Osteogenic Differentiation of Pre-Osteoblasts on Biomimetic Tyrosine-Derived Polycarbonate Scaffolds

Kim, Jinku; Magno, Maria Hanshella R.; Álvarez, Pedro; Darr, Adnan; Kohn, Joachim; Hollinger, Jeffrey O.

doi:10.1021/bm200700d

Cited by 34 publications

(36 citation statements)

References 27 publications

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“…A possible explanation for the performance superiority of TyrPC-based scaffolds may be attributable to chemical and physical properties that promoted cell attachment, amplification and differentiation to an osteogenic phenotype, and degradation in register with bone regeneration, thus improving regenerative outcome with a 50 mg dose versus traditional rhBMP-2 dosing that are five times greater. 8 The minimal dose of rhBMP-2 supplementation of TyrPC scaffolds significantly enhanced bone formation. There is a profound patient benefit when a delivery system (i.e., bone biomimetic substitute) provides a physiological, calibrated dose of rhBMP-2.…”

Section: Discussionmentioning

confidence: 94%

“…By combining these three monomers, the resulting terpolymers can provide precise control of physical, chemical, biomechanical, and biological properties requisite for bone regeneration. 7,8 Polymers in combination with calcium phosphates (CPs) have been used as grafts for bone repair to improve bonescaffold integration, to enhance bone regeneration by promoting the deposition of hydroxyapatite in vivo, and to enhance adhesion and differentiation of osteoprogenitor cells. [9][10][11][12] CPs have been coated on the polymer surface or have been prepared as polymer-CP composites.…”

Section: Introductionmentioning

confidence: 99%

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Bone Regeneration in a Rabbit Critical-Sized Calvarial Model Using Tyrosine-Derived Polycarbonate Scaffolds

Kim

Magno

Waters

et al. 2012

Tissue Engineering Part A

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Porous three-dimensional tyrosine-derived polycarbonate (TyrPC) scaffolds with a bimodal pore distribution were fabricated to mimic bone architecture using a combination of salt-leaching and phase separation techniques. TyrPC scaffolds degraded in register with bone regeneration during the 6-week study period and compressive moduli of the scaffolds were maintained >0.5 MPa at 6 weeks of incubation in PBS at 37 °C. The TyrPC scaffolds either unsupplemented or supplemented with recombinant human bone morphogenetic protein-2 (rhBMP-2) were implanted in a rabbit calvarial critical-sized defect (CSD) model and the TyrPC scaffolds treated with rhBMP-2 or TyrPC coated with calcium phosphate scaffold alone promoted bone regeneration in a rabbit calvarial CSD at 6 weeks postimplantation. A synthetic TyrPC polymeric scaffold either without a biological supplement or with a minimal dose of rhBMP-2 induced bone regeneration comparable to a commercially available bone graft substitute in a nonrodent CSD animal model.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Bone Regeneration in a Rabbit Critical-Sized Calvarial Model Using Tyrosine-Derived Polycarbonate Scaffolds

Kim

Magno

Waters

et al. 2012

Tissue Engineering Part A

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“…Several publications describe the development of a scaffold composition and architecture that promotes bone regeneration [12–14]. These scaffolds are composed of a specific polymer composition (E1001(1k)), selected from a large library of tyrosine-derived polycarbonates.…”

Section: Resultsmentioning

confidence: 99%

“…Cylindrical scaffolds (8 mm diameter by 2 mm in height) were fabricated from a tyrosine-derived polycarbonate designated as E1001(1k) using a combination of lyophilization and particulate leaching and characterized as described previously [12–14]. This particular polymer composition was selected from a large library of tyrosine-derived polycarbonates and was used to create bone regeneration scaffolds with both macro- and micropores having a size 212–450 mm and < 20 mm, respectively, and a compressive modulus of 2 MPa [14].…”

Section: Methodsmentioning

confidence: 99%

Profiling stem cell states in three-dimensional biomaterial niches using high content image informatics

et al. 2016

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A predictive framework for the evolution of stem cell biology in 3-D is currently lacking. In this study we propose deep image informatics of the nuclear biology of stem cells to elucidate how 3-D biomaterials steer stem cell lineage phenotypes. The approach is based on high content imaging informatics to capture minute variations in the 3-D spatial organization of splicing factor SC-35 in the nucleoplasm as a marker to classify emergent cell phenotypes of human mesenchymal stem cells (hMSCs). The cells were cultured in varied 3-D culture systems including hydrogels, electrospun mats and salt leached scaffolds. The approach encompasses high resolution 3-D imaging of SC-35 domains and high content image analysis (HCIA) to compute quantitative 3-D nuclear metrics for SC-35 organization in single cells in concert with machine learning approaches to construct a predictive cell-state classification model. Our findings indicate that hMSCs cultured in collagen hydrogels and induced to differentiate into osteogenic or adipogenic lineages could be classified into the three lineages (stem, adipogenic, osteogenic) with ≥ 80% precision and sensitivity, within 72 hours. Using this framework, the augmentation of osteogenesis by scaffold design exerted by porogen leached scaffolds was also profiled within 72 hours with ~80% high sensitivity. Furthermore, by employing 3-D SC-35 organizational metrics, differential osteogenesis induced by novel electrospun fibrous polymer mats incorporating decellularized matrix could also be elucidated and predictably modeled at just 3 days with high precision. We demonstrate that 3-D SC-35 organizational metrics can be applied to model the stem cell state in 3-D scaffolds. We propose that this methodology can robustly discern minute changes in stem cell states within complex 3-D architectures and map single cell biological readouts that are critical to assessing population level cell heterogeneity.

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“…In order to demonstrate the feasibility of this approach, blends of two degradable tyrosine polycarbonates, poly(desaminotyrosyl-tyrosine ethyl ester carbonate) (pDTEc) and poly(desaminotyrosyl-tyrosine octyl ester carbonate) (pDTOc), were used to fabricate gas-foamed scaffold libraries. Tyrosine polycarbonates are being advanced for use in implantable biomedical devices such as hernia repair meshes, cardiovascular stents and bone tissue engineering scaffolds [25,26]. pDTEc and pDTOc have the same backbone but different side chains (Figure 2).…”

Section: Introductionmentioning

confidence: 99%

Gas-Foamed Scaffold Gradients for Combinatorial Screening in 3D

Chatterjee

Kraigsley

Bolikal

et al. 2012

JFB

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Current methods for screening cell-material interactions typically utilize a two-dimensional (2D) culture format where cells are cultured on flat surfaces. However, there is a need for combinatorial and high-throughput screening methods to systematically screen cell-biomaterial interactions in three-dimensional (3D) tissue scaffolds for tissue engineering. Previously, we developed a two-syringe pump approach for making 3D scaffold gradients for use in combinatorial screening of salt-leached scaffolds. Herein, we demonstrate that the two-syringe pump approach can also be used to create scaffold gradients using a gas-foaming approach. Macroporous foams prepared by a gas-foaming technique are commonly used for fabrication of tissue engineering scaffolds due to their high interconnectivity and good mechanical properties. Gas-foamed scaffold gradient libraries were fabricated from two biodegradable tyrosine-derived polycarbonates: poly(desaminotyrosyl-tyrosine ethyl ester carbonate) (pDTEc) and poly(desaminotyrosyl-tyrosine octyl ester carbonate) (pDTOc). The composition of the libraries was assessed with Fourier transform infrared spectroscopy (FTIR) and showed that pDTEc/pDTOc gas-foamed scaffold gradients could be repeatably fabricated. Scanning electron microscopy showed that scaffold morphology was similar between the pDTEc-rich ends and the pDTOc-rich ends of the gradient. These results introduce a method for fabricating gas-foamed polymer scaffold gradients that can be used for combinatorial screening of cell-material interactions in 3D.

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Osteogenic Differentiation of Pre-Osteoblasts on Biomimetic Tyrosine-Derived Polycarbonate Scaffolds

Cited by 34 publications

References 27 publications

Bone Regeneration in a Rabbit Critical-Sized Calvarial Model Using Tyrosine-Derived Polycarbonate Scaffolds

Bone Regeneration in a Rabbit Critical-Sized Calvarial Model Using Tyrosine-Derived Polycarbonate Scaffolds

Profiling stem cell states in three-dimensional biomaterial niches using high content image informatics

Gas-Foamed Scaffold Gradients for Combinatorial Screening in 3D

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