Modulation of macrophages by bioactive glass/sodium alginate hydrogel is crucial in skin regeneration enhancement

Inflammatory monocytes and tissue-resident macrophages are key regulators of tissue repair, regeneration, and fibrosis. After tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play critical roles during the initiation, maintenance, and resolution phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, such that uncontrolled production of inflammatory mediators and growth factors, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contribute to a state of persistent injury, and this could lead to the development of pathological fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound-healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue-regenerating phenotypes after injury, and we highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically.

Plasticity and functional polarization are hallmarks of the mononuclear phagocyte system. Here we review emerging key properties of different forms of macrophage activation and polarization (M1, M2a, M2b, M2c), which represent extremes of a continuum. In particular, recent evidence suggests that differential modulation of the chemokine system integrates polarized macrophages in pathways of resistance to, or promotion of, microbial pathogens and tumors, or immunoregulation, tissue repair and remodeling.

The manner in which a mutually acceptable co-existence of biomaterials and tissues is developed and sustained has been the focus of attention in biomaterials science for many years, and forms the foundation of the subject of biocompatibility. There are many ways in which materials and tissues can be brought into contact such that this co-existence may be compromised, and the search for biomaterials that are able to provide for the best performance in devices has been based upon the understanding of all the interactions within biocompatibility phenomena. Our understanding of the mechanisms of biocompatibility has been restricted whilst the focus of attention has been long-term implantable devices. In this paper, over 50 years of experience with such devices is analysed and it is shown that, in the vast majority of circumstances, the sole requirement for biocompatibility in a medical device intended for long-term contact with the tissues of the human body is that the material shall do no harm to those tissues, achieved through chemical and biological inertness. Rarely has an attempt to introduce biological activity into a biomaterial been clinically successful in these applications. This essay then turns its attention to the use of biomaterials in tissue engineering, sophisticated cell, drug and gene delivery systems and applications in biotechnology, and shows that here the need for specific and direct interactions between biomaterials and tissue components has become necessary, and with this a new paradigm for biocompatibility has emerged. It is believed that once the need for this change is recognised, so our understanding of the mechanisms of biocompatibility will markedly improve.