Micro- and nanoengineering approaches to control stem cell-biomaterial interactions.

As our population ages, there is a greater need for a suitable supply of engineered tissues to address a range of debilitating ailments. Stem cell based therapies are envisioned to meet this emerging need. Despite significant progress in controlling stem cell differentiation, it is still difficult to engineer human tissue constructs for transplantation. Recent advances in micro- and nanofabrication techniques have enabled the design of more biomimetic biomaterials that may be used to direct the fate of stem cells. These biomaterials could have a significant impact on the next generation of stem cell based therapies. Here, we highlight the recent progress made by micro- and nanoengineering techniques in the biomaterials field in the context of directing stem cell differentiation. Particular attention is given to the effect of surface topography, chemistry, mechanics and micro- and nanopatterns on the differentiation of embryonic, mesenchymal and neural stem cells

Microfluidics for Advanced Drug Delivery Systems.

Considerable efforts have been devoted towards developing effective drug delivery methods. Microfluidic systems, with their capability for precise handling and transport of small liquid quantities, have emerged as a promising platform for designing advanced drug delivery systems. Thus, microfluidic systems have been increasingly used for fabrication of drug carriers or direct drug delivery to a targeted tissue. In this review, the recent advances in these areas are critically reviewed and the shortcomings and opportunities are discussed. In addition, we highlight the efforts towards developing smart drug delivery platforms with integrated sensing and drug delivery components

Microscale Strategies for Generating Cell-Encapsulating Hydrogels

Hydrogels in which cells are encapsulated are of great potential interest for tissue engineering applications. These gels provide a structure inside which cells can spread and proliferate. Such structures benefit from controlled microarchitectures that can affect the behavior of the enclosed cells. Microfabrication-based techniques are emerging as powerful approaches to generate such cell-encapsulating hydrogel structures. In this paper we introduce common hydrogels and their crosslinking methods and review the latest microscale approaches for generation of cell containing gel particles. We specifically focus on microfluidics-based methods and on techniques such as micromolding and electrospinning.National Science Foundation (U.S.) (DMR0847287)National Institutes of Health (U.S.) (EB008392)National Institutes of Health (U.S.) (DE019024)National Institutes of Health (U.S.) (HL099073)National Institutes of Health (U.S.) (AR057837)National Institutes of Health (U.S.) (HL092836)United States. Army Research Office (contract W911NF-07-D-0004)United States. Army Research Office (Institute for Soldier Nanotechnology)United States. Army. Corps of EngineersInnovative Med Tech (Postdoctoral fellowship

Fabrication of nanofibres using bioinspired microfluidic spinning

This is the published version. © Copyright 2013 Royal Society of Chemistr

Micro- and Nanoengineering Approaches to Control Stem Cell-Biomaterial Interactions

As our population ages, there is a greater need for a suitable supply of engineered tissues to address a range of debilitating ailments. Stem cell based therapies are envisioned to meet this emerging need. Despite significant progress in controlling stem cell differentiation, it is still difficult to engineer human tissue constructs for transplantation. Recent advances in micro- and nanofabrication techniques have enabled the design of more biomimetic biomaterials that may be used to direct the fate of stem cells. These biomaterials could have a significant impact on the next generation of stem cell based therapies. Here, we highlight the recent progress made by micro- and nanoengineering techniques in the biomaterials field in the context of directing stem cell differentiation. Particular attention is given to the effect of surface topography, chemistry, mechanics and micro- and nanopatterns on the differentiation of embryonic, mesenchymal and neural stem cells

Toxicity of CdSe Nanoparticles in Caco-2 Cell Cultures

<p>Abstract</p> <p>Background</p> <p>Potential routes of nanomaterial exposure include inhalation, dermal contact, and ingestion. Toxicology of inhalation of ultra-fine particles has been extensively studied; however, risks of nanomaterial exposure via ingestion are currently almost unknown. Using enterocyte-like Caco-2 cells as a small intestine epithelial model, the possible toxicity of CdSe quantum dot (QD) exposure via ingestion was investigated. Effect of simulated gastric fluid treatment on CdSe QD cytotoxicity was also studied.</p> <p>Results</p> <p>Commercially available CdSe QDs, which have a ZnS shell and poly-ethylene glycol (PEG) coating, and in-house prepared surfactant coated CdSe QDs were dosed to Caco-2 cells. Cell viability and attachment were studied after 24 hours of incubation. It was found that cytotoxicity of CdSe QDs was modulated by surface coating, as PEG coated CdSe QDs had less of an effect on Caco-2 cell viability and attachment. Acid treatment increased the toxicity of PEG coated QDs, most likely due to damage or removal of the surface coating and exposure of CdSe core material. Incubation with un-dialyzed in-house prepared CdSe QD preparations, which contained an excess amount of free Cd²⁺, resulted in dramatically reduced cell viability.</p> <p>Conclusion</p> <p>Exposure to CdSe QDs resulted in cultured intestinal cell detachment and death; cytotoxicity depended largely, however, on the QD coating and treatment (e.g. acid treatment, dialysis). Experimental results generally indicated that Caco-2 cell viability correlated with concentration of free Cd²⁺ions present in cell culture medium. Exposure to low (gastric) pH affected cytotoxicity of CdSe QDs, indicating that route of exposure may be an important factor in QD cytotoxicity.</p

Toxicity of CdSe Nanoparticles in Caco-2 Cell Cultures

<p>Abstract</p> <p>Background</p> <p>Potential routes of nanomaterial exposure include inhalation, dermal contact, and ingestion. Toxicology of inhalation of ultra-fine particles has been extensively studied; however, risks of nanomaterial exposure via ingestion are currently almost unknown. Using enterocyte-like Caco-2 cells as a small intestine epithelial model, the possible toxicity of CdSe quantum dot (QD) exposure via ingestion was investigated. Effect of simulated gastric fluid treatment on CdSe QD cytotoxicity was also studied.</p> <p>Results</p> <p>Commercially available CdSe QDs, which have a ZnS shell and poly-ethylene glycol (PEG) coating, and in-house prepared surfactant coated CdSe QDs were dosed to Caco-2 cells. Cell viability and attachment were studied after 24 hours of incubation. It was found that cytotoxicity of CdSe QDs was modulated by surface coating, as PEG coated CdSe QDs had less of an effect on Caco-2 cell viability and attachment. Acid treatment increased the toxicity of PEG coated QDs, most likely due to damage or removal of the surface coating and exposure of CdSe core material. Incubation with un-dialyzed in-house prepared CdSe QD preparations, which contained an excess amount of free Cd²⁺, resulted in dramatically reduced cell viability.</p> <p>Conclusion</p> <p>Exposure to CdSe QDs resulted in cultured intestinal cell detachment and death; cytotoxicity depended largely, however, on the QD coating and treatment (e.g. acid treatment, dialysis). Experimental results generally indicated that Caco-2 cell viability correlated with concentration of free Cd²⁺ions present in cell culture medium. Exposure to low (gastric) pH affected cytotoxicity of CdSe QDs, indicating that route of exposure may be an important factor in QD cytotoxicity.</p

Manufacturing and performance evaluation of carbon nanotube-parylene sandwich thin films

Parylene-C, an inert and relatively mechanically strong polymer, which can be deposited in a conformal manner, is a promising substrate candidate for flexible electronics (Flextronics) devices. Parylene-CNT sandwich-films were fabricated by utilizing single-walled carbon nanotube (SWNT) layers sandwiched between two, 10 μm thick parylene layers. The device was fabricated using shadow mask technology and SWNT drop casting on top of the Parylene substrate. The electrical conductivity and mechanical properties of the samples were tested under tensile loading. The load-unload tests showed small change in electrical resistance (~1%) when applying a strain in the range 0 - 2%, with negligible hysterisis. The tensile test also showed ~32% increase in the elastic modulus (E) of the sandwich film, relative to pure parylene. Potential applications are in interconnects for flexible electronics devices, and strain sensors for biological systems

3D Bioprinting for Tissue and Organ Fabrication

The field of regenerative medicine has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes. Conventional approaches based on scaffolding and microengineering are limited in their capacity of producing tissue constructs with precise biomimetic properties. Three-dimensional (3D) bioprinting technology, on the other hand, promises to bridge the divergence between artificially engineered tissue constructs and native tissues. In a sense, 3D bioprinting offers unprecedented versatility to co-deliver cells and biomaterials with precise control over their compositions, spatial distributions, and architectural accuracy, therefore achieving detailed or even personalized recapitulation of the fine shape, structure, and architecture of target tissues and organs. Here we briefly describe recent progresses of 3D bioprinting technology and associated bioinks suitable for the printing process. We then focus on the applications of this technology in fabrication of biomimetic constructs of several representative tissues and organs, including blood vessel, heart, liver, and cartilage. We finally conclude with future challenges in 3D bioprinting as well as potential solutions for further development.United States. Office of Naval Research. Young Investigator ProgramNational Institutes of Health (U.S.) (Grants EB012597, AR057837, DE021468, HL099073 and R56AI105024)Presidential Early Career Award for Scientists and Engineer