Bone-Integrated Optical Microlasers for In-Vivo Diagnostic Biomechanical Performances

Author(s):  
Omar Cavazos ◽  
Maurizio Manzo ◽  
Erick Ramírez-Cedillo ◽  
Hector R. Siller

Abstract Bones experience mechanical loads on a daily basis. It is difficult to obtain biomechanical performances in-vivo measurements. When implants are integrated with bones after surgery, especially in aged individuals, their osseointegration can compromise the structural integrity of bones; for this reason, it is important to monitor the evolution of the mechanical properties of bones with some in-vivo diagnostic technique. In this study, we propose to integrate optical microsensing devices into bones. To simulate the working principle, a sensor is integrated with a 3-D printed bone. The sensing element is a dye-doped optical microlaser based on the morphology dependent resonance (MDR) shifts also called the whispering gallery mode phenomenon (WGM). When the microlaser is excited by a light source, the fluorescence from the dye couples with the optical resonances. These optical resonances are very sensitive to any perturbation of the microlasers’s morphology. Therefore, the local strain variation of the bone can be related to the shift of the optical resonances. This in-vivo technique monitors the biomechanical performance of bones with implants and prosthetics.

Author(s):  
Maurizio Manzo ◽  
Omar Cavazos ◽  
Erick Ramirez-Cedillo ◽  
Hector R. Siller

Abstract In this article, we propose to use spherical microlasers that can be attached to the surface of bones for in vivo strain monitoring applications. The sensing element is made of mixing polymers, namely, PEGDA-700 (Sigma Aldrich, St. Louis, MO) and Thiocure TMPMP (Evan Chemetics, Teaneck, NJ) at 4:1 ratio in volume doped with rhodamine 6G (Sigma Aldrich, St. Louis, MO) laser dye. Solid-state microlasers are fabricated by curing droplets from the liquid mixture using ultraviolet (UV) light. The sensing principle relies on morphology-dependent resonances; any changes in the strain of the bone causes a shift of the optical resonances, which can be monitored. The specimen is made of a simulated cortical bone fabricated with photopolymer resin via an additive manufacturing process. The light path within the resonator is found to be about perpendicular to the normal stress' direction caused by a bending moment. Therefore, the sensor measures the strain due to bending indirectly using the Poisson effect. Two experiments are conducted: 1) negative bone deflection (called loading) and 2) positive bone deflection (called unloading) for a strain range from 0 to 2.35 × 10−3 m/m. Sensitivity values are ∼19.489 and 19.660 nm/ε for loading and unloading experiments, respectively (percentage difference is less than 1%). In addition, the resolution of the sensor is 1 × 10−3 ε (m/m) and the maximum range is 11.58 × 10−3 ε (m/m). The quality factor of the microlaser is maintaining about constant (order of magnitude 104) during the experiments. This sensor can be used when bone location accessibility is problematic.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Łukasz Kiraga ◽  
Paulina Kucharzewska ◽  
Damian Strzemecki ◽  
Tomasz P. Rygiel ◽  
Magdalena Król

Abstract In vivo tracking of administered cells chosen for specific disease treatment may be conducted by diagnostic imaging techniques preceded by cell labeling with special contrast agents. The most commonly used agents are those with radioactive properties, however their use in research is often impossible. This review paper focuses on the essential aspect of cell tracking with the exclusion of radioisotope tracers, therefore we compare application of different types of non-radioactive contrast agents (cell tracers), methods of cell labeling and application of various techniques for cell tracking, which are commonly used in preclinical or clinical studies. We discuss diagnostic imaging methods belonging to three groups: (1) Contrast-enhanced X-ray imaging, (2) Magnetic resonance imaging, and (3) Optical imaging. In addition, we present some interesting data from our own research on tracking immune cell with the use of discussed methods. Finally, we introduce an algorithm which may be useful for researchers planning leukocyte targeting studies, which may help to choose the appropriate cell type, contrast agent and diagnostic technique for particular disease study.


2020 ◽  
Vol 16 (S5) ◽  
Author(s):  
Milan Nemy ◽  
Michel Grothe ◽  
Jose Barroso ◽  
Stefan J. Teipel ◽  
Eric Westman ◽  
...  

2012 ◽  
Vol 135 (2) ◽  
pp. 391-401 ◽  
Author(s):  
Victor C. K. Lo ◽  
Margarete K. Akens ◽  
Sara Moore ◽  
Albert J. M. Yee ◽  
Brian C. Wilson ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 67 ◽  
Author(s):  
Shara Francesca Rapa ◽  
Rosanna Di Paola ◽  
Marika Cordaro ◽  
Rosalba Siracusa ◽  
Ramona D’Amico ◽  
...  

Intestinal epithelial barrier impairment plays a key pathogenic role in inflammatory bowel diseases (IBDs). In particular, together with oxidative stress, intestinal epithelial barrier alteration is considered as upstream event in ulcerative colitis (UC). In order to identify new products of natural origin with a potential activity for UC treatment, this study evaluated the effects of plumericin, a spirolactone iridoid, present as one of the main bioactive components in the bark of Himatanthus sucuuba (Woodson). Plumericin was evaluated for its ability to improve barrier function and to reduce apoptotic parameters during inflammation, both in intestinal epithelial cells (IEC-6), and in an animal experimental model of 2, 4, 6-dinitrobenzene sulfonic acid (DNBS)-induced colitis. Our results indicated that plumericin increased the expression of adhesion molecules, enhanced IEC-6 cells actin cytoskeleton rearrangement, and promoted their motility. Moreover, plumericin reduced apoptotic parameters in IEC-6. These results were confirmed in vivo. Plumericin reduced the activity of myeloperoxidase, inhibited the expression of ICAM-1, P-selectin, and the formation of PAR, and reduced apoptosis parameters in mice colitis induced by DNBS. These results support a pharmacological potential of plumericin in the treatment of UC, due to its ability to improve the structural integrity of the intestinal epithelium and its barrier function.


1999 ◽  
Vol 19 (1) ◽  
pp. 86-98 ◽  
Author(s):  
David E. Sterner ◽  
Patrick A. Grant ◽  
Shannon M. Roberts ◽  
Laura J. Duggan ◽  
Rimma Belotserkovskaya ◽  
...  

ABSTRACT SAGA, a recently described protein complex in Saccharomyces cerevisiae, is important for transcription in vivo and possesses histone acetylation function. Here we report both biochemical and genetic analyses of members of three classes of transcription regulatory factors contained within the SAGA complex. We demonstrate a correlation between the phenotypic severity of SAGA mutants and SAGA structural integrity. Specifically, null mutations in the Gcn5/Ada2/Ada3 or Spt3/Spt8 classes cause moderate phenotypes and subtle structural alterations, while mutations in a third subgroup, Spt7/Spt20, as well as Ada1, disrupt the complex and cause severe phenotypes. Interestingly, double mutants (gcn5Δ spt3Δand gcn5Δ spt8Δ) causing loss of a member of each of the moderate classes have severe phenotypes, similar tospt7Δ, spt20Δ, or ada1Δmutants. In addition, we have investigated biochemical functions suggested by the moderate phenotypic classes and find that first, normal nucleosomal acetylation by SAGA requires a specific domain of Gcn5, termed the bromodomain. Deletion of this domain also causes specific transcriptional defects at the HIS3 promoter in vivo. Second, SAGA interacts with TBP, the TATA-binding protein, and this interaction requires Spt8 in vitro. Overall, our data demonstrate that SAGA harbors multiple, distinct transcription-related functions, including direct TBP interaction and nucleosomal histone acetylation. Loss of either of these causes slight impairment in vivo, but loss of both is highly detrimental to growth and transcription.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuqing Niu ◽  
Massimiliano Galluzzi ◽  
Ming Fu ◽  
Jinhua Hu ◽  
Huimin Xia

AbstractOne of the main challenges of tissue-engineered vascular prostheses is restenosis due to intimal hyperplasia. The aim of this study is to develop a material for scaffolds able to support cell growth while tolerating physiological conditions and maintaining the patency of carotid artery model. Tubular hyaluronic acid (HA)-functionalized collagen nanofibrous composite scaffolds were prepared by sequential electrospinning method. The tubular composite scaffold has well-controlled biophysical and biochemical signals, providing a good matrix for the adhesion and proliferation of vascular endothelial cells (ECs), but resisting to platelets adhesion when exposed to blood. Carotid artery replacement experiment from 6-week rabbits showed that the HA/collagen nanofibrous composite scaffold grafts with endothelialization on the luminal surface could maintain vascular patency. At retrieval, the composite scaffold maintained good structural integrity and had comparable mechanical strength as the native artery. This study indicating that electrospun scaffolds combined with cells may become an alternative to prosthetic grafts for vascular reconstruction. Graphical Abstract


2021 ◽  
Vol 12 ◽  
Author(s):  
P. Cmielewski ◽  
J. Delhove ◽  
M. Donnelley ◽  
D. Parsons

Cystic Fibrosis (CF) is caused by a defect in the CF transmembrane conductance regulator (CFTR) gene responsible for epithelial ion transport. Nasal potential difference (PD) measurement is a well established diagnostic technique for assessing the efficacy of therapies in CF patients and animal models. The aim was to establish a rapid nasal PD protocol in mice and quantify the efficacy of lentiviral (LV) vector-based CFTR gene therapy. Anaesthetised wild-type (WT) and CF mice were non-surgically intubated and nasal PD measurements were made using a range of buffer flow rates. Addition of the cAMP agonist, isoproterenol, to the buffer sequence was then examined. The optimised rapid PD technique was then used to assess CFTR function produced by second and third generation LV-CFTR vectors. V5 epitope tagged-CFTR in nasal tissue was identified by immunohistochemistry. When intubated, mice tolerated higher flow rates. Isoproterenol could discriminate between WT and CF mice. Improved chloride transport was observed for the second and third generation LV-CFTR vectors, with up to 60% correction of the cAMP-driven chloride response towards WT. V5-CFTR was located in ciliated epithelial cells. The rapid PD technique enables improved functional assessment of the bioelectrical ion transport defect for both current and potential CF therapies.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Peijun Tang ◽  
Mitchell A. Kirby ◽  
Nhan Le ◽  
Yuandong Li ◽  
Nicole Zeinstra ◽  
...  

AbstractCollagen organization plays an important role in maintaining structural integrity and determining tissue function. Polarization-sensitive optical coherence tomography (PSOCT) is a promising noninvasive three-dimensional imaging tool for mapping collagen organization in vivo. While PSOCT systems with multiple polarization inputs have demonstrated the ability to visualize depth-resolved collagen organization, systems, which use a single input polarization state have not yet demonstrated sufficient reconstruction quality. Herein we describe a PSOCT based polarization state transmission model that reveals the depth-dependent polarization state evolution of light backscattered within a birefringent sample. Based on this model, we propose a polarization state tracing method that relies on a discrete differential geometric analysis of the evolution of the polarization state in depth along the Poincare sphere for depth-resolved birefringent imaging using only one single input polarization state. We demonstrate the ability of this method to visualize depth-resolved myocardial architecture in both healthy and infarcted rodent hearts (ex vivo) and collagen structures responsible for skin tension lines at various anatomical locations on the face of a healthy human volunteer (in vivo).


Author(s):  
Logan Lawrence ◽  
James B. Day ◽  
Pier Paolo Claudio ◽  
Roozbeh (Ross) Salary

Abstract Pneumatic MicroExtrusion (PME) is a direct-write additive manufacturing process, which has emerged as a robust, high-resolution method for the fabrication of a broad spectrum of biological tissues and organs. However, the PME process is intrinsically complex, governed by bio-physio-chemical phenomena as well as material-process interactions. Hence, investigation of the influence of consequential factors on bone scaffold fabrication as well as investigation of cell-scaffold interactions would be an inevitable need. The objective of the work is to investigate the biocompatibility as well as the histological properties of PME-fabricated porous bone scaffolds, composed of polycaprolactone (PCL). To achieve this objective, a media extraction of the scaffold material was tested for cytostatic or cytotoxic activity with the aim to: (i) assess the fabricated scaffolds’ feasibility of use in regenerative medicine, and (ii) determine their structural integrity in a modelled in-vivo environment. In addition, the scaffolds were inoculated with an established osteosarcoma cell line (SAOS-2) and cultured for seven days to investigate the scaffold architecture and cell integration potential. A histological examination was performed on the seeded scaffolds for further in-depth analysis of cell-scaffold interaction. Overall, the results of this study pave the way for future investigation of stem cell incorporation into PME-fabricated PCL scaffolds toward the treatment of osseous fractures and defects.


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