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Tissue Engineering. Part A

Chenjun Zhai, Hao Fei, Junzheng Hu, Zhen Wang, Shun Xu, Qiang Zuo, Zeng Li, Zhen Wang, Wenwei Liang, Weimin Fan
Repair of articular cartilage defects using bilayered scaffolds is problematic because tissue-engineered cartilage is prone to overgrowth toward subchondral bone, resulting in structural abnormalities of cartilage and subchondral bone. A "twice freeze-drying" technique was used to construct a dense isolation layer between the cartilage and subchondral bone layers in an integrated bilayered scaffold to prevent cartilage from excessive downgrowth. Briefly, beta-tricalcium phosphate was used for the subchondral bone layer of the scaffold, high-concentration chitosan/gelatin solution for the dense isolation layer, and low-concentration chitosan/gelatin solution for the cartilage layer...
October 19, 2018: Tissue Engineering. Part A
Kentaro Endo, Naoki Fujita, Takayuki Nakagawa, Ryohei Nishimura
Damaged articular cartilage has limited healing capacity due to the lack of blood supply. Tissue engineering using the chondrogenic potential of mesenchymal stem cells (MSCs) is a promising approach for cartilage regenerative therapy. Canines are a relevant animal model for cartilage regeneration, as they suffer from spontaneous cartilage injury similar to humans. However, the chondrogenic capacity and optimal conditions for chondrogenesis in canine MSCs have not been documented. In this study, we investigated the effect of preconditioning with fibroblast growth factor-2 (FGF-2) and fetal bovine serum (FBS) in chondrogenic induction medium on canine MSC chondrogenesis...
October 15, 2018: Tissue Engineering. Part A
Sweelin Chew, Yukai Zeng, David Khoo, Mike Yu Yuan Hong, Sohail Ahmed, Keng-Hwee Chiam
Stem cell fate specification is known to be regulated by mechanical cues such as cell-cell interaction and the rigidity of the extracellular matrix (ECM). At present, spheroid cultures of stem cells are conventional starting materials to generate organoids with tissue-like structures. However, the influence of ECM rigidity on stem cell mechanobiology has only been briefly explored in in vitro 3-dimensional (3D) cultures, which presents better physiological relevance than monolayer cultures. To investigate how ECM rigidity acts on neural stem cell (NSCs) to drive specific biological processes, we performed live 3D-imaging on neurospheres in medium, in 1% and 1...
October 15, 2018: Tissue Engineering. Part A
Gordana Vunjak-Novakovic, Timothy Chen
Ischemia-reperfusion injury is a major but potentially preventable contributor to the final tissue damage after acute myocardial infarction. Many therapies have demonstrated successful reduction of ischemia-reperfusion injury in preclinical settings, but none have 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...
October 12, 2018: Tissue Engineering. Part A
Mark H Murdock, Sherin David, Ilea T Swinehart, Janet E Reing, Kien Tran, Kathrin Gassei, Kyle E Orwig, Stephen F Badylak
Successful human spermatogonial stem cell (hSSC) culture could enable cell therapy for male infertility. Mammalian extracellular matrix (ECM) promotes mitogenesis, migration, and/or differentiation of various stem/progenitor cells and can plausibly facilitate hSSC survival in culture. Hydrogel forms of human testicular ECM (htECM), porcine testicular ECM (ptECM), porcine small intestinal submucosa ECM (SIS), and porcine urinary bladder ECM (UBM) were used to coat tissue culture plates for hSSC culture. In addition, hSSC were cultured on Sandos inbred mice (SIM) 6-thioguanine-resistance, ouabain-resistant (STO) mouse embryonic fibroblast feeder cells (control), murine laminin, or human laminin...
October 12, 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 co-delivered 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...
October 12, 2018: Tissue Engineering. Part A
Qin Mao, Phuong D Nguyen, Rabie M Shanti, Shihong Shi, Pasha Shakoori, Qunzhou Zhang, Anh D Le
A fully functional recovery of peripheral nerve injury remains a major challenge and an unmet clinical need. Recent evidence has reported promising therapeutic effects of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in experimental models of tissue injuries and inflammatory diseases, but less is known about their effects on peripheral nerve regeneration. Here, we investigated the effects of GMSC-derived EVs on peripheral nerve regeneration of crush-injured mice sciatic nerves. In vivo studies mimicking clinical nerve repair showed that locally wrapping gelfoam embedded with GMSC-derived EVs at the crush injury site promoted functional recovery and axonal regeneration, which were comparable to effects conferred by direct transplantation of GMSCs...
October 12, 2018: Tissue Engineering. Part A
Brianna M Roux, Banu Akar, Wei Zhou, Katerina Stojkova, Beatriz Barrera, Jovan Brankov, Eric M Brey
Vascular networks provide nutrients, oxygen, and progenitor cells that are essential for bone function. It has been proposed that a preformed vascular network may enhance the performance of engineered bone. In this study vascular networks were generated from human umbilical vein endothelial cell and mesenchymal stem cell spheroids encapsulated in fibrin scaffolds, and the stability of preformed 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...
October 12, 2018: Tissue Engineering. Part A
Raziel Rojas-Rodriguez, Jorge Lujan-Hernandez, So Yun Min, Tiffany DeSouza, Patrick Teebagy, Anand Desai, Heather Tessier, Robert Slamin, Leah Siegel-Reamer, Cara Berg, Angel Baez, Janice Lalikos, Silvia Corvera
Adipose tissue is used extensively in reconstructive and regenerative therapies, but transplanted fat often undergoes cell death, leading to inflammation, calcification and requirement for further revision surgery. Previously we have found that mesenchymal progenitor cells within human adipose tissue can proliferate in 3-dimensional culture under pro-angiogenic conditions. These cells (Primed ADipose progenitor cells=PADS) robustly differentiate into adipocytes in-vitro (ad-PADS). The goal of the present study is to determine whether ad-PADS can form structured adipose tissue in-vivo, with potential for use in surgical applications...
October 11, 2018: Tissue Engineering. Part A
Megan M Swim, Ambra Albertario, Dominga Iacobazzi, Massimo Caputo, Mohamed T Ghorbel
Current vascular replacement grafts used in congenital heart defect corrective surgery have poor longevity and growth potential. Recipient patients often require multiple reoperations. Tissue engineering has the promise to produce a graft with the potential to grow, remodel and repair. Here we aimed at developing an amnion-based scaffold suitable for cardiovascular tissue engineering applications and in vivo usage. The developed human amnion-based scaffold was made by an enzymatic decellularization process followed by freeze-drying as a single or multi-layered structure...
October 4, 2018: Tissue Engineering. Part A
Yanchun Liu, Yijie Wang, Jason Chakroff, Jed Johnson, Aidan Farrell, Gail E Besner
OBJECTIVE: The objective of this study was to compare the impact of different ages of cell donors on the production of tissue engineered small intestine (TESI). METHODS: Four different ages of Lewis rats were chosen as donors of intestinal organoids: E18 fetuses, 5 day old newborns, 21 day old weanlings, and 6 week old adults. Harvested intestine was exposed to enzymatic digestion to release intestinal stem cell-containing organoids. Organoids were purified, concentrated, and seeded onto tubular polyglycolic acid (PGA) scaffolds...
October 4, 2018: Tissue Engineering. Part A
Ayelen Helling, Priyalakshmi Viswanathan, Katerina Cheliotis, Seyedeh Atefeh Mobasseri, Ying Yang, Alicia J El Haj, Fiona M Watt
The junction between the epidermal and dermal layers of human skin undulates, the width and depth of the undulations varying with age and disease. We previously showed that when primary human epidermal keratinocytes are seeded on collagen-coated undulating static polydimethylsiloxane (PDMS) elastomer substrates, the stem cells, differentiated cells and proliferating cells become patterned in response to cues from the underlying substrate. To investigate how patterning occurs over time, we have now created a dynamic model, in which a collagen-coated PLGA membrane is placed over a polyimide sheet containing circular holes, differing in diameter and spacing...
October 3, 2018: Tissue Engineering. Part A
Rei Kuwabara, Masahide Hamaguchi, Takuya Fukuda, Shimon Sakaguchi, Hiroo Iwata
A method which realizes allogeneic islets transplantation into a subcutaneous site under no immunosuppressive treatment has been desired for the treatment of type 1 diabetes. In this study, two donor-recipient combinations were employed: F344 rat donors (RT-1<sup>lv1</sup>) and ACI rat recipients (RT-1<sup>a</sup>); and Wistar rat donors (closed colony) and Lewis rat recipients (RT-1<sup>l</sup>). An agarose rod , which carried basic fibroblast growth factor (bFGF; 50 μg/rod, agarose-bFGF rod), was implanted into each of two dorsal subcutaneous sites of a streptozotocin induced diabetic rat for 7 days, and the space was formed by removal of the rod...
October 3, 2018: Tissue Engineering. Part A
Xike Chen, Akihiro Yamashita, Miho Morioka, Toshika Senba, Takashi Kamatani, Akira Watanabe, Azuma Kosai, Noriyuki Tsumaki
New cell and tissue sources are needed for the regenerative treatment of articular cartilage damage. Human induced pluripotent stem cells (hiPSCs) are an abundant cell source due to their self-renewal capacity. Hyaline cartilage tissue particles derived from hiPSCs (hiPS-Carts), 1-3 mm in diameter, are one candidate source that can be used for transplantation. When transplanted to fill the defects of articular cartilage, hiPS-Carts form a repair tissue by integrating with each other and with adjacent host tissue...
October 3, 2018: Tissue Engineering. Part A
Wen Zhang, Rodolfo E De La Vega, Michael J Coenen, Sebastian A Müller, Carlos J Peniche Silva, Manish K Aneja, Christian Plank, Martijn van Griensven, Christopher H Evans, Elizabeth R Balmayor
The first therapeutic application of messenger RNA (mRNA) was suggested more than 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 open reading frame in the 5'-untranslated region (UTR) and a polyadenylation element together with an AU-rich tract in the 3'UTR...
October 3, 2018: Tissue Engineering. Part A
Lindsey Tamiko Saldin, Shil Patel, Li Zhang, Luai Huleihel, George S Hussey, David Gabriele Nascari, Lina Maria Quijano, Xue Li, Divya Raghu, Anant Kaur Bajwa, Nicholas G Smith, Christopher Chi-Heng Chung, Ashten N Omstead, Juliann E Kosovec, Blair A Jobe, Neill J Turner, Ali H Zaidi, Stephen F Badylak
Extracellular matrix (ECM) bioscaffolds have been successfully used to treat 5 esophageal adenocarcinoma (EAC) patients following resection of neoplastic mucosal tissue. The present study evaluated the in vitro effect of ECM harvested from non-malignant, decellularized tissue on EAC cell phenotype to understand the molecular mechanisms underlying the clinical findings. Non-malignant (Het-1A), metaplastic (CP-A), and neoplastic (SK-GT-4, OE33) esophageal epithelial cells were exposed to ECM degradation products (250 ug/mL) prepared from heterologous urinary bladder tissue or homologous esophageal mucosa tissue, and evaluated for cell morphology, cell function, and EAC signaling pathways...
September 27, 2018: Tissue Engineering. Part A
Yasaman Alinejad, Atma Adoungotchodo, Michael 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...
September 25, 2018: Tissue Engineering. Part A
HungJun Lin, TsungJen Wang, TingWei Li, YaoYuan Chang, Ming Thau Sheu, Yi-You Huang, Der-Zen Liu
Because of the lack of donor corneas, an important area of research is the development of bioengineered corneal scaffolds in order to treat corneal blindness. Decellularized cornea has become a prominent area of research to satisfy the clinical demand. However, the limitation of its application is that a suitable decellularization procedure has not been developed. Organic acids are naturally constituents in animal tissues and plants, and could be safely neutralized into harmless salts. In this study, we developed decellularized porcine corneal (dPC) scaffolds that were prepared by organic acid treatment...
September 22, 2018: Tissue Engineering. Part A
Raman Deep Singh, Matthew L Hillestad, Christopher Livia, Mark Li, Alexey E Alekseev, Tyra A Witt, Paul G Stalboerger, Satsuki Yamada, Andre Terzic, Atta Behfar
Myocardial infarction occurs every 36 s or nearly 1 million times in the United States. The treatment of acute myocardial infarction (AMI) 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...
September 21, 2018: Tissue Engineering. Part A
Wang Ketao, Li Zhongli, Li Ji, Liao Weixiong, Qin Yuanyuan, Zhang Ning, Huo Xiulin, Mao Ning, 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...
September 20, 2018: Tissue Engineering. Part A
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