A Bimodular Second-Order Orthotropic Stress Constitutive Equation for Cartilage

Author(s):  
Stephen M. Klisch ◽  
Suzanne E. Holtrichter ◽  
Robert L. Sah ◽  
Andrew Davol

The design of tissue-engineered constructs grown in vitro is a promising treatment strategy for degenerated cartilaginous tissues. Cartilaginous tissues such as articular cartilage and the annulus fibrosus are collagen fiber-reinforced composites that exhibit orthotropic behavior and highly asymmetric tensile-compressive responses. They also experience finite deformations in vivo. Successful integration with surrounding tissue upon implantation likely will require cartilage constructs to have similar structural and functional properties as native tissue. Reliable stress constitutive equations that accurately characterize the tissue’s mechanical properties must be developed to achieve this aim. Recent studies have successfully implemented bimodular theories for infinitesimal strains (Soltz et al., 2000; Wang et al., 2003); those models were based on the theory of Curnier et al. (1995).

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ying Liu ◽  
Wenjie Liu ◽  
Ziqiang Yu ◽  
Yan Zhang ◽  
Yinghua Li ◽  
...  

AbstractBromodomain-containing protein 4 (BRD4) has emerged as a promising treatment target for bone-related disorders. (+)-JQ1, a thienotriazolodiazepine compound, has been shown to inhibit pro-osteoclastic activity in a BRD4-dependent approach and impede bone loss caused by ovariectomy (OVX) in vivo. However, clinical trials of (+)-JQ1 are limited because of its poor druggability. In this study, we synthesized a new (+)-JQ1 derivative differing in structure and chirality. One such derivative, (+)-ND, exhibited higher solubility and excellent inhibitory activity against BRD4 compared with its analogue (+)-JQ1. Interestingly, (-)-JQ1 and (-)-ND exhibited low anti-proliferative activity and had no significant inhibitory effect on RANKL-induced osteoclastogenesis as compared with (+)-JQ1 and (+)-ND, suggesting the importance of chirality in the biological activity of compounds. Among these compounds, (+)-ND displayed the most prominent inhibitory effect on RANKL-induced osteoclastogenesis. Moreover, (+)-ND could inhibit osteoclast-specific gene expression, F‐actin ring generation, and bone resorption in vitro and prevent bone loss in OVX mice. Collectively, these findings indicated that (+)-ND represses RANKL‐stimulated osteoclastogenesis and averts OVX-triggered osteoporosis by suppressing MAPK and NF-κB signalling cascades, suggesting that it may be a prospective candidate for osteoporosis treatment.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
N. Callizot ◽  
C. Estrella ◽  
S. Burlet ◽  
A. Henriques ◽  
C. Brantis ◽  
...  

AbstractProgranulin (PGRN) is a protein with multiple functions including the regulation of neuroinflammation, neuronal survival, neurite and synapsis growth. Although the mechanisms of action of PGRN are currently unknown, its potential therapeutic application in treating neurodegenerative diseases is huge. Thus, strategies to increase PGRN levels in patients could provide an effective treatment. In the present study, we investigated the effects of AZP2006, a lysotropic molecule now in phase 2a clinical trial in Progressive Supranuclear Palsy patients, for its ability to increase PGRN level and promote neuroprotection. We showed for the first time the in vitro and in vivo neuroprotective effects of AZP2006 in neurons injured with Aβ1–42 and in two different pathological animal models of Alzheimer’s disease (AD) and aging. Thus, the chronic treatment with AZP2006 was shown to reduce the loss of central synapses and neurons but also to dramatically decrease the massive neuroinflammation associated with the animal pathology. A deeper investigation showed that the beneficial effects of AZP2006 were associated with PGRN production. Also, AZP2006 binds to PSAP (the cofactor of PGRN) and inhibits TLR9 receptors normally responsible for proinflammation when activated. Altogether, these results showed the high potential of AZP2006 as a new putative treatment for AD and related diseases.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Erfan Dashtimoghadam ◽  
Farahnaz Fahimipour ◽  
Andrew N. Keith ◽  
Foad Vashahi ◽  
Pavel Popryadukhin ◽  
...  

AbstractCurrent materials used in biomedical devices do not match tissue’s mechanical properties and leach various chemicals into the body. These deficiencies pose significant health risks that are further exacerbated by invasive implantation procedures. Herein, we leverage the brush-like polymer architecture to design and administer minimally invasive injectable elastomers that cure in vivo into leachable-free implants with mechanical properties matching the surrounding tissue. This strategy allows tuning curing time from minutes to hours, which empowers a broad range of biomedical applications from rapid wound sealing to time-intensive reconstructive surgery. These injectable elastomers support in vitro cell proliferation, while also demonstrating in vivo implant integrity with a mild inflammatory response and minimal fibrotic encapsulation.


2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S191-S192
Author(s):  
Angela R Jockheck-Clark ◽  
Randolph Stone ◽  
Michelle Holik ◽  
Lucy Schaffer ◽  
Shanmugasundaram Natesan ◽  
...  

Abstract Introduction Thermal burns account for 5–10% of casualties sustained in present-day conflicts and are expected to be one of the most common wounds to occur in future conflicts. In prolonged field care (PFC) situations, medical evacuation could be delayed for days. During this time, burn wounds can become infected, detrimentally impact neighboring tissue, and cause systemic immune responses. Therefore, it is essential to test and evaluate non-surgical debridement agents that could be implemented prior to reaching a Role 3 military treatment facility. This work details how the proprietary proteolytic gel SN514 impacts burn debridement when applied within a PFC-like timeline. SN514 contains an enzyme formulation that is thermostable, easy to apply, and selectively degrades non-viable tissue in vitro and in vivo. Methods Deep-partial thickness contact burns were created using an established porcine model and covered with gauze or an antimicrobial incise drape. Four days later, the burns were treated with one of five treatments: 0.2% SN514, 0.8% SN514, a vehicle control, gauze, or an antimicrobial silver dressing. Treatments were re-applied every 24 hours for 72 to 96 hours. The effects of the treatment regiments were compared histologically. Biopsies were also taken to monitor bacterial contamination levels. Results Burns treated with SN514 were partially debrided and visually distinct from those treated with gauze, the silver dressing, or the vehicle control. Preliminary analyses suggest that SN514-treated burns that had been covered with “dry” gauze had a much lower debridement efficiency than those treated with the incise drape. This suggests that SN514 debridement efficiency may depend on the presence of a moist eschar. Preliminary analyses also suggest that there was little difference in burn wound bacterial counts among the five treatment groups. Conclusions SN514 is able to debride burns that experienced delayed treatment, without any evidence of harm to the surrounding tissue or evidence of exacerbating the original burn injury. SN514-treated wounds displayed little to no blood loss and did not increase burn wound infection levels compared to wounds treated with gauze or an antimicrobial silver dressing.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Andrea Scribante ◽  
Pekka K. Vallittu ◽  
Mutlu Özcan ◽  
Lippo V. J. Lassila ◽  
Paola Gandini ◽  
...  

The reinforcement of resins with short or long fibers has multiple applications in various engineering and biomedical fields. The use of fiber reinforced composites (FRCs) in dentistry has been described in the literature from more than 40 years. In vitro studies evaluated mechanical properties such as flexural strength, fatigue resistance, fracture strength, layer thickness, bacterial adhesion, bonding characteristics with long fibers, woven fibers, and FRC posts. Also, multiple clinical applications such as replacement of missing teeth by resin-bonded adhesive fixed dental prostheses of various kinds, reinforcement elements of dentures or pontics, and direct construction of posts and cores have been investigated. In orthodontics, FRCs have been used also for active and passive orthodontic applications, such as anchorage units, en-masse movement units, and postorthodontic tooth retention. FRCs have been extensively tested in the literature, but today the advances in new technologies involving the introduction of nanofillers or new fibers along with understanding the design principles of FRC devices open new fields of research for these materials both in vitro and in vivo. The present review describes past and present applications of FRCs and introduces some future perspectives on the use of these materials.


2017 ◽  
Vol 242 (18) ◽  
pp. 1765-1771 ◽  
Author(s):  
Guinea BC Cardoso ◽  
Erivelto Chacon ◽  
Priscila GL Chacon ◽  
Pedro Bordeaux-Rego ◽  
Adriana SS Duarte ◽  
...  

Our hypothesis was to investigate the fatty acid potential as a bone induction factor. In vitro and in vivo studies were performed to evaluate this approach. Oleic acid was used in a 0.5 wt.% concentration. Polycaprolactone was used as the polymeric matrix by combining solvent-casting and particulate-leaching techniques, with a final porosity of 70 wt.%, investigated by SEM images. Contact angle measurements were produced to investigate the influence of oleic acid on polycaprolactone chains. Cell culture was performed using adipocyte-derived stem cells to evaluate biocompatibility and bioactivity properties. In addition, in vivo studies were performed to evaluate the induction potential of oleic acid addition. Adipocyte-derived stem cells were used to provide differentiation after 21 days of culture. Likewise, information were obtained with in vivo data and cellular invagination was observed on both scaffolds (polycaprolactone and polycaprolactone /oleic acid); interestingly, the scaffold with oleic acid addition demonstrated that cellular migrations are not related to the surrounding tissue, indicating bioactive potential. Our hypothesis is that fatty acid may be used as a potential induction factor for bone tissue engineering. The study’s findings indicate oleic acid as a possible agent for bone induction, according to data on cell differentiation, proliferation, and migration. Impact statement The biomaterial combined in this study on bone regeneration is innovative and shows promising results in the treatment of bone lesions. Polycaprolactone (PCL) and oleic acid have been studied separately. In this research, we combined biomaterials to assess the stimulus and the speed of bone healing.


2017 ◽  
Vol 58 (4) ◽  
Author(s):  
José Manuel Cornejo-Bravo ◽  
Luis Jesús Villarreal-Gómez ◽  
Ricardo Vera-Graziano ◽  
María Raquel Vega-Ríos ◽  
José Luis Pineda-Camacho ◽  
...  

<p>The objective of this work was to evaluate the biocompatibility of scaffolds of poly(<em>L</em>-lactide) with pure and grafted hydroxyapatite, at various concentrations of reinforcement. The biocompatibility tests were carried out <em>in vivo </em>in Wistar rats by implanting the material into the subcutaneous and muscle tissues from 1 to 14 weeks and evaluating the surrounding tissue stained with hematoxylin-eosin. For <em>in vitro </em>assays, MTT and neutral red assay were used to evaluate any cytotoxicity in Mioblast Muscle C2C12 Cells (ATCC® CRL-1772™) and Bovine Coronary Artery Endothelial Cells (BCAEC); <em>Escherichia coli </em>and <em>Staphylococcus aureus </em>were used to evaluate bacterial adhesion. All variants of scaffolds provoked a mild inflammatory response, without showing necrosis. No evidence of cytotoxicity was presented in cell viability tests and good bacterial cell adhesion was visualized for all of the materials studied.</p>


2020 ◽  
Author(s):  
Erfan Dashtimoghadam ◽  
Farahnaz Fahimipour ◽  
Andrew Keith ◽  
Foad Vashahi ◽  
Pavel Popryadukhin ◽  
...  

Abstract Current materials used in biomedical devices do not match tissue’s mechanical properties and leach various chemicals into the body. These deficiencies pose significant health risks that are further exacerbated by invasive implantation procedures. Herein, we leverage the brush-like polymer architecture to design and administer minimally invasive injectable elastomers that cure in vivo into leachable-free implants with mechanical properties matching the surrounding tissue. This strategy allows tuning curing time from minutes to hours, which empowers a broad range of biomedical applications from rapid wound sealing to time-intensive reconstructive surgery. These injectable elastomers support in vitro cell proliferation, while also demonstrating in vivo implant integrity with a mild inflammatory response and minimal fibrotic encapsulation.


Biomaterials ◽  
2019 ◽  
Vol 205 ◽  
pp. 81-93 ◽  
Author(s):  
Maude Gluais ◽  
Johann Clouet ◽  
Marion Fusellier ◽  
Cyrille Decante ◽  
Constantin Moraru ◽  
...  

Author(s):  
Luděk Eyer ◽  
Pavel Svoboda ◽  
Jan Balvan ◽  
Tomáš Vičar ◽  
Matina Raudenská ◽  
...  

Emerging flaviviruses are causative agents of severe and life-threatening diseases, against which no approved therapies are available. Among the nucleoside analogues, which represent a promising group of potentially therapeutic compounds, fluorine-substituted nucleosides are characterized by unique structural and functional properties. Despite having been first synthesized almost 5 decades ago, they still offer new therapeutic opportunities as inhibitors of essential viral or cellular enzymes active in nucleic acid replication/transcription or nucleoside/nucleotide metabolism. Here we report evaluation of the anti-flaviviral activity of 28 nucleoside analogues, each modified with a fluoro substituent at different positions of the ribose ring and/or heterocyclic nucleobase. Our antiviral screening revealed that 3′-deoxy-3′-fluoroadenosine exerted a low-micromolar antiviral effect against tick-borne encephalitis virus (TBEV), Zika virus, and West Nile (WNV) virus (EC50 values from 1.1 ± 0.1 μM to 4.7 ± 1.5 μM), which was manifested in host cell lines of neural and extraneural origin. The compound did not display any measurable cytotoxicity up to concentrations of 25 μM but had an observable cytostatic effect, resulting in suppression of cell proliferation at concentrations of >12.5 μM. Novel approaches based on quantitative phase imaging using holographic microscopy were developed for advanced characterization of antiviral and cytotoxic profiles of 3′-deoxy-3′-fluoroadenosine in vitro. In addition to its antiviral activity in cell cultures, 3′-deoxy-3′-fluoroadenosine was active in vivo in mouse models of TBEV and WNV infection. Our results demonstrate that fluoro-modified nucleosides represent a group of bioactive molecules with excellent potential to serve as prospective broad-spectrum antivirals in antiviral research and drug development.


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