Craig M Neville

Publications of Craig M Neville

• The retention of extracellular matrix proteins and angiogenic and mitogenic cytokines in a decellularized porcine dermis.

  Authors: David M Hoganson, Elisabeth M O'Doherty, Gwen E Owens, Dina O Harilal, Scott M Goldman, Chris M Bowley, Craig M Neville, Russell T Kronengold, Joseph P Vacanti

  Biomaterials. 09/2010; 31(26):6730-7.

  Decellularized dermis materials demonstrate considerable utility in surgical procedures including hernia repair and breast reconstruction. A new decellularized porcine dermis material has beenDecellularized dermis materials demonstrate considerable utility in surgical procedures including hernia repair and breast reconstruction. A new decellularized porcine dermis material has been developed that retains many native extracellular matrix (ECM) proteins and cytokines. This material has substantial mechanical strength with maximum tensile strength of 141.7 +/- 85.4 (N/cm) and suture pull through strength of 47.0 +/- 14.0 (N). After processing, many ECM proteins remained in the material including collagen III, collagen IV, collagen VII, laminin and fibronectin. Glycosaminoglycans, including hyaluronic acid, were also preserved. Among several cytokines whose levels were quantified, more vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-beta) were retained within this material than in comparable decellularized dermis materials. The retention of bioactivity was demonstrated in a cell culture assay. Because this decellularized porcine dermis material both retains significant strength and has substantial biological activity, it may promote rapid integration and repair in clinical applications.

• Preserved extracellular matrix components and retained biological activity in decellularized porcine mesothelium.

  Authors: David M Hoganson, Gwen E Owens, Elisabeth M O'Doherty, Chris M Bowley, Scott M Goldman, Dina O Harilal, Craig M Neville, Russell T Kronengold, Joseph P Vacanti

  Biomaterials. 09/2010; 31(27):6934-40.

  Mesothelium tissues such as peritoneum and pleura have a thin and strong layer of extracellular matrix that supports mesothelial cells capable of rapid healing. Decellularized porcine mesothelium wasMesothelium tissues such as peritoneum and pleura have a thin and strong layer of extracellular matrix that supports mesothelial cells capable of rapid healing. Decellularized porcine mesothelium was characterized for strength, composition of the matrix and biological activity. The tensile strength of the material was 40.65 +/- 21.65 N/cm. Extracellular matrix proteins collagen IV, fibronectin, and laminin as well as glycosaminoglycans were present in the material. Cytokines inherent in the extracellular matrix were preserved. Vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and transforming growth factor beta (TGF-beta) were retained and the levels of VEGF and TGF-beta in the decellularized mesothelium were higher than those found in decellularized small intestinal submucosa (SIS). The decellularized mesothelium also stimulated human fibroblasts to produce more VEGF than fibroblasts grown on tissue culture plastic. Decellularized mesothelium is a sheet material with a combination of strength and biological activity that may have many potential applications in surgical repair and regenerative medicine.

• 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.

• Neural precursor cell lines promote neurite branching.

  Authors: Craig M Neville, Albert Y Huang, Jeffrey Y Shyu, Evan Y Snyder, Tessa A Hadlock, Cathryn A Sundback

  The International journal of neuroscience. 02/2009; 119(1):15-39.

  Schwann cells and primary progenitor cells improve regeneration across peripheral nerve defects. This study examined the impact of immortalized neural precursor cells on regeneration of rat nerveSchwann cells and primary progenitor cells improve regeneration across peripheral nerve defects. This study examined the impact of immortalized neural precursor cells on regeneration of rat nerve defects. Across 10-mm gaps, neuromas formed without neural cables with C17.2- or RN33B-transplanted cells, but neural cables formed across 5-mm gaps seeded with RN33B cells. In vitro, dorsal root ganglia neurites elongated across Schwann and RN33B cells; RN33B cells induced neurite branching with shorter total outgrowth. Neural cable formation in vivo was likely determined by the balance of guidance and branch-inducing factors secreted by Schwann and transplanted precursor cells.

• 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.

• 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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• Normal female sexual development requires neuregulin-erbB receptor signaling in hypothalamic astrocytes.

  Authors: Vincent Prevot, Carlos Rio, Gyeong J Cho, Alejandro Lomniczi, Sabine Heger, Craig M Neville, Nadia A Rosenthal, Sergio R Ojeda, Gabriel Corfas

  The Journal of neuroscience : the official journal of the Society for Neuroscience. 02/2003; 23(1):230-9.

  The initiation of mammalian puberty requires the activation of hypothalamic neurons secreting the neuropeptide luteinizing hormone-releasing hormone (LHRH). It is thought that this activation isThe initiation of mammalian puberty requires the activation of hypothalamic neurons secreting the neuropeptide luteinizing hormone-releasing hormone (LHRH). It is thought that this activation is caused by changes in trans-synaptic input to LHRH neurons. More recently, it has been postulated that the pubertal increase in LHRH secretion in female animals also requires neuron-glia signaling mediated by growth factors of the epidermal growth factor (EGF) family and their astrocytic erbB receptors. Although it appears clear that functional astrocytic erbB1 receptors are necessary for the timely advent of puberty, the physiological contribution that erbB4 receptors may make to this process has not been established. To address this issue, we generated transgenic mice expressing a dominant-negative erbB4 receptor (DN-erbB4) under the control of the GFAP promoter, which targets transgene expression to astrocytes. DN-erbB4 expression is most abundant in hypothalamic astrocytes, where it blocks the ligand-dependent activation of glial erbB4 and erbB2 receptors, without affecting erbB1 (EGF) receptor signaling. Mice carrying the transgene exhibit delayed sexual maturation and a diminished reproductive capacity in early adulthood. These abnormalities are related to a deficiency in pituitary gonadotropin hormone secretion, caused by impaired release of LHRH, the hypothalamic neuropeptide that controls sexual development. In turn, the reduction in LHRH release is caused by the inability of hypothalamic astrocytes to respond to neuregulin (NRG) with production of prostaglandin E(2), which in wild-type animals mediates the stimulatory effect of astroglial erbB receptor activation on neuronal LHRH release. Thus, neuron-astroglia communication via NRG-erbB4/2 receptor signaling appears to be essential for the timely unfolding of the developmental program by which the brain controls mammalian sexual maturation.

• Preserved extracellular matrix components and retained biological activity in decellularized porcine mesothelium

  Authors: David M. Hoganson, Gwen E. Owens, Elisabeth M. O’Doherty, Chris M. Bowley, Scott M. Goldman, Dina O. Harilal, Craig M. Neville, Russell T. Kronengold, Joseph P. Vacanti

  Biomaterials.

  Mesothelium tissues such as peritoneum and pleura have a thin and strong layer of extracellular matrix that supports mesothelial cells capable of rapid healing. Decellularized porcine mesothelium wasMesothelium tissues such as peritoneum and pleura have a thin and strong layer of extracellular matrix that supports mesothelial cells capable of rapid healing. Decellularized porcine mesothelium was characterized for strength, composition of the matrix and biological activity. The tensile strength of the material was 40.65 ± 21.65 N/cm. Extracellular matrix proteins collagen IV, fibronectin, and laminin as well as glycosaminoglycans were present in the material. Cytokines inherent in the extracellular matrix were preserved. Vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and transforming growth factor β (TGF-β) were retained and the levels of VEGF and TGF-β in the decellularized mesothelium were higher than those found in decellularized small intestinal submucosa (SIS). The decellularized mesothelium also stimulated human fibroblasts to produce more VEGF than fibroblasts grown on tissue culture plastic. Decellularized mesothelium is a sheet material with a combination of strength and biological activity that may have many potential applications in surgical repair and regenerative medicine.