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Tissue Engineering. Part A

Maurits Geert Laurent Olthof, Lichun Lu, Marianna A Tryfonidou, Loek Loozen, Behdad Pouran, Michael J Yaszemski, Björn Meij, Wouter Dhert, Jacqueline Alblas, Diederik H R Kempen
The main challenge in BMP-2 based application lies in finding strategies that prolong its effective period, as it has a short biological half-life. Several BMP-2 release profiles have shown to enhance bone formation at various application sites. However, it remains to be determined which BMP-2 release profile best augments bone formation and whether this effect is location-dependent. Therefore, the aim of this study was to investigate the effect of BMP-2 release from oligo[(polyethylene glycol) fumarate] bis(2-(methacryloyloxy)ethyl) phosphate (OPF-BP) composites on the osteoinductive efficacy at ectopic versus orthotopic application...
August 13, 2018: Tissue Engineering. Part A
Giorgio Giatsidis, Julien Succar, Anthony Haddad, Gianluigi Lago, Clara Schaffer, Wangxing Wang, Benjamin Schilling, Evangelina Chnari, Hajime Matsumine, Dennis P Orgill
Autologous adipose tissue grafting is a popular strategy for soft tissue reconstruction; yet its clinical outcomes are often suboptimal. Lack of metabolic and architectural support at recipient sites affects the capacity of cellularized autologous grafts to survive after transplantation. Allograft adipose matrices (AAMs) are composed of the extracellular matrices of adipose tissue. They can provide critical bio-physical cues and create a supportive microenvironment for autologous graft survival. Using murine models, we have optimized the in vivo use of an injectable AAM obtained from human cadaveric tissue and processed to remove lipid and cellular components...
August 7, 2018: Tissue Engineering. Part A
Raman Deep Singh, Matthew Hillestad, Christopher Livia, Mark Li, Alexey Alekseev, Tyra A Witt, Paul G Stalboerger, Satsuki Yamada, Andre Terzic, Atta Behfar
Myocardial infarction occurs every 36 seconds or nearly 1 million times in the United States. The treatment of acute myocardial infarction (AMI) treatment has been revolutionized with coronary reperfusion ensuring over 96% in-hospital survival. There has however been a paucity in technological advancement in the field of acute coronary syndrome, with nearly 30% of individuals progressing toward heart failure after AMI. This has engendered a pandemic of ischemic heart failure worldwide, mandating the development of off-the-shelf regenerative interventions, including gene-encoded therapies, capable to acutely target the injured myocardium...
July 26, 2018: Tissue Engineering. Part A
Jr-Jiun Liou, Benjamin B Rothrauff, Peter G Alexander, Rocky S Tuan
Post-traumatic and focal cartilage defects of the knee affect over 3 million Americans annually. Autologous cell-based cartilage repair, for example, autologous chondrocyte implantation, is limited by the need for ex vivo chondrocyte expansion and donor site morbidity. Mesenchymal stem cells (MSCs), owing to their relative ease of isolation, higher replication activity, and chondrogenic potential, represent an alternative reparative cell type. Platelet-rich plasma (PRP) is an autologous, growth factor-rich biologic preparation that has recently received increasing attention and use as a therapeutic adjunct for the treatment of degenerative joint diseases, and there is evidence suggesting that PRP acts by promoting stem cell proliferation and tissue healing...
July 23, 2018: Tissue Engineering. Part A
Michael House, Jeannie Kelly, Nikolai Klebanov, Kyoko Yoshida, Kristin Myers, David L Kaplan
Preterm birth is a leading cause of morbidity and mortality in newborns. Babies born prematurely are at increased risk of lifelong health problems, including neurodevelopmental abnormalities. Cervical shortening precedes preterm birth in many women. Cervical shortening is caused, in part, by excessive softening of the extracellular matrix (ECM) of the cervical stroma. In clinical obstetrics, cervical shortening prompts treatment with supplemental progesterone to prevent preterm birth. However, progesterone-mediated effects on the cervical ECM are not well understood...
July 23, 2018: Tissue Engineering. Part A
Bart Versteeg, Lenie J van den Broek, Sylvia M Bruisten, Margriet Mullender, Henry J C de Vries, Susan Gibbs
Organotypic models to investigate host-microbiome interactions are still a challenge for the field of tissue engineering. This is particularly the case for organs such as the urethra. Several cell line, animal, and tissue models are available to study Chlamydia trachomatis infections, but none fully reflects natural infection in native human tissue. Therefore, we developed an organotypic reconstructed human urethral model (RhU) to study invasive and noninvasive strains of C. trachomatis. Primary urethra cells were used to reconstruct epithelium on a fibroblast populated collagen-fibrin hydrogel, yielding a RhU...
July 23, 2018: Tissue Engineering. Part A
Loek D Loozen, Moyo C Kruyt, Angela Vandersteen, Angela H M Kragten, Michiel Croes, F Cumhur Öner, Jacqueline Alblas
Ex vivo nonviral gene delivery of bone inductive factors has the potential to heal bone defects. Due to their inherent role in new bone formation, multipotent stromal cells (MSCs) have been studied as the primary target cell for gene delivery in a preclinical setting. The relative contribution of autocrine and paracrine mechanisms, and the need of osteogenic cells, remains unclear. This study investigates the contribution of MSCs as producer of transgenic bone morphogenetic proteins (BMPs) and to what extent the seeded MSCs participate in actual osteogenesis...
July 23, 2018: Tissue Engineering. Part A
Jun Homma, Hidekazu Sekine, Katsuhisa Matsuura, Eiji Kobayashi, Tatsuya Shimizu
Restenosis after catheter or surgical intervention substantially affects the prognosis of arterial occlusive disease. Mesenchymal stem cells (MSCs) may have antistenotic effects on injured arteries. MSC transplantation from the adventitial side of an artery is safer than endovascular transplantation but has not been extensively examined. In this study, a rat model of femoral artery injury was used to compare the antistenotic effects of transplanted cell sheets and transplanted cell suspensions. Rat adipose-derived stem cells (ASCs) were used as the source of MSCs...
July 23, 2018: Tissue Engineering. Part A
Yu Seon Kim, Mollie Marie Smoak, Anthony J Melchiorri, Antonios G Mikos
This report seeks to provide an update of the tissue engineering industry from 2011 to 2018. Public tissue engineering companies with a presence in the United States were the focus of this report due to the publicly accessible financial data that they provide on an annual basis. Over the course of this analysis, 48 tissue engineering companies were identified, 20 of which were in the commercial phase of development and had tissue engineering products on the market. These 20 companies made an estimated $9 billion in sales of tissue engineering-related products in 2017...
July 20, 2018: Tissue Engineering. Part A
Chen Chen, Xiaoping Zhang, Qiao Lin, Nathaniel Remlinger, Thomas W Gilbert, Y Peter Di
The extracellular matrix (ECM) is composed of a complex mixture of structural and functional macromolecules that are important during growth, development, and wound repair. In this study, we seek to determine if an ECM derived from the porcine urinary bladder, specifically urinary bladder matrix (UBM), can act to prevent bacterial infection in the context of lung injury. Here, we examined a digested form of UBM, which prevented bacterial biofilm formed by both Gram-positive bacteria (GPB) such as methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative bacteria (GNB) including Pseudomonas aeruginosa (PA) and Klebsiella pneumoniae (KP) in vitro...
July 18, 2018: Tissue Engineering. Part A
Brianna M Roux, Banu Akar, Wei Zhou, Katerina Stojkova, Beatriz Barrera, Jovan G Brankov, Eric M Brey
Vascular networks provide nutrients, oxygen, and progenitor cells that are essential for bone function. It has been proposed that a pre-formed vascular network may enhance the performance of engineered bone. In this study vascular networks were generated from human umbilical vein endothelial cell (HUVEC) and mesenchymal stem cell (MSC) spheroids encapsulated in fibrin scaffolds, and the stability of pre-formed vascular networks and their effect on bone regeneration were assessed in an in vivo bone model. Under optimized culture conditions, extensive vessel-like networks formed throughout the scaffolds in vitro...
July 18, 2018: Tissue Engineering. Part A
Wen Zhang, Rodolfo E De La Vega, Michael J Coenen, Carlos J Peniche Silva, Manish Aneja, Christian Plank, Martijn van Griensven, Christopher Evans, Elizabeth R Balmayor
The first therapeutic application of mRNA was suggested over two decades ago. However, its application was constrained by the ability of mRNA to activate the innate immune response, cytotoxicity and poor potency. We and others recently demonstrated that these undesirable properties of mRNA may be overcome by alterating its structure. In this study, we developed a new chemically modified mRNA coding for BMP-2 with improved osteogenic features. To develop this new construct, we removed from the mRNA sequence the following undesirable elements: an upstream ORF in the 5'UTR and a polyadenylation element together with an AU-rich tract in the 3'UTR...
July 16, 2018: Tissue Engineering. Part A
Aurimas Širka, Deepak Bushan Raina, Hanna Isaksson, K Elizabeth Tanner, Alfredas Smailys, Ashok Kumar, Šarūnas Tarasevičius, Magnus Tägil, Lars Lidgren
This study investigated bone regeneration in the femoral neck canal of osteoporotic rats using a novel animal model. A calcium sulphate (CS)/hydroxyapatite (HA) carrier was used to deliver a bisphosphonate, zoledronic acid (ZA), locally, with or without added recombinant human bone morphogenic protein-2 (rhBMP-2). Twenty-eight-week-old ovariectomized Sprague-Dawley rats were used. A 1 mm diameter and 8 mm long defect was created in the femoral neck by drilling from the lateral cortex in the axis of the femoral neck, leaving the surrounding cortex intact...
July 16, 2018: Tissue Engineering. Part A
Josephine Lembong, Max J Lerman, Tami J Kingsbury, Curt I Civin, John P Fisher
Stem cell cultures within perfusion bioreactors, while efficient in obtaining cell numbers, often lack the similarity to native tissues and consequently cell phenotype. We develop a three-dimensional (3D)-printed fluidic chamber for dynamic stem cell culture, with emphasis on control over flow and substrate curvature in a 3D environment, two physiologic features of native tissues. The chamber geometry, consisting of an array of vertical cylindrical pillars, facilitates actin-mediated localization of human mesenchymal stem cells (hMSCs) within ∼200 μm distance from the pillars, enabling spatial patterning of hMSCs and endothelial cells in cocultures and subsequent modulation of calcium signaling between these two essential cell types in the bone marrow microenvironment...
July 13, 2018: Tissue Engineering. Part A
Nguyen P T Huynh, Jonathan M Brunger, Catherine C Gloss, Franklin T Moutos, Charles A Gersbach, Farshid Guilak
Tissue engineering approaches for the repair of osteochondral defects using biomaterial scaffolds and stem cells have remained challenging due to the inherent complexities of inducing cartilage-like matrix and bone-like matrix within the same local environment. Members of the transforming growth factor β (TGFβ) family have been extensively utilized in the engineering of skeletal tissues, but have distinct effects on chondrogenic and osteogenic differentiation of progenitor cells. The goal of this study was to develop a method to direct human bone marrow-derived mesenchymal stem cells (MSCs) to deposit either mineralized matrix or a cartilaginous matrix rich in glycosaminoglycan and type II collagen within the same biochemical environment...
July 13, 2018: Tissue Engineering. Part A
Linli Li, Yiqun He, Xujun Chen, Youhai Dong
The physiological reconstruction of artificial vertebral laminae without epidural scar tissue formation or spinal cord compression has been challenging. Mechanical stimulations have been reported to play an important role in bone formation and bone remodeling. In this study, we designed a comparison study to investigate the effect of continuous cerebrospinal fluid pulsation (CSFP) stress on the remodeling of artificial vertebral laminae. Mesenchymal stem cells derived from rabbit umbilical cord Wharton's Jelly were induced for osteogenic differentiation for 3 weeks before seeding on the hydroxyapatite-collagen I scaffolds to construct the tissue-engineered laminae (TEL)...
July 12, 2018: Tissue Engineering. Part A
Tse-Hsiang Chen, Chafik Ghayor, Barbara Siegenthaler, Felix Schuler, Jasmine Rüegg, Michael de Wild, Franz E Weber
Additive manufacturing of bone tissue engineering scaffolds will become a key element to realize personalized bone tissue engineering approaches in the near future. Several additive manufacturing processes are based on extrusion where the deposition of the filament will result in a 3-dimensional lattice structure. Recently we studied diverse lattice structures for bone tissue engineering realized by laser sintering of titanium. Here, we used lithography based ceramic manufacturing of lattice structures to produce scaffolds from tri-calcium phosphates and to compare them in vivo to congruent titanium scaffolds manufactured with the identical CAD data to look for material-based differences in bony healing...
July 12, 2018: Tissue Engineering. Part A
Riddhi A Gangolli, Sean M Devlin, Jonathan Arye Gerstenhaber, Peter Istvan Lelkes, Maobin Yang
<b>Introduction:</b> Regenerative Endodontics (RE) is a clinical procedure that aims to regenerate the dentin-pulp complex (DPC) inside the root canal. Current clinical outcomes of RE are unpredictable, and the regenerated tissue lacks the spatial organization seen in normal DPC. The purpose of this study was to develop and characterize in vitro a bilayered scaffold with distinct porosities on each side that supports differential penetration and odontoblastic differentiation of cultured human dental pulp stem cells (DPSCs)...
July 7, 2018: Tissue Engineering. Part A
Juliane D Glaeser, Khosrowdad Salehi, Linda E A Kanim, Dmitriy Sheyn, Zachary NaPier, Phillip H Behrens, Leslie Garcia, Jason M Cuéllar, Hyun W Bae
Recombinant human bone morphogenic protein-2 (BMP-2)-loaded absorbable collagen sponges (ACS) have been successfully used to enhance bone formation and to induce spinal fusion in humans. However, side effects, such as soft tissue edema and inflammation, have been reported. NEMO binding domain peptide (NBD) inhibits activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a central regulator of immune response. In this study, we investigated NBD's potential to reduce BMP-2-induced soft tissue inflammation without affecting BMP-2-mediated spinal fusion in rat...
July 3, 2018: Tissue Engineering. Part A
Robert D Hume, Lorraine Berry, Stefanie Reichelt, Michael D'Angelo, Jenny Gomm, Ruth E Cameron, Christine J Watson
Adipocytes are one of the major stromal cell components of the human breast. These cells play a key role in the development of the gland and are implicated in breast tumorigenesis. Frequently, directional stromal collagen I fibers are found surrounding aggressive breast tumors. These fibers enhance breast cancer cell migration and are associated with poor patient prognosis. We sought to recapitulate these stromal components in vitro to provide a three-dimensional (3D) model comprising human adipose tissue and anisotropic collagen fibers...
July 3, 2018: Tissue Engineering. Part A
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