3D Microarchitectures Research Articles

MECHANICAL PROPERTIES OF 3D SCAFFOLDS FOR BONE REGENERATION / 3D KARKASŲ, SKIRTŲ KAULŲ REGENERACIJAI, MECHANINIŲ SAVYBIŲ TYRIMAS

One of the biggest challenges in modern tissue engineering is a creation 3D scaffolds for bone tissue regeneration. Until now, in order to restore bone defects are used various bone substitutes (autologous and allogeneic), however, their usage is limited because is required additional surgery, possible complications, also limited their use is associated with ethical point of view. In this work we aim to determine the mechanical properties of 3D printed PLA objects having various orientation woodpile microarchitectures. In this work we chose three different 3D microarchitectures: woodpile BCC (each layer consists of parallel logs which are rotated 90 deg every next layer), woodpile FCC (every layer is additionally shifted half of the period in respect to the previous parallel log layer) and a rotating woodpile 60 deg (each layer is rotated 60 deg in respect to the previous one). Compressive and bending tests were carried out with TIRAtest2300 universal testing machine. We found that 60 deg rotating woodpile geometry had the highest mechanical values which were approximately about 3 times higher than the BCC or FCC microstructures. Vienas didžiausių šiuolaikinės audinių inžinerijos iššūkių yra 3D karkasų, skirtų kaulinio audinio regeneracijai, sukūrimas. Iki šiol, norint atstatyti kaulo defektus, naudojami įvairūs kaulo pakaitalai (autogeniniai ir alogeniniai), kurių naudojimo galimybės jau nebeatitinka poreikių, nes reikalinga papildoma operacija, galimos komplikacijos, taip pat ribotas jų naudojimas, susijęs su etinėmis pažiūromis. Šiame darbe lyginamos 3D spausdintuvu suformuotų mikrodarinių, skirtų kaulinio audinio defektui atkurti, mechaninės savybės. Darbe pasirinktos trys skirtingos 3D karkasų mikrostruktūros: woodpile BCC (kiekvienas sluoksnis susideda iš lygiagrečių rąstų, kurie keičiami 90 laipsnių kampu prieš tai esančio sluoksnio atžvilgiu), woodpile FCC (kiekvienas sluoksnis papildomai keičiasi per pusę periodo sluoksnio, esančio prieš tai, atžvilgiu) ir woodpile 60 deg (besisukanti rąstų rietuvė, kiekvienas tokios gardelės sluoksnis yra pasuktas 60 laipsnių prieš tai esančios atžvilgiu). Gniuždymo ir lenkimo bandymai buvo atlikti TIRAtest 2300 universalia bandymų mašina. Buvo nustatyta, kad, taikant 60 laipsnių kampu besikeičiančią woodpile geometriją, galima pasiekti didžiausias mechanines vertes, kurios buvo maždaug tris kartus didesnės nei woodfile BCC arba woodfile FCCmikrostruktūros.

Engineering 3D Aligned Nanofibers for Regulation of Cell Growth Behavior

3D aligned electrospun fibers hold a promising potential in a wide range of biomedical areas, including biosensors, controlled drug release, tissue engineering, etc. Thus, a cost‐effective and easy way to scale‐up fabrication for 3D aligned nanofibers is highly desired. Herein, a novel yet facile preparation process of 3D aligned nanofibers (3D AFs) by an improved electrospinning technique is reported. The obtained 3D AFs show enhanced controllability on morphology and fiber density, and thus facilitate adhesion and growth of human mesenchymal stem cells within their 3D nanofiber microarchitectures, leading to an excellent in vitro biocompatibility. Moreover, the 3D AFs with aligned morphology can enhance the neuron activities and induce directional cell growth along the direction of nanofiber orientation, thereby providing an excellent cue for the anchorage and migration dependent neurons. Combined with controllable morphology and structure, it is anticipated that this finding can lead to great applications of electrospun fibers in nerve tissue engineering, diagnostics, and other biomedical fields. image

Self-assembled 3D micro-architectures of Sr3V2O8:xSm3+ ‘hydrothermal’ synthesis and luminescent properties

3D microarchitecture Sr3V2O8:xSm3+ phosphors have been fabricated via hydrothermal method, and their crystalline phase, morphology, and luminescent properties were investigated. The SEM results indicate that the broom- and flower-like micorarchitecture is self-assembled by numerous nanorods. The luminescent properties of Sr3V2O8:xSm3+ samples suggest that the most intense emission is located around 648 nm due to 4G5/2 → 6H9/2 transition of Sm3+. The emission intensity is enhanced with Sm doping and the related mechanism is discussed in detail.

UV-assisted three-dimensional printing of polymer nanocomposites based on inorganic fillers

In this work, nanocomposites based on a UV-curable polymeric resin and different inorganic fillers were developed for use in UV-assisted three-dimensional (UV-3D) printing. This technology consists in the additive multilayer deposition of a UV-curable resin for the fabrication of 3D macro structures and microstructures of arbitrary shapes. A systematic investigation on the effect of filler concentration on the rheological properties of the polymer-based nanocomposites was performed. In particular, the rheological characterization of these nanocomposites allowed to identify the optimal printability parameters for these systems based on the shear rate of the materials at the extrusion nozzle. In addition, photocalorimetric measurements were used to assess the effect of the presence of the inorganic fillers on the thermodynamics and kinetics of the photocuring process of the resins. By direct deposition of homogeneous solvent-free nanocomposite dispersions of different fillers in a UV-curable polymeric resin, the effect of UV-3D printing direction, fill density, and fill pattern on the mechanical properties of UV-3D printed specimens was investigated by means of uniaxial tensile tests. Finally, examples of 3D macroarchitectures and microarchitectures, spanning features, and planar transparent structures directly formed upon UV-3D printing of such nanocomposite dispersions were reproducibly obtained and demonstrated, clearly highlighting the suitability of these nanocomposite formulations for advanced UV-3D printing applications. POLYM. COMPOS., 38:1662–1670, 2017. © 2015 Society of Plastics Engineers

Three-Dimensional Cell Culture Assays: Are They More Predictive of In Vivo Efficacy than 2D Monolayer Cell-Based Assays?

ASSAY and Drug Development TechnologiesVol. 13, No. 5 Roundtable DiscussionThree-Dimensional Cell Culture Assays: Are They More Predictive of In Vivo Efficacy than 2D Monolayer Cell-Based Assays?Moderator: Sitta Sittampalam, Participants: Richard Eglen, Stephen Ferguson, Jason Thomas Maynes, Kenneth Olden, Laura Schrader, Todd Shelper, and Marc FerrerModerator: Sitta SittampalamSenior Advisor to the Director, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland.Search for more papers by this author, Participants: Richard EglenVice President and General Manager, Corning Life Sciences, Tewksbury, Massachusetts.Search for more papers by this author, Stephen FergusonChemist, Molecular Toxicology and Informatics Group, Biomolecular Screening, National Institute of Environmental Science, National Institutes of Health, Research Triangle Park, North Carolina.Search for more papers by this author, Jason Thomas MaynesDirector of Research, Anesthesia and Pain Medicine/Staff Anesthesiologist, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.Search for more papers by this author, Kenneth OldenDirector, National Center for Environmental Assessment, Environmental Protection Agency, Arlington, Virginia.Search for more papers by this author, Laura SchraderCEO, 3D Biomatrix, Ann Arbor, Michigan.Search for more papers by this author, Todd ShelperResearch Fellow, Avery Group, Eskitis Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia.Search for more papers by this author, and Marc FerrerLeader, Biomolecular Screening and Probe Development, Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland.Search for more papers by this authorPublished Online:13 Jul 2015https://doi.org/10.1089/adt.2015.29001.rtdAboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited ByUsing 3D in vitro cell culture models in anti-cancer drug discovery26 April 2021 | Expert Opinion on Drug Discovery, Vol. 16, No. 8Precision Oncology Beyond Genomics: The Future Is Here—It Is Just Not Evently Distributed17 April 2021 | Cells, Vol. 10, No. 4Extracellular vesicles from organoids and 3D culture systems31 October 2020 | Biotechnology and Bioengineering, Vol. 118, No. 3Biomaterials for Three-Dimensional Cell Culture: From Applications in Oncology to Nanotechnology13 February 2021 | Nanomaterials, Vol. 11, No. 2TIRF Microscopy‐Based Monitoring of Drug Permeation Across a Lipid Membrane Supported on Mesoporous Silica25 November 2020 | Angewandte Chemie, Vol. 133, No. 4TIRF Microscopy‐Based Monitoring of Drug Permeation Across a Lipid Membrane Supported on Mesoporous Silica23 November 2020 | Angewandte Chemie International Edition, Vol. 60, No. 4Water-Templated, Polysaccharide-rich Bioartificial 3D Microarchitectures as Extra-Cellular Matrix Bioautomatons7 April 2020 | ACS Applied Materials & Interfaces, Vol. 12, No. 18Comparison of 2D and 3D cell cultures of colorectal adenocarcinoma as models for drug screening6 February 2020 | Russian Chemical Bulletin, Vol. 68, No. 12High throughput scaffold-based 3D micro-tumor array for efficient drug screening and chemosensitivity testingBiomaterials, Vol. 198Three-Dimensional in Vitro Cell Culture Models in Drug Discovery and Drug Repositioning23 January 2018 | Frontiers in Pharmacology, Vol. 9A 96-well microplate bioreactor platform supporting individual dual perfusion and high-throughput assessment of simple or biofabricated 3D tissue models1 January 2018 | Lab on a Chip, Vol. 18, No. 18Personalized Medicine8 December 2017A biomimetic hydrogel functionalized with adipose ECM components as a microenvironment for the 3D culture of human and murine adipocytes8 May 2017 | Biotechnology and Bioengineering, Vol. 114, No. 8Designing a bio-inspired biomimetic in vitro system for the optimization of ex vivo studies of pancreatic cancerDrug Discovery Today, Vol. 22, No. 4A semiautomated microfluidic platform for real-time investigation of nanoparticles’ cellular uptake and cancer cells’ trackingNanomedicine, Vol. 12, No. 6Screening out irrelevant cell-based models of disease12 September 2016 | Nature Reviews Drug Discovery, Vol. 15, No. 11Cancer drug discovery: recent innovative approaches to tumor modeling11 August 2016 | Expert Opinion on Drug Discovery, Vol. 11, No. 9State-of-the-Art Metabolic Toxicity Screening and Pathway Evaluation14 April 2016 | Analytical Chemistry, Vol. 88, No. 9 Volume 13Issue 5Jun 2015 InformationCopyright 2015, Mary Ann Liebert, Inc.To cite this article:Moderator:, Sitta Sittampalam, Participants:, Richard Eglen, Stephen Ferguson, Jason Thomas Maynes, Kenneth Olden, Laura Schrader, Todd Shelper, and Marc Ferrer.Three-Dimensional Cell Culture Assays: Are They More Predictive of In Vivo Efficacy than 2D Monolayer Cell-Based Assays?.ASSAY and Drug Development Technologies.Jun 2015.254-261.http://doi.org/10.1089/adt.2015.29001.rtdPublished in Volume: 13 Issue 5: July 13, 2015Online Ahead of Print:June 29, 2015PDF download

Controlled Fabrication of Microparticles with Complex 3D Geometries by Tunable Interfacial Deformation of Confined Polymeric Fluids in 2D Micromolds.

Polymeric microparticles with complex shapes have attracted substantial attention in many application areas because particle shape is a critical parameter to impart programmable functionalities. The formation of specific three-dimensional (3D) microstructures in a simple, scalable, and controllable manner is difficult. Here, we report the controlled fabrication of microparticles with complex 3D shapes based on the simple tuning of mold swelling and capillarity. Specifically, a photocurable solution loaded in micromolds is spatially deformed into complex shapes depending on the degree of molding swelling and capillarity, thereby producing polymeric microparticles with controlled 3D shapes upon photopolymerization. The results show that highly uniform microparticles with controlled two-dimensional (2D) and 3D shapes were fabricated from identical 2D micromolds via the simple tuning of the wetting fluids. This technique can be extended to produce highly complex microarchitectures with controlled 3D geometric domains via 2D mold designs. Finally, multicompartment microparticles with independently controlled 3D shapes for each compartment are produced by a simple combination of fabrication sequences. We envision that this strategy of producing 3D microarchitectures from easily designed simple micromolds could provide a path to new materials and new properties.

Electrodeposition-based 3D Printing of Metallic Microarchitectures with Controlled Internal Structures.

3D printing of metallic microarchitectures with controlled internal structures is realized at room temperature in ambient air conditions by the manipulation of metal ion concentration and pulsed electric potentials in the electrolyte meniscus during the meniscus-guided electrodeposition. Precise control of the printing nozzle enables the drawing of complex 3D microarchitectures with well-defined geometries and positions.

Luminescence and magnetic properties of novel nanoparticle-sheathed 3D Micro-Architectures of Fe0.5R0.5(MoO4)1.5:Ln3+ (R = Gd3+, La3+), (Ln = Eu, Tb, Dy) for bifunctional application

For the first time, we report the successful synthesis of novel nanoparticle-sheathed bipyramid-like and almond-like Fe0.5R0.5(MoO4)1.5:Ln3+ (R = Gd3+, La3+), (Ln = Eu, Tb, Dy) 3D hierarchical microstructures through a simple disodium ethylenediaminetetraacetic acid (Na2EDTA) facilitated hydrothermal method. Interestingly, time-dependent experiments confirm that the assembly-disassembly process is responsible for the formation of self-aggregated 3D architectures via Ostwald ripening phenomena. The resultant products are characterized by x-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM), photoluminescence (PL), and magnetic measurements. The growth and formation mechanisms of the self-assembled 3D micro structures are discussed in detail. To confirm the presence of all the elements in the microstructure, the energy loss induced by the K, L shell electron ionization is observed in order to map the Fe, Gd, Mo, O, and Eu components. The photo luminescence properties of Fe0.5R0.5(MoO4)1.5 doped with Eu3+, Tb3+, Dy3+ are investigated. The room temperature and low temperature magnetic properties suggest that the interaction between the local-fields introduced by the magnetic Fe3+ ions and the R3+ (La, Gd) ions in the dodecahedral sites determine the magnetism in Fe0.5R0.5(MoO4)1.5:Eu3+. This work provides a new approach to synthesizing the novel Fe0.5R0.5(MoO4)1.5:Ln3+ for bi-functional magnetic and luminescence applications.

Bio-inspired fabrication of fibroin cryogels from the muga silkworm Antheraea assamensis for liver tissue engineering

Conventional scaffold fabrication techniques result in narrow pore architectures causing a limited interconnectivity and use of porogens, which affects the bio- or cyto-compatibility. To ameliorate this, cryogels are immensely explored due to their macro-porous nature, ease in fabrication, using ice crystals as porogens, the shape property, easy reproducibility and cost-effective fabrication technique. Cryogels in the present study are prepared from nonmulberry Indian muga silk gland protein fibroin of Antheraea assamensis using two different fabrication temperatures (−20 and −80 °C). Anionic surfactant sodium dodecyl sulfate is used to solubilize fibroin, which in turn facilitates gelation by accelerating the ß-sheet formation. Ethanol is employed to stabilize the 3D network and induces bimodal porosity. The gels thus formed demonstrate increased ß-sheet content (FTIR) and a considerable effect of pre-freezing temperatures on 3D micro-architectures. The cryogels are capable of absorbing large amounts of water and withstanding mechanical compression without structure deformation. Further, cell impregnated cryogels well support the viability of human hepatocarcinoma cells (live/dead assay). The formation of cellular aggregates (confocal laser and scanning electron microscope), derivation in metabolic activity and proliferation rate are obtained in constructs fabricated at different temperatures. In summary, the present work reveals promising insights in the development of a biomimetic functional template for biomedical therapeutics and liver tissue engineering.

Fabrication of 3D cell-laden hydrogel microstructures through photo-mold patterning

Native tissues are characterized by spatially organized three-dimensional (3D) microscaled units which functionally define cells–cells and cells–extracellular matrix interactions. The ability to engineer biomimetic constructs mimicking these 3D microarchitectures is subject to the control over cell distribution and organization. In the present study we introduce a novel protocol to generate 3D cell laden hydrogel micropatterns with defined size and shape. The method, named photo-mold patterning (PMP), combines hydrogel micromolding within polydimethylsiloxane (PDMS) stamps and photopolymerization through a recently introduced biocompatible ultraviolet (UVA) activated photoinitiator (VA-086). Exploiting PDMS micromolds as geometrical constraints for two methacrylated prepolymers (polyethylene glycol diacrylate and gelatin methacrylate), micrometrically resolved structures were obtained within a 3 min exposure to a low cost and commercially available UVA LED. The PMP was validated both on a continuous cell line (human umbilical vein endothelial cells expressing green fluorescent protein, HUVEC GFP) and on primary human bone marrow stromal cells (BMSCs). HUVEC GFP and BMSCs were exposed to 1.5% w/v VA-086 and UVA light (1 W, 385 nm, distance from sample = 5 cm). Photocrosslinking conditions applied during the PMP did not negatively affect cells viability or specific metabolic activity. Quantitative analyses demonstrated the potentiality of PMP to uniformly embed viable cells within 3D microgels, creating biocompatible and favorable environments for cell proliferation and spreading during a seven days' culture. PMP can thus be considered as a promising and cost effective tool for designing spatially accurate in vitro models and, in perspective, functional constructs.

Facile and Biocompatible Fabrication of Chemically Sol−Gel Transitional Hydrogel Free-Standing Microarchitectures

We report a facile method to fabricate free-standing, 3D hydrogel microarchitectures of chemically sol-gel transitional hydrogels, which is based on the use of hydrophilic substrate and aerosol of gelling agent without molding (or sandwiching) process. Using proposed methods, we fabricated hydrogel microarchitectures of sheets, meshes, or microunits without morphological distortions on the microscale. These hydrogel microarchitectures could be easily and stably exfoliated from the substrates and cultured (in the case of containing cells). These free-standing hydrogel microarchitectures in sheets, meshes, or microunits can be easily harvested and assembled as a biofabrication unit to generate complex composites with controlled microscale structures.

Capillary Forming: Diverse 3D Microarchitectures Made by Capillary Forming of Carbon Nanotubes (Adv. Mater. 39/2010)

The cover shows an assembly of carbon nanotube (CNT) microstructures made by capillary forming, a new technique that enables local transformation of vertically aligned filaments into complex 3D microarchitectures. On page 4384, Michael De Volder, Sameh Tawfick, A. John Hart, and coworkers describe their use of capillary forming to fashion diverse CNT microstructures having sloped, bent, and twisted geometries, and multidirectional textures. Capillary forming combines the scalability of planar lithography with the local specificity of self-assembly, paving the way for use in a new generation of 3D microsystems and multifunctional surfaces.

Multiphoton Lithography Using a High-Repetition Rate Microchip Laser

Multiphoton lithography (MPL) provides a means to create prototype, three-dimensional (3D) materials for numerous applications in analysis and cell biology. A major impediment to the broad adoption of MPL in research laboratories is its reliance on high peak-power light sources, a requirement that typically has been met using expensive femtosecond titanium:sapphire lasers. Development of affordable microchip laser sources has the potential to substantially extend the reach of MPL, but previous lasers have provided relatively low pulse repetition rates (low kilohertz range), thereby limiting the rate at which microforms could be produced using this direct-write approach. In this report, we examine the MPL capabilities of a new, high-repetition-rate (36.6 kHz) microchip Nd:YAG laser. We show that this laser enables an approximate 4-fold decrease in fabrication times for protein-based microforms relative to the existing state-of-the-art microchip source and demonstrate its utility for creating complex 3D microarchitectures.

Diverse 3D Microarchitectures Made by Capillary Forming of Carbon Nanotubes

A new technology called capillary forming enables transformation of vertically aligned nanoscale filaments into complex three-dimensional microarchitectures. We demonstrate capillary forming of carbon nanotubes into diverse forms having intricate bends, twists, and multidirectional textures. In addition to their novel geometries, these structures have mechanical stiffness exceeding that of microfabrication polymers, and can be used as masters for replica molding

Hydrothermal synthesis of ordered nanolamella-composed Y 2O 3:Eu 3+ architectures and their luminescent properties

A series of Y 2O 3:Eu 3+ samples with interesting three-dimensional (3D) microarchitectures were synthesized through a facile hydrothermal method in the presence of hexamethylenetetramine (HMT) followed by a subsequent heat treatment. The as-formed precursor via the hydrothermal process could transform to cubic Y 2O 3 with the same morphology after annealing at 500 °C for 2 h. The Y 2O 3 microstructures, with an average diameter about 10–20 μm, were composed of nanolamellas with thickness of about 50 nm. Besides a probable self-assembly mechanism, the Ostwald Ripening process was proposed to explain the formation of the architectures on the basis of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations. The as-synthesized lamella-composed Y 2O 3:Eu 3+ samples showed a strong red emission corresponding to 5D 0→ 7F 2 transition (612 nm), suggesting promising applications in optoelectronics.

Correlations between grey-level variations in 2D projection images (TBS) and 3D microarchitecture: Applications in the study of human trabecular bone microarchitecture

X-ray imaging remains a very cost-effective technique, with many applications in both medical and material science. However, the physical process of X-ray imaging transforms (e.g. projects) the 3-dimensional (3D) microarchitecture of the object or tissue being studied into a complex 2D grey-level texture. The 3D/2D projection process continues to be a difficult mathematical problem, and neither demonstrations nor well-established correlations have positioned 2D texture analysis-based measurement as a valid indirect evaluation of 3D microarchitecture. The trabecular bone score (TBS) is a new grey-level texture measurement which utilizes experimental variograms of 2D projection images. The aim of the present study was to determine the level of correlation between the 3D characteristics of trabecular bone microarchitecture, as evaluated using µCT reconstruction, and TBS, as evaluated using 2D projection images derived directly from 3D µCT reconstruction. Analyses were performed using sets of human cadaver bone samples from different anatomical sites (lumbar spine, femoral neck, and distal radius). Significant correlations were established via standard multiple regression analysis, and via the use of a generic mathematical 3D/2D relationship. In both instances, the correlations established a significant relationship between TBS and two 3D characteristics of bone microarchitecture: bone volume fraction and mean bone thickness. In particular, it appears that TBS permits to accurately differentiate between two 3D microarchitectures that exhibit the same amount of bone, but different trabecular characteristics. These results demonstrate the existence of a robust and generic relationship, taking into consideration a simplified model of a 2D projection image. Ultimately, this may lead to using TBS measurements directly on DXA images obtained in routine clinical practice.

Single-Walled Carbon Nanotube Scaffolds Promote Stem Cell Differentiation into Bone Forming Cells

AbstractThe use of carbon nanotubes for tissue engineering has become one of the most fascinating applications. The exquisite electronic and mechanical properties of carbon nanotubes may provide a three-dimensional (3D) microenvironment that closely mimics in vivo situation for facilitating the use of stem cells in the tissue regeneration. Therefore, it is important to know whether carbon nanotubes enhance the adhesion, proliferation, and differentiation of stem cells. Here, we hypothesized that the carbon nanotubes promote the differentiation of osteoblast progenitors into mature osteoblasts. To test this hypothesis, we quantified the differentiation of murine osteoblast progenitors, with and without pro-differentiating growth factor Bone Morphogenetic Protein-2 (BMP-2), cultured on the 3D scaffolds made by single-walled carbon nanotubes (SWNTs). Three types of SWNT samples, chitosan functionalized SWNTs, acid-oxidized SWNTs, and surfactant-free pristine SWNTs were used for the construction of these 3D microarchitectures. Osteoblast progenitors were harvested from calvariae from 3∼5-day-old mice, and cultured on the 3D scaffolds made by carbon nanotubes until ∼ 80% confluent. Then the cells were treated with BMP-2 (100 ng/ml) for 5 days. It was found that osteoblast progenitors cultured on the SWNTs dramatically increased the level of mature osteoblastic marker osteocalcin in either the absence or the presence of BMP-2, as compared to the cells cultured on the regulate tissue culture plastic plates. The results suggested that SWNTs highly promote osteoblast progenitor differentiation into mature osteoblasts. The finding indicates that SWNTs may provide an ideal scaffold for facilitating the differentiation of osteoblast progenitors in the repair of bone defects.

Design space exploration for 3D architectures

As technology scales, interconnects have become a major performance bottleneck and a major source of power consumption for microprocessors. Increasing interconnect costs make it necessary to consider alternate ways of building modern microprocessors. One promising option is 3D architectures where a stack of multiple device layers with direct vertical tunneling through them are put together on the same chip. As fabrication of 3D integrated circuits has become viable, developing CAD tools and architectural techniques is imperative to explore the design space to 3D microarchitectures. In this article, we give a brief introduction to 3D integration technology, discuss the EDA design tools that can enable the adoption of 3D ICs, and present the implementation of various microprocessor components using 3D technology. An industrial case study is presented as an initial attempt to design 3D microarchitectures.