Osteoimmunomodulatory effects of biomaterial modification strategies on macrophage polarization and bone regeneration

Abstract

Biomaterials as bone substitutes are always considered as foreign bodies that can trigger host immune responses. Traditional designing principles have been always aimed at minimizing the immune reactions by fabricating inert biomaterials. However, clinical evidence revealed that those methods still have limitations and many of which were only feasible in the laboratory. Currently, osteoimmunology, the very pioneering concept is drawing more and more attention—it does not simply regard the immune response as an obstacle during bone healing but emphasizes the intimate relationship of the immune and skeletal system, which includes diverse cells, cytokines, and signaling pathways. Properties of biomaterials like topography, wettability, surface charge, the release of cytokines, mediators, ions and other bioactive molecules can impose effects on immune responses to interfere with the skeletal system. Based on the bone formation mechanisms, the designing methods of the biomaterials change from immune evasive to immune reprogramming. Here, we discuss the osteoimmunomodulatory effects of the new modification strategies—adjusting properties of bone biomaterials to induce a favorable osteoimmune environment. Such strategies showed potential to benefit the development of bone materials and lay a solid foundation for the future clinical application.

Osteoconductive and Osteoinductive Surface Modifications of Biomaterials for Bone Regeneration: A Concise Review

“…Biomaterials applied in bone tissue engineering and regenerative medicine are usually categorized into polymeric, ceramic, metallic, and composite materials [15,16]. The most often used metallic biomaterials are titanium (Ti) and its alloys (e.g., Ti-6Al-4V, Ti-6Al-7Nb, Ti-6Al-2Nb-1Ta-0.8Mo, Ti-15Mo-5Zr-3Al) [17,18], stainless steel, cobalt (Co) and its alloys [15,18], magnesium (Mg) and its alloys, nickel-titanium alloy (Nitinol), tantalum (Ta) [16]. Metallic biomaterials have been commonly used as bone implants due to their corrosion resistance, fatigue strength, high ultimate tensile strength, toughness, durability, and biocompatibility [19,20].…”

“…The organic part of biomaterial provides biomaterial flexibility and improves its biocompatibility [21][22][23], whereas the inorganic part provides load-bearing strength and stiffness [22]. In organic-inorganic composites, the organic matrix may be composed of natural polymers (e.g., chitosan, collagen, hyaluronic acid, fibrin, silk fibroin, alginate, amylopectin, carrageenan, agar, dextran, xanthan gum, pullulan) [15,[23][24][25][26] and/or synthetic polymers (e.g., polylactic acid (PLA), polycaprolactone (PCL), poly(glycolic acid) (PGA), polyanhydride, polyphosphazene, polyether ether ketone (PEEK), polypropylene fumarate (PPF)) [27], whereas the inorganic part may be made of metal alloys [16] and ceramics, such as hydroxyapatite (HA), calcium phosphate bone cements (CPS), α-tricalcium phosphate (α-TCP), β-tricalcium phosphate (β-TCP), Bioglass (BG), glass-ceramics, as well as carbon nanotubes [15,24,27,28].…”

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

“…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 osseointegration and implantation. Thus, it is a host immune response that plays a pivotal role in the success of biomaterial implantation [ 5 ].…”

“…Importantly, each phenotype exerts a different influence on the bone healing process after biomaterial implantation [ 5 ]. M1 macrophages may be identified by the secretion of proinflammatory factors, such as interleukin 1 beta (IL-1β), IL-6, IL-12, IL-23, tumor necrosis factor-alpha (TNF-α) as well as by the production of reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) [ 2 , 5 ]. Secreted by M1 cells, proinflammatory factors promote the development of Th1 lymphocytes and induce inflammation [ 9 ].…”

“…Under in vivo conditions, macrophages may differentiate into different phenotypes depending on the microenvironment and type of the tissue [ 6 ]. Under in vitro conditions, macrophages polarization into the M1 phenotype may be induced by lipopolysaccharide (LPS, known also as endotoxin), interferon-gamma (IFN-γ), or macrophage colony-stimulating factor (M-CSF) [ 5 , 7 , 8 ]. In turn, macrophage transition toward the M2 phenotype may be stimulated by IL-4, IL-13, IL-10, TGF-β, or glucocorticoids [ 7 , 8 ].…”