Surface Area to Volume Ratio of Electrospun Polydioxanone Templates Regulates the Adsorption of Soluble Proteins from Human Serum.

Allison E Fetz,Richard A Smith,Marko Z Radic,Cristina A Fantaziu,Gary L Bowlin

doi:10.3390/bioengineering6030078

Allison E Fetz, Richard A Smith + Show 3 more

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https://doi.org/10.3390/bioengineering6030078

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Abstract

Neutrophils, the first cells that interact with surface-adsorbed proteins on biomaterials, have been increasingly recognized as critical maestros in the foreign body response for guided tissue regeneration. Recent research has shown that small diameter (SD) fibers of electrospun tissue regeneration templates, which have a high surface area to volume ratio (SAVR), enhance the release of neutrophil extracellular traps (NETs) compared to large diameter (LD) fibers, resulting in impaired tissue regeneration. In this study, we evaluated the adsorption of eight human serum proteins on the surface of electrospun templates to investigate how protein adsorption may regulate the release of NETs. Electrospun polydioxanone templates made from SD fibers with high SAVR and LD fibers with low SAVR, were incubated with 0.2% human serum and in situ protein adsorption was quantified with infrared-based immunodetection. Of the detected proteins, IgM and vitronectin adsorbed at low levels, suggesting that they do not play a central role in the release of NETs. Contrastingly, albumin and IgG adsorbed rapidly to the surface of the templates. One-hundred to 200 times more IgG adsorbed on the templates compared to albumin, with significantly greater adsorption occurring on the SD templates with high SAVR. Given that neutrophils express receptors that interact with IgG during phagocytosis and NET release, these results suggest that SAVR-dependent adsorption of IgG on the SD electrospun templates may contribute to the up-regulated release of NETs. Overall, this study may aid in the design of immunomodulatory biomaterials that regulate NET release and thus the potential for neutrophil-driven tissue regeneration.

Highlights

The greatest challenge for the clinical translation of biomaterials in tissue regeneration applications is guiding integrative and functional tissue regeneration
The release of neutrophil extracellular traps (NETs) on the surface of electrospun tissue regeneration templates may function as a significant preconditioning event that orchestrates the progression of the foreign body response and the potential for functional tissue regeneration
Recent research has shown that small diameter (SD) templates, which have high surface area to volume ratio (SAVR), up-regulate the release of NETs compared to large diameter (LD) fibers, resulting in impaired tissue regeneration

Summary

Introduction

The greatest challenge for the clinical translation of biomaterials in tissue regeneration applications is guiding integrative and functional tissue regeneration. In turn, influences the recruitment and attachment of vascular, stromal, and inflammatory cells over the course of several hours to orchestrate the foreign body response, which culminates in fibrous tissue encapsulation or elusive, functional tissue regeneration. While it is generally well-accepted that the outcome is largely dependent on the extent of the foreign body response, it is becoming increasingly recognized that the neutrophil and its interactions with the biomaterial play a central role in establishing the optimal microenvironment for functional tissue regeneration [3]

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