanδ = 0.004) with 0.05 mm thickness has been used as both substrate and superstrate. The proposed antenna is featured with very good miniaturization with the dimensions of 7 × 7 × 0.1 mm3 by employing circular maze shaped structure in radiator. The proposed antenna shows maximum gain of − 23 dBi in a skin phantom model simulation at the frequency of 2.45 GHz. A prototype of antenna has been fabricated and the measurements are conducted in a pork slab. The maximum specific absorption rate has been evaluated for health safety consideration. The obtained margins are in the safe boundary and they satisfy IEEE C95.1-1999 and C95.1-2005 safety rules. The proposed antenna shows noticeable performance improvement compared to the recently proposed antennas.

Discovery of Self-Assembling π-Conjugated Peptides by Active Learning-Directed Coarse-Grained Molecular Simulation.

Electronically active organic molecules have demonstrated great promise as novel soft materials for energy harvesting and transport. Self-assembled nanoaggregates formed from π-conjugated oligopeptides composed of an aromatic core flanked by oligopeptide wings offer emergent optoelectronic properties within a water-soluble and biocompatible substrate. Nanoaggregate properties can be controlled by tuning core chemistry and peptide composition, but the sequence-structure-function relations remain poorly characterized. In this work, we employ coarse-grained molecular dynamics simulations within an active learning protocol employing deep representational learning and Bayesian optimization to efficiently identify molecules capable of assembling pseudo-1D nanoaggregates with good stacking of the electronically active π-cores. We consider the DXXX-OPV3-XXXD oligopeptide family, where D is an Asp residue and OPV3 is an oligophenylenevinylene oligomer (1,4-distyrylbenzene), to identify the top performing XXX tripeptides within all 203 = 8000 possible sequences. By direct simulation of only 2.3% of this space, we identify molecules predicted to exhibit superior assembly relative to those reported in prior work. Spectral clustering of the top candidates reveals new design rules governing assembly. This work establishes new understanding of DXXX-OPV3-XXXD assembly, identifies promising new candidates for experimental testing, and presents a computational design platform that can be generically extended to other peptide-based and peptide-like systems.

Nebulized jet-based printing of bio-electrical scaffolds for neural tissue engineering: a feasibility study

In this paper we investigate the application of a direct writing technique for printing conductive patterns onto a biocompatible electrospun-pyrolysed carbon-fibre-based substrate. The result is a first study towards the production of bio-electrical scaffolds that could be used to enhance the promotion of efficient connections among neurons for in vitro studies in the field of neural tissue engineering. An electrospinning process is employed for production of the materials derived from the precursor polyacrylonitrile, in which the embedding of carbon nanotubes (CNTs) is also investigated. Subsequently, the methodology of research into suitable parameters for the printed electronics, using a commercial silver nanoparticle (Øavg,particle size ∼ 100 nm) ink, is described. The results show values of 2 Ω cm for the resistivity of the carbon-fibre materials and conductive printed lines of resistance ∼50 Ω on glass and less than ∼140 Ω on carbon-fibre samples. Biocompatibility results demonstrate the possibility of using electrospun-pyrolysed mats, also with embedded CNTs, as potential neural substrates for spatially localized electrical stimulation across a tissue. In addition, the data concerning the potential toxicity of silver suspensions are in accordance with the literature, showing a dose-dependent behaviour. This work is a pioneering feasibility study of the use of the flexible and versatile printed electronic approach, combined with engineered biocompatible substrates, to realize integrated bio-electrical scaffolds for in vitro neural tissue engineering applications.