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.

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 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 Encapsulation of Rat Bone Marrow Derived Mesenchymal Stem Cells in Alginate Dialdehyde/Gelatin Microbeads with and without Nanoscaled Bioactive Glass for In Vivo Bone Tissue Engineering

Materials ◽  
2018 ◽  
Vol 11 (10) ◽  
pp. 1880 ◽  
Author(s):  
Ulrike Rottensteiner-Brandl ◽  
Rainer Detsch ◽  
Bapi Sarker ◽  
Lara Lingens ◽  
Katrin Köhn ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Marrow ◽  
Cell Survival ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Immune Reaction ◽  
Three Dimensional ◽  
High Cell ◽  
Rat Bone

Alginate dialdehyde (ADA), gelatin, and nano-scaled bioactive glass (nBG) particles are being currently investigated for their potential use as three-dimensional scaffolding materials for bone tissue engineering. ADA and gelatin provide a three-dimensional scaffold with properties supporting cell adhesion and proliferation. Combined with nanocristalline BG, this composition closely mimics the mineral phase of bone. In the present study, rat bone marrow derived mesenchymal stem cells (MSCs), commonly used as an osteogenic cell source, were evaluated after encapsulation into ADA-gelatin hydrogel with and without nBG. High cell survival was found in vitro for up to 28 days with or without addition of nBG assessed by calcein staining, proving the cell-friendly encapsulation process. After subcutaneous implantation into rats, survival was assessed by DAPI/TUNEL fluorescence staining. Hematoxylin-eosin staining and immunohistochemical staining for the macrophage marker ED1 (CD68) and the endothelial cell marker lectin were used to evaluate immune reaction and vascularization. After in vivo implantation, high cell survival was found after 1 week, with a notable decrease after 4 weeks. Immune reaction was very mild, proving the biocompatibility of the material. Angiogenesis in implanted constructs was significantly improved by cell encapsulation, compared to cell-free beads, as the implanted MSCs were able to attract endothelial cells. Constructs with nBG showed higher numbers of vital MSCs and lectin positive endothelial cells, thus showing a higher degree of angiogenesis, although this difference was not significant. These results support the use of ADA/gelatin/nBG as a scaffold and of MSCs as a source of osteogenic cells for bone tissue engineering. Future studies should however improve long term cell survival and focus on differentiation potential of encapsulated cells in vivo.

scholarly journals Epigallocatechin Gallate-Modified Gelatin Sponges Treated by Vacuum Heating as a Novel Scaffold for Bone Tissue Engineering

Molecules ◽  
2018 ◽  
Vol 23 (4) ◽  
pp. 876 ◽  
Author(s):  
Yoshitomo Honda ◽  
Yoshihiro Takeda ◽  
Peiqi Li ◽  
Anqi Huang ◽  
Satoshi Sasayama ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Epigallocatechin Gallate ◽  
Vacuum Heating ◽  
Novel Scaffold

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

scholarly journals Synthesis and characterization of a novel scaffold for bone tissue engineering based on Wharton's jelly

2017 ◽  
Vol 105 (4) ◽  
pp. 1034-1045 ◽  
Author(s):  
Cristian Martínez ◽  
Carlos Fernández ◽  
Miguel Prado ◽  
Andres Ozols ◽  
Daniel G. Olmedo
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Wharton’S Jelly ◽  
Synthesis And Characterization ◽  
Wharton's Jelly ◽  
Novel Scaffold

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 Physical Properties and Biocompatibility of a Core-Sheath Structure Composite Scaffold for Bone Tissue Engineering In Vitro

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Chuangjian Wang ◽  
Guolin Meng ◽  
Laquan Zhang ◽  
Zuo Xiong ◽  
Jian Liu
Keyword(s):  
Tissue Engineering ◽  
Physical Properties ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Composite Scaffold ◽  
Control Group ◽  
The Novel ◽  
Novel Scaffold ◽  
Sheath Structure

Scaffolds play a critical role in the practical realization of bone tissue engineering. The purpose of this study was to assess whether a core-sheath structure composite scaffold possesses admirable physical properties and biocompatibility in vitro. A novel scaffold composed of poly(lactic-co-glycolic acid)/β-tricalcium phosphate (PLGA/β-TCP) skeleton wrapped with Type I collagen via low-temperature deposition manufacturing (LDM) was prepared, and bone mesenchymal stem cells (BMSCs) were used to evaluate cell behavior on the scaffold. PLGA/β-TCP skeleton was chosen as the control group. Physical properties were evaluated by pority ratio, compressive strength, and Young’s modulus. Scanning electron microscope (SEM) was used to study morphology of cells. Hydrophilicity was evaluated by water absorption ratio. Cell proliferation was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (MTT). Osteogenic differentiation of BMSCs was evaluated by alkaline phosphates activity (ALP). The results indicated that physical properties of the novel scaffold were as good as those of the control group, hydrophilicity was observably better (P<0.01) than that of control group, and abilities of proliferation and osteogenic differentiation of BMSCs on novel scaffold were significantly greater (P<0.05) than those of control group, which suggests that the novel scaffold possesses preferable characteristics and have high value in bone tissue engineering.

scholarly journals Effect of Bone Morphogenic Protein-2-Loaded Mesoporous Strontium Substitution Calcium Silicate/Recycled Fish Gelatin 3D Cell-Laden Scaffold for Bone Tissue Engineering

Processes ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 493 ◽  
Author(s):  
Chun-Ta Yu ◽  
Fu-Ming Wang ◽  
Yen-Ting Liu ◽  
Hooi Yee Ng ◽  
Yi-Rong Jhong ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Calcium Silicate ◽  
Cellular Proliferation ◽  
Recent Decade ◽  
Engineering Research ◽  
Non Union ◽  
Enhanced Secretion ◽  
Novel Scaffold

Bone has a complex hierarchical structure with the capability of self-regeneration. In the case of critical-sized defects, the regeneration capabilities of normal bones are severely impaired, thus causing non-union healing of bones. Therefore, bone tissue engineering has since emerged to solve problems relating to critical-sized bone defects. Amongst the many biomaterials available on the market, calcium silicate-based (CS) cements have garnered huge interest due to their versatility and good bioactivity. In the recent decade, scientists have attempted to modify or functionalize CS cement in order to enhance the bioactivity of CS. Reports have been made that the addition of mesoporous nanoparticles onto scaffolds could enhance the bone regenerative capabilities of scaffolds. For this study, the main objective was to reuse gelatin from fish wastes and use it to combine with bone morphogenetic protein (BMP)-2 and Sr-doped CS scaffolds to create a novel BMP-2-loaded, hydrogel-based mesoporous SrCS scaffold (FGSrB) and to evaluate for its composition and mechanical strength. From this study, it was shown that such a novel scaffold could be fabricated without affecting the structural properties of FGSr. In addition, it was proven that FGSrB could be used for drug delivery to allow stable localized drug release. Such modifications were found to enhance cellular proliferation, thus leading to enhanced secretion of alkaline phosphatase and calcium. The above results showed that such a modification could be used as a potential alternative for future bone tissue engineering research.

scholarly journals Preparation, characterization, bioactivity and degradation behavior in vitro of copper-doped calcium polyphosphate as a candidate material for bone tissue engineering

RSC Advances ◽  
2017 ◽  
Vol 7 (67) ◽  
pp. 42614-42626 ◽  
Author(s):  
Chengrui Guo ◽  
Li Li ◽  
Shuangshuang Li ◽  
Yaping Wang ◽  
Xixun Yu
Keyword(s):  
Tissue Engineering ◽  
Trace Elements ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Human Body ◽  
Degradation Behavior ◽  
Calcium Polyphosphate ◽  
Essential Trace Elements ◽  
Novel Scaffold

In this study, copper, as one of the essential trace elements in the human body, was introduced into calcium polyphosphate (CPP) to prepare a novel scaffold in bone tissue engineering: copper-doped calcium polyphosphate (CCPP) scaffolds.

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