Abstract

Cold physical plasma (CPP), a partially ionized gas that simultaneously generates reactive oxygen and nitrogen species, is suggested to provide advantages in regenerative medicine. Intraoperative CPP therapy targeting pathologies related to diminished bone quality could be promising in orthopedic surgery. Assessment of a clinically approved plasma jet regarding cellular effects on primary bone marrow mesenchymal stromal cells (hBM-MSCs) from relevant arthroplasty patient cohorts is needed to establish CPP-based therapeutic approaches for bone regeneration. Thus, the aim of this study was to derive biocompatible doses of CPP and subsequent evaluation of human primary hBM-MSCs’ osteogenic and immunomodulatory potential. Metabolic activity and cell proliferation were affected in a treatment-time-dependent manner. Morphometric high content imaging analyses revealed a decline in mitochondria and nuclei content and increased cytoskeletal compactness following CPP exposure. Employing a nontoxic exposure regime, investigation on osteogenic differentiation did not enhance osteogenic capacity of hBM-MSCs. Multiplex analysis of major hBM-MSC cytokines, chemokines and growth factors revealed an anti-inflammatory, promatrix-assembling and osteoclast-regulating secretion profile following CPP treatment and osteogenic stimulus. This study can be noted as the first in vitro study addressing the influence of CPP on hBM-MSCs from individual donors of an arthroplasty clientele.

Highlights

  • Cold physical plasma (CPP), generated by adding energy to a neutral gas, contains a plethora of reactive oxygen and nitric species (ROS/RNS) and is employed to combat defective wound healing [1]

  • Treatment with CPP leads to a dose-dependent decrease of hBM-mesenchymal stromal cells (MSCs) proliferation capacity, associated with morphological changes, indicating an exposure time of 30 s/cm2 to be a biocompatible dose for the treatment of hBM-MSCs

  • Single nitrogen-plasma treatment of MC3T3-E1 osteoblasts was biocompatible at a treatment time

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Summary

Introduction

Cold physical plasma (CPP), generated by adding energy to a neutral gas, contains a plethora of reactive oxygen and nitric species (ROS/RNS) and is employed to combat defective wound healing [1]. Novel biomedical applications were suggested to take advantage of such gas plasma technology by bridging physical engineering and medical advances in, for instance, regenerative medicine [2]. One important application of CPP is the treatment of implant surfaces to enhance biocompatibility and ingrowth capacity [3]. Many commonly used titanium-based implant components in arthroplasty are vacuum plasma sprayed to augment an open-pore layer resulting in increased bone integration [4]. Material studies in dentistry provided beneficial effects of CPPinduced surface modifications. Argon-plasma treatment of titanium and zirconium surfaces enhanced cell adhesion and viability of the MC3T3-E1 osteoblastic cell line in vitro [5,6]

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