Immune cell response to orthopedic and craniofacial biomaterials depends on biomaterial composition.

Materials for craniofacial and orthopedic implants are commonly selected based on mechanical properties and corrosion resistance. The biocompatibility of these materials is typically assessed in vitro using cell lines, but little is known about the response of immune cells to these materials. This study aimed to evaluate the inflammatory and immune cell response to four common orthopedic materials [pure titanium (Ti), titanium alloy (TiAlV), 316L stainless steel (SS), polyetheretherketone (PEEK)]. Following implantation into mice, we found high recruitment of neutrophils, pro-inflammatory macrophages, and CD4+ T cells in response to PEEK and SS implants. Neutrophils produced higher levels of neutrophil elastase, myeloperoxidase, and neutrophil extracellular traps in vitro in response to PEEK and SS than neutrophils on Ti or TiAlV. Macrophages co-cultured on PEEK, SS, or TiAlV increased polarization of T cells towards Th1/Th17 subsets and decreased Th2/Treg polarization compared to Ti substrates. Although SS and PEEK are considered biocompatible materials, both induce a more robust inflammatory response than Ti or Ti alloy characterized by high infiltration of neutrophils and T cells, which may cause fibrous encapsulation of these materials. STATEMENT OF SIGNIFICANCE: Materials for craniofacial and orthopedic implants are commonly selected based on their mechanical properties and corrosion resistance. This study aimed to evaluate the immune cell response to four common orthopedic and craniofacial biomaterials: pure titanium, titanium-aluminum-vanadium alloy, 316L stainless steel, and PEEK. Our results demonstrate that while the biomaterials tested have been shown to be biocompatible and clinically successful, the inflammatory response is largely driven by chemical composition of the biomaterials.

Control of innate immune response by biomaterial surface topography, energy, and stiffness.

As the focus of implantable biomaterials has shifted from bioinert implants to bioactive designs, recent research has highlighted the complex interactions between cell physiologic systems and material properties, particularly physical cues. From the cells known to interact with implanted biomaterials, the response of the immune system has been a critical target of study recently. Here, we review studies characterizing the response of innate immune cells to various material cues, particularly of those at the surface of implanted materials.The innate immune system consists of cell types with various roles in inflammation. Neutrophils and macrophages serve both phagocytic and signaling roles, especially early in the inflammatory phase of biomaterial implantation. These cell types ultimately dictate the outcome of implants as chronic inflammation, fibrosis, or integration. Other cell types like dendritic cells, mast cells, natural killer cells, and innate lymphoid cells may also serve an immunomodulatory role in the biomaterial context. This review highlights recent advances in our understanding of the role of innate immunity in the response to implantable biomaterials as well as key mechanobiological findings in innate immune cells underpinning these advances. STATEMENT OF SIGNIFICANCE: This review highlights recent advances in the understanding of the role of innate immunity in the response to implantable biomaterials, especially in neutrophils and macrophages, as well as key mechanobiological findings in innate immune cells underpinning these advances. Here we discuss how physicochemical properties of biomaterials control innate immune cell behavior.

Keratose Hydrogels Promote Vascular Smooth Muscle Differentiation from C-kit-Positive Human Cardiac Stem Cells.

Stem cell-based therapies have demonstrated great potential for the treatment of cardiac diseases, for example, myocardial infarction; however, low cell viability, low retention/engraftment, and uncontrollable in vivo differentiation after transplantation are still major limitations, which lead to low therapeutic efficiency. Biomaterials provide a promising solution to overcome these issues due to their biocompatibility, biodegradability, low/nonimmunogenicity, and low/noncytotoxicity. The present study aimed to investigate the impacts of keratose (KOS) hydrogel biomaterial on cellular viability, proliferation, and differentiation of c-kit+ human cardiac stem cells (hCSCs). Briefly, hCSCs were cultured on both KOS hydrogel-coated dishes and regular tissue culture dishes (Blank control). Cell viability, stemness, proliferation, cellular morphology, and cardiac lineage differentiation were compared between KOS hydrogel and the Blank control at different time points. We found that KOS hydrogel is effective in maintaining hCSCs without any observable toxic effects, although cell size and proliferation rate appeared smaller on the KOS hydrogel compared to the Blank control. To our surprise, KOS hydrogel significantly promoted vascular smooth muscle cell (VSMC) differentiation (∼72%), while on the Blank control dishes, most of the hCSCs (∼78%) became cardiomyocytes. Furthermore, we also observed "endothelial cell tube-like" microstructures formed by differentiated VSMCs only on KOS hydrogel, suggesting a potential capability of the hCSC-derived VSMCs for in vitro angiogenesis. To the best of our knowledge, this is the first report to discover the preferred differentiation of hCSCs toward VSMCs on KOS hydrogel. The underlying mechanism remains unknown. This innovative methodology may offer a new approach to generate a robust number of VSMCs simply by culturing hCSCs on KOS hydrogel, and the resulting VSMCs may be used in animal studies and clinical trials in combination with an injectable KOS hydrogel to treat cardiovascular diseases.