Eli Weinberg

Publications of Eli Weinberg

• Liver-assist device with a microfluidics-based vascular bed in an animal model.

  Authors: Wen-Ming Hsu, Amedeo Carraro, Katherine M Kulig, Mark L Miller, Mohammad Kaazempur-Mofrad, Eli Weinberg, Fateh Entabi, Hassan Albadawi, Michael T Watkins, Jeffrey T Borenstein, Joseph P Vacanti, Craig Neville

  Annals of surgery. 08/2010; 252(2):351-7.

  This study evaluates a novel liver-assist device platform with a microfluidics-modeled vascular network in a femoral arteriovenous shunt in rats. Liver-assist devices in clinical trials that useThis study evaluates a novel liver-assist device platform with a microfluidics-modeled vascular network in a femoral arteriovenous shunt in rats. Liver-assist devices in clinical trials that use pumps to force separated plasma through packed beds of parenchymal cells exhibited significant necrosis with a negative impact on function. Microelectromechanical systems technology was used to design and fabricate a liver-assist device with a vascular network that supports a hepatic parenchymal compartment through a nanoporous membrane. Sixteen devices with rat primary hepatocytes and 12 with human HepG2/C3A cells were tested in athymic rats in a femoral arteriovenous shunt model. Several parenchymal tube configurations were evaluated for pressure profile and cell survival. The blood flow pattern and perfusion status of the devices was examined by laser Doppler scanning. Cell viability and serum protein secretion functions were assessed. Femoral arteriovenous shunt was successfully established in all animals. Blood flow was homogeneous through the vascular bed and replicated native flow patterns. Survival of seeded liver cells was highly dependent on parenchymal chamber pressures. The tube configuration that generated the lowest pressure supported excellent cell survival and function. This device is the first to incorporate a microfluidics network in the systemic circulatory system. The microvascular network supported viability and function of liver cells in a short-term ex vivo model. Parenchymal chamber pressure generated in an arteriovenous shunt model is a critical parameter that affects viability and must be considered in future designs. The microfluidics-based vascular network is a promising platform for generating a large-scale medical device capable of augmenting liver function in a clinical setting.

• Functional endothelialized microvascular networks with circular cross-sections in a tissue culture substrate.

  Authors: Jeffrey Borenstein, Malinda Tupper, Peter Mack, Eli Weinberg, Ahmad Khalil, James Hsiao, Guillermo García-Cardeña

  Biomedical microdevices. 09/2009;

  Functional endothelialized networks constitute a critical building block for vascularized replacement tissues, organ assist devices, and laboratory tools for in vitro discovery and evaluation of newFunctional endothelialized networks constitute a critical building block for vascularized replacement tissues, organ assist devices, and laboratory tools for in vitro discovery and evaluation of new therapeutic compounds. Progress towards realization of these functional artificial vasculatures has been gated by limitations associated with the mechanical and surface chemical properties of commonly used microfluidic substrate materials and by the geometry of the microchannels produced using conventional fabrication techniques. Here we report on a method for constructing microvascular networks from polystyrene substrates commonly used for tissue culture, built with circular cross-sections and smooth transitions at bifurcations. Silicon master molds are constructed using an electroplating process that results in semi-circular channel cross-sections with smoothly varying radii. These master molds are used to emboss polystyrene sheets which are then joined to form closed bifurcated channel networks with circular cross-sections. The mechanical and surface chemical properties of these polystyrene microvascular network structures enable culture of endothelial cells along the inner lumen. Endothelial cell viability was assessed, documenting nearly confluent monolayers within 3D microfabricated channel networks with rounded cross-sections.

• Towards regenerating a human thumb in situ.

  Authors: Christian Weinand, Rajiv Gupta, Eli Weinberg, Ijad Madisch, Craig Neville, Jesse B Jupiter, Joseph Vacanti

  Tissue engineering. Part A. 03/2009;

  Regenerative technology promises to alleviate the problem of limited donor supply for bone or organ transplants. Most expensive and time consuming is cell expansion in laboratories. We propose aRegenerative technology promises to alleviate the problem of limited donor supply for bone or organ transplants. Most expensive and time consuming is cell expansion in laboratories. We propose a method of magnetically enriched osteoprogenitor stem cells, dispersed in self-assembling hydrogels and applied onto new ultra-high resolution, jet-based 3D printing of living human bone in a single-step for in-situ bone regeneration. Human mesenchymal stem-cells (hBMSCs) were enriched with CD 117+ osteoprogenitor cells, dispersed in different collagen I, RAD 16I hydrogels mixes and applied onto 3-dimensional printed (3DP) beta-TCP/PLGA scaffolds, printed from ultra-high-resolution volumetric CT (VCT) images of a human thumb. Constructs were directly implanted subcutaneously into nude mice for 6 weeks. In-vivo radiographic VCT scanning and histological evaluations were performed at 1, 2, 4 and 6 weeks, expression of bone-specific genes and biomechanical compression-testing at 6 weeks endpoint. Time dependant accumulation of bone-like extracellular matrix was most evident in CD 117+ hBMSCs using collagen I/RAD 16I hydrogel mix. This was shown histologically by Toluidine blue, von Kossa and alkaline-phosphatase staining, paralleled by increased radiological densities within implants approximating that of human bone, and confirmed by high expression of bone-specific osteonectin and biomechanical stiffness at 6 weeks. Human origin of newly formed tissue was established by expression of human GAPDH using RT-PCR. Statistical analysis confirmed high correlations between biomechanical stiffness, radiological densities and bone-markers. Bone tissue can be successfully regenerated in-situ using a single-step procedure with constructs comprised of RAD 16I /collagen I hydrogel, CD 117+ enriched hBMSCs and porous beta-TCP/PLGA scaffolds.

• In vitro analysis of a hepatic device with intrinsic microvascular-based channels.

  Authors: Amedeo Carraro, Wen-Ming Hsu, Katherine Kulig, Wing Cheung, Mark Miller, Eli Weinberg, Eric Swart, Mohammad Kaazempur-Mofrad, Jeffrey Borenstein, Joseph Vacanti, Craig Neville

  Biomedical microdevices. 08/2008;

  A novel microfluidics-based bilayer device with a discrete parenchymal chamber modeled upon hepatic organ architecture is described. The microfluidics network was designed using computational modelsA novel microfluidics-based bilayer device with a discrete parenchymal chamber modeled upon hepatic organ architecture is described. The microfluidics network was designed using computational models to provide appropriate flow behavior based on physiological data from human microvasculature. Patterned silicon wafer molds were used to generate films with the vascular-based microfluidics network design and parenchymal chamber by soft lithography. The assembled device harbors hepatocytes behind a nanoporous membrane that permits transport of metabolites and small proteins while protecting them from the effects of shear stress. The device can sustain both human hepatoma cells and primary rat hepatocytes by continuous in vitro perfusion of medium, allowing proliferation and maintaining hepatic functions such as serum protein synthesis and metabolism. The design and fabrication processes are scalable, enabling the device concept to serve as both a platform technology for drug discovery and toxicity, and for the continuing development of an improved liver-assist device.

• Human shaped thumb bone tissue engineered by hydrogel-beta-tricalciumphosphate/poly-epsilon-caprolactone scaffolds and magnetically sorted stem cells.

  Authors: Christian Weinand, Rajiv Gupta, Eli Weinberg, Ijad Madisch, Jesse B Jupiter, Joseph P Vacanti

  Annals of plastic surgery. 08/2007; 59(1):46-52; discussion 52.

  Traumatic amputation of a thumb with bone loss leaves a patient in severe disability. Reconstructive procedures are restricted by limited shape and have the disadvantage of severe donor-siteTraumatic amputation of a thumb with bone loss leaves a patient in severe disability. Reconstructive procedures are restricted by limited shape and have the disadvantage of severe donor-site morbidity. To overcome these limitations, we used a tissue engineering approach to create a distal thumb bone phalanx, combining magnetically sorted 133+ human mesenchymal stem cells (hMSCs) suspended in successful tested hydrogels for bone formation and porous 3-dimensionally printed scaffolds (3DP) in the shape of a distal thumb bone phalanx. Collagen I and fibrin glue hydrogels with suspended hMSCs were first histologically evaluated in vitro for bone formation after 6 weeks.Then 3DP scaffolds, made from a mix of osteoinductive and -conductive beta-tricalciumphosphate (beta-TCP) and poly-epsilon-caprolactone (PCL), with hydrogels and suspended hMSCs, were implanted into nude mice subcutaneously for 15 weeks. Histologic evaluation, high-resolution volumetric CT (VCT) scanning, and biomechanical testing confirmed formation of bonelike tissue. Both hydrogels with CD 133+ hMSCs on 3DP scaffolds supported bone formation. Collagen I resulted in radiologically better bone formation. Bone tissue can be successfully tissue engineered with CD 133+ hMSCs, collagen I hydrogels, and porous 3DP beta-TCP/PCL scaffolds.

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• Comparison of hydrogels in the in vivo formation of tissue-engineered bone using mesenchymal stem cells and beta-tricalcium phosphate.

  Authors: Christian Weinand, Rajiv Gupta, Albert Y Huang, Eli Weinberg, Ijad Madisch, Rameez A Qudsi, Craig M Neville, Irina Pomerantseva, Joseph P Vacanti

  Tissue engineering. 05/2007; 13(4):757-65.

  Availability of grafts and morbidity at the donor site limit autologous transplantation in patients requiring bone reconstruction. A tissue-engineering approach can overcome these limitations byAvailability of grafts and morbidity at the donor site limit autologous transplantation in patients requiring bone reconstruction. A tissue-engineering approach can overcome these limitations by producing bone-like tissue of custom shape and size from isolated cells. Several hydrogels facilitate osteogenesis on porous scaffolds; however, the relative suitability of various hydrogels has not been rigorously assessed. Fibrin glue, alginate, and collagen I hydrogels were mixed with swine bone marrow-derived differentiated mesenchymal stem cells (MSCs), applied to 3-dimensionally printed porous beta-tricalcium phosphate (beta-TCP) scaffolds and implanted subcutaneously in nude mice. Although noninvasive assessment of osteogenesis in 3 dimensions is desirable for monitoring new bone formation in vivo, correlations with traditional histological and mechanical testing need to be established. High-resolution volumetric computed tomography (VCT) scanning, histological examination, biomechanical compression testing, and osteonectin (ON) expression were performed on excised scaffolds after 1, 2, 4, and 6 weeks of subcutaneous implantation in mice. Statistical correlation analyses were performed between radiological density, stiffness, and ON expression. Use of collagen I as a hydrogel carrier produced superior bone formation at 6 weeks, as demonstrated using VCT scanning with densities similar to native bone and the highest compression values. Continued contribution of the seeded MSCs was demonstrated using swine-specific messenger ribonucleic acid probes. Radiological density values correlated closely with the results of histological and biomechanical testing and ON expression. High-resolution VCT is a promising method for monitoring osteogenesis.

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• Hydrogel-beta-TCP scaffolds and stem cells for tissue engineering bone.

  Authors: Christian Weinand, Irina Pomerantseva, Craig M Neville, Rajiv Gupta, Eli Weinberg, Ijad Madisch, Frederic Shapiro, Harutsugi Abukawa, Maria J Troulis, Joseph P Vacanti

  Bone. 05/2006; 38(4):555-63.

  Trabecular bone is a material of choice for reconstruction after trauma and tumor resection and for correction of congenital defects. Autologous bone grafts are available in limited shapes and sizes;Trabecular bone is a material of choice for reconstruction after trauma and tumor resection and for correction of congenital defects. Autologous bone grafts are available in limited shapes and sizes; significant donor site morbidity is another major disadvantage to this approach. To overcome these limitations, we used a tissue engineering approach to create bone replacements in vitro, combining bone-marrow-derived differentiated mesenchymal stem cells (MSCs) suspended in hydrogels and 3-dimensionally printed (3DP) porous scaffolds made of beta-tricalcium-phosphate (beta-TCP). The scaffolds provided support for the formation of bone tissue in collagen I, fibrin, alginate, and pluronic F127 hydrogels during culturing in oscillating and rotating dynamic conditions. Histological evaluation including toluidine blue, alkaline phosphatase, and von Kossa staining was done at 1, 2, 4, and 6 weeks. Radiographic evaluation and high-resolution volumetric CT (VCT) scanning, expression of bone-specific genes and biomechanical compression testing were performed at 6 weeks. Both culture conditions resulted in similar bone tissue formation. Histologically collagen I and fibrin hydrogels specimens had superior bone tissue, although radiopacities were detected only in collagen I samples. VCT scan revealed density values in all but the Pluronic F127 samples, with Houndsfield unit values comparable to native bone in collagen I and fibrin glue samples. Expression of bone-specific genes was significantly higher in the collagen I samples. Pluronic F127 hydrogel did not support formation of bone tissue. All samples cultured in dynamic oscillating conditions had slightly higher mechanical strength than under rotating conditions. Bone tissue can be successfully formed in vitro using constructs comprised of collagen I hydrogel, MSCs, and porous beta-TCP scaffolds.

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