Amine modification of calcium phosphate by low-pressure plasma for bone regeneration

Joe Kodama,Miroslav Michlíček,Takahiro Makino,David Nečas,Shinichi Nakagawa,Ryota Chijimatsu,Shota Takenaka,Takashi Kamatani,Rintaro Okada,Anjar Anggraini Harumningtyas,Hidekazu Kita,Kunihiko Hashimoto,Satoshi Sugimoto,Lenka Zajı́čková ,Tomoko Ito,Satoshi Hamaguchi,Junichi Kushioka,Hiroyuki Tsukazaki,Yusuke Sakai,Daisuke Tateiwa,Yuichiro Ukon,Takashi Kaito

doi:10.1038/s41598-021-97460-8

Abstract

Regeneration of large bone defects caused by trauma or tumor resection remains one of the biggest challenges in orthopedic surgery. Because of the limited availability of autograft material, the use of artificial bone is prevalent; however, the primary role of currently available artificial bone is restricted to acting as a bone graft extender owing to the lack of osteogenic ability. To explore whether surface modification might enhance artificial bone functionality, in this study we applied low-pressure plasma technology as next-generation surface treatment and processing strategy to chemically (amine) modify the surface of beta-tricalcium phosphate (β-TCP) artificial bone using a CH4/N2/He gas mixture. Plasma-treated β-TCP exhibited significantly enhanced hydrophilicity, facilitating the deep infiltration of cells into interconnected porous β-TCP. Additionally, cell adhesion and osteogenic differentiation on the plasma-treated artificial bone surfaces were also enhanced. Furthermore, in a rat calvarial defect model, the plasma treatment afforded high bone regeneration capacity. Together, these results suggest that amine modification of artificial bone by plasma technology can provide a high osteogenic ability and represents a promising strategy for resolving current clinical limitations regarding the use of artificial bone.

Highlights

Regeneration of large bone defects caused by trauma or tumor resection remains one of the biggest challenges in orthopedic surgery
We demonstrate the effects of amine modification on β-TCP by low-pressure plasma for in vitro cell adhesion, osteogenic differentiation, and in vivo bone regeneration with a rat calvarial defect model
The plasma polymerization conditions used in this study, including the selection of the discharge gases and their mixing ratio, were selected to attain stable plasma discharge, a reasonable film deposition rate, and a relatively high amine concentration in the deposited film, using the gas species and discharge conditions that the authors are accustomed to operating the plasma system with for various other plasma polymerization applications[13,25]

Summary

Introduction

Regeneration of large bone defects caused by trauma or tumor resection remains one of the biggest challenges in orthopedic surgery. In a rat calvarial defect model, the plasma treatment afforded high bone regeneration capacity Together, these results suggest that amine modification of artificial bone by plasma technology can provide a high osteogenic ability and represents a promising strategy for resolving current clinical limitations regarding the use of artificial bone. It was previously reported that plasma treatment of interconnected porous hydroxyapatite (HA) artificial bone with O 2/He gas could improve surface hydrophilicity and promote the osteogenic differentiation of rat bone marrow stromal cells (BMSCs)[4,5,6]. We demonstrate the effects of amine modification on β-TCP by low-pressure plasma for in vitro cell adhesion, osteogenic differentiation, and in vivo bone regeneration with a rat calvarial defect model

Methods

Results

Conclusion