Loading icariin on titanium surfaces by phase-transited lysozyme priming and layer-by-layer self-assembly of hyaluronic acid/chitosan to improve surface osteogenesis ability

Abstract

PurposeIcariin (ICA) is one of the main active constituents of Herba Epimedii for improving osteogenesis. It is necessary to create a simple and efficient method to load ICA onto the surface of titanium (Ti) implant. The purpose of this study was to establish a local ICA delivery system via a layer-by-layer (LbL) self-assembly system on phase-transited lysozyme (PTL)-primed Ti surface.Materials and methodsA PTL nanofilm was first firmly coated on the pristine Ti. Then, the ICA-loaded hyaluronic acid/chitosan (HA/CS) multilayer was applied via the LbL system to form the HA/CS-ICA surface. This established HA/CS-ICA surface was characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and contact angle measurement. The ICA release pattern of the HA/CS-ICA surface was also examined. MC3T3-E1 osteoblast culture test and a rat model were used to evaluate the effects of the HA/CS-ICA surface in vitro and in vivo.ResultsSEM, XPS and contact angle measurement demonstrated successful fabrication of the HA/CS-ICA surface. The HA/CS-ICA surfaces with different ICA concentrations revealed a controlled release profile of ICA during a 2-week monitoring span. Osteoblasts grown on the coated substrates displayed higher adhesion, viability, proliferation and ALP activity than those on the polished Ti surface. Furthermore, in vivo histological evaluation revealed much obvious bone formation in the ICA-coated group by histological staining and double fluorescent labeling at 2 weeks after implantation.ConclusionThe present study demonstrated that ICA-immobilized HA/CS multilayer on the PTL-primed Ti surface had a sustained release pattern of ICA which could promote the osteogenesis of osteoblasts in vitro and improve early osseointegration in vivo. This study provides a novel method for creating a sustained ICA delivery system to improve osteoblast response and osseointegration.

Icariin/Aspirin Composite Coating on TiO2 Nanotubes Surface Induce Immunomodulatory Effect of Macrophage and Improve Osteoblast Activity

“…This phenomenon may be explained by that the NT−ICA−ASP/PLGA substrate had an additional prodifferentiation effect on osteoblasts than the NT−ASP/PLGA surface, due to the existence of ICA. It is well accepted that during cell life activity, higher proliferation activity is often inhibited when cell differentiation is promoted and vice versa [12,46]. Therefore, the slightly inhibited cell proliferation of the NT−ICA−ASP/PLGA group may imply its enhanced cell differentiation due to the additional prodifferentiation effect of released ICA, compared to the NT−ASP/PLGA group.…”

“…Epimedium is widely used in traditional Chinese medicine and has the kidney invigorating and bone activating functions [11]. Icariin (ICA), an inexpensive and chemically stable monomer components of Epimedium [12,13], retains the osteogenic function of Epimedium and has antiatherosclerotic, anti-inflammatory and anticancer capabilities [14]. At the same time, icariin can promote the proliferation activity of osteoblasts and inhibit the formation of osteoclasts.…”

Hyaluronic acid as a bioactive component for bone tissue regeneration: Fabrication, modification, properties, and biological functions

“…As one of the important components of the extracellular bone matrix, HA can promote the osseointegration of metallic and hydroxyapatite implants by modulating cell migration, adhesion, and differentiation. Song et al developed HA/chitosan multilayer loaded with icariin onto the surface of the titanium implant via a layer-by-layer self-assembly system [117]. The results showed that the coating enhanced the proliferation, viability, and adhesion of osteoblasts and also promoted early osseointegration in vivo (Figure 8).…”

“…Live/dead and cytoskeleton staining of MC3T3-E1 cells on different surfaces of HA/chitosan multilayer coating[117].…”

<p>A LbL-Assembled Bioactive Coating Modified Nanofibrous Membrane for Rapid Tendon-Bone Healing in ACL Reconstruction</p>

“…A polyelectrolyte multilayer film is a LbL build-up of oppositely charged polyelectrolytes to form a nano/micro-scale film that acts as a reservoir to retain the bioactivity of electrostatically adsorbed molecules. As Chitosan (CS) and hyaluronic acid (HA) are biocompatible materials which were widely used in bone tissue engineering,22,23 in this work, we selected CS and HA as the polyelectrolytes for LbL self-assembly. The primary objective of this study was to investigate whether a delivery system of SDF-1α and BMP-2 could be fabricated using LbL self-assembly and could thus have the potential to induce osteogenic differentiation and recruitment of BMSCs.…”