Papers by Jeffrey Borenstein
The Scaffold, Second Edition, 2014
Pharmaceutics
The goal of this work was to evaluate tissue-device interactions due to implantation of a mechani... more The goal of this work was to evaluate tissue-device interactions due to implantation of a mechanically operated drug delivery system onto the posterior sclera. Two test devices were designed and fabricated to model elements of the drug delivery device-one containing a free-spinning ball bearing and the other encasing two articulating gears. Openings in the base of test devices modeled ports for drug passage from device to sclera. Porous poly(tetrafluoroethylene) (PTFE) membranes were attached to half of the gear devices to minimize tissue ingrowth through these ports. Test devices were sutured onto rabbit eyes for 10 weeks. Tissue-device interactions were evaluated histologically and mechanically after removal to determine effects on device function and changes in surrounding tissue. Test devices were generally well-tolerated during residence in the animal. All devices encouraged fibrous tissue formation between the sclera and the device, fibrous tissue encapsulation and invasion ar...
Technical Digest. IEEE International MEMS 99 Conference. Twelfth IEEE International Conference on Micro Electro Mechanical Systems (Cat. No.99CH36291)
MRS Proceedings
In this work, we present for the first time, the fabrication of a fully biodegradable microfluidi... more In this work, we present for the first time, the fabrication of a fully biodegradable microfluidic device with features of micron-scale precision. This implantable MEMS device is a transition from poorly defined porous scaffolds to reproducible precision scaffolds with built-in convective conduits. First, conventional photolithography is used to create a master mold by bulk micromachining silicon. Next, polydimethylsiloxane (PDMS) silicone elastomer is replica molded to form a flexible inverse mold. The commonly used biodegradable polymer Poly-lactic-co-glycolic acid (PLGA 85:15) is then compression micromolded onto the PDMS to form micropatterned films of the biodegradable polymer. Finally, a thermal fusion bonding process is used to seal the biodegradable PLGA films, forming closed microfluidic channels at the capillary size-scale. Film thicknesses from 100μm-1mm are demonstrated with features having 2μm resolution and 0.2μm precision. Scanning electron micrographs of bonded biode...
Journal of Vacuum Science & Technology B: Microelectronics and Nanometer Structures
ABSTRACT Optical interferometry has been applied to determine the displacement of p++ Si beams. C... more ABSTRACT Optical interferometry has been applied to determine the displacement of p++ Si beams. Clamped-clamped Si beams and cantilevered beams were fabricated with short and long B diffusion processes and characterized. Measurements of beam bending for released Si structures with length varying from 50 to 1000 μm, width varying from 5 to 15 μm, and thickness varying from 6 to 37 μm were obtained. By taking advantage of an etch-diffusion process, thicker beams can be fabricated which have less bending due to stress gradients. A 6.0-μm-thick cantilevered beam had a deflection of 11.2 μm due to stress gradients, while a 36.7-μm-thick beam had a deflection of only 0.3 μm. Beams fabricated using a dissolved wafer process with a 12 h B diffusion were found to bend the same amount as those fabricated with a 4 h diffusion. This indicates that bending in doped Si beams not only depends on the gradients in the B concentrations, it could also be related to the distribution of dislocations. Using the deep-etch shallow-diffusion process, resonating elements that are 20 μm long, 4 μm wide, and 28 μm thick were found to be perfectly flat without any bending. © 1999 American Vacuum Society.
Advanced materials (Deerfield Beach, Fla.), 2017
Hydrogels play a central role in a number of medical applications and new research aims to engine... more Hydrogels play a central role in a number of medical applications and new research aims to engineer their mechanical properties to improve their capacity to mimic the functional dynamics of native tissues. This study shows hierarchical mechanical tuning of hydrogel networks by utilizing mixtures of kinetically distinct reversible covalent crosslinks. A methodology is described to precisely tune stress relaxation in PEG networks formed from mixtures of two different phenylboronic acid derivatives with unique diol complexation rates, 4-carboxyphenylboronic acid, and o-aminomethylphenylboronic acid. Gel relaxation time and the mechanical response to dynamic shear are exquisitely controlled by the relative concentrations of the phenylboronic acid derivatives. The differences observed in the crossover frequencies corresponding to pKa differences in the phenylboronic acid derivatives directly connect the molecular kinetics of the reversible crosslinks to the macroscopic dynamic mechanical...
Nature communications, Mar 28, 2017
The endocrine system dynamically controls tissue differentiation and homeostasis, but has not bee... more The endocrine system dynamically controls tissue differentiation and homeostasis, but has not been studied using dynamic tissue culture paradigms. Here we show that a microfluidic system supports murine ovarian follicles to produce the human 28-day menstrual cycle hormone profile, which controls human female reproductive tract and peripheral tissue dynamics in single, dual and multiple unit microfluidic platforms (Solo-MFP, Duet-MFP and Quintet-MPF, respectively). These systems simulate the in vivo female reproductive tract and the endocrine loops between organ modules for the ovary, fallopian tube, uterus, cervix and liver, with a sustained circulating flow between all tissues. The reproductive tract tissues and peripheral organs integrated into a microfluidic platform, termed EVATAR, represents a powerful new in vitro tool that allows organ-organ integration of hormonal signalling as a phenocopy of menstrual cycle and pregnancy-like endocrine loops and has great potential to be us...
Biomicrofluidics, 2016
In pre-clinical safety studies, drug-induced vascular injury (DIVI) is defined as an adverse resp... more In pre-clinical safety studies, drug-induced vascular injury (DIVI) is defined as an adverse response to a drug characterized by degenerative and hyperplastic changes of endothelial cells and vascular smooth muscle cells. Inflammation may also be seen, along with extravasation of red blood cells into the smooth muscle layer (i.e., hemorrhage). Drugs that cause DIVI are often discontinued from development after considerable cost has occurred. An in vitro vascular model has been developed using endothelial and smooth muscle cells in co-culture across a porous membrane mimicking the internal elastic lamina. Arterial flow rates of perfusion media within the endothelial chamber of the model induce physiologic endothelial cell alignment. Pilot testing with a drug known to cause DIVI induced extravasation of red blood cells into the smooth muscle layer in all devices with no extravasation seen in control devices. This engineered vascular model offers the potential to evaluate candidate dru...
Pnas, 2006
Despite the enormous advances in tissue engineering, several challenges still prevent the widespr... more Despite the enormous advances in tissue engineering, several challenges still prevent the widespread clinical application of tissue engineering products, such as how to acquire adequate number of cells, how to engineer complex vascularized tissues that mimic the complexity of native tissue architecture and functions. The merger of biomaterials and microscale technologies offer new opportunities to overcome the challenges in tissue engineering to fabricate scaffolds and direct stem cell differentiation. In this review, various applications of microscale technologies have been illustrated in controlling stem cell fate and building complex artificial tissue with well-controlled and vascularized structures. It is envisioned that with the rapid growth of this burgeoning research field, microscale technologies will transform the conventional tissue engineering approaches and greatly contribute to the therapeutic potential of tissue engineering.
Angew Chem Int Ed, 2009
Lead-In The interaction of mammalian cells with nanoscale topography has proven to be an importan... more Lead-In The interaction of mammalian cells with nanoscale topography has proven to be an important signaling modality in controlling cell function. Naturally occurring nanotopographic structures within the extracellular matrix present surrounding cells with mechanotransductive cues that influence local migration, cell polarization, and other functions. Synthetically nanofabricated topography can also influence cell morphology, alignment, adhesion, migration, proliferation, and cytoskeleton organization. Here we review the use of in vitro synthetic cell-nanotopography interactions to control cell behavior and influence complex cellular processes including stem cell differentiation and tissue organization. Future challenges and opportunities in cell-nanotopography engineering will also be discussed including the elucidation of mechanisms and applications in tissue engineering.
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Papers by Jeffrey Borenstein