Abstract
The critical role of the immune system in host defense against foreign bodies and pathogens has been long recognized. With the introduction of a new field of research called osteoimmunology, the crosstalk between the immune and bone-forming cells has been studied more thoroughly, leading to the conclusion that the two systems are intimately connected through various cytokines, signaling molecules, transcription factors and receptors. The host immune reaction triggered by biomaterial implantation determines the in vivo fate of the implant, either in new bone formation or in fibrous tissue encapsulation. The traditional biomaterial design consisted in fabricating inert biomaterials capable of stimulating osteogenesis; however, inconsistencies between the in vitro and in vivo results were reported. This led to a shift in the development of biomaterials towards implants with osteoimmunomodulatory properties. By endowing the orthopedic biomaterials with favorable osteoimmunomodulatory properties, a desired immune response can be triggered in order to obtain a proper bone regeneration process. In this context, various approaches, such as the modification of chemical/structural characteristics or the incorporation of bioactive molecules, have been employed in order to modulate the crosstalk with the immune cells. The current review provides an overview of recent developments in such applied strategies.
Highlights
Millions of people suffer from common bone defects caused by trauma, infection, tumor resection and pathological processes [1,2]
Sussman et al [267] used poly(2-hydroxyethyl methacrylate) and poly(methyl methacrylate) (PMMA) to evaluate the effect of the microsized pores on macrophage polarization and the results showed that surfaces with a pore size of 34 μm promoted the expression of M1 phenotype markers upon host implantation
The response of the host immune system triggered by biomaterial implantation is one of the most significant critical issues that needs to be overcome for the development of bone implants
Summary
Millions of people suffer from common bone defects caused by trauma, infection, tumor resection and pathological processes [1,2]. Because of the limitations associated with the conventional treatment, in the last few decades, various implantable biomaterials have been developed and tested as promising bone substitute alternatives Their wide usability relies on their ability to act as biocompatible supports and delivery platforms for biologically active molecules, which can be tailored for a specific purpose (e.g., modification of the chemical and physical properties) [8,9,10,11]. Almost 30 years later, the term “osteoimmunology” was first coined and used to describe the introduction of a new direction in research and of a new interdisciplinary field [26,27] With this advancement in bone biology, it was detrimental that a shift in the design paradigm should take place, from biomaterials capable of direct activation of cells responsible for the osteogenic process, towards biomaterials capable of modulating the local immune environment in favor of bone healing and regeneration [13,28,29]. We highlight the interplay between the skeletal and immune system and discuss how the specific characteristics of the biomaterials could be tailored in order to tune the immune response elicited by the implantable biomaterials for favorable tissue regeneration
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