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1.
The applications of regenerative medicine in sinus lift procedures: A systematic review.
Correia, F, Pozza, DH, Gouveia, S, Felino, A, Faria E Almeida, R
Clinical implant dentistry and related research. 2018;(2):229-242
Abstract
BACKGROUND Findings in regenerative medicine applied to the sinus lift procedures. PURPOSE Evaluate the effectiveness of regenerative medicine in sinus lift. MATERIALS AND METHODS An extensive search for manuscripts were performed by using different combinations of keywords and MeSH terms (Pub-med; Embase; Scopus; Web of Science Core Collection; Medline; Current Contents Connect; Derwent Innovations Index; Scielo Citation Index; Cochrane library). The full text selected articles are written in English, Portuguese, Spanish, Italian, German, or French, and published until 28 of November 2016. Inclusion criteria were: implant osteointegration, radiographic, histologic, and/or histomorphometric analysis, clinical studies in humans using of regenerative medicine. This systematic review was performed by selecting only randomized controlled clinical trials and controlled clinical trials. RESULTS Eighteen published studies (11 CT and 7 RCT) were considered eligible for inclusion in the present systematic review. These studies demonstrated considerable variation of biomaterial and cell technics used, study design, sinus lift technic, outcomes, follow-up, and results. CONCLUSION Only few studies have demonstrated potential of regenerative medicine in sinus lift; further randomized clinical trials are needed to achieve more accurate results.
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2.
Perfusion applied to a 3D model of bone metastasis results in uniformly dispersed mechanical stimuli.
Liu, B, Han, S, Hedrick, BP, Modarres-Sadeghi, Y, Lynch, ME
Biotechnology and bioengineering. 2018;(4):1076-1085
Abstract
Breast cancer most frequently metastasizes to the skeleton. Bone metastatic cancer is incurable and induces wide-spread bone osteolysis, resulting in significant patient morbidity and mortality. Mechanical cues in the skeleton are an important microenvironmental parameter that modulate tumor formation, osteolysis, and tumor cell-bone cell signaling, but which mechanical signals are the most beneficial and the corresponding molecular mechanisms are unknown. We focused on interstitial fluid flow based on its well-known role in bone remodeling and in primary breast cancer. We created a full-scale, microCT-based computational model of a 3D model of bone metastasis undergoing applied perfusion to predict the internal mechanical environment during in vitro experimentation. Applied perfusion resulted in uniformly dispersed, heterogeneous fluid velocities, and wall shear stresses throughout the scaffold's interior. The distributions of fluid velocity and wall shear stress did not change within model sub-domains of varying diameter and location. Additionally, the magnitude of these stimuli is within the range of anabolic mechanical signals in the skeleton, verifying that our 3D model reflects previous in vivo studies using anabolic mechanical loading in the context of bone metastasis. Our results indicate that local populations of cells throughout the scaffold would experience similar mechanical microenvironments.
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3.
Alternatives to Autologous Bone Graft in Alveolar Cleft Reconstruction: The State of Alveolar Tissue Engineering.
Liang, F, Leland, H, Jedrzejewski, B, Auslander, A, Maniskas, S, Swanson, J, Urata, M, Hammoudeh, J, Magee, W
The Journal of craniofacial surgery. 2018;(3):584-593
Abstract
Alveolar cleft reconstruction has historically relied on autologous iliac crest bone grafting (ICBG), but donor site morbidity, pain, and prolonged hospitalization have prompted the search for bone graft substitutes. The authors evaluated bone graft substitutes with the highest levels of evidence, and highlight the products that show promise in alveolar cleft repair and in maxillary augmentation. This comprehensive review guides the craniofacial surgeon toward safe and informed utilization of biomaterials in the alveolar cleft.A literature search was performed to identify in vitro human studies that fulfilled the following criteria: Level I or Level II of evidence, ≥30 subjects, and a direct comparison between a autologous bone graft and a bone graft substitute. A second literature search was performed that captured all studies, regardless of level of evidence, which evaluated bone graft substitutes for alveolar cleft repair or alveolar augmentation for dental implants. Adverse events for each of these products were tabulated as well.Sixteen studies featuring 6 bone graft substitutes: hydroxyapatite, demineralized bone matrix (DBM), β-tricalcium phosphate (TCP), calcium phosphate, recombinant human bone morphogenic protein-2 (rhBMP-2), and rhBMP7 fit the inclusion criteria for the first search. Through our second search, the authors found that DBM, TCP, rhBMP-2, and rhBMP7 have been studied most extensively in the alveolar cleft literature, though frequently in studies using less rigorous methodology (Level III evidence or below). rhBMP-2 was the best studied and showed comparable efficacy to ICBG in terms of volume of bone regeneration, bone density, and capacity to accommodate tooth eruption within the graft site. Pricing for products ranged from $290 to $3110 per 5 mL.The balance between innovation and safety is a complex process requiring constant vigilance and evaluation. Here, the authors profile several bone graft substitutes that demonstrate the most promise in alveolar cleft reconstruction.
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4.
From skeletal development to the creation of pluripotent stem cell-derived bone-forming progenitors.
Tam, WL, Luyten, FP, Roberts, SJ
Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 2018;(1750)
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Abstract
Bone has many functions. It is responsible for protecting the underlying soft organs, it allows locomotion, houses the bone marrow and stores minerals such as calcium and phosphate. Upon damage, bone tissue can efficiently repair itself. However, healing is hampered if the defect exceeds a critical size and/or is in compromised conditions. The isolation or generation of bone-forming progenitors has applicability to skeletal repair and may be used in tissue engineering approaches. Traditionally, bone engineering uses osteochondrogenic stem cells, which are combined with scaffold materials and growth factors. Despite promising preclinical data, limited translation towards the clinic has been observed to date. There may be several reasons for this including the lack of robust cell populations with favourable proliferative and differentiation capacities. However, perhaps the most pertinent reason is the failure to produce an implant that can replicate the developmental programme that is observed during skeletal repair. Pluripotent stem cells (PSCs) can potentially offer a solution for bone tissue engineering by providing unlimited cell sources at various stages of differentiation. In this review, we summarize key embryonic signalling pathways in bone formation coupled with PSC differentiation strategies for the derivation of bone-forming progenitors.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.
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5.
Generation and characterisation of decellularised human corneal limbus.
Spaniol, K, Witt, J, Mertsch, S, Borrelli, M, Geerling, G, Schrader, S
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2018;(3):547-557
Abstract
PURPOSE Limbal epithelial stem cells (LESC) reside in a niche in the corneo-scleral transition zone. Deficiency leads to pain, corneal opacity, and eventually blindness. LESC transplantation of ex-vivo expanded human LESC on a carrier such as human amniotic membrane is a current treatment option. We evaluated decellularised human limbus (DHL) as a potential carrier matrix for the transplantation of LESC. METHODS Human corneas were obtained from the local eye bank. The limbal tissue was decellularised by sodium desoxychelate and DNase solution and sterilised by γ-irradiation. Native limbus- and DHL-surface structures were assessed by scanning electron microscopy and collagen ultrastructure using transmission electron microscopy. Presence and preservation of limbal basement membrane proteins in native limbus and DHL were analysed immunohistochemically. Absence of DNA after decellularisation was assessed by Feulgen staining and DNA quantification. Presence of immune cells was explored by CD45 staining, and potential cytotoxicity was tested using a cell viability assay. RESULTS In the DHL, the DNA content was reduced from 1.5 ± 0.3 μg/mg to 0.15 ± 0.01 μg/mg; the three-dimensional structure and the arrangement of the collagen fibrils were preserved. Main basement membrane proteins such as collagen IV, laminin, and fibronectin were still present after decellularisation and γ-irradiation. CD45-expressing cells were evident neither in the native limbus nor in the DHL. DHL did not convey cytotoxicity. CONCLUSIONS The extracellular matrix (ECM) of the limbus provides a tissue specific morphology and three-dimensionality consisting of particular ECM proteins. It therefore represents a substantial component of the stem cell niche. The DHL provides a specific limbal niche surrounding, and might serve as an easily producible carrier matrix for LESC transplantation.
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Donor Site Location Is Critical for Proliferation, Stem Cell Capacity, and Osteogenic Differentiation of Adipose Mesenchymal Stem/Stromal Cells: Implications for Bone Tissue Engineering.
Reumann, MK, Linnemann, C, Aspera-Werz, RH, Arnold, S, Held, M, Seeliger, C, Nussler, AK, Ehnert, S
International journal of molecular sciences. 2018;(7)
Abstract
Human adipose mesenchymal stem/stromal cells (Ad-MSCs) have been proposed as a suitable option for bone tissue engineering. However, donor age, weight, and gender might affect the outcome. There is still a lack of knowledge of the effects the donor tissue site might have on Ad-MSCs function. Thus, this study investigated proliferation, stem cell, and osteogenic differentiation capacity of human Ad-MSCs obtained from subcutaneous fat tissue acquired from different locations (abdomen, hip, thigh, knee, and limb). Ad-MSCs from limb and knee showed strong proliferation despite the presence of osteogenic stimuli, resulting in limited osteogenic characteristics. The less proliferative Ad-MSCs from hip and thigh showed the highest alkaline phosphatase (AP) activity and matrix mineralization. Ad-MSCs from the abdomen showed good proliferation and osteogenic characteristics. Interestingly, the observed differences were not dependent on donor age, weight, or gender, but correlated with the expression of Sox2, Lin28A, Oct4α, and Nanog. Especially, low basal Sox2 levels seemed to be pivotal for osteogenic differentiation. Our data clearly show that the donor tissue site affects the proliferation and osteogenic differentiation of Ad-MSCs significantly. Thus, for bone tissue engineering, the donor site of the adipose tissue from which the Ad-MSCs are derived should be adapted depending on the requirements, e.g., cell number and differentiation state.
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Atrial-like Engineered Heart Tissue: An In Vitro Model of the Human Atrium.
Lemme, M, Ulmer, BM, Lemoine, MD, Zech, ATL, Flenner, F, Ravens, U, Reichenspurner, H, Rol-Garcia, M, Smith, G, Hansen, A, et al
Stem cell reports. 2018;(6):1378-1390
Abstract
Cardiomyocytes (CMs) generated from human induced pluripotent stem cells (hiPSCs) are under investigation for their suitability as human models in preclinical drug development. Antiarrhythmic drug development focuses on atrial biology for the treatment of atrial fibrillation. Here we used recent retinoic acid-based protocols to generate atrial CMs from hiPSCs and establish right atrial engineered heart tissue (RA-EHT) as a 3D model of human atrium. EHT from standard protocol-derived hiPSC-CMs (Ctrl-EHT) and intact human muscle strips served as comparators. RA-EHT exhibited higher mRNA and protein concentrations of atrial-selective markers, faster contraction kinetics, lower force generation, shorter action potential duration, and higher repolarization fraction than Ctrl-EHTs. In addition, RA-EHTs but not Ctrl-EHTs responded to pharmacological manipulation of atrial-selective potassium currents. RA- and Ctrl-EHTs' behavior reflected differences between human atrial and ventricular muscle preparations. Taken together, RA-EHT is a model of human atrium that may be useful in preclinical drug screening.
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Development of a synthetic tissue engineered three-dimensional printed bioceramic-based bone graft with homogenously distributed osteoblasts and mineralizing bone matrix in vitro.
Adel-Khattab, D, Giacomini, F, Gildenhaar, R, Berger, G, Gomes, C, Linow, U, Hardt, M, Peleska, B, Günster, J, Stiller, M, et al
Journal of tissue engineering and regenerative medicine. 2018;(1):44-58
Abstract
Over the last decade there have been increasing efforts to develop three-dimensional (3D) scaffolds for bone tissue engineering from bioactive ceramics with 3D printing emerging as a promising technology. The overall objective of the present study was to generate a tissue engineered synthetic bone graft with homogenously distributed osteoblasts and mineralizing bone matrix in vitro, thereby mimicking the advantageous properties of autogenous bone grafts and facilitating usage for reconstructing segmental discontinuity defects in vivo. To this end, 3D scaffolds were developed from a silica-containing calcium alkali orthophosphate, using, first, a replica technique - the Schwartzwalder-Somers method - and, second, 3D printing, (i.e. rapid prototyping). The mechanical and physical scaffold properties and their potential to facilitate homogenous colonization by osteogenic cells and extracellular bone matrix formation throughout the porous scaffold architecture were examined. Osteoblastic cells were dynamically cultured for 7 days on both scaffold types with two different concentrations of 1.5 and 3 × 109 cells/l. The amount of cells and bone matrix formed and osteogenic marker expression were evaluated using hard tissue histology, immunohistochemical and histomorphometric analysis. 3D-printed scaffolds (RPS) exhibited more micropores, greater compressive strength and silica release. RPS seeded with 3 × 109 cells/l displayed greatest cell and extracellular matrix formation, mineralization and osteocalcin expression. In conclusion, RPS displayed superior mechanical and biological properties and facilitated generating a tissue engineered synthetic bone graft in vitro, which mimics the advantageous properties of autogenous bone grafts, by containing homogenously distributed terminally differentiated osteoblasts and mineralizing bone matrix and therefore is suitable for subsequent in vivo implantation for regenerating segmental discontinuity bone defects. Copyright © 2016 John Wiley & Sons, Ltd.
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Interactions of methacryloylated gelatin and heparin modulate physico-chemical properties of hydrogels and release of vascular endothelial growth factor.
Claaßen, C, Southan, A, Grübel, J, Tovar, GEM, Borchers, K
Biomedical materials (Bristol, England). 2018;(5):055008
Abstract
Gelatin hydrogels are used as tissue engineering scaffolds and systems for controlled release due to their inherent biodegradability and biocompatibility. In this study gelatin methacryloyl(-acetyl) (GM/A) with various degrees of methacryloylation (DM) and methacryl-modified heparin (HepM) were cross-linked radically via thermal-redox initiation. Investigation of gel yields (79.4%-85.8%) and equilibrium degrees of swelling (EDS; 564.8%-750.3%) by an experimental design approach suggested interaction effects between the applied HepM mass fraction and the DM of gelatin. HepM reduced the cross-linking effectivity (gel yield) only when added to GM with low DM (83% without HepM, 79% with HepM) but not when added to GM with high DM. For EDS combined impacts of the physical and chemical nature of the applied biopolymers are indicated: the elevated hydrophilicity and low cross-linking potential of HepM enhanced EDS in GM gels with low DM (Ø 1.1-fold increase), and lowered the storage moduli of all GM formulations (Ø 1.2-fold decrease). Vascular endothelial growth factor (VEGF) loading before cross-linking of gels resulted in major loss of functional growth factor (Ø 0.5% release), while loading after cross-linking was successful and significant release was detected over 28 days (6.4%-10.4% release). Release kinetics were mainly controlled by the VEGF concentration used for loading, and thus VEGF release and physico-chemical properties of the hydrogels can be tuned independently from each other in a broad range.
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A review on versatile applications of blends and composites of pullulan with natural and synthetic polymers.
Tabasum, S, Noreen, A, Maqsood, MF, Umar, H, Akram, N, Nazli, ZI, Chatha, SAS, Zia, KM
International journal of biological macromolecules. 2018;(Pt A):603-632
Abstract
Pullulan is a non-ionic, linear, water-soluble and a neutral polysaccharide. It is composed of α-(1,6) repeated maltotriose units via α-(1,4) glycosidic bond having chemical formula (C6H10O5)n. It shows non-immunogenic, non-toxic, non-carcinogenic and non-mutagenic properties. It is used in food edible coatings, films, as flocculant, foaming agent and adhesive. It may also be used as a carrier for bioactive compounds and a protective packaging for food and pharmaceutical products. Therefore, it is blended with different polymers such as carrageenan, mucilages, chitosan, cellulose, sodium alginate, starch, polyethyleneimine, whey-protein, polyisopropylacrylamide, histone, jeffamine, polyamidoamine, pemulen, hyaluronic acid, polyvinyl alcohol and caboxymethyl cellulose. In this article, a comprehensive overview of combination of pullulan with natural and synthetic polymers and their applications in biomedical field involving drug delivery system, tissue engineering, wound healing and gene therapy, is presented. It also describes the utilization of pullulan based materials in food industry, water treatment and pharmaceutical industry. All the technical scientific issues have been addressed; highlighting the recent advancements.