The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform

Paul J Santerre - One of the best experts on this subject based on the ideXlab platform.

  • paracrine signalling from monocytes enables desirable extracellular matrix accumulation and temporally appropriate phenotype of vascular smooth muscle cell like cells derived from adipose stromal cells
    Acta Biomaterialia, 2020
    Co-Authors: Xiaoqing Zhang, Craig A Simmons, Paul J Santerre
    Abstract:

    Abstract In vascular tissue engineering, the ability to obtain a robust and safe vascular tissue cell source (e.g. vascular smooth muscle cells (VSMCs)) and to promote vascular tissue-specific extracellular matrix (ECM) protein production is critically important. Mature blood vessel-derived VSMCs are not practical for in vitro vascular tissue regeneration. The authors have conceived a strategy to differentiate adipose derived stromal cells (ASCs) into VSMC-like cells (ASC-VSMCs) that were similar to mature umbilical artery VSMCs at the transcriptional, protein and contraction function levels. Monocytes/macrophages are known as important regulators of the inflammation and regeneration processes within different tissue types of the body. However, our understanding of the potential interactions between specific tissue-like cells differentiated from stem/stromal cells (e.g. ASC-VSMCs) and monocytes/macrophages (cued by specific biomaterial Scaffolds) is still limited. In this study, indirect and direct ASC-VSMC-monocyte co-cultures were constructed within a porous Polyurethane Scaffold (D-PHI) previously shown to have an immunomodulatory character. The effects of monocytes/macrophages on the cellularity (cell number detected with DNA quantification assay), ECM (glycosaminoglycan (GAG), collagen, and elastin) accumulation as well as the maintenance of contractile VSMC markers (calponin and smoothelin) of the ASC-VSMCs after a month of co-culture were investigated. It was found that monocyte paracrine signalling in D-PHI positively affected the cellularity and ECM accumulation of ASC-VSMCs in co-culture. Cause-effect relationships were also identified between the release of pro-inflammatory/anti-inflammatory factors (i.e. IL6, TGF-β1) in co-culture and the expression of contractile proteins (calponin and smoothelin) by ASC-VSMCs. This study demonstrated the importance of combining an immune cell strategy with stromal cell derived VSMCs (i.e. ASC-VSMCs) to achieve a practical vascular tissue engineering outcome. Statement of significance Adipose stromal cell derived-vascular smooth muscle cells (ASC-VSMCs) are a promising cell source for vascular tissue engineering. Monocytes/monocyte derived macrophages can be harnessed as an immune-assisted strategy to promote vascular tissue regeneration. This study demonstrated that the co-culture of human ASC-VSMCs with monocytes significantly enhanced the cellularity and extracellular matrix (ECM) accumulation within anionic Polyurethane (D-PHI) Scaffolds, partially mediated by monocyte paracrine signalling mechanisms. In addition, specific VSMC contractile markers (calponin and smoothelin) were still present in ASC-VSMCs when the cells were exposed to monocytes for a month in vitro. This study corroborated the potential selection of ASC-VSMCs for in vitro engineering of vascular tissue in an immunomodulatory biomaterial Scaffold (e.g. D-PHI ) based co-culture system containing monocytes.

  • paracrine signalling from monocytes enables desirable extracellular matrix accumulation and temporally appropriate phenotype of vascular smooth muscle cell like cells derived from adipose stromal cells
    Acta Biomaterialia, 2020
    Co-Authors: Xiaoqing Zhang, Craig A Simmons, Paul J Santerre
    Abstract:

    Abstract In vascular tissue engineering, the ability to obtain a robust and safe vascular tissue cell source (e.g. vascular smooth muscle cells (VSMCs)) and to promote vascular tissue-specific extracellular matrix (ECM) protein production is critically important. Mature blood vessel-derived VSMCs are not practical for in vitro vascular tissue regeneration. The authors have conceived a strategy to differentiate adipose derived stromal cells (ASCs) into VSMC-like cells (ASC-VSMCs) that were similar to mature umbilical artery VSMCs at the transcriptional, protein and contraction function levels. Monocytes/macrophages are known as important regulators of the inflammation and regeneration processes within different tissue types of the body. However, our understanding of the potential interactions between specific tissue-like cells differentiated from stem/stromal cells (e.g. ASC-VSMCs) and monocytes/macrophages (cued by specific biomaterial Scaffolds) is still limited. In this study, indirect and direct ASC-VSMC-monocyte co-cultures were constructed within a porous Polyurethane Scaffold (D-PHI) previously shown to have an immunomodulatory character. The effects of monocytes/macrophages on the cellularity (cell number detected with DNA quantification assay), ECM (glycosaminoglycan (GAG), collagen, and elastin) accumulation as well as the maintenance of contractile VSMC markers (calponin and smoothelin) of the ASC-VSMCs after a month of co-culture were investigated. It was found that monocyte paracrine signalling in D-PHI positively affected the cellularity and ECM accumulation of ASC-VSMCs in co-culture. Cause-effect relationships were also identified between the release of pro-inflammatory/anti-inflammatory factors (i.e. IL6, TGF-β1) in co-culture and the expression of contractile proteins (calponin and smoothelin) by ASC-VSMCs. This study demonstrated the importance of combining an immune cell strategy with stromal cell derived VSMCs (i.e. ASC-VSMCs) to achieve a practical vascular tissue engineering outcome. Statement of significance Adipose stromal cell derived-vascular smooth muscle cells (ASC-VSMCs) are a promising cell source for vascular tissue engineering. Monocytes/monocyte derived macrophages can be harnessed as an immune-assisted strategy to promote vascular tissue regeneration. This study demonstrated that the co-culture of human ASC-VSMCs with monocytes significantly enhanced the cellularity and extracellular matrix (ECM) accumulation within anionic Polyurethane (D-PHI) Scaffolds, partially mediated by monocyte paracrine signalling mechanisms. In addition, specific VSMC contractile markers (calponin and smoothelin) were still present in ASC-VSMCs when the cells were exposed to monocytes for a month in vitro. This study corroborated the potential selection of ASC-VSMCs for in vitro engineering of vascular tissue in an immunomodulatory biomaterial Scaffold (e.g. D-PHI ) based co-culture system containing monocytes.

  • establishing a gingival fibroblast phenotype in a perfused degradable Polyurethane Scaffold mediation by tgf β1 fgf 2 β1 integrin and focal adhesion kinase
    Biomaterials, 2014
    Co-Authors: Jane W C Cheung, Christopher A Mcculloch, Paul J Santerre
    Abstract:

    Medium perfusion has been shown to enhance cell proliferation and matrix protein production. In more recent work, under perfusion, a degradable/polar/hydrophobic/ionic Polyurethane (D-PHI) Scaffold was shown to enhance growth and production of collagen by human gingival fibroblasts (HGFs). However, the nature of the HGFs cultured in the perfused D-PHI Scaffolds, and the mechanisms by which medium perfusion activates these cells to facilitate proliferation and collagen production are not defined. The current study sought to investigate HGF interaction within the D-PHI Scaffolds under perfusion by examining the production and the spatial distribution of α-smooth muscle actin (α-SMA) and type I collagen (Col I), the secretion of transforming growth factor (TGF)-β1 and basic fibroblast growth factor (FGF-2) in the conditioned medium, with a goal of defining the mechanistic pathways affecting the production of these markers in the dynamic culture. It was found that the perfused D-PHI Scaffold shifted the HGF phenotype from myofibroblast-like (upregulation of α-SMA) to fibroblast-like (downregulation of α-SMA) over the course of 28 days. Both TGF-β1 and FGF-2 were significantly greater in the dynamic vs. static culture at day 1. Although TGF-β1 has been often reported to increase α-SMA and collagen expression, the D-PHI material and significant high level of FGF-2 at day 1 of dynamic culture appear to play a role in regulating α-SMA production while allowing HGFs to increase Col I production. β1-integrin production was increased and focal adhesion kinase (FAK) were activated 2 h after HGFs were exposed to medium perfusion, which may have in part promoted cell growth, α-SMA and Col I production in the early dynamic culture. Consequently, the D-PHI material and medium perfusion has modulated fibroblast phenotype, and enhanced cell growth and Col I production through the coordinated actions of TGF-β1, FGF-2, β1-integrin and FAK.

  • perfused culture of gingival fibroblasts in a degradable polar hydrophobic ionic Polyurethane d phi Scaffold leads to enhanced proliferation and metabolic activity
    Acta Biomaterialia, 2013
    Co-Authors: Jane W C Cheung, Emily Rose, Paul J Santerre
    Abstract:

    Abstract Periodontal diseases cause the breakdown of the tooth-supporting gingival tissue. In treatments aimed at gingival tissue regeneration, tissue engineering is preferred over the common treatments such as scaling. Perfused (dynamic) culture has been shown to increase cell growth in tissue-engineered Scaffolds. Since gingival tissues are highly vascularized, it was desired to investigate the influence of perfusion on the function of human gingival fibroblasts (HGF) when cultured in a degradable/polar/hydrophobic/ionic Polyurethane Scaffold during the early culture phase (4 weeks) of engineering gingival tissues. It was observed that the growth of HGF was continuous over 28 days in dynamic culture (3-fold increase, p p

  • co culturing monocytes with smooth muscle cells improves cell distribution within a degradable Polyurethane Scaffold and reduces inflammatory cytokines
    Acta Biomaterialia, 2012
    Co-Authors: Joanne E Mcbane, Rosalind S. Labow, Kuihua Cai, Paul J Santerre
    Abstract:

    Abstract Activated monocytes can promote inflammation or wound repair, depending on the nature of the implant environment. Recent work showed that a degradable, polar-hydrophobic-ionic Polyurethane (D-PHI) induced an anti-inflammatory monocyte phenotype. In the current study it is hypothesized that wound-healing phenotype monocytes (activated by D-PHI material chemistry) will promote human vascular smooth muscle cells (hVSMC) to attach and migrate into porous D-PHI Scaffolds. hVSMC migration is necessary for hVSMC population of the Scaffold and tissue formation to occur, and then, once tissue formation is complete, the monocyte should promote contractile phenotype markers in the hVSMC. hVSMC were cultured for up to 28 days with or without monocytes and analyzed for cell viability, attachment (DNA) and migration. Lysates were analyzed for the hVSMC contractile phenotype markers calponin and α-smooth muscle actin (α-SMA) as well as urokinase plasminogen activator (uPA; pro-migration marker) using immunoblotting analysis. Histological staining showed that hVSMC alone remained around the perimeter of the Scaffold, whereas co-culture samples had co-localization of monocytes with hVSMC in the pores, a more even cell distribution throughout the Scaffold and increased total cell attachment ( P

Qin Zou - One of the best experts on this subject based on the ideXlab platform.

  • Preparation and cell infiltration of lotus-type porous nano-hydroxyapatite/Polyurethane Scaffold for bone tissue regeneration
    Materials Letters, 2015
    Co-Authors: Minghui Zhao, Yi Zuo, Qin Zou
    Abstract:

    Abstract The pore size, porosity and pore connectivity are important structural parameters that affect the mechanical strength and biological performance of a Scaffold for bone tissue regeneration. A lotus-type porous nano-hydroxyapatite/Polyurethane (n-HA/PU) Scaffold was designed and fabricated, and its mechanical property and cell behavior were evaluated. The results showed that the Scaffold had an anisotropic pore structure, the porosity was about 84% and the macropore size on cross-section was uniform, close to 600 µm. The mechanical properties also showed an anisotropic feature according to the oriented pore structure. When stress applied parallel to the pore orientation, the longitudinal compressive strength and elastic modulus were 3.52 MPa and 44.25 MPa respectively, much higher than the lateral 2.59 MPa and 10.42 MPa. Cell culture indicated that the lotus-type n-HA/PU Scaffold exhibited good cell affinity and cytocompatibility, the proper pore size and high pore’s connectivity were favourable for cell infiltration into the inner part of the Scaffold. The lotus-type n-HA/PU Scaffold has promising prospect in bone tissue regeneration field.

  • preparation and cell infiltration of lotus type porous nano hydroxyapatite Polyurethane Scaffold for bone tissue regeneration
    Materials Letters, 2015
    Co-Authors: Minghui Zhao, Yi Zuo, Qin Zou
    Abstract:

    Abstract The pore size, porosity and pore connectivity are important structural parameters that affect the mechanical strength and biological performance of a Scaffold for bone tissue regeneration. A lotus-type porous nano-hydroxyapatite/Polyurethane (n-HA/PU) Scaffold was designed and fabricated, and its mechanical property and cell behavior were evaluated. The results showed that the Scaffold had an anisotropic pore structure, the porosity was about 84% and the macropore size on cross-section was uniform, close to 600 µm. The mechanical properties also showed an anisotropic feature according to the oriented pore structure. When stress applied parallel to the pore orientation, the longitudinal compressive strength and elastic modulus were 3.52 MPa and 44.25 MPa respectively, much higher than the lateral 2.59 MPa and 10.42 MPa. Cell culture indicated that the lotus-type n-HA/PU Scaffold exhibited good cell affinity and cytocompatibility, the proper pore size and high pore’s connectivity were favourable for cell infiltration into the inner part of the Scaffold. The lotus-type n-HA/PU Scaffold has promising prospect in bone tissue regeneration field.

  • hydroxyapatite Polyurethane Scaffold incorporated with drug loaded ethyl cellulose microspheres for bone regeneration
    Journal of Biomedical Materials Research Part B, 2010
    Co-Authors: Haohuai Liu, Li Zhang, Qin Zou, Pujiang Shi, Yi Zuo
    Abstract:

    The Research Center for Nano-Biomaterials, Analytical and Testing Center, Sichuan University, Chengdu 610064, ChinaReceived 20 November 2009; revised 8 May 2010; accepted 10 May 2010Published online 27 July 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.b.31680Abstract: The purpose of this study is to explore and developbiodegradable Scaffold for bone regeneration or tissueengineering with the capacity of controlled drug delivery.Ceftazidime as a model drug was encapsulated in ethyl cellu-lose (EC) microspheres, which were subsequently incorpo-rated in a hydroxyapatite/Polyurethane (HA/PU) compositeScaffold to generate an antibiotic drug delivery system. HA/PU Scaffolds had an interconnected pore network with an av-erage porosity of about 83%. The presence of microspheresin the composite Scaffolds was confirmed by scanning elec-tron microscopy. The drug-loaded EC microspheres were uni-formly distributed in the HA/PU Scaffold matrix and showedno significant effect on the pore structure of the Scaffold.Incorporation of microspheres into Scaffolds significantlyreduced the initial burst release, and the system exhibited asustained release of the model drug for up to 60 days. More-over, the Scaffold with drug-loaded microspheres was proved tobe an effective drug delivery system with good cytocompatibilityand antibacterial properties. The novel drug-loaded microsphere/Scaffold composites developed in this study are promising toserve as vehicles for controlled drug delivery in bone regenera-tion or bone tissue engineering.

Achim Goepferich - One of the best experts on this subject based on the ideXlab platform.

  • In Vitro and In Vivo Cartilage Engineering Using a Combination of Chondrocyte-Seeded Long-Term Stable Fibrin Gels and Polycaprolactone-Based Polyurethane Scaffolds
    Tissue Engineering, 2007
    Co-Authors: Daniela Eyrich, Hinrich Wiese, Daniel Skodacek, Hatem A. Sarhan, Joerg Tessmar, M. Wenzel, Rainer Staudenmaier, Gerhard Maier, Bernhard Appel, Achim Goepferich
    Abstract:

    The use of either a hydrogel or a solid polymeric Scaffold alone is often associated with distinct drawbacks in many tissue engineering applications. Therefore, in this study, we investigated the potential of a combination of long-term stable fibrin gels and Polyurethane Scaffolds for cartilage engineering. Primary bovine chondrocytes were suspended in fibrin gel and subsequently injected into a polycaprolactone-based Polyurethane Scaffold. Cells were homogeneously distributed within this composite system and produced high amounts of cartilage-specific extracellular matrix (ECM) components, namely glycosaminoglycans (GAGs) and collagen type II, within 4 weeks of in vitro culture. In contrast, cells seeded directly onto the Scaffold without fibrin resulted in a lower seeding efficiency and distinctly less homogeneous matrix distribution. Cell-fibrin-Scaffold constructs implanted into the back of nude mice promoted the formation of adequate engineered cartilaginous tissue within the Scaffold after 1, 3, and...

  • In Vitro and In Vivo Cartilage Engineering Using a Combination of Chondrocyte-Seeded Long-Term Stable Fibrin Gels and Polycaprolactone-Based Polyurethane Scaffolds
    Tissue engineering, 2007
    Co-Authors: Daniela Eyrich, Hinrich Wiese, Daniel Skodacek, Hatem A. Sarhan, Joerg Tessmar, M. Wenzel, Rainer Staudenmaier, Gerhard Maier, Bernhard Appel, Achim Goepferich
    Abstract:

    The use of either a hydrogel or a solid polymeric Scaffold alone is often associated with distinct drawbacks in many tissue engineering applications. Therefore, in this study, we investigated the potential of a combination of long-term stable fibrin gels and Polyurethane Scaffolds for cartilage engineering. Primary bovine chondrocytes were suspended in fibrin gel and subsequently injected into a polycaprolactone-based Polyurethane Scaffold. Cells were homogeneously distributed within this composite system and produced high amounts of cartilage-specific extracellular matrix (ECM) components, namely glycosaminoglycans (GAGs) and collagen type II, within 4 weeks of in vitro culture. In contrast, cells seeded directly onto the Scaffold without fibrin resulted in a lower seeding efficiency and distinctly less homogeneous matrix distribution. Cell-fibrin-Scaffold constructs implanted into the back of nude mice promoted the formation of adequate engineered cartilaginous tissue within the Scaffold after 1, 3, and 6 months in vivo, containing evenly distributed ECM components, such as GAGs and collagen. Again, in constructs seeded without fibrin, histology showed an inhomogeneous and, thus, not adequate ECM distribution compared to seeding with fibrin, even after 6 months in vivo. Strikingly, a precultivation for 1 week in vitro elicited similar results in vivo compared to precultivation for 4 weeks; that is, a precultivation for longer than 1 week did not enhance tissue development. The presented composite system is suggested as a promising alternative toward clinical application of engineered cartilaginous tissue for plastic and reconstructive surgery.

Craig A Simmons - One of the best experts on this subject based on the ideXlab platform.

  • paracrine signalling from monocytes enables desirable extracellular matrix accumulation and temporally appropriate phenotype of vascular smooth muscle cell like cells derived from adipose stromal cells
    Acta Biomaterialia, 2020
    Co-Authors: Xiaoqing Zhang, Craig A Simmons, Paul J Santerre
    Abstract:

    Abstract In vascular tissue engineering, the ability to obtain a robust and safe vascular tissue cell source (e.g. vascular smooth muscle cells (VSMCs)) and to promote vascular tissue-specific extracellular matrix (ECM) protein production is critically important. Mature blood vessel-derived VSMCs are not practical for in vitro vascular tissue regeneration. The authors have conceived a strategy to differentiate adipose derived stromal cells (ASCs) into VSMC-like cells (ASC-VSMCs) that were similar to mature umbilical artery VSMCs at the transcriptional, protein and contraction function levels. Monocytes/macrophages are known as important regulators of the inflammation and regeneration processes within different tissue types of the body. However, our understanding of the potential interactions between specific tissue-like cells differentiated from stem/stromal cells (e.g. ASC-VSMCs) and monocytes/macrophages (cued by specific biomaterial Scaffolds) is still limited. In this study, indirect and direct ASC-VSMC-monocyte co-cultures were constructed within a porous Polyurethane Scaffold (D-PHI) previously shown to have an immunomodulatory character. The effects of monocytes/macrophages on the cellularity (cell number detected with DNA quantification assay), ECM (glycosaminoglycan (GAG), collagen, and elastin) accumulation as well as the maintenance of contractile VSMC markers (calponin and smoothelin) of the ASC-VSMCs after a month of co-culture were investigated. It was found that monocyte paracrine signalling in D-PHI positively affected the cellularity and ECM accumulation of ASC-VSMCs in co-culture. Cause-effect relationships were also identified between the release of pro-inflammatory/anti-inflammatory factors (i.e. IL6, TGF-β1) in co-culture and the expression of contractile proteins (calponin and smoothelin) by ASC-VSMCs. This study demonstrated the importance of combining an immune cell strategy with stromal cell derived VSMCs (i.e. ASC-VSMCs) to achieve a practical vascular tissue engineering outcome. Statement of significance Adipose stromal cell derived-vascular smooth muscle cells (ASC-VSMCs) are a promising cell source for vascular tissue engineering. Monocytes/monocyte derived macrophages can be harnessed as an immune-assisted strategy to promote vascular tissue regeneration. This study demonstrated that the co-culture of human ASC-VSMCs with monocytes significantly enhanced the cellularity and extracellular matrix (ECM) accumulation within anionic Polyurethane (D-PHI) Scaffolds, partially mediated by monocyte paracrine signalling mechanisms. In addition, specific VSMC contractile markers (calponin and smoothelin) were still present in ASC-VSMCs when the cells were exposed to monocytes for a month in vitro. This study corroborated the potential selection of ASC-VSMCs for in vitro engineering of vascular tissue in an immunomodulatory biomaterial Scaffold (e.g. D-PHI ) based co-culture system containing monocytes.

  • paracrine signalling from monocytes enables desirable extracellular matrix accumulation and temporally appropriate phenotype of vascular smooth muscle cell like cells derived from adipose stromal cells
    Acta Biomaterialia, 2020
    Co-Authors: Xiaoqing Zhang, Craig A Simmons, Paul J Santerre
    Abstract:

    Abstract In vascular tissue engineering, the ability to obtain a robust and safe vascular tissue cell source (e.g. vascular smooth muscle cells (VSMCs)) and to promote vascular tissue-specific extracellular matrix (ECM) protein production is critically important. Mature blood vessel-derived VSMCs are not practical for in vitro vascular tissue regeneration. The authors have conceived a strategy to differentiate adipose derived stromal cells (ASCs) into VSMC-like cells (ASC-VSMCs) that were similar to mature umbilical artery VSMCs at the transcriptional, protein and contraction function levels. Monocytes/macrophages are known as important regulators of the inflammation and regeneration processes within different tissue types of the body. However, our understanding of the potential interactions between specific tissue-like cells differentiated from stem/stromal cells (e.g. ASC-VSMCs) and monocytes/macrophages (cued by specific biomaterial Scaffolds) is still limited. In this study, indirect and direct ASC-VSMC-monocyte co-cultures were constructed within a porous Polyurethane Scaffold (D-PHI) previously shown to have an immunomodulatory character. The effects of monocytes/macrophages on the cellularity (cell number detected with DNA quantification assay), ECM (glycosaminoglycan (GAG), collagen, and elastin) accumulation as well as the maintenance of contractile VSMC markers (calponin and smoothelin) of the ASC-VSMCs after a month of co-culture were investigated. It was found that monocyte paracrine signalling in D-PHI positively affected the cellularity and ECM accumulation of ASC-VSMCs in co-culture. Cause-effect relationships were also identified between the release of pro-inflammatory/anti-inflammatory factors (i.e. IL6, TGF-β1) in co-culture and the expression of contractile proteins (calponin and smoothelin) by ASC-VSMCs. This study demonstrated the importance of combining an immune cell strategy with stromal cell derived VSMCs (i.e. ASC-VSMCs) to achieve a practical vascular tissue engineering outcome. Statement of significance Adipose stromal cell derived-vascular smooth muscle cells (ASC-VSMCs) are a promising cell source for vascular tissue engineering. Monocytes/monocyte derived macrophages can be harnessed as an immune-assisted strategy to promote vascular tissue regeneration. This study demonstrated that the co-culture of human ASC-VSMCs with monocytes significantly enhanced the cellularity and extracellular matrix (ECM) accumulation within anionic Polyurethane (D-PHI) Scaffolds, partially mediated by monocyte paracrine signalling mechanisms. In addition, specific VSMC contractile markers (calponin and smoothelin) were still present in ASC-VSMCs when the cells were exposed to monocytes for a month in vitro. This study corroborated the potential selection of ASC-VSMCs for in vitro engineering of vascular tissue in an immunomodulatory biomaterial Scaffold (e.g. D-PHI ) based co-culture system containing monocytes.

  • immunomodulatory polymeric Scaffold enhances extracellular matrix production in cell co cultures under dynamic mechanical stimulation
    Acta Biomaterialia, 2015
    Co-Authors: Kyle G Battiston, Craig A Simmons, Rosalind S. Labow, J P Santerre
    Abstract:

    Abstract Despite the importance of immune cells in regulating the wound healing process following injury, there are few examples of synthetic biomaterials that have the capacity to push the body’s immune cells toward pro-regeneration phenotypes, and fewer still that are designed with the intention of achieving this immunomodulatory character. While monocytes and their derived macrophages have been recognized as important contributors to tissue remodeling in vivo , this is primarily believed to be due to their ability to regulate other cell types. The ability of monocytes and macrophages to generate tissue products themselves, however, is currently not well appreciated within the field of tissue regeneration. Furthermore, while monocytes/macrophages are found in remodeling tissue that is subjected to mechanical loading, the effect this biomechanical strain on monocytes/macrophages and their ability to regulate tissue-specific cellular activity has not been understood due to the complexity of the many factors involved in the in vivo setting, hence necessitating the use of controlled in vitro culture platforms to investigate this phenomenon. In this study, human monocytes were co-cultured with human coronary artery smooth muscle cells (VSMCs) on a tubular (3 mm ID) degradable Polyurethane Scaffold, with a unique combination of non-ionic polar, hydrophobic and ionic chemistry (D-PHI). The goal was to determine if such a synthetic matrix could be used in a co-culture system along with dynamic biomechanical stimulus (10% circumferential strain, 1 Hz) conditions in order to direct monocytes to enhance tissue generation, and to better comprehend the different ways in which monocytes/macrophages may contribute to new tissue production. Mechanical strain and monocyte co-culture had a complementary and non-mitigating effect on VSMC growth. Co-culture samples demonstrated increased deposition of sulphated glycosaminoglycans (GAGs) and elastin, as well as increases in the release of FGF-2, a growth factor that can stimulate VSMC growth, while dynamic culture supported increases in collagen I and III as well as increased mechanical properties (elastic modulus, tensile strength) vs. static controls. Macrophage polarization toward an M1 state was not promoted by the biomaterial or culture conditions tested. Monocytes/macrophages cultured on D-PHI were also shown to produce vascular extracellular matrix components, including collagen I, collagen III, elastin, and GAGs. This study highlights the use of synthetic biomaterials having immunomodulatory character in order to promote cell and tissue growth when used in tissue engineering strategies, and identifies ECM deposition by monocytes/macrophages as an unexpected source of this new tissue. Statement of Significance The ability of biomaterials to regulate macrophage activation towards a wound healing phenotype has recently been shown to support positive tissue regeneration. However, the ability of immunomodulatory biomaterials to harness monocyte/macrophage activity to support tissue engineering strategies in vitro holds enormous potential that has yet to be investigated. This study used a monocyte co-culture on a degradable Polyurethane (D-PHI) to regulate the response of VSMCs in combination with biomechanical strain in a vascular tissue engineering context. Results demonstrate that immunomodulatory biomaterials, such as D-PHI, that support a desirable macrophage activation state can be combined with biomechanical strain to augment vascular tissue production in vitro , in part due to the novel and unexpected contribution of monocytes/macrophages themselves producing vascular ECM proteins.

  • monocyte macrophage cytokine activity regulates vascular smooth muscle cell function within a degradable Polyurethane Scaffold
    Acta Biomaterialia, 2014
    Co-Authors: Kyle G Battiston, Craig A Simmons, Rosalind S. Labow, Ben Ouyang, J P Santerre
    Abstract:

    Abstract Tissue engineering strategies rely on the ability to promote cell proliferation and migration into porous biomaterial constructs, as well as to support specific phenotypic states of the cells in vitro. The present study investigated the use of released factors from monocytes and their derived macrophages (MDM) and the mechanism by which they regulate vascular smooth muscle cell (VSMC) response in a VSMC–monocyte co-culture system within a porous degradable Polyurethane (D-PHI) Scaffold. VSMCs cultured in monocyte/MDM-conditioned medium (MCM), generated from the culture of monocytes/MDM on D-PHI Scaffolds for up to 28 days, similarly affected VSMC contractile marker expression, growth and three-dimensional migration when compared to direct VSMC–monocyte co-culture. Monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) were identified as two cytokines present in MCM, at concentrations that have previously been shown to influence VSMC phenotype. VSMCs cultured alone on D-PHI Scaffolds and exposed to MCP-1 (5 ng ml −1 ) or IL-6 (1 ng ml −1 ) for 7 days experienced a suppression in contractile marker expression (with MCP-1 or IL-6) and increased growth (with MCP-1) compared to no cytokine medium supplementation. These effects were also observed in VSMC–monocyte co-culture on D-PHI. Neutralization of IL-6, but not MCP-1, was subsequently shown to decrease VSMC growth and enhance calponin expression for VSMC–monocyte co-cultures on D-PHI Scaffolds for 7 days, implying that IL-6 mediates VSMC response in monocyte–VSMC co-cultures. This study highlights the use of monocytes and their derived macrophages in conjunction with immunomodulatory biomaterials, such as D-PHI, as agents for regulating VSMC response, and demonstrates the importance of monocyte/MDM-released factors, such as IL-6 in particular, in this process.

  • Functional characterization of human coronary artery smooth muscle cells under cyclic mechanical strain in a degradable Polyurethane Scaffold
    Biomaterials, 2011
    Co-Authors: Soroor Sharifpoor, Craig A Simmons, Rosalind S. Labow, J. Paul Santerre
    Abstract:

    There are few synthetic elastomeric biomaterials that simultaneously provide the required biological conditioning and the ability to translate biomechanical stimuli to vascular smooth muscle cells (VSMCs). Biomechanical stresses are important physiological elements that regulate VSMC function, and Polyurethane elastomers are a class of materials capable of facilitating the translation of stress induced biomechanics. In this study, human coronary artery smooth muscle cells (hCASMCs), which were seeded into a porous degradable polar/hydrophobic/ionic (D-PHI) Polyurethane Scaffold, were subjected to uniaxial cyclic mechanical strain (CMS) over a span of four weeks using a customized bioreactor. The distribution, proliferation and contractile protein expression of hCASMCs in the Scaffold were then analyzed and compared to those grown under static conditions. Four weeks of CMS, applied to the elastomeric Scaffold, resulted in statistically greater DNA mass, more cell area coverage and a better distribution of cells deeper within the Scaffold construct. Furthermore, CMS samples demonstrated improved tensile mechanical properties following four weeks of culture, suggesting the generation of more extracellular matrix within the Polyurethane constructs. The expression of smooth muscle α-actin, calponin and smooth muscle myosin heavy chain and the absence of Ki-67+ cells in both static and CMS cultures, throughout the 4 weeks, suggest that hCASMCs retained their contractile character on these biomaterials. The study highlights the importance of implementing physiologically-relevant biomechanical stimuli in the development of synthetic elastomeric tissue engineering Scaffolds.

Sylwester Gogolewski - One of the best experts on this subject based on the ideXlab platform.

  • structure property relations and cytotoxicity of isosorbide based biodegradable Polyurethane Scaffolds for tissue repair and regeneration
    Journal of Biomedical Materials Research Part A, 2008
    Co-Authors: Sylwester Gogolewski, Katarzyna Gorna, Ewa Zaczynska, Anna Czarny
    Abstract:

    Microporous Scaffolds with potential applications for tissue engineering were produced from the biodegradable aliphatic isosorbide-based Polyurethane using a combined salt leaching–solvent evaporation–coagulation process. Alkaline sodium phosphate heptahydrate crystals were used as a solid porogene, and acetone–water mixture was used as a nonsolvent–coagulant. The Scaffolds used in this study had interconnected pores with sizes in the range of 70–120 μm and a pore-to-volume ratio of 87%. The XPS measurements showed that the residence of the Scaffold in an aqueous solution of the alkaline porogene changed its surface atomic composition, that is increased the surface concentration of oxygen and nitrogen and reduced the surface concentration of hydrocarbons relative to the control material. This also enhanced the hydrophilicity of the Scaffold's surfaces as assessed from contact angle measurements. The alkaline porogene did not affect the polymer's molecular weight. The MTT cytotoxicity assay showed that the isosorbide-based Polyurethane Scaffold is noncytotoxic. The amounts of interleukin-6 and interlukin-8 proinflammatory cytokines released from human blood leukocytes exposed to the Polyurethane Scaffolds in vitro were comparable and/or lower than the amount of the cytokines released by leukocytes exposed to the culture-grade polystyrene control. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008

  • biodegradable porous Polyurethane Scaffolds for tissue repair and regeneration
    Journal of Biomedical Materials Research Part A, 2006
    Co-Authors: Katarzyna Gorna, Sylwester Gogolewski
    Abstract:

    Critical-size bone defects usually require the insertion of autogenous bone graft to heal. Harvesting of bone is traumatic and results in high morbidity at the donor site. A potential alternative to bone graft may be a bone substitute with adequate biocompatibility and biological properties produced from ceramics or bioresorbable/biodegradable polymers. In the present study, new elastomeric biodegradable Polyurethanes with an enhanced affinity toward cells and tissues were synthesized using aliphatic diisocyanate, poly(ϵ-caprolactone) diol, and biologically active 1,4:3,6-dianhydro-D-sorbitol (isosorbide diol) as chain extender. The polymers were processed into 3D porous Scaffolds by applying a combined salt leaching-phase inverse process. The critical parameters controlling pore size and geometry were the solvents and nonsolvents used for Scaffold preparation and the sizes of the solid porogen crystals. Scaffolds prepared from the polymer solution in solvents such as dimethylsulfoxide or methyl-2-pyrrolidone did not have a homogenous pore structure. Many pores were interconnected, but numerous pores were closed. Irrespective of the high pore-to-volume ratio (75%), the Scaffolds showed poor water permeability. The best solvent for the preparation of Scaffolds from the Polyurethane used in the study was dimethylformamide (DMF). The type of nonsolvent admixed to the polymer solution in DMF strongly affected the Scaffolds' pore structure. The elastomeric Polyurethane Scaffold prepared from the optimal solvent–nonsolvent mixture had regular interconnected pores, high water permeability, and a pore-to-volume ratio of 90%. The osteoconductive properties of the 3D porous Polyurethane Scaffolds can be additionally promoted by loading them with calcium phosphate salts such as hydroxyapatite or tricalcium phosphate, thus making them promising candidates for bone graft substitutes. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006

  • the use of biodegradable Polyurethane Scaffolds for cartilage tissue engineering potential and limitations
    Biomaterials, 2003
    Co-Authors: Sibylle Grad, Laszlo Kupcsik, Katarzyna Gorna, Sylwester Gogolewski, Mauro Alini
    Abstract:

    The aim of the present study was to evaluate the capability of novel biodegradable Polyurethane Scaffolds to support attachment, growth and maintenance of differentiated chondrocytes in vitro for up to 42 days. After an initial decrease, although not significant, the DNA content of the constructs remained constant over the culture time. A progressive increase in glycosaminoglycans and collagen was observed during the culture period. However, a significant release of matrix molecules into the culture medium was also noticeable. At the transcriptional level, a decrease in aggrecan and procollagen II mRNA expression was noticeable, whereas procollagen I expression was increased. To conclude, the present data demonstrate that biodegradable Polyurethane porous Scaffolds seeded with articular chondrocytes support cell attachment and the production of extracellular matrix proteins. The limitations of the system are the diffusion of large amounts of matrix molecules into the culture medium and the dedifferentiation of the chondrocytes with prolonged time in culture. However, due to the favourable mechanical properties of the Polyurethane Scaffold, stimulation of chondrocytes by mechanical loading can be considered in order to improve the formation of a functional cartilage-like extracellular matrix.