Irina Pomerantseva

Publications of Irina Pomerantseva

• The tissue-engineered auricle: past, present, and future.

  Authors: David A Bichara, Niamh-Anna O'Sullivan, Irina Pomerantseva, Xing Zhao, Cathryn A Sundback, Joseph P Vacanti, Mark A Randolph

  Tissue engineering. Part B, Reviews. 08/2011; 18(1):51-61.

  The reconstruction, repair, and regeneration of the external auricular framework continue to be one of the greatest challenges in the field of tissue engineering. To replace like with like, we shouldThe reconstruction, repair, and regeneration of the external auricular framework continue to be one of the greatest challenges in the field of tissue engineering. To replace like with like, we should emulate the native structure and composition of auricular cartilage by combining a suitable chondrogenic cell source with an appropriate scaffold under optimal in vitro and in vivo conditions. Due to the fact that a suitable and reliable substitute for auricular cartilage has yet to be engineered, hand-carved autologous costal cartilage grafts and ear-shaped porous polyethylene implants are the current treatment modalities for auricular reconstruction. However, over the last decade, significant advances have been made in the field of regenerative medicine and tissue engineering. A variety of scaffolds and innovative approaches have been investigated as alternatives to using autologous carved costal cartilage or porous polyethylene implants. A review of recent developments and the current state of the art and science is presented, focusing on scaffolds, cell sources, seeding densities, and mechanical characteristics of tissue-engineered auricular cartilage.

• Engineering ear constructs with a composite scaffold to maintain dimensions.

  Authors: Libin Zhou, Irina Pomerantseva, Erik K Bassett, Chris M Bowley, Xing Zhao, David A Bichara, Katherine M Kulig, Joseph P Vacanti, Mark A Randolph, Cathryn A Sundback

  Tissue engineering. Part A. 02/2011; 17(11-12):1573-81.

  Engineered cartilage composed of a patient's own cells can become a feasible option for auricular reconstruction. However, distortion and shrinkage of ear-shaped constructs during scaffoldEngineered cartilage composed of a patient's own cells can become a feasible option for auricular reconstruction. However, distortion and shrinkage of ear-shaped constructs during scaffold degradation and neocartilage maturation in vivo have hindered the field. Scaffolds made of synthetic polymers often generate degradation products that cause an inflammatory reaction and negatively affect neocartilage formation in vivo. Porous collagen, a natural material, is a promising candidate; however, it cannot withstand the contractile forces exerted by skin and surrounding tissue during normal wound healing. We hypothesised that a permanent support in the form of a coiled wire embedded into a porous collagen scaffold will maintain the construct's size and ear-specific shape. Half-sized human adult ear-shaped fibrous collagen scaffolds with and without embedded coiled titanium wire were seeded with sheep auricular chondrocytes, cultured in vitro for up to 2 weeks, and implanted subcutaneously on the backs of nude mice. After 6 weeks, the dimensional changes in all implants with wire support were minimal (2.0% in length and 4.1% in width), whereas significant reduction in size occurred in the constructs without embedded wire (14.4% in length and 16.5% in width). No gross distortion occurred over the in vivo study period. There were no adverse effects on neocartilage formation from the embedded wire. Histologically, mature neocartilage extracellular matrix was observed throughout all implants. The amount of DNA, glycosaminoglycan, and hydroxyproline in the engineered cartilage were similar to that of native sheep ear cartilage. The embedded wire support was essential for avoiding shrinkage of the ear-shaped porous collagen constructs.

• Regeneration and orthotopic transplantation of a bioartificial lung.

  Authors: Harald C Ott, Ben Clippinger, Claudius Conrad, Christian Schuetz, Irina Pomerantseva, Laertis Ikonomou, Darrell Kotton, Joseph P Vacanti

  Nature medicine. 08/2010; 16(8):927-33.

  About 2,000 patients now await a donor lung in the United States. Worldwide, 50 million individuals are living with end-stage lung disease. Creation of a bioartificial lung requires engineering ofAbout 2,000 patients now await a donor lung in the United States. Worldwide, 50 million individuals are living with end-stage lung disease. Creation of a bioartificial lung requires engineering of viable lung architecture enabling ventilation, perfusion and gas exchange. We decellularized lungs by detergent perfusion and yielded scaffolds with acellular vasculature, airways and alveoli. To regenerate gas exchange tissue, we seeded scaffolds with epithelial and endothelial cells. To establish function, we perfused and ventilated cell-seeded constructs in a bioreactor simulating the physiologic environment of developing lung. By day 5, constructs could be perfused with blood and ventilated using physiologic pressures, and they generated gas exchange comparable to that of isolated native lungs. To show in vivo function, we transplanted regenerated lungs into orthotopic position. After transplantation, constructs were perfused by the recipient's circulation and ventilated by means of the recipient's airway and respiratory muscles, and they provided gas exchange in vivo for up to 6 h after extubation.

• Engineered vascularized bone grafts.

  Authors: Olga Tsigkou, Irina Pomerantseva, Joel A Spencer, Patricia A Redondo, Alison R Hart, Elisabeth O'Doherty, Yunfeng Lin, Claudia C Friedrich, Laurence Daheron, Charles P Lin, Cathryn A Sundback, Joseph P Vacanti, Craig Neville

  Proceedings of the National Academy of Sciences of the United States of America. 02/2010; 107(8):3311-6.

  Clinical protocols utilize bone marrow to seed synthetic and decellularized allogeneic bone grafts for enhancement of scaffold remodeling and fusion. Marrow-derived cytokines induce hostClinical protocols utilize bone marrow to seed synthetic and decellularized allogeneic bone grafts for enhancement of scaffold remodeling and fusion. Marrow-derived cytokines induce host neovascularization at the graft surface, but hypoxic conditions cause cell death at the core. Addition of cellular components that generate an extensive primitive plexus-like vascular network that would perfuse the entire scaffold upon anastomosis could potentially yield significantly higher-quality grafts. We used a mouse model to develop a two-stage protocol for generating vascularized bone grafts using mesenchymal stem cells (hMSCs) from human bone marrow and umbilical cord-derived endothelial cells. The endothelial cells formed tube-like structures and subsequently networks throughout the bone scaffold 4-7 days after implantation. hMSCs were essential for stable vasculature both in vitro and in vivo; however, contrary to expectations, vasculature derived from hMSCs briefly cultured in medium designed to maintain a proliferative, nondifferentiated state was more extensive and stable than that with hMSCs with a TGF-beta-induced smooth muscle cell phenotype. Anastomosis occurred by day 11, with most hMSCs associating closely with the network. Although initially immature and highly permeable, at 4 weeks the network was mature. Initiation of scaffold mineralization had also occurred by this period. Some human-derived vessels were still present at 5 months, but the majority of the graft vasculature had been functionally remodeled with host cells. In conclusion, clinically relevant progenitor sources for pericytes and endothelial cells can serve to generate highly functional microvascular networks for tissue engineered bone grafts.

• Mechanical dissociation of swine liver to produce organoid units for tissue engineering and in vitro disease modeling.

  Authors: Katayun Irani, Irina Pomerantseva, Alison R Hart, Cathryn A Sundback, Craig M Neville, Joseph P Vacanti

  Artificial organs. 01/2010; 34(1):75-8.

  The complex intricate architecture of the liver is crucial to hepatic function. Standard protocols used for enzymatic digestion to isolate hepatocytes destroy tissue structure and result inThe complex intricate architecture of the liver is crucial to hepatic function. Standard protocols used for enzymatic digestion to isolate hepatocytes destroy tissue structure and result in significant loss of synthetic, metabolic, and detoxification processes. We describe a process using mechanical dissociation to generate hepatic organoids with preserved intrinsic tissue architecture from swine liver. Oxygen-supplemented perfusion culture better preserved organoid viability, morphology, serum protein synthesis, and urea production, compared with standard and oxygen-supplemented static culture. Hepatic organoids offer an alternative source for hepatic assist devices, engineered liver, disease modeling, and xenobiotic testing.

• Bone marrow derived pluripotent cells are pericytes which contribute to vascularization.

  Authors: Xiaoxiao Cai, Yunfeng Lin, Claudia C Friedrich, Craig Neville, Irina Pomerantseva, Cathryn A Sundback, Parul Sharma, Zhiyuan Zhang, Joseph P Vacanti, Peter V Hauschka, Brian E Grottkau

  Stem cell reviews. 12/2009; 5(4):437-45.

  Pericytes are essential to vascularization, but the purification and characterization of pericytes remain unclear. Smooth muscle actin alpha (alpha-SMA) is one marker [corrected] of pericytes. ThePericytes are essential to vascularization, but the purification and characterization of pericytes remain unclear. Smooth muscle actin alpha (alpha-SMA) is one marker [corrected] of pericytes. The aim of this study is to purify the alpha-SMA positive cells from bone marrow and study the characteristics of these cells and the interaction between alpha-SMA positive cells and endothelial cells. The bone marrow stromal cells were harvested from alpha-SMA-GFP transgenic mice, and the alpha-SMA-GFP positive cells were sorted by FACS. The proliferative characteristics and multilineage differentiation ability of the alpha-SMA-GFP positive cells were tested. A 3-D culture model was then applied to test their vascularization by loading alpha-SMA-GFP positive cells and endothelial cells on collagen-fibronectin gel. Results demonstrated that bone marrow stromal cells are mostly alpha-SMA-GFP positive cells which are pluripotent, and these cells expressed alpha-SMA during differentiation. The alpha-SMA-GFP positive cells could stimulate the endothelial cells to form tube-like structures and subsequently robust vascular networks in 3-D culture. In conclusion, the bone marrow derived pluripotent cells include [corrected] pericytes and can contribute to vascularization.

• Erratum to: Bone Marrow Derived Pluripotent Cells are Pericytes which Contribute to Vascularization.

  Authors: Xiaoxiao Cai, Yunfeng Lin, Claudia Friedrich, Craig Neville, Irina Pomerantseva, Cathryn Sundback, Zhiyuan Zhang, Joseph Vacanti, Peter Hauschka, Brian Grottkau

  Stem cell reviews and reports. 11/2009;

• Bone marrow Derived Pluripotent Cells are Pericytes which Contribute to Vascularization.

  Authors: Xiaoxiao Cai, Yunfeng Lin, Claudia Friedrich, Craig Neville, Irina Pomerantseva, Cathryn Sundback, Parul Sharma, Zhiyuan Zhang, Joseph Vacanti, Peter Hauschka, Brian Grottkau

  Stem cell reviews and reports. 10/2009;

  Pericytes are essential to vascularization, but the purification and characterization of pericytes remain unclear. Smooth muscle actin alpha (alpha-SMA) is one maker of pericytes. The aim of thisPericytes are essential to vascularization, but the purification and characterization of pericytes remain unclear. Smooth muscle actin alpha (alpha-SMA) is one maker of pericytes. The aim of this study is to purify the alpha-SMA positive cells from bone marrow and study the characteristics of these cells and the interaction between alpha-SMA positive cells and endothelial cells. The bone marrow stromal cells were harvested from alpha-SMA-GFP transgenic mice, and the alpha-SMA-GFP positive cells were sorted by FACS. The proliferative characteristics and multilineage differentiation ability of the alpha-SMA-GFP positive cells were tested. A 3-D culture model was then applied to test their vascularization by loading alpha-SMA-GFP positive cells and endothelial cells on collagen-fibronectin gel. Results demonstrated that bone marrow stromal cells are mostly alpha-SMA-GFP positive cells which are pluripotent, and these cells expressed alpha-SMA during differentiation. The alpha-SMA-GFP positive cells could stimulate the endothelial cells to form tube-like structures and subsequently robust vascular networks in 3-D culture. In conclusion, the bone marrow derived pluripotent cells are pericytes and can contribute to vascularization.

• Degradation behavior of poly(glycerol sebacate).

  Authors: Irina Pomerantseva, Nicholas Krebs, Alison Hart, Craig M Neville, Albert Y Huang, Cathryn A Sundback

  Journal of biomedical materials research. Part A. 01/2009;

  Poly(glycerol sebacate) (PGS), a promising scaffold material for soft tissue engineering applications, is a soft, tough elastomer with excellent biocompatibility. However, the rapid in vivoPoly(glycerol sebacate) (PGS), a promising scaffold material for soft tissue engineering applications, is a soft, tough elastomer with excellent biocompatibility. However, the rapid in vivo degradation rate of PGS limits its use as a scaffold material. To determine the impact of crosslink density on degradation rate, a family of PGS materials was synthesized by incrementally increasing the curing time from 42 to 144 h, at 120 degrees C and 10 mTorr vacuum. As expected, PGS became a stiffer, tougher, and stronger elastomer with increasing curing time. PGS disks were subcutaneously implanted into rats and periodically harvested; only mild tissue responses were observed and the biocompatibility remained excellent. Regardless of crosslink density, surface erosion degradation was observed. The sample dimensions linearly decreased with implantation time, and the mass loss rates were constant after 1-week implantation. As surface erosion degradation frequently correlates with enzymatic digestion, parallel in vitro digestion studies were conducted in lipase solutions which hydrolyze ester bonds. Enzymatic digestion played a significant role in degrading PGS, and the mass loss rates were not a function of curing time. Alternative chemistry approaches will be required to decrease the enzymatic hydrolysis rate of the ester bonds in PGS polymers. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009.

• A biodegradable and biocompatible gecko-inspired tissue adhesive.

  Authors: Alborz Mahdavi, Lino Ferreira, Cathryn Sundback, Jason W Nichol, Edwin P Chan, David J D Carter, Chris J Bettinger, Siamrut Patanavanich, Loice Chignozha, Eli Ben-Joseph [......] Howard Pryor, Irina Pomerantseva, Peter T Masiakos, William Faquin, Andreas Zumbuehl, Seungpyo Hong, Jeffrey Borenstein, Joseph Vacanti, Robert Langer, Jeffrey M Karp

  Proceedings of the National Academy of Sciences of the United States of America. 03/2008; 105(7):2307-12.

  There is a significant medical need for tough biodegradable polymer adhesives that can adapt to or recover from various mechanical deformations while remaining strongly attached to the underlyingThere is a significant medical need for tough biodegradable polymer adhesives that can adapt to or recover from various mechanical deformations while remaining strongly attached to the underlying tissue. We approached this problem by using a polymer poly(glycerol-co-sebacate acrylate) and modifying the surface to mimic the nanotopography of gecko feet, which allows attachment to vertical surfaces. Translation of existing gecko-inspired adhesives for medical applications is complex, as multiple parameters must be optimized, including: biocompatibility, biodegradation, strong adhesive tissue bonding, as well as compliance and conformability to tissue surfaces. Ideally these adhesives would also have the ability to deliver drugs or growth factors to promote healing. As a first demonstration, we have created a gecko-inspired tissue adhesive from a biocompatible and biodegradable elastomer combined with a thin tissue-reactive biocompatible surface coating. Tissue adhesion was optimized by varying dimensions of the nanoscale pillars, including the ratio of tip diameter to pitch and the ratio of tip diameter to base diameter. Coating these nanomolded pillars of biodegradable elastomers with a thin layer of oxidized dextran significantly increased the interfacial adhesion strength on porcine intestine tissue in vitro and in the rat abdominal subfascial in vivo environment. This gecko-inspired medical adhesive may have potential applications for sealing wounds and for replacement or augmentation of sutures or staples.

• 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.

  Download

• 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.

  Download

• Hydrogel optimization for cultured elastic chondrocytes seeded onto a polyglycolic acid scaffold.

  Authors: Shinichi Terada, Hiroshi Yoshimoto, Julie R Fuchs, Michio Sato, Irina Pomerantseva, Martin K Selig, Didier Hannouche, Joseph P Vacanti

  Journal of biomedical materials research. Part A. 01/2006; 75(4):907-16.

  The purpose of this study was to compare the effect of different hydrogels on the production of tissue-engineered cartilage based on polyglycolic acid (PGA). Chondrocytes were isolated from adultThe purpose of this study was to compare the effect of different hydrogels on the production of tissue-engineered cartilage based on polyglycolic acid (PGA). Chondrocytes were isolated from adult sheep auricles. Alginate, Type I collagen, methylcellulose, and pluronic F127 hydrogels were evaluated, as were controls prepared without hydrogels. Proliferated chondrocytes were mixed with each hydrogel at 20 x 10(6) cells/mL and seeded onto PGA (1 x 1 x 0.2 cm, n = 60). The constructs were cultured with serum-free medium containing 5 ng/mL TGF-beta(2) and 5 ng/mL des(1-3)IGF-I in rotational bioreactors for up to 6 weeks. The cellular morphology, histology, and biochemistry were analyzed. Type I collagen, methylcellulose, and pluronic F127 displayed improved cartilage matrix deposition in terms of histology and biochemistry compared to alginate. It was not concluded that the combined seeding of chondrocytes and hydrogels on a PGA scaffold had significantly better effects than cell seeding without hydrogels. However, the histology and other useful findings in this ECM analyses suggested that Type I collagen and MC hydrogels were the best candidates for cartilage regeneration, because of their stimulation for chondrocyte proliferation in a three-dimensional culture as well as cartilage regeneration.

• Fetal tissue engineering: in vitro analysis of muscle constructs.

  Authors: Julie R Fuchs, Irina Pomerantseva, Erin R Ochoa, Joseph P Vacanti, Dario O Fauza

  Journal of pediatric surgery. 09/2003; 38(9):1348-53.

  BACKGROUND/PURPOSE: This study was aimed at examining the impact of different tissue engineering techniques on fetal muscle construct architecture. METHODS: Myoblasts from ovine specimens of fetalBACKGROUND/PURPOSE: This study was aimed at examining the impact of different tissue engineering techniques on fetal muscle construct architecture. METHODS: Myoblasts from ovine specimens of fetal skeletal muscle were expanded in culture and their growth rates determined. Cells were seeded at different densities onto 3 scaffold types, namely polyglycolic acid (PGA) treated with poly-l-lactic acid (PLLA), a composite of PGA with poly-4-hydroxybutyrate (P4HB), and a collagen hydrogel. Constructs were maintained in a bioreactor and submitted to histologic, scanning electron microscopy, and DNA analyses at different time-points. Statistical analysis was by the likelihood ratio and paired Student's t tests (P <.05). RESULTS: Fetal myoblasts proliferated at faster rates than expected from neonatal cells. Cell attachment was enhanced in the PGA/PLLA matrix and collagen hydrogel when compared with the PGA/P4HB composite. Necrosis was observed at the center of all constructs, directly proportional to cell seeding density and time in the bioreactor. CONCLUSIONS: Fetal myoblasts can be expanded rapidly in culture and attach well to PGA/PLLA, as well as collagen hydrogel but less optimally to PGA/P4HB. Excessive cell seeding density and bioreactor time may worsen final construct architecture. These findings should be considered during in vivo trials of muscle replacement by engineered fetal constructs.

• Percutaneous transvenous cellular cardiomyoplasty. A novel nonsurgical approach for myocardial cell transplantation.

  Authors: Craig A Thompson, Boris A Nasseri, Joshua Makower, Stuart Houser, Michael McGarry, Theodore Lamson, Irina Pomerantseva, John Y Chang, Herman K Gold, Joseph P Vacanti, Stephen N Oesterle

  Journal of the American College of Cardiology. 07/2003; 41(11):1964-71.

  OBJECTIVES: The study evaluated a nonsurgical means of intramyocardial cell introduction using the coronary venous system for direct myocardial access and cell delivery. BACKGROUND: Direct myocardialOBJECTIVES: The study evaluated a nonsurgical means of intramyocardial cell introduction using the coronary venous system for direct myocardial access and cell delivery. BACKGROUND: Direct myocardial cell repopulation has been proposed as a potential method to treat heart failure. METHODS: We harvested bone marrow from Yorkshire swine (n = 6; 50 to 60 kg), selected culture-flask adherent cells, labeled them with the gene for green fluorescence protein, expanded them in culture, and resuspended them in a collagen hydrogel. Working through the coronary sinus, a specialized catheter system was easily delivered to the anterior interventricular coronary vein. The composite catheter system (TransAccess) incorporates a phased-array ultrasound tip for guidance and a sheathed, extendable nitinol needle for transvascular myocardial access. A microinfusion (IntraLume) catheter was advanced through the needle, deep into remote myocardium, and the autologous cell-hydrogel suspension was injected into normal heart. Animals were sacrificed at days 0 (n = 2), 14 (n = 1, + 1 control/collagen biogel only), and 28 (n = 2), and the hearts were excised and examined. RESULTS: We gained widespread intramyocardial access to the anterior, lateral, septal, apical, and inferior walls from the anterior interventicular coronary vein. No death, cardiac tamponade, ventricular arrhythmia, or other procedural complications occurred. Gross inspection demonstrated no evidence of myocardial perforation, and biogel/black tissue dye was well localized to sites corresponding to fluoroscopic landmarks for delivery. Histologic analysis demonstrated needle and microcatheter tracts and accurate cell-biogel delivery. CONCLUSIONS: Percutaneous intramyocardial access is safe and feasible by a transvenous approach through the coronary venous system. The swine offers an opportunity to refine approaches used for cellular cardiomyoplasty.

• Dynamic rotational seeding and cell culture system for vascular tube formation.

  Authors: Boris A Nasseri, Irina Pomerantseva, Mohammad R Kaazempur-Mofrad, Fraser W H Sutherland, Tjorvi Perry, Erin Ochoa, Craig A Thompson, John E Mayer, Stephen N Oesterle, Joseph P Vacanti

  Tissue engineering. 05/2003; 9(2):291-9.

  Optimization of cell seeding and culturing is an important step for the successful tissue engineering of vascular conduits. We evaluated the effectiveness of using a hybridization oven for rotationalOptimization of cell seeding and culturing is an important step for the successful tissue engineering of vascular conduits. We evaluated the effectiveness of using a hybridization oven for rotational seeding and culturing of ovine vascular myofibroblasts onto biodegradable polymer scaffolds suitable for replacement of small- and large-diameter blood vessels. Large tubes (12 mm internal diameter and 60 mm length, n = 4) and small tubes (5 mm internal diameter and 20 mm length, n = 4) were made from a combination of polyglycolic acid/poly-4-hydroxybutyrate and coated with collagen solution. Tubes were then placed in culture vessels containing a vascular myofibroblast suspension (10(6) cells/cm(2)) and rotated at 5 rpm in a hybridization oven at 37 degrees C. Light and scanning electron microscopy analyses were performed after 5, 7, and 10 days. Myofibroblasts had formed confluent layers over the outer and inner surfaces of both large and small tubular scaffolds by day 5. Cells had aligned in the direction of flow by day 7. Multiple spindle-shaped cells were observed infiltrating the polymer mesh. Cell density increased between day 5 and day 10. All conduits maintained their tubular shape throughout the experiment. We conclude that dynamic rotational seeding and culturing in a hybridization oven is an easy, effective, and reliable method to deliver and culture vascular myofibroblasts onto tubular polymer scaffolds.

• A novel pulsatile, laminar flow bioreactor for the development of tissue-engineered vascular structures.

  Authors: Craig A Thompson, Pedro Colon-Hernandez, Irina Pomerantseva, Brian D MacNeil, Boris Nasseri, Joseph P Vacanti, Stephen N Oesterle

  Tissue engineering. 01/2003; 8(6):1083-8.

  Exposure of vascular cell-seeded, tubular, biodegradable polymers to pulsatile flow conditions has been proposed as a method to develop tissue-engineered blood vessels by "maturing" structuralExposure of vascular cell-seeded, tubular, biodegradable polymers to pulsatile flow conditions has been proposed as a method to develop tissue-engineered blood vessels by "maturing" structural integrity, and increasing collagen content, suture retention, burst pressure, and tissue formation. These in vitro tissue-engineered arteries demonstrate contractile responses to pharmacologic agents and express markers of vascular differentiation. Current methods to induce pulsatile flow in a bioreactor system are limited by the creation of nonphysiologic pressure waveforms and noncompliant reservoirs to house the tissue-engineered vascular constructs. We have developed a novel method for the in vitro development of tubular vascular structures by using a mechanical ventilator to induce pulsatile, laminar flow into a fluid column, resulting in pressurized waveforms similar to mammalian physiology. The vascular constructs are housed in semicompliant tubing to facilitate an additional variable of circumferential stretch as a potential signaling mechanism. This approach more closely approximates mammalian physiology and we hypothesize that it will facilitate mechanical signaling necessary for the development of tissue-engineered vessels for clinical applications.

• Toward a new blood vessel.

  Authors: Briain D MacNeill, Irina Pomerantseva, Harry C Lowe, Stephen N Oesterle, Joseph P Vacanti

  Vascular medicine (London, England). 09/2002; 7(3):241-6.

  Strategies to treat atherosclerotic coronary artery disease include coronary artery bypass grafting (CABG), in which grafts are used to bypass atherosclerotic vessels and restore blood flow to theStrategies to treat atherosclerotic coronary artery disease include coronary artery bypass grafting (CABG), in which grafts are used to bypass atherosclerotic vessels and restore blood flow to the ischemic myocardium. The grafts used include healthy arteries or veins harvested from a separate site. Results with arterial grafts have been superior to venous grafts; promoting the practice of total arterial revascularization using only arterial grafts. Suitable arterial grafts, however, are scarce and harvest procedures add to morbidity and cost. Tissue engineering combines the principles of engineering with life sciences for the development of biological substitutes and restore, maintain or improve tissue function. Advances in this field have included the development of tissue-engineered blood vessels, with the potential to serve as arterial grafts, conduits or fistulae. This review describes the history of tissue engineering arteries, the techniques used, and progress to date. The source of cells and the future direction of this field are explored.