scholarly journals The Body’s Cellular and Molecular Response to Protein-Coated Medical Device Implants: A Review Focused on Fibronectin and BMP Proteins

2020 ◽  
Vol 21 (22) ◽  
pp. 8853
Author(s):  
Yi-Fan Chen ◽  
Clyde Goodheart ◽  
Diego Rua

Recent years have seen a marked rise in implantation into the body of a great variety of devices: hip, knee, and shoulder replacements, pacemakers, meshes, glucose sensors, and many others. Cochlear and retinal implants are being developed to restore hearing and sight. After surgery to implant a device, adjacent cells interact with the implant and release molecular signals that result in attraction, infiltration of the tissue, and attachment to the implant of various cell types including monocytes, macrophages, and platelets. These cells release additional signaling molecules (chemokines and cytokines) that recruit tissue repair cells to the device site. Some implants fail and require additional revision surgery that is traumatic for the patient and expensive for the payer. This review examines the literature for evidence to support the possibility that fibronectins and BMPs could be coated on the implants as part of the manufacturing process so that the proteins could be released into the tissue surrounding the implant and improve the rate of successful implantation.

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Austin B. Gardner ◽  
Simon K. C. Lee ◽  
Elliot C. Woods ◽  
Abhinav P. Acharya

The immune system is traditionally considered from the perspective of defending against bacterial or viral infections. However, foreign materials like implants can also illicit immune responses. These immune responses are mediated by a large number of molecular signals, including cytokines, antibodies and reactive radical species, and cell types, including macrophages, neutrophils, natural killer cells, T-cells, B-cells, and dendritic cells. Most often, these molecular signals lead to the generation of fibrous encapsulation of the biomaterials, thereby shielding the body from these biomaterials. In this review we will focus on two different types of biomaterials: those that actively modulate the immune response, as seen in antigen delivery vehicles for vaccines, and those that illicit relatively small immune response, which are important for implantable materials. The first serves to actively influence the immune response by co-opting certain immune pathways, while the second tries to mimic the properties of the host in an attempt to remain undetected by the immune system. As these are two very different end points, each type of biomaterial has been studied and developed separately and in recent years, many advances have been made in each respective area, which will be highlighted in this review.


2020 ◽  
Vol 2 (1) ◽  
pp. R59-R71
Author(s):  
Chia-Pei Denise Hsu ◽  
Joshua D Hutcheson ◽  
Sharan Ramaswamy

Forces generated by blood flow are known to contribute to cardiovascular development and remodeling. These hemodynamic forces induce molecular signals that are communicated from the endothelium to various cell types. The cardiovascular system consists of the heart and the vasculature, and together they deliver nutrients throughout the body. While heart valves and blood vessels experience different environmental forces and differ in morphology as well as cell types, they both can undergo pathological remodeling and become susceptible to calcification. In addition, while the plaque morphology is similar in valvular and vascular diseases, therapeutic targets available for the latter condition are not effective in the management of heart valve calcification. Therefore, research in valvular and vascular pathologies and treatments have largely remained independent. Nonetheless, understanding the similarities and differences in development, calcific/fibrous pathologies and healthy remodeling events between the valvular and vascular systems can help us better identify future treatments for both types of tissues, particularly for heart valve pathologies which have been understudied in comparison to arterial diseases.


Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1445
Author(s):  
Taisa Nogueira Pansani ◽  
Thanh Huyen Phan ◽  
Qingyu Lei ◽  
Alexey Kondyurin ◽  
Bill Kalionis ◽  
...  

Extracellular vesicles (EVs) are nanoparticles released by cells that contain a multitude of biomolecules, which act synergistically to signal multiple cell types. EVs are ideal candidates for promoting tissue growth and regeneration. The tissue regenerative potential of EVs raises the tantalizing possibility that immobilizing EVs on implant surfaces could potentially generate highly bioactive and cell-instructive surfaces that would enhance implant integration into the body. Such surfaces could address a critical limitation of current implants, which do not promote bone tissue formation or bond bone. Here, we developed bioactive titanium surface coatings (SurfEV) using two types of EVs: secreted by decidual mesenchymal stem cells (DEVs) and isolated from fermented papaya fluid (PEVs). For each EV type, we determined the size, morphology, and molecular composition. High concentrations of DEVs enhanced cell proliferation, wound closure, and migration distance of osteoblasts. In contrast, the cell proliferation and wound closure decreased with increasing concentration of PEVs. DEVs enhanced Ca/P deposition on the titanium surface, which suggests improvement in bone bonding ability of the implant (i.e., osteointegration). EVs also increased production of Ca and P by osteoblasts and promoted the deposition of mineral phase, which suggests EVs play key roles in cell mineralization. We also found that DEVs stimulated the secretion of secondary EVs observed by the presence of protruding structures on the cell membrane. We concluded that, by functionalizing implant surfaces with specialized EVs, we will be able to enhance implant osteointegration by improving hydroxyapatite formation directly at the surface and potentially circumvent aseptic loosening of implants.


2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Yang Zhao ◽  
Hao Guo ◽  
Wenda Wang ◽  
Guoyang Zheng ◽  
Zhan Wang ◽  
...  

Abstract Objective Tuberous sclerosis complex (TSC) is a rare autosomal dominant disease characterized by lesions throughout the body. Our previous study showed the abnormal up-regulation of miRNAs plays an important part in the pathogenesis of TSC-related renal angiomyolipoma (TSC-RAML). circRNAs were known as important regulators of miRNA, but little is known about the circRNAs in TSC-RAMLs. Methods Microarray chips and RNA sequencing were used to identify the circRNAs and mRNAs that were differently expressed between the TSC-RAML and normal kidney tissue. A competitive endogenous RNA (ceRNA) regulatory network was constructed to reveal the regulation of miRNAs and mRNAs by the circRNAs. The biological functions of circRNA and mRNA were analyzed by pathway analysis. Microenvironmental cell types were estimated with the MCP-counter package. Results We identified 491 differentially expressed circRNAs (DECs) and 212 differentially expressed genes (DEGs), and 6 DECs were further confirmed by q-PCR. A ceRNA regulatory network which included 6 DECs, 5 miRNAs, and 63 mRNAs was established. Lipid biosynthetic process was significantly up-regulated in TSC-RAML, and the humoral immune response and the leukocyte chemotaxis pathway were found to be down-regulated. Fibroblasts are enriched in TSC-RAML, and the up-regulation of circRNA_000799 and circRNA_025332 may be significantly correlated to the infiltration of the fibroblasts. Conclusion circRNAs may regulate the lipid metabolism of TSC-RAML by regulation of the miRNAs. Fibroblasts are enriched in TSC-RAMLs, and the population of fibroblast may be related to the alteration of circRNAs of TSC-RAML. Lipid metabolism in fibroblasts is a potential treatment target for TSC-RAML.


2021 ◽  
Vol 22 (7) ◽  
pp. 3649
Author(s):  
Patricia Ramos-Ramírez ◽  
Omar Tliba

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GRα and GRβ, generated through alternative splicing mechanisms. While GRα is the classic receptor responsible for GC actions, GRβ has been implicated in the impairment of GRα-mediated activities. Interestingly, in contrast to the popular belief that GRβ actions are restricted to its dominant-negative effects on GRα-mediated responses, GRβ has been shown to have intrinsic activities and “directly” regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GRα-independent manner. Furthermore, GRβ has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GRβ-mediated responses, with a focus on the GRα-independent/intrinsic effects of GRβ and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.


2018 ◽  
Vol 29 (1) ◽  
pp. 41-84 ◽  
Author(s):  
Narpat Ram Sangwa ◽  
Kuldip Singh Sangwan

Purpose The purpose of this paper is to propose an integrated performance measurement framework to measure the effect of lean implementation throughout all functions of an organization. Design/methodology/approach The paper identifies the seven categories representing all organizational functions. These categories have been divided into 26 performance dimensions and key performance indicators (KPIs) for each performance dimension have been identified to measure lean performance. The interrelationship of each category with lean principles and/or lean wastes has been identified. KPIs are developed on the basis of identified criteria, frequency analysis of existing literature, and discussion with industry professionals. Finally, an integrated performance measurement framework is proposed. Findings The proposed framework evaluates the organization under seven categories – manufacturing process, new product development (NPD), human resource management, finance, administration, customer management, and supplier management. In total, 26 dimensions and 119 key performance indicators have been identified under the seven categories. Research limitations/implications The proposed framework is a conceptual framework and it is to be tested by empirical and cross-sectional studies. Originality/value The main novelty of the research is that the leanness of the organization has been measured throughout the supply chain of the organization in an integrated way. The various areas of measurement are manufacturing process, NPD, finance, administration, customer management, and supplier management. Further, the proposed KPIs are also categorized as qualitative or quantitative, strategic or operational, social or technical, financial or non-financial, leading or lagging, static or dynamic. This paper contributes to the body of knowledge in performance measurement.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuan-chi Teng ◽  
Alfredo Leonardo Porfírio-Sousa ◽  
Giulia Magri Ribeiro ◽  
Marcela Corso Arend ◽  
Lindolfo da Silva Meirelles ◽  
...  

Abstract Background Peripheral arterial disease (PAD) affects millions of people and compromises quality of life. Critical limb ischemia (CLI), which is the most advanced stage of PAD, can cause nonhealing ulcers and strong chronic pain, and it shortens the patients’ life expectancy. Cell-based angiogenic therapies are becoming a real therapeutic approach to treat CLI. Pericytes are cells that surround vascular endothelial cells to reinforce vessel integrity and regulate local blood pressure and metabolism. In the past decade, researchers also found that pericytes may function as stem or progenitor cells in the body, showing the potential to differentiate into several cell types. We investigated the gene expression profiles of pericytes during the early stages of limb ischemia, as well as the alterations in pericyte subpopulations to better understand the behavior of pericytes under ischemic conditions. Methods In this study, we used a hindlimb ischemia model to mimic CLI in C57/BL6 mice and explore the role of pericytes in regeneration. To this end, muscle pericytes were isolated at different time points after the induction of ischemia. The phenotypes and transcriptomic profiles of the pericytes isolated at these discrete time points were assessed using flow cytometry and RNA sequencing. Results Ischemia triggered proliferation and migration and upregulated the expression of myogenesis-related transcripts in pericytes. Furthermore, the transcriptomic analysis also revealed that pericytes induce or upregulate the expression of a number of cytokines with effects on endothelial cells, leukocyte chemoattraction, or the activation of inflammatory cells. Conclusions Our findings provide a database that will improve our understanding of skeletal muscle pericyte biology under ischemic conditions, which may be useful for the development of novel pericyte-based cell and gene therapies.


2021 ◽  
Author(s):  
Andrew D. Beale ◽  
Priya Crosby ◽  
Utham K. Valekunja ◽  
Rachel S. Edgar ◽  
Johanna E. Chesham ◽  
...  

AbstractCellular circadian rhythms confer daily temporal organisation upon behaviour and physiology that is fundamental to human health and disease. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body. Being naturally anucleate, RBC circadian rhythms share key elements of post-translational, but not transcriptional, regulation with other cell types. The physiological function and developmental regulation of RBC circadian rhythms is poorly understood, however, partly due to the small number of appropriate techniques available. Here, we extend the RBC circadian toolkit with a novel biochemical assay for haemoglobin oxidation status, termed “Bloody Blotting”. Our approach relies on a redox-sensitive covalent haem-haemoglobin linkage that forms during cell lysis. Formation of this linkage exhibits daily rhythms in vitro, which are unaffected by mutations that affect the timing of circadian rhythms in nucleated cells. In vivo, haemoglobin oxidation rhythms demonstrate daily variation in the oxygen-carrying and nitrite reductase capacity of the blood, and are seen in human subjects under controlled laboratory conditions as well as in freely-behaving humans. These results extend our molecular understanding of RBC circadian rhythms and suggest they serve an important physiological role in gas transport.


2004 ◽  
Vol 8 (5) ◽  
pp. 353-356
Author(s):  
Fara P. Redlick ◽  
James C. Shaw

Background: Segmental neurofibromatosis type 1 (NF-1) has the characteristic features of generalized NF-1 but is isolated to a particular segment of the body. Segmental NF-1 results from a postzygotic mutation during embryogenesis in the NF-1 gene on chromosome 17. The embryologic timing of the mutation and cell types affected predict the clinical phenotype. Objective: We present a case of a 52-year-old woman with segmental neurofibromas isolated to the right cheek and neck. We review the recent literature on the genetic and cellular differences between the various clinical manifestations of segmental NF-1. Methods: A MEDLINE search for cases of segmental neurofibromatosis was conducted. Results: In patients with segmental NF-1 presenting as neurofibromas-only, the distribution follows a neural distribution in dermatomes because the genetic mutation appears to be limited to Schwann cells. In patients with pigmentary changes only, the NF-1 mutation has been shown to occur in fibroblasts and the distribution tends to follow the lines of Blaschko. Conclusion: Our patient's neurofibromas were secondary to a postzygotic mutation in the NF-1 gene of neural crest–derived cells. This mutation most likely occurred later in embryogenesis in cells that had already differentiated to Schwann cells and were committed to the dermatomal distribution of the right neck and cheek region (C2).


Author(s):  
C. E. Carr

The weakly electric fish Eigenmannia is able to detect temporal disparities as small as 400 nanoseconds between two signals from different parts of the body surface. The elements of this time comparison circuit have been identified by EM reconstruction of its component cells.Information about the timing of the zero-crossings of signals on each area of the body surface is coded by phase coder receptors, a subset of tuberous electroreceptors. Electroreceptors on the body surface are innervated by primary afferents with a central termination on the spherical cells of the medullary electrosensory lateral line lobe. These cells project to lamina IV of the midbrain torus, a structure similar to the inferior colliculus. Afferents entering lamina VI form a very restricted terminal arbor in which they synapse upon the three cell types of this lamina.


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