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Tissue Engineering. Part A

Ellen van Geffen, Arjan P M van Caam, Elly L Vitters, Henk M van Beuningen, Fons A van de Loo, Peter L E M van Lent, Marije I Koenders, Peter M van der Kraan
Introduction Osteoarthritis (OA) is characterized by progressive loss of articular cartilage. Because cartilage has limited regenerative capacity there is need for methods to repair damaged cartilage. Human mesenchymal stem cells (MSCs) have potential to differentiate into chondrocytes and can be used for cartilage tissue engineering in vitro and in vivo. However, the inflammatory micro-environment of a damaged joint impairs cartilage formation. The goal of this study was to investigate the potential protective effect of the anti-inflammatory cytokine interleukin-37 (IL37) on MSC-based cartilage formation in an OA-like micro-environment...
December 10, 2018: Tissue Engineering. Part A
Adriana Blazeski, Justin Lowenthal, Yin Wang, Roald Teuben, Renjun Zhu, Sharon Gerecht, Gordon Tomaselli, Leslie Tung
Arrhythmogenic cardiomyopathy (AC), a cause of sudden cardiac death among young and otherwise healthy individuals, is a heritable disease that can be modeled in vitro using patient-specific cardiac myocytes (CMs) from induced pluripotent stem cells. An understanding of underlying disease mechanisms, particularly in the early concealed stages, could lead to new diagnosis and treatment strategies. However, multicellular syncytial models are needed to understand how genetically-encoded mutations of the desmosomes that interconnect cells lead to aberrant electrical conduction and arrhythmias...
December 6, 2018: Tissue Engineering. Part A
Song-Yi Choi, Eun-Chong Han, Su-Hyung Hong, Tae-Geon Kwon, Youngkyun Lee, Heon-Jin Lee
Exosomes are membranous nanovesicles that naturally transport bio-molecules, including miRNAs, and play critical roles in intercellular communication. We found that the growth condition milieu of pre-osteoblast exosomes contains a high level of the let-7 miRNAs. After blocking exosome secretion, we found that osteogenic differentiation of pre-osteoblasts (MC3T3-E1 cells) decreased significantly whereas addition of exosomes from growth condition recovered osteogenic ability. The expression levels of osteogenic markers in MC3T3-E1 cells were changed through the ectopic expression of the let-7 mimics or inhibitors...
December 6, 2018: Tissue Engineering. Part A
Makwese Johannes Maepa, Cornelius Canu Ssemakulu, Keolebogile Shirley Caroline M Motaung
Articular cartilage defects are common, causing significant pain and morbidities. To date, tissue engineering techniques using adipose-derived mesenchymal stem cells have offered a promising modality for cartilage repair. In this study, we investigated the effects of Eucomis autumnalis (E. autumnalis) aqueous crude extracts in porcine adipose-derived mesenchymal stem cells (pADMSCs) to determine whether they can differentiate pADMSCs into chondrocytes. Porcine ADMSCs were prepared and treated with different concentrations of E...
December 4, 2018: Tissue Engineering. Part A
Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Marwa Hussein, Warda Hamitou, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade
Melanoma cell sensitivity to targeted therapy molecules is dependent on the tumor microenvironment (cell-cell and cell-extracellular matrix interactions). Three dimensional (3D) in vitro cell culture systems better reflect the native structural architecture of tissues and are attractive to investigate cellular interactions. We have developed and compared several metastatic melanoma models: melanoma cells (SK-MEL-28 and SK-MEL-3, BRAF V600E mutant and SK-MEL-2 BRAF wt) cultured as a monolayer (2D) and co-cultured on 3D dermal equivalents with fibroblasts to better unravel factors modulating cell sensitivity to a BRAF inhibitor (BRAFi, vemurafenib)...
December 1, 2018: Tissue Engineering. Part A
Joana Witt, Maria Borrelli, Sonja Mertsch, Gerd Geerling, Kristina Spaniol, Stefan Schrader
Conjunctival repair is a crucial part of ocular surface reconstruction. Due to limitations of currently used substitute tissues, there is a need for the development of new scaffolds of consistent quality for conjunctival reconstruction. This study explored the biocompatibility and surgical usability of plastic compressed collagen (PCC) as an alternative conjunctival substitute. PCC gels were produced by polymerization of collagen type I followed by plastic compression. Conjunctival defects were trepanned in rabbits and grafted using PCC or human amniotic membrane (AM) or remained ungrafted...
December 1, 2018: Tissue Engineering. Part A
Ilana Santos Ramalho, Edmara Tatiely Pedroso Bergamo, Adolfo Coelho de Oliveira Lopes, Camille Medina-Cintrón, Rodrigo Neiva, Lukasz Witek, Paulo G Coelho
AIM: To evaluate the influence of brain-derived neurotrophic factor (BDNF) in combination with collagen sponges on periodontal tissue regeneration. METHODS: Unilateral, "box-type" (4x5mm), one-wall intrabony defects were surgically created at posterior mandibular teeth in 14 Beagle dogs. Animals received all experimental groups and the defects were randomly treated as follow: Emdogain® (positive control) [EMD]; HeliPlug®+BDNF [H/B]; RCP®+BDNF [R/B]; negative control [Control]; TeruPlug®+BDNF [Tp/B] and TeruPlug®+BDNF2 [Ts/B]...
November 29, 2018: Tissue Engineering. Part A
Harold D Love, Mingfang Ao, Seiver Jorgensen, Lindsey Swearingen, Nicholas J Ferrell, Rachel C Evans, Leslie Gewin, Raymond C Harris, Roy Zent, Shuvo Roy, William H Fissell
End-stage renal disease afflicts nearly 750,000 Americans and claims over 100,000 lives annually in the United States. Kidney transplantation is associated with longest survival and least cost but is limited by scarcity of donor organs. Most patients are treated with hemodialysis. Each hemodialysis treatment consumes over 160 liters of water and anchors the patient to a machine for 12-15 hours per week. Cultured tubule cells can reduce the obligate fluid requirements of a bioengineered artificial kidney by concentrating wastes and reabsorbing filtered salt and water...
November 28, 2018: Tissue Engineering. Part A
Ji-Yun Ko, Jimin Lee, Jungsun Lee, Yang Hwan Ryu, Gun-Il Im
The authors developed <i>SOX-6, 9</i>-transfected human adipose stem cells (<sup><i>SOX-6, 9</i></sup>ASCs) to treat osteoarthritis (OA) and tested their effectiveness in arresting OA progression when injected intra-articularly (IA) in a surgically-induced OA caprine model. <i><sup>SOX-6, 9</sup></i>ASCs demonstrated similar <i>in vitro</i> chondrogenic potential, as determined by proteoglycan production, to ASCs treated with TGF-β<sub>2</sub> and BMP-7 (positive controls)...
November 28, 2018: Tissue Engineering. Part A
Timothy Chen, Gordana Vunjak-Novakovic
Ischemia-reperfusion injury (IRI) is a major, but potentially preventable contributor to the final tissue damage after an acute myocardial infarction. Many therapies have demonstrated successful reduction of IRI in preclinical settings, but none has shown improved outcomes in clinical studies. Part of the failure to translate new therapies to clinical settings can be attributed to the reliance on small animal models in preclinical studies. While animal models encapsulate the complexity of the systemic in vivo environment, they do not necessarily recapitulate human physiology...
November 20, 2018: Tissue Engineering. Part A
Ketao Wang, Zhongli Li, Ji Li, Weixiong Liao, Yuanyuan Qin, Ning Zhang, Xiulin Huo, Ning Mao, Heng Zhu
Platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) are promising tools for muscular-skeletal regeneration. However, increasing evidence has demonstrated controversial effects of PRP on the tissue regeneration. To obtain optimum PRP concentrations for MSC expansion and to accurately control osteogenic, adipocytic, and chondrogenic differentiation, MSCs were exposed to PRP alone or in combination with induction medium. We found that PRPs with the platelet concentration beyond 1500 × 109 pl/L were preferable to promote MSC proliferation...
November 20, 2018: Tissue Engineering. Part A
Xifeng Liu, Kevin A Fundora, Zifei Zhou, Alan Lee Miller, Lichun Lu
Current delivery of chemotherapy drugs to osteosarcoma is limited by the difficulties in overcoming the solid tumor microenvironment and the cardiotoxicity of doxorubicin (DOX). In previous work we found that phase separation could generate microspheres with high porosity. In this study, we applied these phase-separated porous microspheres as carriers for long-term anticancer drug delivery. Novel poly(propylene fumarate)-co-poly(l-lactic acid) microspheres incorporating DOX were fabricated by thermally induced phase separation...
November 20, 2018: Tissue Engineering. Part A
Xenos Petridis, Bas Pieter Beems, Phillip Tomson, Ben Scheven, Ben Giepmans, Jeroen Kuipers, Luc van der Sluis, Martin C Harmsen
In teeth with an injured pulp, dentin matrix orchestrates hard tissue repair through the release of dentin extracellular matrix components (dEMCs). dEMCs regulate the differentiation of resident mesenchymal stromal cells (MSCs), thereby affecting mineral deposition. Here, we show that low concentration solubilized dEMCs in osteogenic cultures of human umbilical cord mesenchymal stromal cells (UC-MSCs) and dental pulp stromal cells (DPSCs) enhanced mineral deposition, while adipose stromal cells (ASCs) were barely affected...
November 16, 2018: Tissue Engineering. Part A
Madison Marcinczyk, Andrew J Dunn, Gabriel Haas, Josh Madsen, Robert Scheidt, Krishna Patel, Muhamed Talovic, Koyal Garg
Volumetric muscle loss (VML) is characterized by a critical loss of muscle tissue that is accompanied by severe functional impairment and often long-term disability. Clinical therapies currently employed in the treatment of VML are ineffective at regenerating lost muscle and restoring function. In this study, we used a novel hydrogel composed of fibrinogen and laminin-111, to promote regeneration and recovery of VML traumatized muscle. Our previous study showed that these hydrogels exhibit fibrous structure and Young's modulus of ~2kPa while supporting C2C12 myoblast proliferation, myogenic marker expression, and pro-regenerative growth factor secretion in vitro...
November 14, 2018: Tissue Engineering. Part A
Elizabeth R Balmayor, Christopher Evans
RNA has several theoretical advantages as a therapeutic agent, but exploiting RNA in this fashion has faced several major hurdles. RNA is unstable and difficult to deliver across hydrophobic cell membranes. Moreover, extraneous RNAs activate innate immune nucleic acid sensors which make them toxic and inflammatory.
November 14, 2018: Tissue Engineering. Part A
Brittany Taylor, Sarah Indano, Yasonia Yankannah, Pushpendra Patel, Xiomara I Perez, Joseph W Freeman
Significant bone loss due to disease or traumatic injury requires surgical intervention to modulate the natural healing process of bone. The current bone grafting options, autografts and allografts, can potentially lead to donor site morbidity or mechanical failure over time. The use of tissue engineering is a promising alternative, but the mechanical stability and integrated vasculature in vivo still remains a major challenge. In this work, we introduce a scaffold that mimics the cylindrical structure of native cortical bone and provides biological cues without the addition of growth factors to promote the differentiation of stem cells along the angiogenic lineage...
November 13, 2018: Tissue Engineering. Part A
Lauren Grant, Ritu Raman, Caroline Cvetkovic, Meghan C Ferrall-Fairbanks, Gelson J Pagan-Diaz, Pierce Hadley, Eunkyung Ko, Manu O Platt, Rashid Bashir
Tissue engineered skeletal muscle plays an important role not only in the field of regenerative medicine, but also in emerging areas such as soft robotics, organ-on-a-chip disease models, and drug testing. However, further expansion of the applications of tissue engineered skeletal muscle models requires a suitable method for their long-term storage and shipment. Cryopreservation has long been the standard for cell storage, but the freezing of 3D tissues is accompanied by many complications due to heat and mass transfer limitations...
November 9, 2018: Tissue Engineering. Part A
Adeline Decambron, Nausikaa Devriendt, Nathanael Larochette, Mathieu Manassero, Marianne Bourguignon, Hanane El-Hafci, Hervé Petite, Véronique Viateau, Delphine Logeart-Avramoglou
The addition of bone morphogenetic protein-2 (BMP-2) with multipotent stromal cells (MSC) is an attractive strategy to enhance the bone-forming potential of MSC-based tissue engineering (TE) constructs. However, the effective dosage of BMP-2 remains to be determined. In this study, we evaluated the effects of human MSCs codelivered with BMP-2 at either low or high dosage on the bone-forming potential of constructs in a mice ectopic model. Our results showed that the addition of only low dose of BMP-2 was beneficial to enhance the bone-forming potential of MSCs, whereas high dose of BMP-2 overcame the advantage of combining this growth factor with MSCs...
November 9, 2018: Tissue Engineering. Part A
Yasaman Alinejad, Atma Adoungotchodo, Michael P Grant, Laura M Epure, John Antoniou, Fackson Mwale, Sophie Lerouge
Intervertebral disc (IVD) degeneration has been implicated as a major component of spine pathology. As the IVD degenerates, the tissue becomes dehydrated, fibrotic, fissured, acellular, and calcified. These changes can lead to disc bulging, herniation, Schmorl's nodes, inflammation, and hyperinnervation. Injectable hydrogels have received much attention in recent years as scaffold for seeding cells to replenish disc cellularity and restore disc properties and function. However, they generally present poor mechanical properties...
November 9, 2018: Tissue Engineering. Part A
Yanchun Liu, Yijie Wang, Jason Chakroff, Jed Johnson, Aidan Farrell, Gail E Besner
This study compared side-by-side the impact of donor age on the production of tissue-engineered small intestine (TESI). Each age represents a specific period of life: E18 for fetuses, 5-day-old pups for neonates, 21-day-old rats for weanlings, and 6-week-old rats for adults. The TESI produced was compared macroscopically and microscopically. The mechanism(s) contributing to the differences observed was explored by detecting proliferating cells in the TESI and by analyzing intestinal stem cell gene expression in donor cells...
November 7, 2018: Tissue Engineering. Part A
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