The Chitosan/Agarose/NanoHA Bone Scaffold-Induced M2 Macrophage Polarization and Its Effect on Osteogenic Differentiation In Vitro.

Paulina Kazimierczak,Agata Przekora,Malgorzata Koziol

doi:10.3390/ijms22031109

Paulina Kazimierczak, Agata Przekora + Show 1 more

Open Access

https://doi.org/10.3390/ijms22031109

Copy DOI

Abstract

Chronic immune response to bone implant may lead to delayed healing and its failure. Thus, newly developed biomaterials should be characterized by high biocompatibility. Moreover, it is well known that macrophages play a crucial role in the controlling of biomaterial-induced inflammatory response. Immune cells synthesize also a great amount of signaling molecules that regulate cell differentiation and tissue remodeling. Non-activated macrophages (M0) may be activated (polarized) into two main types of macrophage phenotype: proinflammatory type 1 macrophages (M1) and anti-inflammatory type 2 macrophages (M2). The aim of the present study was to assess the influence of the newly developed chitosan/agarose/nanohydroxyapatite bone scaffold (Polish Patent) on the macrophage polarization and osteogenic differentiation. Obtained results showed that macrophages cultured on the surface of the biomaterial released an elevated level of anti-inflammatory cytokines (interleukin-4, -10, -13, transforming growth factor-beta), which is typical of the M2 phenotype. Moreover, an evaluation of cell morphology confirmed M2 polarization of the macrophages on the surface of the bone scaffold. Importantly, in this study, it was demonstrated that the co-culture of macrophages-seeded biomaterial with bone marrow-derived stem cells (BMDSCs) or human osteoblasts (hFOB 1.19) enhanced their osteogenic ability, confirming the immunomodulatory effect of the macrophages on the osteogenic differentiation process. Thus, it was proved that the developed biomaterial carries a low risk of inflammatory response and induces macrophage polarization into the M2 phenotype with osteopromotive properties, which makes it a promising bone scaffold for regenerative medicine applications.

Highlights

Introduction published maps and institutional affilBiomaterials for tissue engineering applications should possess appropriate structural and mechanical characteristics as well as represent the ability to promote cell adhesion, proliferation, and differentiation, avoiding inflammatory reactions after implantation [1].The chronic immune response may either hinder healing or induce implant loosening and its failure [1,2]
Sci. 2021, 22, 1109 bone scaffold—chit/aga/HA, monocyte-derived macrophages were cultured on the surface of the biomaterial for 3 and 7 days and the level of proinflammatory (IL-1β, IL-6, TNF-α), and anti-inflammatory (IL-4, Il-10, IL-13, TGF-β1) factors in the cell culture supernatants were evaluated
Mentioned cultures served as reference M0, M1, and M2 macrophages to compare the release profile of proinflammatory and anti-inflammatory cytokines with the cytokine release profile of macrophages cultured on the biomaterial

Summary

Introduction

Introduction published maps and institutional affilBiomaterials for tissue engineering applications should possess appropriate structural and mechanical characteristics as well as represent the ability to promote cell adhesion, proliferation, and differentiation, avoiding inflammatory reactions after implantation [1].The chronic immune response may either hinder healing or induce implant loosening and its failure [1,2]. Within the first minutes upon implantation, the surface of the biomaterial is rapidly covered by blood plasma and host tissue proteins (e.g., immunoglobulins, albumin, fibronectin, fibrinogen, vitronectin), causing the settlement of host cells, such as monocytes and fibroblasts, onto the implant surface by interactions primarily with adsorbed proteins [2,3,4]. A few days later, the implant is coated by a layer of fibrotic tissue consisting of collagen, fibroblasts, macrophages, and foreign body giant cells [2,4]. As a result of prolonged inflammation, the biomaterial becomes encapsulated by a dense fibrotic tissue that separates it from the surrounding environment, leading to the failure of iations

Objectives

Methods

Results