Patents by Inventor Khalil Bitar
Khalil Bitar has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 11311367Abstract: Methods are disclosed for forming tissue engineered, tubular gut-sphincter complexes from intestinal circular smooth muscle cells, sphincteric smooth muscle cells and enteric neural progenitor cells. The intestinal smooth muscle cells and neural progenitor cells can be seeded on a mold with a surface texture that induces longitudinal alignment of the intestinal smooth muscle cells and co-cultured until an innervated aligned smooth muscle sheet is obtained. The innervated smooth muscle sheet can then be wrapped around a tubular scaffold to form an intestinal tissue construct. Additionally, the sphincteric smooth muscle cells and additional enteric neural progenitor cells can be mixed in a biocompatiable gel solution, and the gel and admixed cells applied to a mold having a central post such that the sphinteric smooth muscle and neural progenitor cells can be cultured to form an innervated sphincter construct around the mold post.Type: GrantFiled: October 8, 2020Date of Patent: April 26, 2022Assignee: Wake Forest University Health SciencesInventor: Khalil Bitar
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Publication number: 20220016316Abstract: The present disclosure provides methods of bioengineering sphincters having autologous smooth muscle cells isolated from human internal anal sphincter and autologous enteric neurospheres (neural progenitor cells) isolated from human small intestine (jejunum). The isolated neural progenitor cells and smooth muscle cells are co -cultured using dual layered hydrogels and allowed to form circular, intrinsically innervated internal anal sphincter constructs. Such innervated internal anal sphincter constructs, bioengineered internal anal sphincter constructs are useful as additive implants in the treatment of fecal incontinence.Type: ApplicationFiled: November 14, 2019Publication date: January 20, 2022Inventor: Khalil BITAR
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Publication number: 20210137668Abstract: Methods are disclosed for forming tissue engineered, tubular gut-sphincter complexes from intestinal circular smooth muscle cells, sphincteric smooth muscle cells and enteric neural progenitor cells. The intestinal smooth muscle cells and neural progenitor cells can be seeded on a mold with a surface texture that induces longitudinal alignment of the intestinal smooth muscle cells and co-cultured until an innervated aligned smooth muscle sheet is obtained. The innervated smooth muscle sheet can then be wrapped around a tubular scaffold to form an intestinal tissue construct. Additionally, the sphincteric smooth muscle cells and additional enteric neural progenitor cells can be mixed in a biocompatiable gel solution, and the gel and admixed cells applied to a mold having a central post such that the sphinteric smooth muscle and neural progenitor cells can be cultured to form an innervated sphincter construct around the mold post.Type: ApplicationFiled: October 8, 2020Publication date: May 13, 2021Inventor: Khalil BITAR
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Patent number: 10828143Abstract: Methods are disclosed for forming tissue engineered, tubular bowel constructs from intestinal circular smooth muscle cells and enteric neural progenitor cells. The intestinal smooth muscle cells and neural progenitor cells can be seeded on a mold with a surface texture that induces longitudinal alignment of the intestinal smooth muscle cells and co-cultured until an innervated aligned smooth muscle sheet is obtained. The innervated smooth muscle sheet can then be wrapped around a tubular scaffold to form an intestinal tissue construct.Type: GrantFiled: November 9, 2017Date of Patent: November 10, 2020Assignee: Wake Forest University Health SciencesInventor: Khalil Bitar
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Publication number: 20200024572Abstract: Differentiation and stability of neural stem cells can be enhanced by in vitro or in vivo culturing with one or more extracellular matrix (ECM) compositions, such as collagen I, IV, laminin and/or a heparan sulfate proteoglycan. In one aspect of the invention, adult mammalian enteric neuronal progenitor cells can be induced to differentiate on various substrates derived from components or combinations of neural ECM compositions. Collagen I and IV supported neuronal differentiation and extensive glial differentiation individually and in combination. Addition of laminin or heparan sulfate to collagen substrates unexpectedly improved neuronal differentiation, increasing neuron number, branching of neuronal processes, and initiation of neuronal network formation. In another aspect, neuronal subtype differentiation was affected by varying ECM compositions in hydrogels overlaid on intestinal smooth muscle sheets.Type: ApplicationFiled: August 12, 2019Publication date: January 23, 2020Inventor: Khalil BITAR
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Patent number: 10377985Abstract: Differentiation and stability of neural stem cells can be enhanced by in vitro or in vivo culturing with one or more extracellular matrix (ECM) compositions, such as collagen I, IV, laminin and/or a heparan sulfate proteoglycan. In one aspect of the invention, adult mammalian enteric neuronal progenitor cells can be induced to differentiate on various substrates derived from components or combinations of neural ECM compositions. Collagen I and IV supported neuronal differentiation and extensive glial differentiation individually and in combination. Addition of laminin or heparan sulfate to collagen substrates unexpectedly improved neuronal differentiation, increasing neuron number, branching of neuronal processes, and initiation of neuronal network formation. In another aspect, neuronal subtype differentiation was affected by varying ECM compositions in hydrogels overlaid on intestinal smooth muscle sheets.Type: GrantFiled: January 19, 2018Date of Patent: August 13, 2019Assignee: WAKE FOREST UNIVERSITY HEALTH SCIENCESInventor: Khalil Bitar
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Publication number: 20190015190Abstract: Methods are disclosed for forming tissue engineered, tubular gut-sphincter complexes from intestinal circular smooth muscle cells, sphincteric smooth muscle cells and enteric neural progenitor cells. The intestinal smooth muscle cells and neural progenitor cells can be seeded on a mold with a surface texture that induces longitudinal alignment of the intestinal smooth muscle cells and co-cultured until an innervated aligned smooth muscle sheet is obtained. The innervated smooth muscle sheet can then be wrapped around a tubular scaffold to form an intestinal tissue construct. Additionally, the sphincteric smooth muscle cells and additional enteric neural progenitor cells can be mixed in a biocompatiable gel solution, and the gel and admixed cells applied to a mold having a central post such that the sphinteric smooth muscle and neural progenitor cells can be cultured to form an innervated sphincter construct around the mold post.Type: ApplicationFiled: December 28, 2016Publication date: January 17, 2019Inventor: Khalil BITAR
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Publication number: 20180256647Abstract: Methods of generating an innervated muscle structures are disclosed as well as bioengineered structures for tissue repair or regeneration. The methods can include the steps of obtaining populations of smooth muscle cells and neuronal progenitor cells and then seeding the cells together onto a matrix material, followed by culturing the seeded cells to form an innervated smooth muscle cell construct of directionally oriented smooth muscle cells. In one embodiment, the neuronal progenitor cells can be seeded first as neurospheres in a biocompatiable solution, e.g., a collagen/laminin solution, and allowed to gel. Next, a second suspension of smooth muscle cells can be deposited as separate layer. Multiple layer structures of alternating muscle or neuron composition can also be formed in this manner. Differentiation of the neuronal progenitor cells can be induced by exposure to a differentiation medium, such as Neurobasal A medium and/or exposure to a differentiating agent, such as B-27 supplement.Type: ApplicationFiled: May 10, 2018Publication date: September 13, 2018Inventor: Khalil Bitar
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Patent number: 9993505Abstract: Methods of generating an innervated muscle structures are disclosed as well as bioengineered structures for tissue repair or regeneration. The methods can include the steps of obtaining populations of smooth muscle cells and neuronal progenitor cells and then seeding the cells together onto a matrix material, followed by culturing the seeded cells to form an innervated smooth muscle cell construct of directionally oriented smooth muscle cells. In one embodiment, the neuronal progenitor cells can be seeded first as neurospheres in a biocompatible solution, e.g., a collagen/laminin solution, and allowed to gel. Next, a second suspension of smooth muscle cells can be deposited as separate layer. Multiple layer structures of alternating muscle or neuron composition can also be formed in this manner. Differentiation of the neuronal progenitor cells can be induced by exposure to a differentiation medium, such as Neurobasal A medium and/or exposure to a differentiating agent, such as B-27 supplement.Type: GrantFiled: January 31, 2013Date of Patent: June 12, 2018Assignee: Wake Forest University Health SciencesInventor: Khalil Bitar
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Publication number: 20180155684Abstract: Differentiation and stability of neural stem cells can be enhanced by in vitro or in vivo culturing with one or more extracellular matrix (ECM) compositions, such as collagen I, IV, laminin and/or a heparan sulfate proteoglycan. In one aspect of the invention, adult mammalian enteric neuronal progenitor cells can be induced to differentiate on various substrates derived from components or combinations of neural ECM compositions. Collagen I and IV supported neuronal differentiation and extensive glial differentiation individually and in combination. Addition of laminin or heparan sulfate to collagen substrates unexpectedly improved neuronal differentiation, increasing neuron number, branching of neuronal processes, and initiation of neuronal network formation. In another aspect, neuronal subtype differentiation was affected by varying ECM compositions in hydrogels overlaid on intestinal smooth muscle sheets.Type: ApplicationFiled: January 19, 2018Publication date: June 7, 2018Inventor: Khalil Bitar
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Publication number: 20180093016Abstract: Methods are disclosed for forming tissue engineered, tubular bowel constructs from intestinal circular smooth muscle cells and enteric neural progenitor cells. The intestinal smooth muscle cells and neural progenitor cells can be seeded on a mold with a surface texture that induces longitudinal alignment of the intestinal smooth muscle cells and co-cultured until an innervated aligned smooth muscle sheet is obtained. The innervated smooth muscle sheet can then be wrapped around a tubular scaffold to form an intestinal tissue construct.Type: ApplicationFiled: November 9, 2017Publication date: April 5, 2018Inventor: Khalil Bitar
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Patent number: 9896656Abstract: Differentiation and stability of neural stem cells can be enhanced by in vitro or in vivo culturing with one or more extracellular matrix (ECM) compositions, such as collagen I, IV, laminin and/or a heparan sulfate proteoglycan. In one aspect of the invention, adult mammalian enteric neuronal progenitor cells can be induced to differentiate on various substrates derived from components or combinations of neural ECM compositions. Collagen I and IV supported neuronal differentiation and extensive glial differentiation individually and in combination. Addition of laminin or heparan sulfate to collagen substrates unexpectedly improved neuronal differentiation, increasing neuron number, branching of neuronal processes, and initiation of neuronal network formation. In another aspect, neuronal subtype differentiation was affected by varying ECM compositions in hydrogels overlaid on intestinal smooth muscle sheets.Type: GrantFiled: March 17, 2014Date of Patent: February 20, 2018Assignee: Wake Forest University Health SciencesInventor: Khalil Bitar
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Patent number: 9862924Abstract: Differentiation and stability of neural stem cells can be enhanced by in vitro or in vivo culturing with one or more extracellular matrix (ECM) compositions, such as collagen I, IV, laminin and/or a heparan sulfate proteoglycan. In one aspect of the invention, adult mammalian enteric neuronal progenitor cells can be induced to differentiate on various substrates derived from components or combinations of neural ECM compositions. Collagen I and IV supported neuronal differentiation and extensive glial differentiation individually and in combination. Addition of laminin or heparan sulfate to collagen substrates unexpectedly improved neuronal differentiation, increasing neuron number, branching of neuronal processes, and initiation of neuronal network formation. In another aspect, neuronal subtype differentiation was affected by varying ECM compositions in hydrogels overlaid on intestinal smooth muscle sheets.Type: GrantFiled: March 17, 2014Date of Patent: January 9, 2018Assignee: Wake Forest University Health SciencesInventor: Khalil Bitar
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Patent number: 9675646Abstract: Methods of generating tubular, bioengineered, smooth muscle structures are disclosed as well as bioengineered tissue for tubular organ repair or replacement. The methods can include the steps of obtaining smooth muscle cells; culturing the muscle cells to form a smooth muscle cell construct of directionally oriented smooth muscle cells; disposing the smooth muscle cell construct around a tubular scaffold; and culturing construct and scaffold in a growth media until a smooth muscle cell structure is achieved. The step of obtain smooth muscle cells can further include obtaining autologous smooth muscle cells from a subject. In one preferred embodiment, the muscle cells can first be on a fibrin substrate to form a muscle construct, which is then disposed around a tubular scaffold, for example, a chitosan scaffold. The methods of the present invention can further include connecting two or more tubular structures together to form an elongate composite structure.Type: GrantFiled: January 31, 2013Date of Patent: June 13, 2017Assignee: Wake Forest University Health SciencesInventor: Khalil Bitar
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Publication number: 20160017285Abstract: Differentiation and stability of neural stem cells can be enhanced by in vitro or in vivo culturing with one or more extracellular matrix (ECM) compositions, such as collagen I, IV, laminin and/or a heparan sulfate proteoglycan. In one aspect of the invention, adult mammalian enteric neuronal progenitor cells can be induced to differentiate on various substrates derived from components or combinations of neural ECM compositions. Collagen I and IV supported neuronal differentiation and extensive glial differentiation individually and in combination. Addition of laminin or heparan sulfate to collagen substrates unexpectedly improved neuronal differentiation, increasing neuron number, branching of neuronal processes, and initiation of neuronal network formation. In another aspect, neuronal subtype differentiation was affected by varying ECM compositions in hydrogels overlaid on intestinal smooth muscle sheets.Type: ApplicationFiled: March 17, 2014Publication date: January 21, 2016Inventor: Khalil Bitar
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Publication number: 20140379083Abstract: Methods of generating tubular, bioengineered, smooth muscle structures are disclosed as well as bioengineered tissue for tubular organ repair or replacement. The methods can include the steps of obtaining smooth muscle cells; culturing the muscle cells to form a smooth muscle cell construct of directionally oriented smooth muscle cells; disposing the smooth muscle cell construct around a tubular scaffold; and culturing construct and scaffold in a growth media until a smooth muscle cell structure is achieved. The step of obtain smooth muscle cells can further include obtaining autologous smooth muscle cells from a subject. In one preferred embodiment, the muscle cells can first be on a fibrin substrate to form a muscle construct, which is then disposed around a tubular scaffold, for example, a chitosan scaffold. The methods of the present invention can further include connecting two or more tubular structures together to form an elongate composite structure.Type: ApplicationFiled: January 31, 2013Publication date: December 25, 2014Applicant: WAKE FOREST UNIVERSITY HEALTH SCIENCESInventor: Khalil Bitar
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Publication number: 20140377232Abstract: Methods of generating an innervated muscle structures are disclosed as well as bioengineered structures for tissue repair or regeneration. The methods can include the steps of obtaining populations of smooth muscle cells and neuronal progenitor cells and then seeding the cells together onto a matrix material, followed by culturing the seeded cells to form an innervated smooth muscle cell construct of directionally oriented smooth muscle cells. In one embodiment, the neuronal progenitor cells can be seeded first as neurospheres in a biocompatible solution, e.g., a collagen/laminin solution, and allowed to gel. Next, a second suspension of smooth muscle cells can be deposited as separate layer. Multiple layer structures of alternating muscle or neuron composition can also be formed in this manner. Differentiation of the neuronal progenitor cells can be induced by exposure to a differentiation medium, such as Neurobasal A medium and/or exposure to a differentiating agent, such as B-27 supplement.Type: ApplicationFiled: January 31, 2013Publication date: December 25, 2014Applicant: WAKE FOREST UNIVERSITY HEALTH SCIENCESInventor: Khalil Bitar
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Publication number: 20140271905Abstract: Differentiation and stability of neural stem cells can be enhanced by in vitro or in vivo culturing with one or more extracellular matrix (ECM) compositions, such as collagen I, IV, laminin and/or a heparan sulfate proteoglycan. In one aspect of the invention, adult mammalian enteric neuronal progenitor cells can be induced to differentiate on various substrates derived from components or combinations of neural ECM compositions. Collagen I and IV supported neuronal differentiation and extensive glial differentiation individually and in combination. Addition of laminin or heparan sulfate to collagen substrates unexpectedly improved neuronal differentiation, increasing neuron number, branching of neuronal processes, and initiation of neuronal network formation. In another aspect, neuronal subtype differentiation was affected by varying ECM compositions in hydrogels overlaid on intestinal smooth muscle sheets.Type: ApplicationFiled: March 17, 2014Publication date: September 18, 2014Applicant: Wake Forest University Health SciencesInventor: Khalil Bitar
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Publication number: 20060134076Abstract: This invention relates to a three dimensional bioengineered sphincter such as a bioengineered internal anal sphincter (IAS) and three-dimensional physiological models of smooth muscle cells. The invention also related to methods for generating a bioengineered sphincter and smooth muscle rings in culture. In addition, the invention provides for methods of using a bioengineered sphincter or bioengineered smooth muscle ring to identify agents that modify contractile force and relaxation in smooth muscle cells.Type: ApplicationFiled: November 23, 2005Publication date: June 22, 2006Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGANInventors: Khalil Bitar, Louise Hecker, Keith Baar, Sita Somara