Research Items (12)
- Mar 2019
The field of organic bioelectronics is advancing rapidly in the development of materials and devices to precisely monitor and control biological signals. Electronics and biology can interact on multiple levels: organs, complex tissues, cells, cell membranes, proteins, and even small molecules. Compared to traditional electronic materials such as metals and inorganic semiconductors, conjugated polymers (CPs) have several key advantages for biological interactions: tunable physiochemical properties, adjustable form factors, and mixed conductivity (ionic and electronic). Herein, the use of CPs in five biologically oriented research topics, electrophysiology, tissue engineering, drug release, biosensing, and molecular bioelectronics, is discussed. In electrophysiology, implantable devices with CP coating or CP‐only electrodes are showing improvements in signal performance and tissue interfaces. CP‐based scaffolds supply highly favorable static or even dynamic interfaces for tissue engineering. CPs also enable delivery of drugs through a variety of mechanisms and form factors. For biosensing, CPs offer new possibilities to incorporate biological sensing elements in a conducting matrix. Molecular bioelectronics is today used to incorporate (opto)electronic functions in living tissue. Under each topic, the limits of the utility of CPs are discussed and, overall, the major challenges toward implementation of CPs and their devices to real‐world applications are highlighted. Conjugated polymers provide functional and versatile interfaces with biological systems at many levels. Recent progress in leveraging conjugated polymers to assess and control biological functions is reviewed, focusing on electrophysiology, tissue engineering, drug delivery, biosensors, and molecular bioelectronics. A perspective is given on the future steps needed to move these technologies from the laboratory to real‐world applications.
Objective: Neural electrophysiology is often conducted with traditional, rigid depth probes. The mechanical mismatch between these probes and soft brain tissue is unfavorable for tissue interfacing. Making probes compliant can improve biocompatibility, but as a consequence, they become more difficult to insert into the brain. Therefore, new methods for inserting compliant neural probes must be developed. Approach: Here, we present a new bioresorbable shuttle based on the hydrolytically degradable poly(vinyl alcohol) (PVA) and poly(lactic-co-glycolic acid) (PLGA). We show how to fabricate the PVA/PLGA shuttles on flexible and thin parylene probes. The method consists of PDMS molding used to fabricate a PVA shuttle aligned with the probe and to also impart a sharp tip necessary for piercing brain tissue. The PVA shuttle is then dip-coated with PLGA to create a bi-layered shuttle. Main results: While single layered PVA shuttles are able to penetrate agarose brain models, only limited depths were achieved and repositioning was not possible due to the fast degradation. We demonstrate that a bilayered approach incorporating a slower dissolving PLGA layer prolongs degradation and enables facile insertion for at least several millimeters depth. Impedances of electrodes before and after shuttle preparation were characterized and showed that careful deposition of PLGA is required to maintain low impedance. Facilitated by the shuttles, compliant parylene probes were also successfully implanted into anaesthetized mice and enabled the recording of high quality local field potentials. Significance: This work thereby presents a solution towards addressing a key challenge of implanting compliant neural probes using a two polymer system. PVA and PLGA are polymers with properties ideal for translation: commercially available, biocompatible with FDA-approved uses and bioresorbable. By presenting new ways to implant compliant neural probes, we can begin to fully evaluate their chronic biocompatibility and performance compared to traditional, rigid electronics.
Bioprinting, the three-dimensional (3D) printing of cell-laden inks, will be a truly revolutionary technology for the biomaterials community. The number of bioink studies, especially aimed at functional tissues, remains significantly limited, and furthermore, current bioinks are limited by a narrow window of printability. This can be largely attributed to the fact that the preparation of bioinks and their 3D printing is significantly complicated by the presence of cells, which require strict conditions for their viability. This article discusses how cells should be considered during bioink synthesis, 3D printing, and post-printing processing. We also discuss what has been reported thus far with regard to the relationships between bioink material properties and cells. This underlines the need for next-generation bioinks that simultaneously achieve excellent printability, high cell viability, and a wide range of material properties.
Emerging additive manufacturing techniques enable investigation of the effects of pore geometry on cell behavior and function. Here, we 3D print microporous hydrogel scaffolds to test how varying pore geometry, accomplished by manipulating the advancing angle between printed layers, affects the survival of ovarian follicles. 30° and 60° scaffolds provide corners that surround follicles on multiple sides while 90° scaffolds have an open porosity that limits follicle–scaffold interaction. As the amount of scaffold interaction increases, follicle spreading is limited and survival increases. Follicle-seeded scaffolds become highly vascularized and ovarian function is fully restored when implanted in surgically sterilized mice. Moreover, pups are born through natural mating and thrive through maternal lactation. These findings present an in vivo functional ovarian implant designed with 3D printing, and indicate that scaffold pore architecture is a critical variable in additively manufactured scaffold design for functional tissue engineering.
- Nov 2016
- Polymeric Hydrogels as Smart Biomaterials
Protein-based hydrogels are composed of isolated or enriched proteins from natural extracellular matrix. Inherent and controllable bioactivity makes these hydrogels promising candidates as smart biomaterials for drug delivery, tissue engineering and regenerative medicine, and other applications. Desirable characteristics for these applications include natural cell binding, cell degradable, and growth factor-binding sequences. This chapter covers the unique properties of a variety of proteins (collagen, gelatin, fibrin, silk, elastin, keratin, and decellularized, tissue-specific extracellular matrix) as well as hydrogel synthesis, fabrication, modification, and established applications. Conditions of solubility and the mechanism of the sol–gel transition are discussed. Since each protein presented undergoes self-assembly to form a gel network, gelation parameters that affect this assembly and subsequently the gel ultrastructure are specifically presented. Emerging applications and technologies for protein-based hydrogels are also briefly mentioned.
Despite substantial attention given to the development of osteoregenerative biomaterials, severe deficiencies remain in current products. These limitations include an inability to adequately, rapidly, and reproducibly regenerate new bone; high costs and limited manufacturing capacity; and lack of surgical ease of handling. To address these shortcomings, we generated a new, synthetic osteoregenerative biomaterial, hyperelastic "bone" (HB). HB, which is composed of 90 weight % (wt %) hydroxyapatite and 10 wt % polycaprolactone or poly(lacticco- glycolic acid), could be rapidly three-dimensionally (3D) printed (up to 275 cm3/hour) from room temperature extruded liquid inks. The resulting 3D-printed HB exhibited elastic mechanical properties (32 to 67% strain to failure, ~4 to 11 MPa elastic modulus), was highly absorbent (50% material porosity), supported cell viability and proliferation, and induced osteogenic differentiation of bone marrow-derived human mesenchymal stem cells cultured in vitro over 4 weeks without any osteo-inducing factors in the medium. We evaluated HB in vivo in a mouse subcutaneous implant model for material biocompatibility (7 and 35 days), in a rat posterolateral spinal fusion model for new bone formation (8 weeks), and in a large, non-human primate calvarial defect case study (4 weeks). HB did not elicit a negative immune response, became vascularized, quickly integrated with surrounding tissues, and rapidly ossified and supported new bone growth without the need for added biological factors.
- Jan 2016
3D biomaterial printing has emerged as a potentially revolutionary technology, promising to transform both research and medical therapeutics. Although there has been recent progress in the field, on-demand fabrication of functional and transplantable tissues and organs is still a distant reality. To advance to this point, there are two major technical challenges that must be overcome. The first is expanding upon the limited variety of available 3D printable biomaterials (biomaterial inks), which currently do not adequately represent the physical, chemical, and biological complexity and diversity of tissues and organs within the human body. Newly developed biomaterial inks and the resulting 3D printed constructs must meet numerous interdependent requirements, including those that lead to optimal printing, structural, and biological outcomes. The second challenge is developing and implementing comprehensive biomaterial ink and printed structure characterization combined with in vitro and in vivo tissue- and organ-specific evaluation. This perspective outlines considerations for addressing these technical hurdles that, once overcome, will facilitate rapid advancement of 3D biomaterial printing as an indispensable tool for both investigating complex tissue and organ morphogenesis and for developing functional devices for a variety of diagnostic and regenerative medicine applications.
The exceptional properties of graphene enable applications in electronics, optoelectronics, energy storage, and structural composites. Here we demonstrate a 3D printable graphene (3DG) composite consisting of majority graphene and minority polylactide-co-glycolide, a biocompatible elastomer, 3D printed from a liquid ink. This ink can be utilized under ambient conditions via extrusion-based 3D printing to create graphene structures with features as small as 100 µm comprised of as few as two layers (<300 µm thick object) or many hundreds of layers (>10 cm thick object). The resulting 3DG material is mechanically robust and flexible while retaining electrical conductivities greater than 800 S/m, an order of magnitude increase over previously reported 3D printed carbon materials. In vitro experiments in simple growth medium, in the absence of neurogenic stimuli, reveal that 3DG supports human mesenchymal stem cell (hMSC) adhesion, viability, proliferation, and neurogenic differentiation with significant upregulation of glial and neuronal genes. This coincides with hMSCs adopting highly elongated morphologies with features similar to axons and presynaptic terminals. In vivo experiments indicate that 3DG has promising biocompatibility over the course of at least 30 days. Surgical tests using a human cadaver nerve model also illustrate that 3DG has exceptional handling characteristics and can be intraoperatively manipulated and applied to fine surgical procedures. With this unique set of properties, combined with ease of fabrication, 3DG could be applied towards the design and fabrication of a wide range of functional electronic, biological, and bioelectronic medical and non-medical devices.
- Jan 2015
A multimaterial bioink method using polyethylene glycol crosslinking is presented for expanding the biomaterial palette required for 3D bioprinting more mimetic and customizable tissue and organ constructs. Lightly crosslinked, soft hydrogels are produced from precursor solutions of various materials and 3D printed. Rheological and biological characterizations are presented, and the promise of this new bioink synthesis strategy is discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
A one-step, large-scale preparation of alkyne-containing hyper-branched polyglycerols (HPG) is reported. The HPGs undergo click reactions to organic azides allowing a range of applications.