Bone Tissue Engineering Under Xenogeneic-Free Conditions in a Large Animal Model as a Basis for Early Clinical Applicability

2017 ◽  
Vol 23 (5-6) ◽  
pp. 208-222 ◽  
Author(s):  
Annika Weigand ◽  
Justus P. Beier ◽  
Rafael Schmid ◽  
Tobias Knorr ◽  
David Kilian ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Animal Model ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Large Animal Model ◽  
Large Animal ◽  
Clinical Applicability

THE IMPORTANCE OF LARGE ANIMAL MODELS FOR TRANSLATIONAL RESEARCH IN BONE TISSUE ENGINEERING

2012 ◽  
Vol 24 (1) ◽  
pp. 287
Author(s):  
S. J. Hollister ◽  
M. B. Wheeler ◽  
S. E. Feinberg ◽  
W. L. Murphy
Keyword(s):  
Tissue Engineering ◽  
Animal Model ◽  
Animal Models ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Large Animal ◽  
Engineering Studies ◽  
Large Animal Models ◽  
Clinical Indications ◽  
Human Situation

The translation of bone tissue engineering (BTE) research to clinical use has been absymal1. Outside of bone void filler biomaterials, only Bone Morphogenetic Protein 2 (BMP2) has made significant inroads to clinical practice, and even BMP2 use has been associated with significant complications including death, dysphagia, and ectopic bone formation. The dearth of BTE products can be attributed to two main causes: (1) the need to develop BTE systems, that successfully integrate scaffolds, growth factors like BMP2 and cells and (2) the need to adapt and implement such systems for a wide variety of clinical indications in CranioMaxilloFacial (CMF), Spine and Orthopedic Surgery. Of course, to fully develop BTE systems (Issue 1) and adapt them to realistic clinical indications, we must be able to test such systems in bone defects that are as close to the human situation as possible. Thus, the use of domestic large animals for bone tissue engineering is critical, as these animals provide challenges in both defect volume and functional loading that can mimic the human situation. In addition, FDA approval for BTE products either through a 510K or IDE/IND/PMA pathway requires the use of a large pre-clinical animal model. However, despite this need, only approximately 60 large animal bone tissue-engineering studies have been published in the past 10 years. Furthermore, NIH has funded only 8% of these studies, and of the 17 bone tissue engineering studies supported by NIH in 2010, only three utilized a large animal model, and none of these used an animal larger than a rabbit. Clearly, increased translation and regulatory approval of BTE therapies will require greater testing in large animal models. We will discuss the current dearth of relevant pre-clinical studies in BTE, and present our work addressing these issues by developing BTE systems (integrated scaffold, growth factor and stem-cell constructs) and testing these systems for realistic clinical applications using the Yorkshire and other swine species as a large pre-clinical animal model. We will detail our work in developing BTE systems for CMF reconstruction and spine fusion in the swine model. Reference Hollister S. J. and Murphy W. L. Scaffold translation: barriers between concept and clinic. Tissue Eng. B. (in press).

scholarly journals Brazilian minipig as a large-animal model for basic research and stem cell-based tissue engineering. Characterization and in vitro differentiation of bone marrow-derived mesenchymal stem cells

2014 ◽  
Vol 22 (3) ◽  
pp. 218-227 ◽  
Author(s):  
Roberta Targa STRAMANDINOLI-ZANICOTTI ◽  
André Lopes CARVALHO ◽  
Carmen Lúcia Kuniyoshi REBELATTO ◽  
Laurindo Moacir SASSI ◽  
Maria Fernanda TORRES ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Bone Marrow ◽  
Animal Model ◽  
Mesenchymal Stem Cells ◽  
Basic Research ◽  
Large Animal Model ◽  
Large Animal ◽  
In Vitro Differentiation

Acceleration of Vascularized Bone Tissue-Engineered Constructs in a Large Animal Model Combining Intrinsic and Extrinsic Vascularization

2015 ◽  
Vol 21 (9-10) ◽  
pp. 1680-1694 ◽  
Author(s):  
Annika Weigand ◽  
Justus P. Beier ◽  
Andreas Hess ◽  
Thomas Gerber ◽  
Andreas Arkudas ◽  
...  
Keyword(s):  
Animal Model ◽  
Bone Tissue ◽  
Large Animal Model ◽  
Large Animal ◽  
Model Combining ◽  
Vascularized Bone

scholarly journals Characterization of an Ovine Bilateral Critical Sized Bone Defect Iliac Wing Model to Examine Treatment Modalities Based on Bone Tissue Engineering

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jennifer L. Lansdowne ◽  
Declan Devine ◽  
Ursula Eberli ◽  
Pieter Emans ◽  
Tim J. M. Welting ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Bone Defect ◽  
Bone Growth ◽  
Treatment Modalities ◽  
Large Animal ◽  
New Treatment ◽  
Negative Controls ◽  
Positive Controls

Critical sized bone defect (CSBD) animal models are used to evaluate and confirm efficacy and potency of new treatment modalities based on bone tissue engineering before the latter can be applied in clinical practice. In this study, a bilateral CSBD model in the iliac wings of sheep is described in detail. To demonstrate that this is a large animal CSBD model in sheep, bone healing within the defect left empty (negative control) or filled with autologous corticocancellous bone graft (clinical gold standard, positive control) was assessed using micro-CT, histology, histomorphometric, and fluorochrome analysis. After three months, new bone into the defect site was formed across the whole defect in the positive controls but limited to the edge of the defects in the negative controls. Bone volume in the positive controls was statistically higher than in the negative controls, with the latter having less than 10% new bone growth. There were no intraoperative or postoperative complications. The model described here represents a reliable and reproducible bilateral CSBD in sheep with low morbidity that can be used forin vivoevaluation of new treatment modalities based on bone tissue engineering.

scholarly journals Use of Perfusion Bioreactors and Large Animal Models for Long Bone Tissue Engineering

2014 ◽  
Vol 20 (2) ◽  
pp. 126-146 ◽  
Author(s):  
Leandro S. Gardel ◽  
Luís A. Serra ◽  
Rui L. Reis ◽  
Manuela E. Gomes
Keyword(s):  
Tissue Engineering ◽  
Animal Models ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Long Bone ◽  
Large Animal ◽  
Large Animal Models ◽  
Perfusion Bioreactors

scholarly journals 3D-Printing of Hierarchically Designed and Osteoconductive Bone Tissue Engineering Scaffolds

Materials ◽  
2020 ◽  
Vol 13 (8) ◽  
pp. 1836 ◽  
Author(s):  
Nicolas Söhling ◽  
Jonas Neijhoft ◽  
Vinzenz Nienhaus ◽  
Valentin Acker ◽  
Jana Harbig ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Survival ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Modular Design ◽  
Negative Impact ◽  
Frame Structure ◽  
Large Animal ◽  
Large Animal Models ◽  
Novel Scaffold

In Bone Tissue Engineering (BTE), autologous bone-regenerative cells are combined with a scaffold for large bone defect treatment (LBDT). Microporous, polylactic acid (PLA) scaffolds showed good healing results in small animals. However, transfer to large animal models is not easily achieved simply by upscaling the design. Increasing diffusion distances have a negative impact on cell survival and nutrition supply, leading to cell death and ultimately implant failure. Here, a novel scaffold architecture was designed to meet all requirements for an advanced bone substitute. Biofunctional, porous subunits in a load-bearing, compression-resistant frame structure characterize this approach. An open, macro- and microporous internal architecture (100 µm–2 mm pores) optimizes conditions for oxygen and nutrient supply to the implant’s inner areas by diffusion. A prototype was 3D-printed applying Fused Filament Fabrication using PLA. After incubation with Saos-2 (Sarcoma osteogenic) cells for 14 days, cell morphology, cell distribution, cell survival (fluorescence microscopy and LDH-based cytotoxicity assay), metabolic activity (MTT test), and osteogenic gene expression were determined. The adherent cells showed colonization properties, proliferation potential, and osteogenic differentiation. The innovative design, with its porous structure, is a promising matrix for cell settlement and proliferation. The modular design allows easy upscaling and offers a solution for LBDT.

scholarly journals A comparison of the microarchitecture of lower limb long bones between some animal models and humans: a review

2013 ◽  
Vol 58 (No. 7) ◽  
pp. 339-351 ◽  
Author(s):  
VJ Cvetkovic ◽  
SJ Najman ◽  
JS Rajkovic ◽  
ALj Zabar ◽  
PJ Vasiljevic ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Animal Model ◽  
Animal Models ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Lower Limb ◽  
Bone Microarchitecture ◽  
Anatomical Location ◽  
Long Bones ◽  
Canal Diameter

Animal models are unavoidable and indispensable research tools in the fields of bone tissue engineering and experimental orthopaedics. The fact that there is not ideal animal model as well as the differences in the bone microarchitecture and physiology between animals and humans are complicate factors and make model implementation difficult. Therefore, the tendency should be directed towards extrapolation of the results from one animal model to another or from animal model to humans. So far, this is the first paper which provides an overview on the microarchitecture of lower limb long bones and discusses data related to osteon diameter, osteon canal diameter and their orientation, as well as intracortical canals and trabecular tissue microarchitecture in commonly used animal models compared to humans depending on age, gender and anatomical location of the bone. Understanding the differences between animal model and human bone microarchitecture should enable a more accurate extrapolation of experimental results from one animal model to another or from animal models to humans in the fields of bone tissue engineering and experimental orthopaedics. Also, this should be helpful in making decisions on which animal models are the most suitable for particular preclinical testing.  

HYDROXYAPATITE, ALGINATE, AND CHITOSAN FOR BONE SCAFFOLDS: SPECTROSCOPY STUDY

2016 ◽  
Vol 19 (2) ◽  
pp. 93-100
Author(s):  
Lalita El Milla
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Functional Groups ◽  
Bone Growth ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Tissue Engineering Scaffolds ◽  
Hydroxyapatite Powder ◽  
Materials Used

Scaffolds is three dimensional structure that serves as a framework for bone growth. Natural materials are often used in synthesis of bone tissue engineering scaffolds with respect to compliance with the content of the human body. Among the materials used to make scafffold was hydroxyapatite, alginate and chitosan. Hydroxyapatite powder obtained by mixing phosphoric acid and calcium hydroxide, alginate powders extracted from brown algae and chitosan powder acetylated from crab. The purpose of this study was to examine the functional groups of hydroxyapatite, alginate and chitosan. The method used in this study was laboratory experimental using Fourier Transform Infrared (FTIR) spectroscopy for hydroxyapatite, alginate and chitosan powders. The results indicated the presence of functional groups PO43-, O-H and CO32- in hydroxyapatite. In alginate there were O-H, C=O, COOH and C-O-C functional groups, whereas in chitosan there were O-H, N-H, C=O, C-N, and C-O-C. It was concluded that the third material containing functional groups as found in humans that correspond to the scaffolds material in bone tissue engineering.

PLGA+HA/βTCP scaffold incorporating simvastatin: a promising biomaterial for bone tissue engineering

2020 ◽  
Author(s):  
Mariane Beatriz Sordi ◽  
Ariadne Cristiane Cabral da Cruz ◽  
Águedo Aragones ◽  
Mabel Mariela Rodríguez Cordeiro ◽  
Ricardo de Souza Magini
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Thermal Analyses ◽  
Chemical Properties ◽  
Biological Properties ◽  
Scanning Calorimetry ◽  
Evaporation Technique ◽  
Porosity Analysis ◽  
Biphasic Ceramic

The aim of this study was to synthesize, characterize, and evaluate degradation and biocompatibility of poly(lactic-co-glycolic acid) + hydroxyapatite / β-tricalcium phosphate (PLGA+HA/βTCP) scaffolds incorporating simvastatin (SIM) to verify if this biomaterial might be promising for bone tissue engineering. Samples were obtained by the solvent evaporation technique. Biphasic ceramic particles (70% HA, 30% βTCP) were added to PLGA in a ratio of 1:1. Samples with SIM received 1% (m:m) of this medication. Scaffolds were synthesized in a cylindric-shape and sterilized by ethylene oxide. For degradation analysis, samples were immersed in PBS at 37 °C under constant stirring for 7, 14, 21, and 28 days. Non-degraded samples were taken as reference. Mass variation, scanning electron microscopy, porosity analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetry were performed to evaluate physico-chemical properties. Wettability and cytotoxicity tests were conducted to evaluate the biocompatibility. Microscopic images revealed the presence of macro, meso, and micropores in the polymer structure with HA/βTCP particles homogeneously dispersed. Chemical and thermal analyses presented very similar results for both PLGA+HA/βTCP and PLGA+HA/βTCP+SIM. The incorporation of simvastatin improved the hydrophilicity of scaffolds. Additionally, PLGA+HA/βTCP and PLGA+HA/βTCP+SIM scaffolds were biocompatible for osteoblasts and mesenchymal stem cells. In summary, PLGA+HA/βTCP scaffolds incorporating simvastatin presented adequate structural, chemical, thermal, and biological properties for bone tissue engineering.

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