Effects of PLGA Nano Patterns on the Responses of Healthy Osteoblasts

2012 ◽  
Vol 1412 ◽  
Author(s):  
Yongchen Wang ◽  
Lijuan Zhang ◽  
Linlin Sun ◽  
Thomas J. Webster

ABSTRACTPoly(lactic-co-glycolic acid) (PLGA) films with flat surfaces and with 27nm, 190nm, 300nm, 400nm, and 520nm surface features were synthesized using a template method with polydimethylsiloxane (PDMS) molds. The nano patterns were transferred from the self-assembled polystyrene beads to the PLGA films through PDMS molds. After synthesis, the nano patterns were confirmed by AFM height scans. In order to investigate the influence of the materials on bone cells, healthy human osteoblasts were cultured on the PLGA films. The 27nm PLGA surface showed the maximum osteoblast adhesion density and a significant increase compared with the other surface features. For these reasons, and since previous studies have highlighted that similar nanometer surface features on PLGA decreased functions of other cancer cells, this study suggests that PLGA with 27nm surface features should be further studied for bone cancer applications where healthy bone cell functions need to be promoted and cancerous bone cell functions inhibited.

2008 ◽  
Vol 1136 ◽  
Author(s):  
Phong A. Tran ◽  
Love Sarin ◽  
Robert H. Hurt ◽  
Thomas J. Webster

ABSTRACTCurrent orthopedic implants have numerous problems that include poor osseointegration, stress shielding and wear debris-associated bone cell death. In addition, numerous patients receive orthopedic implants as a result of bone cancer resection, yet none of the current orthopedic materials are designed to prevent either the occurrence or reoccurrence of cancer. The objective of this study was to transform a traditional orthopedic material into an implant that can both restore bone and prevent bone cancer growth at the implant-tissue interface. Elemental selenium was chosen as the biologically active agent in this material because of its known chemopreventive and chemotherapeutic properties. It was found that when selenite salts were reduced by glutathione in the presence of an immersed substrate (titanium (Ti), stainless steel (SS) or ultra high molecular weigh polyethylene (UHMWPE)), elemental selenium nucleated and grew into adherent, hemispherical nanoclusters. For each type of substrate (Ti, SS and UHMWPE), three types of surfaces with different selenium surface densities were fabricated. The zero oxidation state of selenium was confirmed on Ti substrates by XPS profiles. Compared to uncoated Ti and SS substrates, the high-density selenium-coated surfaces inhibited cancerous bone cell functions while promoting healthy bone cell functions. Very little selenium was also found to release (about 250ppb) into the cell culture media after 3 days of immersion. These findings showed for the first time the potential of using selenium nanoclusters as a coating to transform a traditional orthopedic material into a bone cancer inhibiting implant.


2005 ◽  
Vol 873 ◽  
Author(s):  
Huinan Liu ◽  
Elliott B. Slamovich ◽  
Thomas J. Webster

AbstractBone substitutes are often required to replace damaged tissue due to injuries, diseases and genetic malformations. Traditional bone substitutes, such as autografts, allografts, xenografts and metal implants, are far from ideal as each have their own specific problems and limitations. Bone tissue engineering offers a promising opportunity for bone regeneration in a natural way. However, currently the scientific challenges of bone tissue engineering lie in the development of suitable scaffold materials that can improve bone cell adhesion, proliferation and differentiation. The design of nanophase titania/polymer composites offers an exciting approach to combine the advantages of a degradable polymer with nano-size ceramic grains that optimize biological properties for bone regeneration. Importantly, nanophase titania mimics the size scale of constituent components of bone since bone itself is a nanostructured composite composed of nanometer hydroxyapatite crystals well-dispersed in a mostly collagen matrix. Previous studies have shown significant improvement in protein adsorption, osteoblast (bone-forming cell) adhesion and long-term functions on nano-grain ceramic materials compared to traditional micron-grain ceramic materials. This study used nanometer grain size titania dispersed in a model polymer (PLGA or poly-lactic-co-glycolic acid) matrix by using various sonication powers to increase osteoblast adhesion. The surface characteristics of the composites, such as topography, titania surface area coverage and surface roughness, were studied by scanning electron microscopy and atomic force microscopy. Of all the composites formulated in this study, osteoblast adhesion was the greatest on nanophase titania/PLGA (30/70 wt.%) sonicated at 118.75 for 10 minutes; this composite was the closest in terms of nanometer surface roughness compared to bone of all the composites formulated. In this manner, this study suggests that nanophase titania sonicated in PLGA under these conditions should be further studied for orthopedic applications.


2020 ◽  
Vol 15 (6) ◽  
pp. 531-546 ◽  
Author(s):  
Hwa-Yong Lee ◽  
In-Sun Hong

Recent studies on the mechanisms that link metabolic changes with stem cell fate have deepened our understanding of how specific metabolic pathways can regulate various stem cell functions during the development of an organism. Although it was originally thought to be merely a consequence of the specific cell state, metabolism is currently known to play a critical role in regulating the self-renewal capacity, differentiation potential, and quiescence of stem cells. Many studies in recent years have revealed that metabolic pathways regulate various stem cell behaviors (e.g., selfrenewal, migration, and differentiation) by modulating energy production through glycolysis or oxidative phosphorylation and by regulating the generation of metabolites, which can modulate multiple signaling pathways. Therefore, a more comprehensive understanding of stem cell metabolism could allow us to establish optimal culture conditions and differentiation methods that would increase stem cell expansion and function for cell-based therapies. However, little is known about how metabolic pathways regulate various stem cell functions. In this context, we review the current advances in metabolic research that have revealed functional roles for mitochondrial oxidative phosphorylation, anaerobic glycolysis, and oxidative stress during the self-renewal, differentiation and aging of various adult stem cell types. These approaches could provide novel strategies for the development of metabolic or pharmacological therapies to promote the regenerative potential of stem cells and subsequently promote their therapeutic utility.


2021 ◽  
Vol 22 (15) ◽  
pp. 8182
Author(s):  
Yongguang Gao ◽  
Suryaji Patil ◽  
Jingxian Jia

Osteoporosis is one of the major bone disorders that affects both women and men, and causes bone deterioration and bone strength. Bone remodeling maintains bone mass and mineral homeostasis through the balanced action of osteoblasts and osteoclasts, which are responsible for bone formation and bone resorption, respectively. The imbalance in bone remodeling is known to be the main cause of osteoporosis. The imbalance can be the result of the action of various molecules produced by one bone cell that acts on other bone cells and influence cell activity. The understanding of the effect of these molecules on bone can help identify new targets and therapeutics to prevent and treat bone disorders. In this article, we have focused on molecules that are produced by osteoblasts, osteocytes, and osteoclasts and their mechanism of action on these cells. We have also summarized the different pharmacological osteoporosis treatments that target different molecular aspects of these bone cells to minimize osteoporosis.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3128
Author(s):  
Thomas R. Coughlin ◽  
Ali Sana ◽  
Kevin Voss ◽  
Abhilash Gadi ◽  
Upal Basu-Roy ◽  
...  

Osteosarcoma (OS) is an aggressive bone cancer originating in the mesenchymal lineage. Prognosis for metastatic disease is poor, with a mortality rate of approximately 40%; OS is an aggressive disease for which new treatments are needed. All bone cells are sensitive to their mechanical/physical surroundings and changes in these surroundings can affect their behavior. However, it is not well understood how OS cells specifically respond to fluid movement, or substrate stiffness—two stimuli of relevance in the tumor microenvironment. We used cells from spontaneous OS tumors in a mouse engineered to have a bone-specific knockout of pRb-1 and p53 in the osteoblast lineage. We silenced Sox2 (which regulates YAP) and tested the effect of fluid flow shear stress (FFSS) and substrate stiffness on YAP expression/activity—which was significantly reduced by loss of Sox2, but that effect was reversed by FFSS but not by substrate stiffness. Osteogenic gene expression was also reduced in the absence of Sox2 but again this was reversed by FFSS and remained largely unaffected by substrate stiffness. Thus we described the effect of two distinct stimuli on the mechanosensory and osteogenic profiles of OS cells. Taken together, these data suggest that modulation of fluid movement through, or stiffness levels within, OS tumors could represent a novel consideration in the development of new treatments to prevent their progression.


2001 ◽  
Author(s):  
Debra Chenet Millon ◽  
Darren L. Hitt ◽  
Stephan J. LaPointe

Abstract A bunion is a common foot disorder caused by an abnormal outward projection of the joint and inward turning of the toe. Surgery to correct the malformation involves cutting the first metatarsal head, repositioning and setting it; the bone is then left to heal itself over time. A potentially serious by-product of the bone cutting is the frictional heat generated. While the heat susceptibility of individual bone cells varies throughout bone and is difficult to quantify, studies have shown that when injured, bone may not always heal as bone but rather as a fibrous tissue of varying degrees of differentiation. Prolonged heat exposure at or above critical temperatures may also lead to fat and bone cell resorption, a subsequent fat cell degeneration of the tissue, local swelling of cells as well as denaturation of the enzymatic and membrane proteins (Eriksson & Albrektsson, 1983, Li et al, 1999).


1992 ◽  
Vol 73 (2) ◽  
pp. S10-S13 ◽  
Author(s):  
S. B. Doty ◽  
E. R. Morey-Holton ◽  
G. N. Durnova ◽  
A. S. Kaplansky

The Soviet biosatellite COSMOS 2044 carried adult rats on a spaceflight that lasted 13.8 days and was intended to repeat animal studies carried out on COSMOS 1887. Skeletal tissue and tendon from animals flown on COSMOS 2044 were studied by light and electron microscopy, histochemistry, and morphometric techniques. Studies were confined to the bone cells and vasculature from the weight-bearing tibias. Results indicated that vascular changes at the periosteal and subperiosteal region of the tibia were not apparent by light microscopy or histochemistry. However, electron microscopy indicated that vascular inclusions were present in bone samples from the flight animals. A unique combination of microscopy and histochemical techniques indicated that the endosteal osteoblasts from this same mid-diaphyseal region demonstrated a slight (but not statistically significant) reduction in bone cell activity. Electron-microscopic studies of the tendons from metatarsal bones showed a collagen fibril disorganization as a result of spaceflight. Thus changes described for COSMOS 1887 were present in COSMOS 2044, but the changes ascribed to spaceflight were not as evident.


Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1012-1017 ◽  
Author(s):  
Tatsuya Kobayashi ◽  
Henry Kronenberg

Regulation of gene expression by transcription factors is one of the major mechanisms for controlling cellular functions. Recent advances in genetic manipulation of model animals has allowed the study of the roles of various genes and their products in physiological settings and has demonstrated the importance of specific transcription factors in bone development. Three lineages of bone cells, chondrocytes, osteoblasts, and osteoclasts, develop and differentiate according to their distinct developmental programs. These cells go through multiple differentiation stages, which are often regulated by specific transcription factors. In this minireview, we will discuss selected transcription factors that have been demonstrated to critically affect bone cell development. Further study of these molecules will lead to deeper understanding in mechanisms that govern development of bone.


2022 ◽  
Vol 5 (1) ◽  
pp. 8
Author(s):  
Giorgia Borciani ◽  
Giorgia Montalbano ◽  
Nicola Baldini ◽  
Chiara Vitale-Brovarone ◽  
Gabriela Ciapetti

New biomaterials and scaffolds for bone tissue engineering (BTE) applications require to be tested in a bone microenvironment reliable model. On this assumption, the in vitro laboratory protocols with bone cells represent worthy experimental systems improving our knowledge about bone homeostasis, reducing the costs of experimentation. To this day, several models of the bone microenvironment are reported in the literature, but few delineate a protocol for testing new biomaterials using bone cells. Herein we propose a clear protocol to set up an indirect co-culture system of human-derived osteoblasts and osteoclast precursors, providing well-defined criteria such as the cell seeding density, cell:cell ratio, the culture medium, and the proofs of differentiation. The material to be tested may be easily introduced in the system and the cell response analyzed. The physical separation of osteoblasts and osteoclasts allows distinguishing the effects of the material onto the two cell types and to evaluate the correlation between material and cell behavior, cell morphology, and adhesion. The whole protocol requires about 4 to 6 weeks with an intermediate level of expertise. The system is an in vitro model of the bone remodeling system useful in testing innovative materials for bone regeneration, and potentially exploitable in different application fields. The use of human primary cells represents a close replica of the bone cell cooperation in vivo and may be employed as a feasible system to test materials and scaffolds for bone substitution and regeneration.


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