J. Taboas | University of Pittsburgh (original) (raw)
Papers by J. Taboas
![Research paper thumbnail of Erratum to “Update in cartilage bio-engineering” [Joint Bone Spine 77 (2010) 283–6]](https://attachments.academia-assets.com/86892549/thumbnails/1.jpg)
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Revue du Rhumatisme, 2010
Orthodontics and Craniofacial Research, 2005
Objective-To develop an integrated approach for engineering craniofacial scaffolds and to demonst... more Objective-To develop an integrated approach for engineering craniofacial scaffolds and to demonstrate that these engineered scaffolds would have mechanical properties in the range of craniofacial tissue and support bone regeneration for craniofacial reconstruction. Experimental Variable-Scaffold architecture designed to achieve desired elasticity and permeability. Scaffold external shape designed to match craniofacial anatomy. Outcome Measure-Final fabricated biomaterial scaffolds. Compressive mechanical modulus and strength. Bone regeneration as measured by micro-CT scanning, mechanical testing and histology.
Orthodontics and Craniofacial Research, 2005
Biomaterials, 2003
Precise control over scaffold material, porosity, and internal pore architecture is essential for... more Precise control over scaffold material, porosity, and internal pore architecture is essential for tissue engineering. By coupling solid free form (SFF) manufacturing with conventional sponge scaffold fabrication procedures, we have developed methods for casting scaffolds that contain designed and controlled locally porous and globally porous internal architectures. These methods are compatible with numerous bioresorbable and non-resorbable polymers, ceramics, and biologic materials. Phase separation, emulsion-solvent diffusion, and porogen leaching were used to create poly(l)lactide (PLA) scaffolds containing both computationally designed global pores (500, 600, or 800 mm wide channels) and solvent fashioned local pores (50-100 mm wide voids or 5-10 mm length plates). Globally porous PLA and polyglycolide/PLA discrete composites were made using melt processing. Biphasic scaffolds with mechanically interdigitated PLA and sintered hydroxyapatite regions were fabricated with 500 and 600 mm wide global pores. PLA scaffolds with complex internal architectures that mimicked human trabecular bone were produced. Our indirect fabrication using casting in SFF molds provided enhanced control over scaffold shape, material, porosity and pore architecture, including size, geometry, orientation, branching, and interconnectivity. These scaffolds that contain concurrent local and global pores, discrete material regions, and biomimetic internal architectures may prove valuable for multi-tissue and structural tissue interface engineering.
Biomaterials, 2002
Bone tissue engineering scaffolds must shape regenerating tissue, provide temporary mechanical su... more Bone tissue engineering scaffolds must shape regenerating tissue, provide temporary mechanical support and enhance tissue regeneration. These requirements result in conflicting design goals. For example, increased temporary mechanical function requires a dense scaffold while enhanced cell/gene delivery requires a porous scaffold. This paper demonstrates an image-based homogenization optimization approach that can design scaffold microstructure, scaffold material and regenerate tissue microstructure to meet conflicting design requirements. In addition, constraints to ensure adequate cell/gene delivery can be introduced using a minimum porosity threshold. Homogenization theory was used to compute relationships between scaffold microstructure and effective stiffness. The functional relationships were used in the MATLAB optimization toolbox to compute optimal pore dimensions and scaffold material such that the scaffold and regenerate tissue effective stiffness matched that of native bone stiffness. The scaffold design was converted into STL format for solid free-form fabrication. Scaffolds were designed that matched mandibular condyle trabecular bone properties. Results showed excellent agreement between native bone properties and designed scaffold properties (all R2 > 0.89). Finally, example scaffolds were built from hydroxyapatite using a SFF casting technique.
Acta Biomaterialia, 2011
When culturing cells on flexible surfaces, it is important to consider extracellular matrix treat... more When culturing cells on flexible surfaces, it is important to consider extracellular matrix treatments that will remain on the surface under mechanical strain. Here we investigate differences in laminin deposited on oxidized polydimethylsiloxane (PDMS) with plasma treatment (plasma-only) vs. plasma and aminopropyltrimethoxysilane treatment (silane-linked). We use specular X-ray reflectivity (SXR), transmission electron microscopy (TEM), and immunofluorescence to probe the quantity and uniformity of laminin. The surface coverage of laminin is approximately 45% for the plasma-only and 50% for the silane-linked treatment as determined by SXR. TEM and immunofluorescence reveal additional islands of laminin aggregates on the plasma-only PDMS compared with the relatively smooth and uniform silane-linked laminin surface. We also examine laminin retention under strain and vascular smooth muscle cell viability and proliferation under static and strain conditions. Equibiaxial stretching of the PDMS surfaces shows greatly improved retention of the silane-linked laminin over plasma-only. There are significantly more cells on the silane-linked surface after 4 days of equibiaxial strain.
Annals of Biomedical Engineering
Molecular & Cellular Biomechanics
2009 IEEE 35th Annual Northeast Bioengineering Conference, 2009
We are interested in engineering cartilage that is resistant to arthritic disease. We hypothesize... more We are interested in engineering cartilage that is resistant to arthritic disease. We hypothesized that suppression of terminal differentiation pathways would lead to decreased chondrocyte catabolic response to inflammatory cytokines and used a Bcl-2 over-expression gene therapy approach targeting chondrocyte apoptosis. Retrovirally transduced chondrocytes were cultured in 1.25% alginate hydrogels and subjected to interleukin 1beta (IL-1beta) stimulation (5 ng/ml) over
Osteoarthritis and Cartilage, 2011
Objective-Cell-based tissue engineering strategies are currently in clinical use and continue to ... more Objective-Cell-based tissue engineering strategies are currently in clinical use and continue to be developed at a rapid pace for the repair of cartilage defects. Regardless of the repair methodology, chondrocytes within newly regenerated cartilage remain susceptible to the abnormal inflammatory and mechanical environments that underlie osteoarthritic disease, likely compromising the implant's integration, function, and longevity. The present study investigates the use of parathyroid hormone-related peptide (PTHrP) overexpression for chondroprotection. Design-Bovine articular chondrocytes were transfected with human PTHrP (hPTHrP) constructs (1-141 or 1-173) and subjected to injurious cyclic tensile strain (CTS; 0.5 Hz and 16% elongation) for 48 hours. mRNA expression of matrix remodeling, inflammatory signaling, hypertrophic, and apoptotic genes were examined with real-time reverse transcription polymerase chain reaction. Nitric oxide (NO) and prostaglandin E 2 (PGE 2) production were measured using the Griess assay and enzyme immunoassay, respectively. Results-CTS induced an arthritic phenotype in articular chondrocytes as indicated by increased gene expression of collagenases and aggrecanases and increased production of NO and PGE 2. Additionally, CTS increased collagen type X (Col10a1) mRNA expression, whereas overexpression of either hPTHrP isoform inhibited CTS-induced Col10a1 gene expression. However, hPTHrP 1-141 augmented CTS-induced NO and PGE 2 production, and neither hPTHrP isoform had any significant effect on apoptotic genes.
Osteoarthritis and Cartilage, 2011
Objective-Cell-based tissue engineering strategies are currently in clinical use and continue to ... more Objective-Cell-based tissue engineering strategies are currently in clinical use and continue to be developed at a rapid pace for the repair of cartilage defects. Regardless of the repair methodology, chondrocytes within newly regenerated cartilage remain susceptible to the abnormal inflammatory and mechanical environments that underlie osteoarthritic disease, likely compromising the implant's integration, function, and longevity. The present study investigates the use of parathyroid hormone-related peptide (PTHrP) overexpression for chondroprotection. Design-Bovine articular chondrocytes were transfected with human PTHrP (hPTHrP) constructs (1-141 or 1-173) and subjected to injurious cyclic tensile strain (CTS; 0.5 Hz and 16% elongation) for 48 hours. mRNA expression of matrix remodeling, inflammatory signaling, hypertrophic, and apoptotic genes were examined with real-time reverse transcription polymerase chain reaction. Nitric oxide (NO) and prostaglandin E 2 (PGE 2) production were measured using the Griess assay and enzyme immunoassay, respectively. Results-CTS induced an arthritic phenotype in articular chondrocytes as indicated by increased gene expression of collagenases and aggrecanases and increased production of NO and PGE 2. Additionally, CTS increased collagen type X (Col10a1) mRNA expression, whereas overexpression of either hPTHrP isoform inhibited CTS-induced Col10a1 gene expression. However, hPTHrP 1-141 augmented CTS-induced NO and PGE 2 production, and neither hPTHrP isoform had any significant effect on apoptotic genes.
Revue Du Rhumatisme, 2010
![Research paper thumbnail of Erratum to “Update in cartilage bio-engineering” [Joint Bone Spine 77 (2010) 283–6]](https://attachments.academia-assets.com/44109325/thumbnails/1.jpg)
](
Matrix Biology, 2012
Leiomyoma are common tumors arising within the uterus that feature excessive deposition of a stif... more Leiomyoma are common tumors arising within the uterus that feature excessive deposition of a stiff, disordered extracellular matrix (ECM). Mechanical stress is a critical determinant of excessive ECM deposition and increased mechanical stress has been shown to be involved in tumorigenesis. Here we tested the viscoelastic properties of leiomyoma and characterized dynamic and static mechanical signaling in leiomyoma cells using three approaches, including measurement of active RhoA. We found that the peak strain and pseudo-dynamic modulus of leiomyoma tissue was significantly increased relative to matched myometrium. In addition, leiomyoma cells demonstrated an attenuated response to applied cyclic uniaxial strain and to variation in substrate stiffness, relative to myometrial cells. However, on a flexible pronectin-coated silicone substrate, basal levels and lysophosphatidic acid-stimulated levels of activated RhoA were similar between leiomyoma and myometrial cells. In contrast, leiomyoma cells plated on a rigid polystyrene substrate had elevated levels of active RhoA, compared to myometrial cells. The results indicate that viscoelastic properties of the ECM of leiomyoma contribute significantly to the tumor's inherent stiffness and that leiomyoma cells have an attenuated sensitivity to mechanical cues. The findings suggest there may be a fundamental alteration in the communication between the external mechanical environment (extracellular forces) and reorganization of the actin cytoskeleton mediated by RhoA in leiomyoma cells. Additional research will be needed to elucidate the mechanism(s) responsible for the attenuated mechanical signaling in leiomyoma cells.
Fertility and Sterility, 2009
OBJECTIVE: Leiomyoma cells reside in an extracellular matrix (ECM) of increased mechanical stress... more OBJECTIVE: Leiomyoma cells reside in an extracellular matrix (ECM) of increased mechanical stress that they create (Rogers et al. 2008), although it is unclear why this transformation occurs. Normal cells respond to increased mechanical stress with activation of Rho signaling, which leads to re-organization of the cell cytoskeleton. Here we tested whether leiomyoma cells appropriately sense ambient mechanical cues.
Revue du Rhumatisme, 2010
Orthodontics and Craniofacial Research, 2005
Objective-To develop an integrated approach for engineering craniofacial scaffolds and to demonst... more Objective-To develop an integrated approach for engineering craniofacial scaffolds and to demonstrate that these engineered scaffolds would have mechanical properties in the range of craniofacial tissue and support bone regeneration for craniofacial reconstruction. Experimental Variable-Scaffold architecture designed to achieve desired elasticity and permeability. Scaffold external shape designed to match craniofacial anatomy. Outcome Measure-Final fabricated biomaterial scaffolds. Compressive mechanical modulus and strength. Bone regeneration as measured by micro-CT scanning, mechanical testing and histology.
Orthodontics and Craniofacial Research, 2005
Biomaterials, 2003
Precise control over scaffold material, porosity, and internal pore architecture is essential for... more Precise control over scaffold material, porosity, and internal pore architecture is essential for tissue engineering. By coupling solid free form (SFF) manufacturing with conventional sponge scaffold fabrication procedures, we have developed methods for casting scaffolds that contain designed and controlled locally porous and globally porous internal architectures. These methods are compatible with numerous bioresorbable and non-resorbable polymers, ceramics, and biologic materials. Phase separation, emulsion-solvent diffusion, and porogen leaching were used to create poly(l)lactide (PLA) scaffolds containing both computationally designed global pores (500, 600, or 800 mm wide channels) and solvent fashioned local pores (50-100 mm wide voids or 5-10 mm length plates). Globally porous PLA and polyglycolide/PLA discrete composites were made using melt processing. Biphasic scaffolds with mechanically interdigitated PLA and sintered hydroxyapatite regions were fabricated with 500 and 600 mm wide global pores. PLA scaffolds with complex internal architectures that mimicked human trabecular bone were produced. Our indirect fabrication using casting in SFF molds provided enhanced control over scaffold shape, material, porosity and pore architecture, including size, geometry, orientation, branching, and interconnectivity. These scaffolds that contain concurrent local and global pores, discrete material regions, and biomimetic internal architectures may prove valuable for multi-tissue and structural tissue interface engineering.
Biomaterials, 2002
Bone tissue engineering scaffolds must shape regenerating tissue, provide temporary mechanical su... more Bone tissue engineering scaffolds must shape regenerating tissue, provide temporary mechanical support and enhance tissue regeneration. These requirements result in conflicting design goals. For example, increased temporary mechanical function requires a dense scaffold while enhanced cell/gene delivery requires a porous scaffold. This paper demonstrates an image-based homogenization optimization approach that can design scaffold microstructure, scaffold material and regenerate tissue microstructure to meet conflicting design requirements. In addition, constraints to ensure adequate cell/gene delivery can be introduced using a minimum porosity threshold. Homogenization theory was used to compute relationships between scaffold microstructure and effective stiffness. The functional relationships were used in the MATLAB optimization toolbox to compute optimal pore dimensions and scaffold material such that the scaffold and regenerate tissue effective stiffness matched that of native bone stiffness. The scaffold design was converted into STL format for solid free-form fabrication. Scaffolds were designed that matched mandibular condyle trabecular bone properties. Results showed excellent agreement between native bone properties and designed scaffold properties (all R2 > 0.89). Finally, example scaffolds were built from hydroxyapatite using a SFF casting technique.
Acta Biomaterialia, 2011
When culturing cells on flexible surfaces, it is important to consider extracellular matrix treat... more When culturing cells on flexible surfaces, it is important to consider extracellular matrix treatments that will remain on the surface under mechanical strain. Here we investigate differences in laminin deposited on oxidized polydimethylsiloxane (PDMS) with plasma treatment (plasma-only) vs. plasma and aminopropyltrimethoxysilane treatment (silane-linked). We use specular X-ray reflectivity (SXR), transmission electron microscopy (TEM), and immunofluorescence to probe the quantity and uniformity of laminin. The surface coverage of laminin is approximately 45% for the plasma-only and 50% for the silane-linked treatment as determined by SXR. TEM and immunofluorescence reveal additional islands of laminin aggregates on the plasma-only PDMS compared with the relatively smooth and uniform silane-linked laminin surface. We also examine laminin retention under strain and vascular smooth muscle cell viability and proliferation under static and strain conditions. Equibiaxial stretching of the PDMS surfaces shows greatly improved retention of the silane-linked laminin over plasma-only. There are significantly more cells on the silane-linked surface after 4 days of equibiaxial strain.
Annals of Biomedical Engineering
Molecular & Cellular Biomechanics
2009 IEEE 35th Annual Northeast Bioengineering Conference, 2009
We are interested in engineering cartilage that is resistant to arthritic disease. We hypothesize... more We are interested in engineering cartilage that is resistant to arthritic disease. We hypothesized that suppression of terminal differentiation pathways would lead to decreased chondrocyte catabolic response to inflammatory cytokines and used a Bcl-2 over-expression gene therapy approach targeting chondrocyte apoptosis. Retrovirally transduced chondrocytes were cultured in 1.25% alginate hydrogels and subjected to interleukin 1beta (IL-1beta) stimulation (5 ng/ml) over
Osteoarthritis and Cartilage, 2011
Objective-Cell-based tissue engineering strategies are currently in clinical use and continue to ... more Objective-Cell-based tissue engineering strategies are currently in clinical use and continue to be developed at a rapid pace for the repair of cartilage defects. Regardless of the repair methodology, chondrocytes within newly regenerated cartilage remain susceptible to the abnormal inflammatory and mechanical environments that underlie osteoarthritic disease, likely compromising the implant's integration, function, and longevity. The present study investigates the use of parathyroid hormone-related peptide (PTHrP) overexpression for chondroprotection. Design-Bovine articular chondrocytes were transfected with human PTHrP (hPTHrP) constructs (1-141 or 1-173) and subjected to injurious cyclic tensile strain (CTS; 0.5 Hz and 16% elongation) for 48 hours. mRNA expression of matrix remodeling, inflammatory signaling, hypertrophic, and apoptotic genes were examined with real-time reverse transcription polymerase chain reaction. Nitric oxide (NO) and prostaglandin E 2 (PGE 2) production were measured using the Griess assay and enzyme immunoassay, respectively. Results-CTS induced an arthritic phenotype in articular chondrocytes as indicated by increased gene expression of collagenases and aggrecanases and increased production of NO and PGE 2. Additionally, CTS increased collagen type X (Col10a1) mRNA expression, whereas overexpression of either hPTHrP isoform inhibited CTS-induced Col10a1 gene expression. However, hPTHrP 1-141 augmented CTS-induced NO and PGE 2 production, and neither hPTHrP isoform had any significant effect on apoptotic genes.
Osteoarthritis and Cartilage, 2011
Objective-Cell-based tissue engineering strategies are currently in clinical use and continue to ... more Objective-Cell-based tissue engineering strategies are currently in clinical use and continue to be developed at a rapid pace for the repair of cartilage defects. Regardless of the repair methodology, chondrocytes within newly regenerated cartilage remain susceptible to the abnormal inflammatory and mechanical environments that underlie osteoarthritic disease, likely compromising the implant's integration, function, and longevity. The present study investigates the use of parathyroid hormone-related peptide (PTHrP) overexpression for chondroprotection. Design-Bovine articular chondrocytes were transfected with human PTHrP (hPTHrP) constructs (1-141 or 1-173) and subjected to injurious cyclic tensile strain (CTS; 0.5 Hz and 16% elongation) for 48 hours. mRNA expression of matrix remodeling, inflammatory signaling, hypertrophic, and apoptotic genes were examined with real-time reverse transcription polymerase chain reaction. Nitric oxide (NO) and prostaglandin E 2 (PGE 2) production were measured using the Griess assay and enzyme immunoassay, respectively. Results-CTS induced an arthritic phenotype in articular chondrocytes as indicated by increased gene expression of collagenases and aggrecanases and increased production of NO and PGE 2. Additionally, CTS increased collagen type X (Col10a1) mRNA expression, whereas overexpression of either hPTHrP isoform inhibited CTS-induced Col10a1 gene expression. However, hPTHrP 1-141 augmented CTS-induced NO and PGE 2 production, and neither hPTHrP isoform had any significant effect on apoptotic genes.
Revue Du Rhumatisme, 2010
Matrix Biology, 2012
Leiomyoma are common tumors arising within the uterus that feature excessive deposition of a stif... more Leiomyoma are common tumors arising within the uterus that feature excessive deposition of a stiff, disordered extracellular matrix (ECM). Mechanical stress is a critical determinant of excessive ECM deposition and increased mechanical stress has been shown to be involved in tumorigenesis. Here we tested the viscoelastic properties of leiomyoma and characterized dynamic and static mechanical signaling in leiomyoma cells using three approaches, including measurement of active RhoA. We found that the peak strain and pseudo-dynamic modulus of leiomyoma tissue was significantly increased relative to matched myometrium. In addition, leiomyoma cells demonstrated an attenuated response to applied cyclic uniaxial strain and to variation in substrate stiffness, relative to myometrial cells. However, on a flexible pronectin-coated silicone substrate, basal levels and lysophosphatidic acid-stimulated levels of activated RhoA were similar between leiomyoma and myometrial cells. In contrast, leiomyoma cells plated on a rigid polystyrene substrate had elevated levels of active RhoA, compared to myometrial cells. The results indicate that viscoelastic properties of the ECM of leiomyoma contribute significantly to the tumor's inherent stiffness and that leiomyoma cells have an attenuated sensitivity to mechanical cues. The findings suggest there may be a fundamental alteration in the communication between the external mechanical environment (extracellular forces) and reorganization of the actin cytoskeleton mediated by RhoA in leiomyoma cells. Additional research will be needed to elucidate the mechanism(s) responsible for the attenuated mechanical signaling in leiomyoma cells.
Fertility and Sterility, 2009
OBJECTIVE: Leiomyoma cells reside in an extracellular matrix (ECM) of increased mechanical stress... more OBJECTIVE: Leiomyoma cells reside in an extracellular matrix (ECM) of increased mechanical stress that they create (Rogers et al. 2008), although it is unclear why this transformation occurs. Normal cells respond to increased mechanical stress with activation of Rho signaling, which leads to re-organization of the cell cytoskeleton. Here we tested whether leiomyoma cells appropriately sense ambient mechanical cues.