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European Cells & Materials

J Riegger, H G Palm, R E Brenner
Considering the poor intrinsic healing potential of articular cartilage, resident chondrogenic stem/progenitor cells (CSPCs) have gained attention in recent years. Although, CSPCs are attracted by a cartilage injury, knowledge about the post-traumatic behaviour and functional role of this cell population is fairly basic. The present study, not only elaborated on the regenerative capacities of CSPCs, but also illuminated potential immunomodulatory properties after cartilage trauma. Estimation of the CSPC population size within previously impacted cartilage explants by flow-cytometry revealed an increased percentage of CSPC-marker positive cells as compared to unimpacted tissue...
September 14, 2018: European Cells & Materials
L Germain, D Larouche, B Nedelec, I Perreault, L Duranceau, P Bortoluzzi, C Beaudoin Cloutier, H Genest, L Caouette-Laberge, A Dumas, A Bussière, E Boghossian, J Kanevsky, Y Leclerc, J Lee, M T Nguyen, V Bernier, B M Knoppers, V J Moulin, F A Auger
Split-thickness skin autografts (AGs) are the standard surgical treatment for severe burn injuries. However, the treatment of patients with substantial skin loss is limited by the availability of donor sites for skin harvesting. As an alternative to skin autografts, our research group developed autologous self-assembled skin substitutes (SASSs), allowing the replacement of both dermis and epidermis in a single surgical procedure. The aim of the study was to assess the clinical outcome of the SASSs as a permanent coverage for full-thickness burn wounds...
September 13, 2018: European Cells & Materials
R Castro-Viñuelas, C Sanjurjo-Rodríguez, M Piñeiro-Ramil, T Hermida-Gómez, I M Fuentes-Boquete, F J de Toro-Santos, F J Blanco-García, S M Díaz-Prado
The establishment of cartilage regenerative medicine is an important clinical issue, but the search for cell sources able to restore cartilage integrity proves to be challenging. Human mesenchymal stromal cells (MSCs) are prone to form epiphyseal or hypertrophic cartilage and have an age-related limited proliferation. On the other hand, it is difficult to obtain functional chondrocytes from human embryonic stem cells (ESCs). Moreover, the ethical issues associated with human ESCs are an additional disadvantage of using such cells...
September 11, 2018: European Cells & Materials
J Antons, M G Marascio, P Aeberhard, G Weissenberger, N Hirt-Burri, L A Applegate, P E Bourban, D P Pioletti
Tissue decellularisation has gained much attention in regenerative medicine as an alternative to synthetic materials. In decellularised tissues, biological cues can be maintained and provide cellular environments still unmet by synthetic materials. Supercritical CO2 (scCO2 ) has recently emerged as a promising alternative decellularisation technique to aggressive detergents; in addition, scCO2 provides innate sterilisation. However, to date, decellularisation with scCO2 is limited to only a few tissue types with low cellular density...
September 4, 2018: European Cells & Materials
T Onishi, T Shimizu, M Akahane, S Omokawa, A Okuda, T Kira, Y Inagak, Y Tanaka
The application of extracellular matrix (ECM) sheets without a scaffold is not extensively reported in bone regenerative medicine. The aim of the present study was to demonstrate that an osteogenic ECM sheet (OECMS) can retain ECM integrity and growth factors to enhance bone formation in a rat non-union model. OECMS was produced from osteogenic cell sheets (OCS). Collagen and growth factor [bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factors (VFGFs), basic fibroblast growth factor (bFGF) and transforming growth factor β1 (TGF-β1)] concentrations in the OECMS were quantified by enzyme-linked immunosorbent assay (ELISA)...
August 2, 2018: European Cells & Materials
J Melke, F Zhao, B van Rietbergen, K Ito, S Hofmann
Spinner flask bioreactors have often been employed for bone tissue engineering. However, the reasons for their success in facilitating bone growth remain inconclusive. It was hypothesised that engineered bone tissue formation can be attributed to mechanical stimuli, which can be predicted in the tissue engineered construct. To test the hypothesis and draw conclusions as to how mechanical stimulation affects cell behaviour, a multi- disciplinary approach using cell culture experiments and computational fluid dynamics (CFD) to simulate the complex flow within the spinner flask and scaffold was employed...
July 31, 2018: European Cells & Materials
R Bell, M A Robles-Harris, M Anderson, D Laudier, M B Schaffler, E L Flatow, N Andarawis-Puri
Tendinopathy is a common and progressive musculoskeletal disease. Increased apoptosis is an end-stage tendinopathy manifestation, but its contribution to the pathology of the disease is unknown. A previously established in vivo model of fatigue damage accumulation shows that increased apoptosis is correlated with the severity of induced tendon damage, even in early onset of the disease, supporting its implication in the pathogenesis of the disease. Consequently, this study aimed to determine: (1) whether apoptosis could be inhibited after fatigue damage and (2) whether its inhibition could lead to remodeling of the extracellular matrix (ECM) and pericellular matrix (PCM), to ultimately improve the mechanical properties of fatigue-damaged tendons...
July 30, 2018: European Cells & Materials
A K Haudenschild, B E Sherlock, X Zhou, J C Hu, J K Leach, L Marcu, K A Athanasiou
Tissue engineers utilize a battery of expensive, time-consuming and destructive techniques to assess the composition and function of engineered tissues. A nondestructive solution to monitor tissue maturation would reduce costs and accelerate product development. As a first step toward this goal, two nondestructive, label-free optical techniques, namely multispectral fluorescent lifetime imaging (FLIm) and time-resolved fluorescence spectroscopy (TRFS), were investigated for their potential in evaluating the biochemical and mechanical properties of articular cartilage...
July 27, 2018: European Cells & Materials
C L Yang, Y H Sun, W H Yu, X Z Yin, J Weng, B Feng
Pro-inflammatory phenotype (M1) macrophages initiate angiogenesis, while their prolonged activation can induce chronic inflammation. Anti-inflammatory phenotype (M2) macrophages promote vessel maturation and tissue regeneration. Biomaterials which can promote M2 polarisation after appropriate inflammation should enhance angiogenesis and wound healing. Herein, Interleukin-4 (IL-4), an anti-inflammatory cytokine, was adsorbed onto a titanium surface. Then, a genipin cross-linked gelatine hydrogel was coated onto the surface to delay IL-4 release...
July 25, 2018: European Cells & Materials
M M Gao, Q N Su, T Z Liang, J X Ma, T Z Liang, M J Stoddart, R G Richards, Z Y Zhou, N X Zou
Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is the main source of extracellular pyrophosphate. Along with tissue-nonspecific alkaline phosphatase (TNAP), ENPP1 plays an important role in balancing bone mineralisation. Although well established in pre-osteoblasts, the regulating mechanisms of ENPP1 in osteoblasts and osteocytes remain largely unknown. Using bioinformatic methods, osterix (Osx), an essential transcription factor in osteoblast differentiation and osteocyte function, was found to have five predicted binding sites on the ENPP1 promoter...
July 25, 2018: European Cells & Materials
V Fischer, M Haffner-Luntzer, M Amling, A Ignatius
Calcium and vitamin D are essential for maintaining bone health. Therefore, deficiencies in calcium and vitamin D are major risk factors for osteoporosis development. Because sufficient amounts of calcium are also required for fracture-callus mineralisation, compromised bone repair that is frequently observed in osteoporotic patients might be attributed to calcium and vitamin D deficiencies. Consequently, calcium and vitamin D supplementation represents a potential strategy for treating compromised fracture healing in osteoporotic patients...
June 22, 2018: European Cells & Materials
C S Chang, C Y Yang, H Y Hsiao, L Chen, I M Chu, M H Cheng, C H Tsao
Tissue engineering has the potential to overcome the limitations of tracheal reconstruction. To tissue-engineer a tracheal cartilage, auricular chondrocytes were encapsulated in a photocurable poly(ethylene glycol)/poly(ε-caprolactone) (PEG/PCL) hydrogel. Chondrogenic genes, including Sox9, Acan and Col2a1, were up-regulated in auricular chondrocytes after 2 weeks of in vitro cultivation in the PEG/PCL hydrogel. Co-cultivation of 70 % auricular chondrocytes and 30 % bone marrow mesenchymal stem cells (BMSCs) accelerated the chondrogenic genes' expression in the PEG/PCL hydrogel...
June 21, 2018: European Cells & Materials
M Majewski, P Heisterbach, C Jaquiéry, L Dürselen, A Todorov, I Martin, C H Evans, S A Müller
Several growth factors (GFs) are expressed as tendons heal, but it remains unknown whether their combined application enhances the healing process. This matter was addressed by applying a combination of basic fibroblast growth factor (bFGF), bone morphogenetic protein 12 (BMP-12) and transforming growth factor beta 1 (TGFβ1) in a rat Achilles tendon transection model. GFs were applied in one of the three following ways: i) direct application of all three factors at the time of surgery; ii) sequential, tiered percutaneous injection of individual factors immediately after surgery, 48 h and 96 h later; iii) load of all three factors onto a collagen sponge implanted at the time of surgery...
June 13, 2018: European Cells & Materials
B J Klotz, K S Lim, Y X Chang, B G Soliman, I Pennings, F P W Melchels, T B F Woodfield, A J Rosenberg, J Malda, D Gawlitta
In engineering of tissue analogues, upscaling to clinically-relevant sized constructs remains a significant challenge. The successful integration of a vascular network throughout the engineered tissue is anticipated to overcome the lack of nutrient and oxygen supply to residing cells. This work aimed at developing a multiscale bone-tissue-specific vascularisation strategy. Engineering pre-vascularised bone leads to biological and fabrication dilemmas. To fabricate channels endowed with an endothelium and suitable for osteogenesis, rather stiff materials are preferable, while capillarisation requires soft matrices...
May 30, 2018: European Cells & Materials
D M Varma, H A Lin, R G Long, G T Gold, A C Hecht, J C Iatridis, S B Nicoll
Back and neck pain are commonly associated with intervertebral disc (IVD) degeneration. Structural augmentation of diseased nucleus pulposus (NP) tissue with biomaterials could restore degeneration-related IVD height loss and degraded biomechanical behaviors; however, effective NP replacement biomaterials are not commercially available. This study developed a novel, crosslinked, dual-polymer network (DPN) hydrogel comprised of methacrylated carboxymethylcellulose (CMC) and methylcellulose (MC), and used in vitro, in situ and in vivo testing to assess its efficacy as an injectable, in situ gelling, biocompatible material that matches native NP properties and restores IVD biomechanical behaviors...
May 30, 2018: European Cells & Materials
J A Núñez, A Goring, B Javaheri, H Razi, D Gomez-Nicola, A A Pitsillides, P J Thurner, D Gomez-Nicola, P Schneider, C E Clarkin
Cortical bone is permeated by a system of pores, occupied by the blood supply and osteocytes. With ageing, bone mass reduction and disruption of the microstructure are associated with reduced vascular supply. Insight into the regulation of the blood supply to the bone could enhance the understanding of bone strength determinants and fracture healing. Using synchrotron radiation-based computed tomography, the distribution of vascular canals and osteocyte lacunae was assessed in murine cortical bone and the influence of age on these parameters was investigated...
May 23, 2018: European Cells & Materials
P Karschnia, C Scheuer, A Heß, T Später, M D Menger, M W Laschke
The seeding of tissue constructs with adipose tissue-derived microvascular fragments (ad-MVF) is an emerging pre-vascularisation strategy. Ad-MVF rapidly reassemble into new microvascular networks after in vivo implantation. Herein it was analysed whether this process was improved by erythropoietin (EPO). Ad-MVF were isolated from green fluorescent protein (GFP)+ as well as wild-type C57BL/6 mice and cultivated for 24 h in medium supplemented with EPO (20 IU/mL) or vehicle. Freshly isolated, non-cultivated ad-MVF served as controls...
May 9, 2018: European Cells & Materials
J G Sykes, J H Kuiper, J B Richardson, S Roberts, K T Wright, N J Kuiper
High hopes have been pinned on regenerative medicine strategies in order to prevent the progression of cartilage damage to osteoarthritis, particularly by autologous chondrocyte implantation (ACI). The loss of chondrocyte phenotype during in vitro monolayer expansion, a necessary step to obtain sufficient cell numbers, may be a key limitation in ACI. In this study, it was determined whether a shorter monolayer expansion approach could improve chondrogenic differentiation. The effects of two supplement types, foetal bovine serum (FBS) and Stemulate™ (a commercial source of human platelet lysate), on the expansion and re-differentiation potential of human chondrocytes, isolated from five individuals, were compared...
May 1, 2018: European Cells & Materials
D Mumcuoglu, S Fahmy-Garcia, Y Ridwan, J Nicke, E Farrell, S G Kluijtmans, G J van Osch
The aim of the current study was to reduce the clinically used supra-physiological dose of bone morphogenetic protein-2 (BMP-2) (usually 1.5 mg/mL), which carries the risk of adverse events, by using a more effective release system. A slow release system, based on an injectable hydrogel composed of BMP-2-loaded recombinant collagen-based microspheres and alginate, was previously developed. Time- and dose-dependent subcutaneous ectopic bone formation within this system and bone regeneration capacity in a calvarial defect model were investigated...
April 26, 2018: European Cells & Materials
M Wallenborn, O Petters, D Rudolf, H Hantmann, M Richter, P Ahnert, L Rohani, J J Smink, G C Bulwin, W Krupp, R M Schulz, H Holland
In the development of cell-based medicinal products, it is crucial to guarantee that the application of such an advanced therapy medicinal product (ATMP) is safe for the patients. The consensus of the European regulatory authorities is: "In conclusion, on the basis of the state of art, conventional karyotyping can be considered a valuable and useful technique to analyse chromosomal stability during preclinical studies". 408 chondrocyte samples (84 monolayers and 324 spheroids) from six patients were analysed using trypsin-Giemsa staining, spectral karyotyping and fluorescence in situ hybridisation, to evaluate the genetic stability of chondrocyte samples from non-clinical studies...
April 23, 2018: European Cells & Materials
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