Strength Retention of a New Microbial Cellulose Scaffold and Existing Collagen-Based Scaffolds After In Vivo Implantation in a Rabbit Model

Author(s):  
Michael I. Dishowitz ◽  
Miltiadis H. Zgonis ◽  
Jeremy J. Harris ◽  
Constance Ace ◽  
Louis J. Soslowsky

Rotator cuff tendon tears often require large tensions for repair [1] and these tensions are associated with poor outcomes including rerupture [2]. To address this, repairs are often augmented with collagen-based scaffolds. Microbial cellulose, produced by A. xylinum as a laminar non-woven matrix, is another candidate for repair augmentation [3]. An ideal augmentation scaffold would shield the repair site from damaging loads as they change throughout the healing process. Although the initial mechanical properties of clinically used scaffolds have been well characterized [4–6], their mechanical behavior following implantation is not known. As a result, the role of these scaffolds throughout the healing process remains unknown. Therefore, the objective of this study is to characterize the mechanical behavior of existing collagen-based scaffolds and a new, microbial cellulose scaffold over time using an in vivo model. We hypothesize that: 1) collagen-based scaffolds will show decreased stiffness (1a) and suture pullout loads (1b) over time when compared to initial values while the microbial cellulose scaffold will not; and 2) the collagen-based scaffolds will have decreased stiffness (2a) and suture pullout loads (2b) when compared to the new, microbial cellulose scaffold at all timepoints.

2010 ◽  
Vol 1274 ◽  
Author(s):  
Taher Saif ◽  
Jagannathan Rajagopalan ◽  
Alireza Tofangchi

AbstractWe used high resolution micromechanical force sensors to study the in vivo mechanical response of embryonic Drosophila neurons. Our experiments show that Drosophila axons have a rest tension of a few nN and respond to mechanical forces in a manner characteristic of viscoelastic solids. In response to fast externally applied stretch they show a linear force-deformation response and when the applied stretch is held constant the force in the axons relaxes to a steady state value over time. More importantly, when the tension in the axons is suddenly reduced by releasing the external force the neurons actively restore the tension, sometimes close to their resting value. Along with the recent findings of Siechen et al (Proc. Natl. Acad. Sci. USA 106, 12611 (2009)) showing a link between mechanical tension and synaptic plasticity, our observation of active tension regulation in neurons suggest an important role for mechanical forces in the functioning of neurons in vivo.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3812
Author(s):  
Mai-Huong T. Ngo ◽  
Sue-Wei Peng ◽  
Yung-Che Kuo ◽  
Chun-Yen Lin ◽  
Ming-Heng Wu ◽  
...  

The role of a YAP-IGF-1R signaling loop in HCC resistance to sorafenib remains unknown. Method: Sorafenib-resistant cells were generated by treating naïve cells (HepG2215 and Hep3B) with sorafenib. Different cancer cell lines from databases were analyzed through the ONCOMINE web server. BIOSTORM–LIHC patient tissues (46 nonresponders and 21 responders to sorafenib) were used to compare YAP mRNA levels. The HepG2215_R-derived xenograft in SCID mice was used as an in vivo model. HCC tissues from a patient with sorafenib failure were used to examine differences in YAP and IGF-R signaling. Results: Positive associations exist among the levels of YAP, IGF-1R, and EMT markers in HCC tissues and the levels of these proteins increased with sorafenib failure, with a trend of tumor-margin distribution in vivo. Blocking YAP downregulated IGF-1R signaling-related proteins, while IGF-1/2 treatment enhanced the nuclear translocation of YAP in HCC cells through PI3K-mTOR regulation. The combination of YAP-specific inhibitor verteporfin (VP) and sorafenib effectively decreased cell viability in a synergistic manner, evidenced by the combination index (CI). Conclusion: A YAP-IGF-1R signaling loop may play a role in HCC sorafenib resistance and could provide novel potential targets for combination therapy with sorafenib to overcome drug resistance in HCC.


2020 ◽  
Vol 31 (9) ◽  
pp. 865-880 ◽  
Author(s):  
Anton Desch ◽  
Nadine Freifrau von Maltzahn ◽  
Nico Stumpp ◽  
Marly Dalton ◽  
Ines Yang ◽  
...  

1999 ◽  
Vol 276 (2) ◽  
pp. L269-L279 ◽  
Author(s):  
K. Zay ◽  
S. Loo ◽  
C. Xie ◽  
D. V. Devine ◽  
J. Wright ◽  
...  

Mineral dusts produce emphysema, and administration of dust to rats results in the rapid appearance of desmosine and hydroxyproline in lavage fluid, confirming that dusts directly induce connective tissue breakdown. To examine the role of neutrophils and α1-antitrypsin (α1-AT) in this process, we instilled silica or coal into normal rats or rats that had been pretreated with antiserum against neutrophils. One day after dust exposure, lavage fluid neutrophils and desmosine and hydroxyproline levels were all elevated; treatment with antiserum against neutrophils reduced neutrophils by 75%, desmosine by 40–50%, and hydroxyproline by 25%. By 7 days, lavage fluid neutrophils and desmosine level had decreased, whereas macrophages and hydroxyproline level had increased. By ELISA analysis, lavage fluid α1-AT levels were increased four- to eightfold at both times. On Western blot, some of the α1-AT appeared as degraded fragments, and by HPLC analysis, 5–10% of the methionine residues were oxidized. At both times, lavage fluid exhibited considerably elevated serine elastase inhibitory capacity and also showed elevations in metalloelastase activity. We conclude that, in this model, connective tissue breakdown is initially driven largely by neutrophil-derived proteases and that markedly elevated levels of functional α1-AT do not prevent breakdown, thus providing in vivo support for the concept of quantum proteolysis proposed by Liou and Campbell (T. G. Liou and E. J. Campbell. Biochemistry 34: 16171–16177, 1995). Macrophage-derived proteases may be of increasing importance over time, especially in coal-treated animals.


2011 ◽  
Vol 127 (2) ◽  
pp. AB152-AB152
Author(s):  
A.M. Ghaemmaghami ◽  
M. Emara ◽  
L. Martinez-Pomares ◽  
F. Shakib

Author(s):  
Ryan E. Gleason ◽  
Kristy T. S. Palomares ◽  
Thomas A. Einhorn ◽  
Louis C. Gerstenfeld ◽  
Elise F. Morgan

Skeletal repair and regeneration involve a dynamic interplay of biological processes that result in spatially and temporally varying patterns of tissue formation and remodeling. For example, during bone fracture healing the cartilaginous callus that is formed initially in the fracture site is subsequently mineralized and remodeled to restore the original form and function to the injured bone. During much of this healing process, the fracture callus is comprised of a heterogeneous mixture of cartilage, fibrocartilage, multipotent mesenchymal tissue, and bone. Adding to this complexity, mechanical stimuli are known to influence the rate and type of tissues formed during skeletal healing [1]. Given the growing body of evidence that controlled mechanical stimulation may be used to enhance healing, it is of substantial interest to elucidate relationships between the distributions of local stresses and strains that develop within the healing region and the distribution of tissue types that form. While histomorphometry is a well established approach for characterizing the latter, it has historically been limited to analyses of a small number of two-dimensional sections of tissue. Such 2D sampling may be inadequate for quantitative characterization of the irregular geometry and heterogeneous composition of healing tissues. In this study, we report on a 3D histomorphometric method and apply this method to an in vivo model of skeletal repair [2] in which a bending stimulus delivered to a healing bone defect results in the formation of predominantly cartilage tissue, rather than bone.


2012 ◽  
Vol 57 (No. 2) ◽  
pp. 77-82 ◽  
Author(s):  
F. Sabol ◽  
L. Dancakova ◽  
P. Gal ◽  
T. Vasilenko ◽  
M. Novotny ◽  
...  

The complexity of the wound healing process, which is still poorly understood, prompted us to perform an immunohistochemical investigation using rat skin as an in vivo model. Fifteen Sprague-Dawley rats were included in the experiment. Two round full thickness wounds, 4 mm in diameter, were made on the backs of all rats. Haematoxylin and eosin basic staining as well as antibodies against wide spectrum keratin, keratin 10, keratin 14, α-smooth muscle actin, vimentin, fibronectin, collagens Type 1 and 3, and the transcription factor Sox-2 were applied to paraffin and frozen sections of skin wound specimens two, six and fourteen days after surgery, respectively. New hair follicles with Sox-2-positive cells were present after fourteen days; keratin/vimentin positivity was restricted to specimens of day two. Collagen-3 expression prevailed over collagen-1 expression at all evaluated time intervals, except in the uninjured part of the dermis. In conclusion, rat skin wound healing is a dynamic process which can serve as a model for studying phenomena such as cell-cell interactions and transitions in vivo.


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