Joseph Vacanti

Publications of Joseph Vacanti

• 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.

• Tissue engineering and regenerative medicine: from first principles to state of the art.

  Authors: Joseph Vacanti

  Journal of pediatric surgery. 02/2010; 45(2):291-4.

  This lecture updates pediatric surgeons on the state of the science of tissue engineering and regenerative medicine.

• Principles of Biomimetic Vascular Network Design Applied to a Tissue Engineered Liver Scaffold.

  Authors: David M Hoganson, Howard I Pryor Ii, Ira D Spool, Owen H Burns, J Randall Gilmore, Joseph Vacanti

  Tissue engineering. Part A. 12/2009;

  Branched vascular networks are a central component of scaffold architecture for solid organ tissue engineering. In this work, seven biomimetic principles were established as the major guidingBranched vascular networks are a central component of scaffold architecture for solid organ tissue engineering. In this work, seven biomimetic principles were established as the major guiding technical design considerations of a branched vascular network for a tissue engineered scaffold. These biomimetic design principles were applied to a branched radial architecture to develop a liver specific vascular network. Iterative design changes and computational fluid dynamic analysis were used to optimize the network prior to mold manufacturing. The vascular network mold was created using a new mold technique that achieves a 1:1 aspect ratio for all channels. In vitro blood flow testing confirmed the physiologic hemodynamics of the network as predicted by CFD analysis. These results indicate that this biomimetic liver vascular network design will provide a foundation for developing complex vascular networks for solid organ tissue engineering which achieve physiologic blood flow.

• 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.

• 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.

• 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.

• Tissue Engineering and Organ Structure: A Vascularized Approach to Liver and Lung.

  Authors: David Hoganson, Howard Pryor, Joseph Vacanti

  Pediatric research. 02/2008;

  Over the past two decades, great strides have been made in the field of tissue engineering. Many of the initial attempts to develop an engineered tissue construct were based on the concept of seedingOver the past two decades, great strides have been made in the field of tissue engineering. Many of the initial attempts to develop an engineered tissue construct were based on the concept of seeding cells onto an avascular scaffold. Using advanced manufacturing technologies, the creation of a pre-formed vascular scaffold has become a reality. This manuscript discusses some of the issues surrounding the development of such a vascular scaffold. We then examine of the challenges associated with applying this scaffold technology to two vital organ constructs: liver and lung.

• Consequences of cold-ischemia time on primary nonfunction and patient and graft survival in liver transplantation: a meta-analysis.

  Authors: James E Stahl, Jennifer E Kreke, Fawaz Ali Abdul Malek, Andrew J Schaefer, Joseph Vacanti

  PLoS ONE. 02/2008; 3(6):e2468.

  INTRODUCTION: The ability to preserve organs prior to transplant is essential to the organ allocation process. OBJECTIVE: The purpose of this study is to describe the functional relationship betweenINTRODUCTION: The ability to preserve organs prior to transplant is essential to the organ allocation process. OBJECTIVE: The purpose of this study is to describe the functional relationship between cold-ischemia time (CIT) and primary nonfunction (PNF), patient and graft survival in liver transplant. METHODS: To identify relevant articles Medline, EMBASE and the Cochrane database, including the non-English literature identified in these databases, was searched from 1966 to April 2008. Two independent reviewers screened and extracted the data. CIT was analyzed both as a continuous variable and stratified by clinically relevant intervals. Nondichotomous variables were weighted by sample size. Percent variables were weighted by the inverse of the binomial variance. RESULTS: Twenty-six studies met criteria. Functionally, PNF% = -6.678281+0.9134701*CIT Mean+0.1250879*(CIT Mean-9.89535)2-0.0067663*(CIT Mean-9.89535)3, r2 = .625, , p<.0001. Mean patient survival: 93% (1 month), 88% (3 months), 83% (6 months) and 83% (12 months). Mean graft survival: 85.9% (1 month), 80.5% (3 months), 78.1% (6 months) and 76.8% (12 months). Maximum patient and graft survival occurred with CITs between 7.5-12.5 hrs at each survival interval. PNF was also significantly correlated with ICU time, % first time grafts and % immunologic mismatches. CONCLUSION: The results of this work imply that CIT may be the most important pre-transplant information needed in the decision to accept an organ.

• Manufacture of porous polymer nerve conduits by a novel low-pressure injection molding process.

  Authors: Cathryn Sundback, Tessa Hadlock, Mack Cheney, Joseph Vacanti

  Biomaterials. 03/2003; 24(5):819-30.

  A method to fabricate porous, biodegradable conduits using a combined injection molding, thermally induced phase transition technique was developed which produced conduits with dimensionallyA method to fabricate porous, biodegradable conduits using a combined injection molding, thermally induced phase transition technique was developed which produced conduits with dimensionally toleranced, longitudinally aligned channels. The geometry of the channels was designed to approximate the architecture of peripheral nerves and to support the monolayer adherence of physiologically relevant numbers of Schwann cells. The channel configuration could be varied from a single 1.35 mm diameter channel up to 100 0.08 mm diameter channels. A conduit with 100 channels has approximately 12.5 times the lumenal surface area of a single channel conduit and supports the adherence of five times the number of Schwann cells in the native peripheral nerve. In this study, poly(DL-lactide-co-glycolide) (DL-PLGA) was dissolved in acetic acid and injected into a cold mold which induced solid-liquid phase separation and, ultimately, solidification of the polymer solution. The acetic acid was removed by sublimation and the resulting foam had a macrostructure of high anisotropy. Semi-permeable skins formed on the outer and lumen diameters of the conduit as a consequence of rapid quenching. Macropores were organized into bundles of channels, up to 20 microm wide, in the DL-PLGA matrix and represented remnants of acetic acid that crystallized during solidification.