The Experts below are selected from a list of 291 Experts worldwide ranked by ideXlab platform
Ronen Schweitzer - One of the best experts on this subject based on the ideXlab platform.
-
Loss of Smad4 in the scleraxis Cell lineage results in postnatal joint contracture.
Developmental biology, 2020Co-Authors: Saundra Y. Schlesinger, Seongkyung Seo, Brian A. Pryce, Sara F. Tufa, Douglas R. Keene, Alice H. Huang, Ronen SchweitzerAbstract:Growth of the musculoskeletal system requires precise coordination between bone, muscle, and Tendon during development. Insufficient elongation of the muscle-Tendon unit relative to bone growth results in joint contracture, a condition characterized by reduction or complete loss of joint range of motion. Here we establish a novel murine model of joint contracture by targeting Smad4 for deletion in the Tendon Cell lineage using Scleraxis-Cre (ScxCre). Smad4ScxCre mutants develop a joint contracture shortly after birth. The contracture is stochastic in direction and increases in severity with age. Smad4ScxCre mutant Tendons exhibited a stable reduction in Cellularity and a progressive reduction in extraCellular matrix volume. Collagen fibril diameters were reduced in the Smad4ScxCre mutants, suggesting a role for Smad4 signaling in the regulation of matrix accumulation. Although ScxCre also has sporadic activity in both cartilage and muscle, we demonstrate an essential role for Smad4 loss in Tendons for the development of joint contractures. Disrupting the canonical TGFβ-pathway in Smad2;3ScxCre mutants did not result in joint contractures. Conversely, disrupting the BMP pathway by targeting BMP receptors (Alk3ScxCre/Alk6null) recapitulated many features of the Smad4ScxCre contracture phenotype, suggesting that joint contracture in Smad4ScxCre mutants is caused by disruption of BMP signaling. Overall, these results establish a model of murine postnatal joint contracture and a role for BMP signaling in Tendon elongation and extraCellular matrix accumulation.
-
Tgfβ signaling is critical for maintenance of the Tendon Cell fate.
eLife, 2020Co-Authors: Guak-kim Tan, Brian A. Pryce, Sara F. Tufa, Douglas R. Keene, Anna Stabio, John V. Brigande, Chaojie Wang, Zheng Xia, Ronen SchweitzerAbstract:Studies of Cell fate focus on specification, but little is known about maintenance of the differentiated state. In this study, we find that the mouse Tendon Cell fate requires continuous maintenance in vivo and identify an essential role for TGFβ signaling in maintenance of the Tendon Cell fate. To examine the role of TGFβ signaling in tenocyte function the TGFβ type II receptor (Tgfbr2) was targeted in the Scleraxis-expressing Cell lineage using the ScxCre deletor. Tendon development was not disrupted in mutant embryos, but shortly after birth tenocytes lost differentiation markers and reverted to a more stem/progenitor state. Viral reintroduction of Tgfbr2 to mutants prevented and even rescued tenocyte dedifferentiation suggesting a continuous and Cell autonomous role for TGFβ signaling in Cell fate maintenance. These results uncover the critical importance of molecular pathways that maintain the differentiated Cell fate and a key role for TGFβ signaling in these processes.
-
disruption of tgfβ signaling in the scleraxis Cell lineage leads to tenocyte dedifferentiation and Tendon degeneration
Journal of Bone and Joint Surgery-british Volume, 2015Co-Authors: G K Tan, John V. Brigande, B A Pryce, Ronen SchweitzerAbstract:Introduction We previously reported that disruption of TGFβ signaling in limb mesenchyme resulted in complete failure of Tendon differentiation. Materials and Methods To bypass this early function and study additional roles of TGFβ signaling in Tendon development we disrupted TGFβ signaling in tenocytes after they assumed the Tendon Cell fate by using the Tendon deletor ScxCre to target the floxed type2 TGFβ receptor. Results Most mutant (Tgfbr2;ScxCre) pups appeared normal at birth but exhibited movement difficulties and splayed limbs by P3. ScxGFP signal revealed that Tendon formation was not affected in CKO embryos. Nonetheless, three distinct Tendon phenotypes were manifested later in development: (a) a single flexor Tendon consistently snapped at late embryonic stage; whereas at post-natal stage, some Tendons that appeared intact at birth were (b) eventually eliminated or (c) retained structural integrity with a substantial loss of the ScxGFP signal. Interestingly, the ScxGFP-negative Cells also lost other Tendon marker genes. Lineage tracing revealed that these Cells were derived from Scx-expressing Cells, suggesting a disruption of the Tendon Cell fate (dedifferentiation) but we found no evidence of transdifferentiation. Varying degrees of Tendon degeneration were also seen in CKO pups, as indicated by disrupted collagen fibrils, septation of the Tendon and altered epitenon. Another striking feature we identified in the Tgfbr2;ScxCre Tendon phenotype was recruitment of new Cells into the degenerating Tendon. Finally, our data also indicates that the Tgfbr2f;ScxCre Tendon phenotype is not due to a direct requirement for TGFβ signaling in tenocytes. Discussion This analysis thus highlights an unexpected possibility for loss of differentiated characteristics in tenocytes as a key factor in a Tendon degenerative process. We hypothesize that the Tendon phenotypes may represent a disruption of Cell-Cell or Cell-matrix interactions, and investigations are currently underway to test this hypothesis. Moreover, this is the first demonstration of active Cell recruitment into a non-injured Tendon that may be used to identify the origin and activation mechanisms for Tendon stem/progenitor Cells. Taken together, our findings reveal an essential and non-Cell autonomous role of TGFβ signaling in maintenance of the Tendon Cell fate.
-
molecular regulation of Tendon Cell fate during development
Journal of Orthopaedic Research, 2015Co-Authors: Alice H. Huang, Ronen SchweitzerAbstract:Although there have been several advances identifying novel mediators of Tendon induction, differentiation, and patterning, much of the basic landscape of Tendon biology from developmental stages onward remain almost completely undefined. During the New Frontiers in Tendon Research meeting, a group of developmental biologists with expertise across musculoskeletal disciplines identified key challenges for the Tendon development field. The tools generated and the molecular regulators identified in developmental research have enhanced mechanistic studies in Tendon injury and repair, both by defining benchmarks for success, as well as informing regenerative strategies. To address the needs of the orthopedic research community, this review will therefore focus on three key areas in Tendon development that may have critical implications for the fields of Tendon repair/regeneration and Tendon tissue engineering, including functional markers of Tendon Cell identity, signaling regulators of Tendon induction and differentiation, and in vitro culture models for Tendon Cell differentiation. Our goal is to provide a useful list of the currently known molecular players and their function in Tendon differentiation within the context of development.
Gloria Fong - One of the best experts on this subject based on the ideXlab platform.
-
alpha 2 adrenergic stimulation triggers achilles tenocyte hyperCellularity comparison between two model systems
Scandinavian Journal of Medicine & Science in Sports, 2013Co-Authors: Ludvig J Backman, Alex Scott, Gloria Fong, Gustav Andersson, Håkan Alfredson, Patrik DanielsonAbstract:The histopathology of Tendons with painful tendinopathy is often tendinosis, a fibrosis-like condition of unclear pathogenesis characterized by tissue changes including hyperCellularity. The primary Tendon Cells (tenocytes) have been shown to express adrenoreceptors (mainly alpha-2A) as well as markers of catecholamine production, particularly in tendinosis. It is known that adrenergic stimulation can induce proliferation in other Cells. The present study investigated the effects of an exogenously administered alpha-2 adrenergic agonist in an established in vivo Achilles tendinosis model (rabbit) and also in an in vitro human Tendon Cell culture model. The catecholamine producing enzyme tyrosine hydroxylase and the alpha-2A-adrenoreceptor (α2A AR) were expressed by tenocytes, and alpha-2 adrenergic stimulation had a proliferative effect on these Cells, in both models. The proliferation was inhibited by administration of an α2A AR antagonist, and the in vitro model further showed that the proliferative alpha-2A effect was mediated via a mitogenic Cell signaling pathway involving phosphorylation of extraCellular-signal-regulated kinases 1 and 2. The results indicate that catecholamines produced by tenocytes in tendinosis might contribute to the proliferative nature of the pathology through stimulation of the α2A AR, pointing to a novel target for future therapies. The study furthermore shows that animal models are not necessarily required for all aspects of this research.
-
human tenocytes are stimulated to proliferate by acetylcholine through an egfr signalling pathway
Cell and Tissue Research, 2013Co-Authors: Alex Scott, Ludvig J Backman, Gloria Fong, Gustav Andersson, Patrik DanielsonAbstract:Studies of human patellar and Achilles Tendons have shown that primary Tendon fibroblasts (tenocytes) not only have the capacity to produce acetylcholine (ACh) but also express muscarinic ACh receptors (mAChRs) through which ACh can exert its effects. In patients with tendinopathy (chronic Tendon pain) with tendinosis, the Tendon tissue is characterised by hyperCellularity and angiogenesis, both of which might be influenced by ACh. In this study, we have tested the hypothesis that ACh increases the proliferation rate of tenocytes through mAChR stimulation and have examined whether this mechanism operates via the extraCellular activation of the epidermal growth factor receptor (EGFR), as shown in other fibroblastic Cells. By use of primary human Tendon Cell cultures, we identified Cells expressing vimentin, tenomodulin and scleraxis and found that these Cells also contained enzymes related to ACh synthesis and release (choline acetyltransferase and vesicular acetylcholine transporter). The Cells furthermore expressed mAChRs of several subtypes. Exogenously administered ACh stimulated proliferation and increased the viability of tenocytes in vitro. When the Cells were exposed to atropine (an mAChR antagonist) or the EGFR inhibitor AG1478, the proliferative effect of ACh decreased. Western blot revealed increased phosphorylation, after ACh stimulation, for both EGFR and the extraCellular-signal-regulated kinases 1 and 2. Given that tenocytes have been shown to produce ACh and express mAChRs, this study provides evidence of a possible autocrine loop that might contribute to the hyperCellularity seen in tendinosis Tendon tissue.
-
substance p enhances collagen remodeling and mmp 3 expression by human tenocytes
Journal of Orthopaedic Research, 2013Co-Authors: Gloria Fong, Alex Scott, Ludvig J Backman, Patrik Danielson, David A Hart, Bob MccormackAbstract:The loss of collagen organization is considered a hallmark histopathologic feature of tendinosis. At the Cellular level, tenocytes have been shown to produce signal substances that were once thought to be restricted to neurons. One of the main neuropeptides implicated in tendinosis, substance P (SP), is known to influence collagen organization, particularly after injury. The aim of this study was to examine the influence of SP on collagen remodeling by primary human Tendon Cells cultured in vitro in three-dimensional collagen lattices. We found that SP stimulation led to an increased rate of collagen remodeling mediated via the neurokinin-1 receptor (NK-1 R), the preferred Cell receptor for SP. Gene expression analysis showed that SP stimulation resulted in significant increases in MMP3, COL3A1 and ACTA2 mRNA levels in the collagen lattices. Furthermore, cyclic tensile loading of Tendon Cell cultures along with the administration of exogenous SP had an additive effect on MMP3 expression. Immunoblotting confirmed that SP increased MMP3 protein levels via the NK-1 R. This study indicates that SP, mediated via NK-1 R, increases collagen remodeling and leads to increased MMP3 mRNA and protein expression that is further enhanced by cyclic mechanical loading.
-
substance p is a mechanoresponsive autocrine regulator of human tenocyte proliferation
PLOS ONE, 2011Co-Authors: Alex Scott, Ludvig J Backman, Gloria Fong, Gustav Andersson, Patrik DanielsonAbstract:It has been hypothesised that substance P (SP) may be produced by primary fibroblastic Tendon Cells (tenocytes), and that this production, together with the widespread distribution of the neurokinin-1 receptor (NK-1 R) in Tendon tissue, could play an important role in the development of tendinopathy, a condition of chronic Tendon pain and thickening. The aim of this study was to examine the possibility of endogenous SP production and the expression of NK-1 R by human tenocytes. Because tendinopathy is related to overload, and because the predominant tissue pathology (tendinosis) underlying early tendinopathy is characterized by tenocyte hyperCellularity, the production of SP in response to loading/strain and the effects of exogenously administered SP on tenocyte proliferation were also studied. A Cell culture model of primary human Tendon Cells was used. The vast majority of Tendon Cells were immunopositive for the tenocyte/fibroblast markers tenomodulin and vimentin, and immunocytochemical counterstaining revealed that positive immunoreactions for SP and NK-1 R were seen in a majority of these Cells. Gene expression analyses showed that mechanical loading (strain) of Tendon Cell cultures using the FlexCell© technique significantly increased the mRNA levels of SP, whereas the expression of NK-1 R mRNA decreased in loaded as compared to unloaded Tendon Cells. Reduced NK-1 R protein was also observed, using Western blot, after exogenously administered SP at a concentration of 10−7 M. SP exposure furthermore resulted in increased Cell metabolism, increased Cell viability, and increased Cell proliferation, all of which were found to be specifically mediated via the NK-1 R; this in turn involving a common mitogenic Cell signalling pathway, namely phosphorylation of ERK1/2. This study indicates that SP, produced by tenocytes in response to mechanical loading, may regulate proliferation through an autocrine loop involving the NK-1 R.
Alan T Nurden - One of the best experts on this subject based on the ideXlab platform.
-
autologous fibrin matrices a potential source of biological mediators that modulate Tendon Cell activities
Journal of Biomedical Materials Research Part A, 2006Co-Authors: Eduardo Anitua, Mikel Sanchez, Juan Azofra, Maria De La Fuente, Alan T Nurden, Mar Zalduendo, Gorka Orive, Isabel AndiaAbstract:The use of autologous fibrin matrices has been proposed as a therapeutic strategy for the local and physiological delivery of growth factors in the treatment of several clinical conditions requiring Tendon healing or Tendon graft remodelling. In the present work, we investigated the proliferation, synthesis of type-I collagen and angiogenic factors by Tendon Cells seeded on platelet-rich (PR) and platelet-poor (PP) matrices. Furthermore, in vivo Cellular and vascular effects of each treatment were examined after infiltration in Achilles Tendon in sheep. Results showed that the presence of platelets within the fibrin matrices increased significantly the proliferation of Tendon Cells. Additionally, cultured Tendon Cells synthesised type I collagen and angiogenic factors such as VEGF and HGF. The synthesis of VEGF, but not of HGF, was significantly higher when platelets were present within the matrix. In the sheep model, the injection of pre-clotted plasma within Tendons increased Cellular density and promoted neovascularization. These results indicate that administration of fibrin matrices is a safe and easy strategy that may open new avenues for enhancing tissue healing and remodelling and influences the process of regeneration in clinical situations characterised by a poor healing outcome.
-
autologous preparations rich in growth factors promote proliferation and induce vegf and hgf production by human Tendon Cells in culture
Journal of Orthopaedic Research, 2005Co-Authors: Eduardo Anitua, Isabel Andia, Mikel Sanchez, Juan Azofra, M Del Mar Zalduendo, Maria De La Fuente, Paquita Nurden, Alan T NurdenAbstract:Blood platelets become activated and aggregate at the site of vessel injury. Upon activation by thrombin, platelets release storage pools of proteins and growth factors (GFs), including those involved in tissue repair. Our goal was to evaluate the potential beneficial effect of proteins released from platelet-rich clots on Tendon healing. PDGF, TGF-beta-1, IGF-I, HGF, VEGF and EGF were measured in human platelet-poor plasma (PPP) and in the releasates collected from either platelet-poor or platelet-rich clots prepared in vitro. We then studied the effects of the releasates on human Tendon Cells in culture. Releasates from both platelet-rich and platelet-poor clots stimulated Tendon Cell proliferation, in contrast to un-clotted PPP. The mitogenic activity of the supernatants was not decreased by the thrombin inhibitor, hirudin. Cultured Tendon Cells synthesise VEGF and HGF in the presence of PPP-clots and PRP-clot releasates, thus the synthesised amount was significantly higher with supernatants from platelet-rich clots than supernatants from a platelet-poor clot (p < 0.05). These results suggest that administering autologous platelet-rich clots may be beneficial to the treatment of Tendon injuries by inducing Cell proliferation and promoting the synthesis of angiogenic factors during the healing process.
-
autologous preparations rich in growth factors promote proliferation and induce vegf and hgf production by human Tendon Cells in culture
Journal of Orthopaedic Research, 2005Co-Authors: Eduardo Anitua, Mikel Sanchez, Juan Azofra, Maria De La Fuente, Paquita Nurden, Isabel Andi, Ma Del Mar Zalduendo, Alan T NurdenAbstract:Blood platelets become activated and aggregate at the site of vessel injury. Upon activation by thrombin, platelets release storage pools of proteins and growth factors (GFs), including those involved in tissue repair. Our goal was to evaluate the potential beneficial effect of proteins released from platelet-rich clots on Tendon healing. PDGF, TGF-b-1, IGF-I, HGF, VEGF and EGF were measured in human platelet-poor plasma (PPP) and in the releasates collected from either platelet-poor or platelet-rich clots prepared in vitro. We then studied the effects of the releasates on human Tendon Cells in culture. Releasates from both platelet-rich and platelet-poor clots stimulated Tendon Cell proliferation, in contrast to un-clotted PPP. The mitogenic activity of the supernatants was not decreased by the thrombin inhibitor, hirudin. Cultured Tendon Cells synthesise VEGF and HGF in the presence of PPP-clots and PRP-clot releasates, thus the synthesised amount was significantly higher with supernatants from platelet-rich clots than supernatants from a platelet-poor clot (p < 0.05). These results suggest that administering autologous platelet-rich clots may be beneficial to the treatment of Tendon injuries by inducing Cell proliferation and promoting the synthesis of angiogenic factors during the healing process.
Alex Scott - One of the best experts on this subject based on the ideXlab platform.
-
alpha 2 adrenergic stimulation triggers achilles tenocyte hyperCellularity comparison between two model systems
Scandinavian Journal of Medicine & Science in Sports, 2013Co-Authors: Ludvig J Backman, Alex Scott, Gloria Fong, Gustav Andersson, Håkan Alfredson, Patrik DanielsonAbstract:The histopathology of Tendons with painful tendinopathy is often tendinosis, a fibrosis-like condition of unclear pathogenesis characterized by tissue changes including hyperCellularity. The primary Tendon Cells (tenocytes) have been shown to express adrenoreceptors (mainly alpha-2A) as well as markers of catecholamine production, particularly in tendinosis. It is known that adrenergic stimulation can induce proliferation in other Cells. The present study investigated the effects of an exogenously administered alpha-2 adrenergic agonist in an established in vivo Achilles tendinosis model (rabbit) and also in an in vitro human Tendon Cell culture model. The catecholamine producing enzyme tyrosine hydroxylase and the alpha-2A-adrenoreceptor (α2A AR) were expressed by tenocytes, and alpha-2 adrenergic stimulation had a proliferative effect on these Cells, in both models. The proliferation was inhibited by administration of an α2A AR antagonist, and the in vitro model further showed that the proliferative alpha-2A effect was mediated via a mitogenic Cell signaling pathway involving phosphorylation of extraCellular-signal-regulated kinases 1 and 2. The results indicate that catecholamines produced by tenocytes in tendinosis might contribute to the proliferative nature of the pathology through stimulation of the α2A AR, pointing to a novel target for future therapies. The study furthermore shows that animal models are not necessarily required for all aspects of this research.
-
human tenocytes are stimulated to proliferate by acetylcholine through an egfr signalling pathway
Cell and Tissue Research, 2013Co-Authors: Alex Scott, Ludvig J Backman, Gloria Fong, Gustav Andersson, Patrik DanielsonAbstract:Studies of human patellar and Achilles Tendons have shown that primary Tendon fibroblasts (tenocytes) not only have the capacity to produce acetylcholine (ACh) but also express muscarinic ACh receptors (mAChRs) through which ACh can exert its effects. In patients with tendinopathy (chronic Tendon pain) with tendinosis, the Tendon tissue is characterised by hyperCellularity and angiogenesis, both of which might be influenced by ACh. In this study, we have tested the hypothesis that ACh increases the proliferation rate of tenocytes through mAChR stimulation and have examined whether this mechanism operates via the extraCellular activation of the epidermal growth factor receptor (EGFR), as shown in other fibroblastic Cells. By use of primary human Tendon Cell cultures, we identified Cells expressing vimentin, tenomodulin and scleraxis and found that these Cells also contained enzymes related to ACh synthesis and release (choline acetyltransferase and vesicular acetylcholine transporter). The Cells furthermore expressed mAChRs of several subtypes. Exogenously administered ACh stimulated proliferation and increased the viability of tenocytes in vitro. When the Cells were exposed to atropine (an mAChR antagonist) or the EGFR inhibitor AG1478, the proliferative effect of ACh decreased. Western blot revealed increased phosphorylation, after ACh stimulation, for both EGFR and the extraCellular-signal-regulated kinases 1 and 2. Given that tenocytes have been shown to produce ACh and express mAChRs, this study provides evidence of a possible autocrine loop that might contribute to the hyperCellularity seen in tendinosis Tendon tissue.
-
substance p enhances collagen remodeling and mmp 3 expression by human tenocytes
Journal of Orthopaedic Research, 2013Co-Authors: Gloria Fong, Alex Scott, Ludvig J Backman, Patrik Danielson, David A Hart, Bob MccormackAbstract:The loss of collagen organization is considered a hallmark histopathologic feature of tendinosis. At the Cellular level, tenocytes have been shown to produce signal substances that were once thought to be restricted to neurons. One of the main neuropeptides implicated in tendinosis, substance P (SP), is known to influence collagen organization, particularly after injury. The aim of this study was to examine the influence of SP on collagen remodeling by primary human Tendon Cells cultured in vitro in three-dimensional collagen lattices. We found that SP stimulation led to an increased rate of collagen remodeling mediated via the neurokinin-1 receptor (NK-1 R), the preferred Cell receptor for SP. Gene expression analysis showed that SP stimulation resulted in significant increases in MMP3, COL3A1 and ACTA2 mRNA levels in the collagen lattices. Furthermore, cyclic tensile loading of Tendon Cell cultures along with the administration of exogenous SP had an additive effect on MMP3 expression. Immunoblotting confirmed that SP increased MMP3 protein levels via the NK-1 R. This study indicates that SP, mediated via NK-1 R, increases collagen remodeling and leads to increased MMP3 mRNA and protein expression that is further enhanced by cyclic mechanical loading.
-
substance p is a mechanoresponsive autocrine regulator of human tenocyte proliferation
PLOS ONE, 2011Co-Authors: Alex Scott, Ludvig J Backman, Gloria Fong, Gustav Andersson, Patrik DanielsonAbstract:It has been hypothesised that substance P (SP) may be produced by primary fibroblastic Tendon Cells (tenocytes), and that this production, together with the widespread distribution of the neurokinin-1 receptor (NK-1 R) in Tendon tissue, could play an important role in the development of tendinopathy, a condition of chronic Tendon pain and thickening. The aim of this study was to examine the possibility of endogenous SP production and the expression of NK-1 R by human tenocytes. Because tendinopathy is related to overload, and because the predominant tissue pathology (tendinosis) underlying early tendinopathy is characterized by tenocyte hyperCellularity, the production of SP in response to loading/strain and the effects of exogenously administered SP on tenocyte proliferation were also studied. A Cell culture model of primary human Tendon Cells was used. The vast majority of Tendon Cells were immunopositive for the tenocyte/fibroblast markers tenomodulin and vimentin, and immunocytochemical counterstaining revealed that positive immunoreactions for SP and NK-1 R were seen in a majority of these Cells. Gene expression analyses showed that mechanical loading (strain) of Tendon Cell cultures using the FlexCell© technique significantly increased the mRNA levels of SP, whereas the expression of NK-1 R mRNA decreased in loaded as compared to unloaded Tendon Cells. Reduced NK-1 R protein was also observed, using Western blot, after exogenously administered SP at a concentration of 10−7 M. SP exposure furthermore resulted in increased Cell metabolism, increased Cell viability, and increased Cell proliferation, all of which were found to be specifically mediated via the NK-1 R; this in turn involving a common mitogenic Cell signalling pathway, namely phosphorylation of ERK1/2. This study indicates that SP, produced by tenocytes in response to mechanical loading, may regulate proliferation through an autocrine loop involving the NK-1 R.
Halil Murat Aydin - One of the best experts on this subject based on the ideXlab platform.
-
use of cyclic strain bioreactor for the upregulation of key tenocyte gene expression on poly glycerol sebacate pgs sheets
Materials Science and Engineering: C, 2020Co-Authors: Pelin Deniz, Selcan Guler, Ekin Celik, Pezhman Hosseinian, Halil Murat AydinAbstract:Abstract The inadequate donor source and the difficulty of using natural grafts in Tendon repair and regeneration has led researchers to develop biodegradable and biocompatible synthetic based tissue equivalents. Poly(glycerol sebacate) (PGS) is a surface-erodible bioelastomer and has been increasingly investigated in a variety of biomedical applications. In this study, PGS elastomeric sheets were prepared by using a facile microwave method and used as elastomeric platform for the first time under mechanical stimulation to induct the tenocyte gene expression. It is revealed that elastomeric PGS sheets promote progenitor Tendon Cell structure by increasing proliferation and gene expression with regard to Tendon extraCellular matrix components. Human tenocytes were seeded onto poly(glycerol-sebacate) sheets and were cultured two days prior to transfer to dynamic culture in a bioreactor system. Cell culture studies were carried out for 12 days under 0%, 3% and 6% strain at 0.33 Hz. The PGS-Cell constructs were examined by using Scanning Electron Microscopy (SEM), Cell viability via live/dead staining using confocal microscopy, and GAG/DNA analysis. In addition, gene expression was examined using real-time polymerase chain reaction (RT-PCR). Tenocytes cultured upon PGS scaffolds under 6% cyclic strain exhibited Tendon-like gene expression profile compared to 3% and 0% strain groups. The results of this study show that PGS is a suitable material in promoting Tendon tissue formation under dynamic conditions.
