scholarly journals Enhancing the regenerative effectiveness of growth factors by local inhibition of interleukin-1 receptor signaling

2020 ◽  
Vol 6 (24) ◽  
pp. eaba7602
Author(s):  
Ziad Julier ◽  
Rezvan Karami ◽  
Bhavana Nayer ◽  
Yen-Zhen Lu ◽  
Anthony J. Park ◽  
...  

Although growth factors (GFs) are key molecules for regenerative medicine, their use has been limited by issues associated with suboptimal delivery systems and incomplete understanding of their signaling dynamics. Here, we explored how proinflammatory signals affect GF regenerative potential. Using bone regeneration in mouse, we found that the regenerative capacity of two clinically relevant GFs (BMP-2 and PDGF-BB) is impaired by interleukin-1 receptor (IL-1R1). Mechanistically, IL-1R1 activation in bone-forming cells desensitizes them to GFs and accelerates senescence. Moreover, administration of the GFs triggers IL-1 release by macrophages. To provide localized and sustained IL-1R1 inhibition, we engineered IL-1R antagonist (IL-1Ra) to bind the extracellular matrix (ECM) very strongly and demonstrate that codelivering GFs with ECM-binding IL-1Ra induces superior regeneration. Thus, we highlight that GF regenerative activity is hindered by proinflammatory signals, and GF-based therapies should integrate immunomodulation. Particularly, ECM-binding IL-1Ra holds clinical translational potential by enhancing efficacy of GF therapies.

Author(s):  
Stefano Sivolella ◽  
Marleen De ◽  
Giulia Brunello ◽  
Sara Ricci ◽  
Drazen Tadic ◽  
...  

2015 ◽  
Vol 94 ◽  
pp. 41-52 ◽  
Author(s):  
Mikaël M. Martino ◽  
Priscilla S. Briquez ◽  
Kenta Maruyama ◽  
Jeffrey A. Hubbell

2017 ◽  
Vol 19 (3) ◽  
pp. 703-711 ◽  
Author(s):  
Jakob M. Townsend ◽  
S. Connor Dennis ◽  
Jonathan Whitlow ◽  
Yi Feng ◽  
Jinxi Wang ◽  
...  

Author(s):  
Sayanti Datta ◽  
Arun Prabhu Rameshbabu ◽  
Kamakshi Bankoti ◽  
Subhodeep Jana ◽  
Sabyasachi Roy ◽  
...  

Biomimetic delivery of osteoinductive growth factors via an osteoconductive matrix is an interesting approach for stimulating bone regeneration. In this context, bone extracellular matrix (ECM) has been explored as an...


Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 95 ◽  
Author(s):  
Kaoru Aoki ◽  
Naoto Saito

Regenerative medicine has been widely researched for the treatment of bone defects. In the field of bone regenerative medicine, signaling molecules and the use of scaffolds are of particular importance as drug delivery systems (DDS) or carriers for cell differentiation, and various materials have been explored for their potential use. Although calcium phosphates such as hydroxyapatite and tricalcium phosphate are clinically used as synthetic scaffold material for bone regeneration, biodegradable materials have attracted much attention in recent years for their clinical application as scaffolds due their ability to facilitate rapid localized absorption and replacement with autologous bone. In this review, we introduce the types, features, and performance characteristics of biodegradable polymer scaffolds in their role as DDS for bone regeneration therapy.


2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Isaac A. Rodriguez ◽  
Emily A. Growney Kalaf ◽  
Gary L. Bowlin ◽  
Scott A. Sell

Human bone is a tissue with a fairly remarkable inherent capacity for regeneration; however, this regenerative capacity has its limitations, and defects larger than a critical size lack the ability to spontaneously heal. As such, the development and clinical translation of effective bone regeneration modalities are paramount. One regenerative medicine approach that is beginning to gain momentum in the clinical setting is the use of platelet-rich plasma (PRP). PRP therapy is essentially a method for concentrating platelets and their intrinsic growth factors to stimulate and accelerate a healing response. While PRP has shown some efficacy in bothin vitroandin vivoscenarios, to date its use and delivery have not been optimized for bone regeneration. Issues remain with the effective delivery of the platelet-derived growth factors to a localized site of injury, the activation and temporal release of the growth factors, and the rate of growth factor clearance. This review will briefly describe the physiological principles behind PRP use and then discuss how engineering its method of delivery may ultimately impact its ability to successfully translate to widespread clinical use.


2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Mateusz Hecold ◽  
Roma Buczkowska ◽  
Aleksandra Mucha ◽  
Jakub Grzesiak ◽  
Olga Rac-Rumijowska ◽  
...  

The aim of this work was to assess the effect of different stabilizing agents, for example, polyethylenimine (PEI) and polyvinylpyrrolidone (PVP), on gold nanoparticles (AuNPs) and their influence on equine platelet activation and release of particular growth factors. The gold nanoparticles were produced by chemical reduction of chloroauric acid. UV-Vis spectroscopy confirmed the presence of gold nanoparticles in investigated solutions. The AuNPs were incubated with whole blood at various concentrations. The morphology of platelets in PRP prepared from the blood incubated with AuNPs was characterized by scanning transmission electron microscopy, whereas the concentrations of growth factors and cytokines were evaluated by ELISA assays. The most promising results were obtained with equine platelets incubated with 5% AuNPs stabilized by PEI, which lead to secretion of bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factor (VEGF), and fibroblast growth factor 1 (FGF-1) and simultaneously cause decrease in concentration of interleukin-1 alpha (IL-1α). The qRT-PCR confirmed ELISA test results. The incubation with 5% AuNPs stabilized by PEI leads to upregulation of BMP-2 and VEGF transcripts of mRNA level and to downregulating expression of interleukin-6 (IL-6). Obtained data shed a promising light on gold nanoparticle application for future regenerative medicine application.


2009 ◽  
Vol 81 (3) ◽  
pp. 623-629 ◽  
Author(s):  
Lydia M. Ferreira ◽  
Alfredo Gragnani ◽  
Fabianne Furtado ◽  
Bernardo Hochman

There comes a time when the understanding of the cutaneous healing process becomes essential due to the need for a precocious tissue repair to reduce the physical, social, and psychological morbidity. Advances in the knowledge on the control of interaction among cells, matrix and growth factors will provide more information on the Regenerative Medicine, an emerging area of research in medical bioengineering. However, considering the dynamism and complexity of the cutaneous healing response, it is fundamental to understand the control mechanism exerted by the interaction and synergism of both systems, cutaneous nervous and central nervous, via hypothalamus hypophysis-adrenal axis, a relevant subject, but hardly ever explored. The present study reviews the neuro-immune-endocrine physiology of the skin responsible for its multiple functions and the extreme disturbances of the healing process, like the excess and deficiency of the extracellular matrix deposition.


Nanomaterials ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 659 ◽  
Author(s):  
Manabu Tanaka ◽  
Kaoru Aoki ◽  
Hisao Haniu ◽  
Takayuki Kamanaka ◽  
Takashi Takizawa ◽  
...  

Scaffolds are essential for bone regeneration due to their ability to maintain a sustained release of growth factors and to provide a place where cells that form new bone can enter and proliferate. In recent years, scaffolds made of various materials have been developed and evaluated. Functionally effective scaffolds require excellent cell affinity, chemical properties, mechanical properties, and safety. Carbon nanotubes (CNTs) are fibrous nanoparticles with a nano-size diameter and have excellent strength and chemical stability. In the industrial field, they are used as fillers to improve the performance of materials. Because of their excellent physicochemical properties, CNTs are studied for their promising clinical applications as biomaterials. In this review article, we focused on the results of our research on CNT scaffolds for bone regeneration, introduced the promising properties of scaffolds for bone regeneration, and described the potential of CNT scaffolds.


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