scholarly journals Hydroxyapatite for Biomedical Applications: A Short Overview

Ceramics ◽  
2021 ◽  
Vol 4 (4) ◽  
pp. 542-563
Author(s):  
Elisa Fiume ◽  
Giulia Magnaterra ◽  
Abbas Rahdar ◽  
Enrica Verné ◽  
Francesco Baino
Keyword(s):  
Calcium Phosphates ◽  
Three Dimensional ◽  
Good Alternative ◽  
Great Promise ◽  
Comprehensive Overview ◽  
Current Trends ◽  
Mechanical Performances ◽  
Potential Use

Calcium phosphates (CaPs) are biocompatible and biodegradable materials showing a great promise in bone regeneration as good alternative to the use of auto- and allografts to guide and support tissue regeneration in critically-sized bone defects. This can be certainly attributed to their similarity to the mineral phase of natural bone. Among CaPs, hydroxyapatite (HA) deserves a special attention as it, actually is the main inorganic component of bone tissue. This review offers a comprehensive overview of past and current trends in the use of HA as grafting material, with a focus on manufacturing strategies and their effect on the mechanical properties of the final products. Recent advances in materials processing allowed the production of HA-based grafts in different forms, thus meeting the requirements for a range of clinical applications and achieving enthusiastic results both in vitro and in vivo. Furthermore, the growing interest in the optimization of three-dimensional (3D) porous grafts, mimicking the trabecular architecture of human bone, has opened up new challenges in the development of bone-like scaffolds showing suitable mechanical performances for potential use in load bearing anatomical sites.

scholarly journals Three-Dimensional Spheroids as In Vitro Preclinical Models for Cancer Research

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1186
Author(s):  
Bárbara Pinto ◽  
Ana C. Henriques ◽  
Patrícia M. A. Silva ◽  
Hassan Bousbaa
Keyword(s):  
Cancer Research ◽  
Low Cost ◽  
Three Dimensional ◽  
3D Culture ◽  
Comprehensive Overview ◽  
Culture Techniques ◽  
Drug Candidates ◽  
In Vivo Testing

Most cancer biologists still rely on conventional two-dimensional (2D) monolayer culture techniques to test in vitro anti-tumor drugs prior to in vivo testing. However, the vast majority of promising preclinical drugs have no or weak efficacy in real patients with tumors, thereby delaying the discovery of successful therapeutics. This is because 2D culture lacks cell–cell contacts and natural tumor microenvironment, important in tumor signaling and drug response, thereby resulting in a reduced malignant phenotype compared to the real tumor. In this sense, three-dimensional (3D) cultures of cancer cells that better recapitulate in vivo cell environments emerged as scientifically accurate and low cost cancer models for preclinical screening and testing of new drug candidates before moving to expensive and time-consuming animal models. Here, we provide a comprehensive overview of 3D tumor systems and highlight the strategies for spheroid construction and evaluation tools of targeted therapies, focusing on their applicability in cancer research. Examples of the applicability of 3D culture for the evaluation of the therapeutic efficacy of nanomedicines are discussed.

scholarly journals Trauma induced tissue survival in vitro with a muscle-biomaterial based osteogenic organoid system: a proof of concept study

2019 ◽  
Author(s):  
Tao He ◽  
Jörg Hausdorf ◽  
Yan Chevalier ◽  
Roland Manfred Klar
Keyword(s):  
Skeletal Muscle ◽  
Bone Tissue ◽  
Muscle Tissue ◽  
Three Dimensional ◽  
Good Alternative ◽  
Clinical Environment ◽  
In Vitro Systems ◽  
Osteogenic Gene Expression

Abstract Background The translation from animal research into the clinical environment remains problematic, as animal systems do not adequately replicate the human in vivo environment. Bioreactors have emerged as a good alternative that can reproduce part of the human in vivo processes at an in vitro level. However, in vitro bone formation platforms primarily utilizes stem cells only, with tissue based in vitro systems remaining poorly investigated. As such, the present pilot study explored the tissue behavior and cell survival capability within a new in vitro skeletal muscle tissue-based biomaterial organoid bioreactor system to maximize future bone tissue engineering prospects. Results Three dimensional printed β-tricalcium phosphate/hydroxyapatite devices were either wrapped in a sheet of rat muscle tissue or first implanted in a heterotopic muscle pouch that was then excised and cultured in vitro for up to 30 days. Devices wrapped in muscle tissue showed cell death by day 15. Contrarily, devices in muscle pouches showed angiogenic and limited osteogenic gene expression tendencies with consistent TGF-ß 1 , COL4A1 , VEGF-A , RUNX-2 , and BMP-2 upregulation, respectively. Histologically, muscle tissue degradation and fibrin release was seen being absorbed by devices acting possibly as a support for new tissue formation in the bioceramic scaffold that supports progenitor stem cell osteogenic differentiation.Conclusions These results therefore demonstrate that the skeletal muscle pouch-based biomaterial culturing system can support tissue survival over a prolonged culture period and represents a novel organoid tissue model that with further adjustments could generate bone tissue for direct clinical transplantations.

Octacalcium Phosphate as a Precursor in Biomineral Formation

1987 ◽  
Vol 1 (2) ◽  
pp. 306-313 ◽  
Author(s):  
W.E. Brown ◽  
N. Eidelman ◽  
B. Tomazic
Keyword(s):  
Thermogravimetric Analysis ◽  
Calcium Phosphates ◽  
Three Dimensional ◽  
Octacalcium Phosphate ◽  
Basic Form ◽  
Vacancy Defects ◽  
Impurity Ions

What are biominerals and how are they formed? It is usually assumed: (i) that the prototype for most apatitic biominerals is hydroxyapatite (OHAp), Ca5(PO4) 3OH; and (ii) that the OHAp structure has been modified by the presence of impurity ions and vacancy defects in specific OHAp lattice sites. The usual answer, at least implicitly, to the second question is that the apatitic mineral is formed directly by the precipitation of ions from the surrounding solution. Our answers are: (i) that apatitic biominerals are formed through a precursor mechanism in which octacalcium phosphate (OCP), Ca8H 2(PO4)6·5H2O, precipitates first and then hydrolyzes ireversibly in situ to a transition product intermediate to OCP and OHAp; and (ii) that this product, "octacalcium phosphate hydrolyzate" (OCPH), may contain (a) OHAp-like and OCP-like domains in varying amounts, (b) vacancy defects and impurity ions in lattice sites in these domains, and (c) various kinds of one-, two-, and three-dimensional defects which are not present in either the OHAp or the OCP lattice, these defects being formed during the in situ hydrolysis step. A calcification model of this type was first proposed in 1957, but full acceptance was delayed because most of the evidence was circumstantial and in vitro in nature. The situation has changed radically because of three unrelated studies that are in vivo in nature but lead to the same conclusion: I. 32P-pyrolysis studies of rat enamel: The results clearly demonstrated that an acidic calcium phosphate precursor was involved. II. Precipitation of calcium phosphates in serum. Ultrafiltered serum was equilibrated with brushite. Subsequent changes in the ionic concentrations revealed that OCP was formed at first and then hydrolyzed to a more basic form, OCPH, but never reached the solubility of OHAp. III. Physicochemical properties of cardiovascular biominerals: We recently characterized biominerals in cardiovascular deposits in an encompassing variety of ways. As an overall conclusion, OCPH was the prototype most compatible with the data [including indices of refraction, solubility, P2O74- formation on pyrolysis, thermogravimetric analysis (TGA) measurements, presence of water, and incorporation of CO32-, Na+, and Mg2+]. This calcification model has important consequences relative to all kinds of calcification and decalcification processes, including those of enamel.

scholarly journals Robust Three-dimensional (3D) Expansion of Bovine Intestinal Stem Cells: A Model for Replacement of Animal Experiments

2021 ◽  
Author(s):  
Bo Ram Lee ◽  
Hyeon Yang ◽  
Sang In Lee ◽  
Inamul Haq ◽  
Sun A Ock ◽  
...  
Keyword(s):  
Stem Cells ◽  
Small Intestine ◽  
Functional Characterization ◽  
Animal Experiments ◽  
Three Dimensional ◽  
Intestinal Stem Cells ◽  
Great Promise ◽  
Intestinal Organoids

Abstract Background Intestinal organoids offer great promise for disease modelling based host-pathogen interactions and nutritional research for feed efficiency measurement in livestock as well as regenerative medicine for therapeutic purposes. However, very limited studies are available on the functional characterization and three-dimensional (3D) expansion of adult stem cells in livestock species compared to mammals. Therefore, we characterized intestinal stem cells derived from small intestine in adult bovine and cultivated intestinal organoids under in vitro 3D culture system.Results In this study, we successfully established intestinal organoids in bovine. Intestinal organoids were long-term cultivated over several passages of culture without loss of the recapitulating capacity of crypts and they had the specific expression of several specific markers involved in intestinal stem cells, intestinal epithelium and nutrient absorption. In addition, they showed the key functionality with regard to a high permeability for compounds of up to FITC-dextran 4 kDa, while FITC-dextran 40 kDa failed to enter the organoid lumen. Furthermore, the genetic properties of intestinal organoids were highly similar to those of in vivo based on QuantSeq 3’ mRNA-Seq. data.Conclusions Collectively, these results provide a reliable method for efficient isolation of intestinal crypts from small intestine and robust 3D expansion of intestinal stem cells in adult bovine and demonstrate the in vitro 3D organoids mimics the in vivo tissue topology and functionality. Finally, intestinal organoids are potential alternatives to in vivo system and will facilitate the practical use of a model to replace animal experiments in the fields of animal biotechnology for various purposes.

scholarly journals Robust Three-Dimensional (3D) Expansion of Bovine Intestinal Organoids: An In Vitro Model as a Potential Alternative to an In Vivo System

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 2115
Author(s):  
Bo-Ram Lee ◽  
Hyeon Yang ◽  
Sang-In Lee ◽  
Inamul Haq ◽  
Sun-A Ock ◽  
...  
Keyword(s):  
Stem Cells ◽  
Small Intestine ◽  
Adult Stem Cells ◽  
Three Dimensional ◽  
3D Culture ◽  
Great Promise ◽  
Specific Expression ◽  
Intestinal Organoids

Intestinal organoids offer great promise for disease-modelling-based host–pathogen interactions and nutritional research for feed efficiency measurement in livestock and regenerative medicine for therapeutic purposes. However, very limited studies are available on the functional characterisation and three-dimensional (3D) expansion of adult stem cells in livestock species compared to other species. Intestinal crypts derived from intestinal organoids under a 3D culture system from the small intestine in adult bovine were successfully established and characterised for functionality testing, including the cellular potentials and genetic properties based on immunohistochemistry, immunocytochemistry, epithelial barrier permeability assay, QuantSeq 3′ mRNA-Seq. data and quantitative reverse transcription-polymerase chain reaction. Intestinal organoids were long-term cultivated over several passages of culture without loss of the recapitulating capacity of crypts, and they had the specific expression of several specific markers involved in intestinal stem cells, intestinal epithelium, and nutrient absorption. In addition, they showed the key functionality with regard to a high permeability for compounds of up to FITC-dextran 4 kDa, while FITC-dextran 40 kDa failed to enter the organoid lumen and revealed that the genetic properties of bovine intestinal organoids were highly similar to those of in vivo. Collectively, these results provide a reliable method for efficient isolation of intestinal crypts from the small intestine and robust 3D expansion of intestinal organoids in adult bovine and demonstrate the in vitro 3D organoids mimics the in vivo tissue topology and functionality. Finally, intestinal organoids are potential alternatives to in vivo systems and will be facilitated as the practical model to replace animal experiments for various purposes in the fields of animal biotechnology.

Engineering Embryonic Stem Cell Microenvironments for Tailored Cellular Differentiation

2015 ◽  
Vol 6 (4) ◽  
Author(s):  
Chenyu Huang ◽  
Alexander Melerzanov ◽  
Yanan Du
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Small Molecules ◽  
Three Dimensional ◽  
Embryonic Stem ◽  
Research Direction ◽  
Lineage Commitment ◽  
Great Promise

The rapid progress of embryonic stem cell (ESCs) research offers great promise for drug discovery, tissue engineering, and regenerative medicine. However, a major limitation in translation of ESCs technology to pharmaceutical and clinical applications is how to induce their differentiation into tailored lineage commitment with satisfactory efficiency. Many studies indicate that this lineage commitment is precisely controlled by the ESC microenvironment in vivo. Engineering and biomaterial-based approaches to recreate a biomimetic cellular microenvironment provide valuable strategies for directing ESCs differentiation to specific lineages in vitro. In this review, we summarize and examine the recent advances in application of engineering and biomaterial-based approaches to control ESC differentiation. We focus on physical strategies (e.g., geometrical constraint, mechanical stimulation, extracellular matrix (ECM) stiffness, and topography) and biochemical approaches (e.g., genetic engineering, soluble bioactive factors, coculture, and synthetic small molecules), and highlight the three-dimensional (3D) hydrogel-based microenvironment for directed ESC differentiation. Finally, future perspectives in ESCs engineering are provided for the subsequent advancement of this promising research direction.

scholarly journals Epidermal Growth Factor (EGF) Treatment on Multipotential Stromal Cells (MSCs). Possible Enhancement of Therapeutic Potential of MSC

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Kenichi Tamama ◽  
Haruhisa Kawasaki ◽  
Alan Wells
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Great Promise ◽  
Paracrine Secretion ◽  
Epidermal Growth ◽  
Potential Use

Adult bone marrow multipotential stromal cells (MSCs) hold great promise in regenerative medicine and tissue engineering. However, due to their low numbers upon harvesting, MSCs need to be expanded in vitro without biasing future differentiation for optimal utility. In this concept paper, we focus on the potential use of epidermal growth factor (EGF), prototypal growth factor for enhancing the harvesting and/or differentiation of MSCs. Soluble EGF was shown to augment MSC proliferation while preserving early progenitors within MSC population, and thus did not induce differentiation. However, tethered form of EGF was shown to promote osteogenic differentiation. Soluble EGF was also shown to increase paracrine secretions including VEGF and HGF from MSC. Thus, soluble EGF can be used not only to expand MSC in vitro, but also to enhance paracrine secretion through drug-releasing MSC-encapsulated scaffolds in vivo. Tethered EGF can also be utilized to direct MSC towards osteogenic lineage both in vitro and in vivo.

scholarly journals Trauma induced tissue survival in vitro with a muscle-biomaterial based osteogenic organoid system: a proof of concept study

2019 ◽  
Author(s):  
Tao He ◽  
Jörg Hausdorf ◽  
Yan Chevalier ◽  
Roland Manfred Klar
Keyword(s):  
Skeletal Muscle ◽  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Muscle Tissue ◽  
Three Dimensional ◽  
Good Alternative ◽  
Clinical Environment

Abstract Background: The translation from animal research into the clinical environment remains problematic, as animal systems do not adequately replicate the human in vivo environment. Bioreactors have emerged as a good alternative that can reproduce part of the human in vivo processes at an in vitro level. Bone tissue-engineering bioreactors, however, still are cell based with tissue based in vitro systems remaining poorly investigated. As such, the present pilot study explored the tissue behavior and cell survival capability within a new in vitro skeletal muscle tissue-based biomaterial organoid bioreactor system to maximize future bone tissue engineering prospects. Results: Three dimensional printed β-tricalcium phosphate/hydroxyapatite devices were either wrapped in a sheet of rat muscle tissue or first implanted in a heterotopic muscle pouch that was then excised and cultured in vitro for up to 30 days. Devices wrapped in muscle tissue showed cell death by day 15. Contrarily, devices in muscle pouches showed angiogenic and limited osteogenic gene expression tendencies with consistent TGF-ß1, COL4A1, VEGF-A, RUNX-2, and BMP-2 upregulation, respectively. Histologically, muscle tissue degradation and fibrin release was seen being absorbed by devices acting possibly as a support for new tissue formation in the bioceramic scaffold that supports progenitor stem cell osteogenic differentiation.Conclusions: These results therefore demonstrate that the skeletal muscle pouch-based biomaterial culturing system can support tissue survival over a prolonged culture period and represents a novel organoid tissue model that with further adjustments could generate bone tissue for direct clinical transplantations.

In vitro and in vivo polysaccharides assembly: ultrastructural and cytochemical study of growing plant cell wall components.

1978 ◽  
Vol 36 (2) ◽  
pp. 434-435
Author(s):  
D. Reis ◽  
B. Vian ◽  
J. C. Roland
Keyword(s):  
Cell Wall ◽  
Self Assembly ◽  
Plant Cell Wall ◽  
Higher Plants ◽  
Three Dimensional ◽  
Cytochemical Study ◽  
Wall Components

Wall morphogenesis in higher plants is a problem still open to controversy. Until now the possibility of a transmembrane control and the involvement of microtubules were mostly envisaged. Self-assembly processes have been observed in the case of walls of Chlamydomonas and bacteria. Spontaneous gelling interactions between xanthan and galactomannan from Ceratonia have been analyzed very recently. The present work provides indications that some processes of spontaneous aggregation could occur in higher plants during the formation and expansion of cell wall.Observations were performed on hypocotyl of mung bean (Phaseolus aureus) for which growth characteristics and wall composition have been previously defined.In situ, the walls of actively growing cells (primary walls) show an ordered three-dimensional organization (fig. 1). The wall is typically polylamellate with multifibrillar layers alternately transverse and longitudinal. Between these layers intermediate strata exist in which the orientation of microfibrils progressively rotates. Thus a progressive change in the morphogenetic activity occurs.

Epithelial Organotypic Cultures: A Viable Model to Address Mechanisms of Carcinogenesis by Epitheliotropic Viruses

2018 ◽  
Vol 18 (4) ◽  
pp. 246-255 ◽  
Author(s):  
Lara Termini ◽  
Enrique Boccardo
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Experimental Models ◽  
Biological Research ◽  
Specific Gene ◽  
Specific Cell ◽  
Organotypic Cultures ◽  
Skin Physiology

In vitro culture of primary or established cell lines is one of the leading techniques in many areas of basic biological research. The use of pure or highly enriched cultures of specific cell types obtained from different tissues and genetics backgrounds has greatly contributed to our current understanding of normal and pathological cellular processes. Cells in culture are easily propagated generating an almost endless source of material for experimentation. Besides, they can be manipulated to achieve gene silencing, gene overexpression and genome editing turning possible the dissection of specific gene functions and signaling pathways. However, monolayer and suspension cultures of cells do not reproduce the cell type diversity, cell-cell contacts, cell-matrix interactions and differentiation pathways typical of the three-dimensional environment of tissues and organs from where they were originated. Therefore, different experimental animal models have been developed and applied to address these and other complex issues in vivo. However, these systems are costly and time consuming. Most importantly the use of animals in scientific research poses moral and ethical concerns facing a steadily increasing opposition from different sectors of the society. Therefore, there is an urgent need for the development of alternative in vitro experimental models that accurately reproduce the events observed in vivo to reduce the use of animals. Organotypic cultures combine the flexibility of traditional culture systems with the possibility of culturing different cell types in a 3D environment that reproduces both the structure and the physiology of the parental organ. Here we present a summarized description of the use of epithelial organotypic for the study of skin physiology, human papillomavirus biology and associated tumorigenesis.

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