Abstract
The extent of regeneration following biomaterial implantation is dependent on the microenvironment surrounding the implant. Since implant composition can have a profound effect on inflammation, it is essential to understand this process as a non-resolving inflammatory response can lead to fibrous encapsulation and insufficient integration. Incorporation of particulates into implants confers structural and functional benefits, thus optimizing particulate characteristics to enhance immune mediated efficacy is important. We investigated the relationship between the nature of hydroxyapatite (HA) particles and the innate immune response, focusing on how particle size (0.1 µm, 5 µm, 20 µm, 100 µm) and morphology (needle-shaped/spherical; smooth/rough surface) modulates inflammatory responses. We observed a shape and size-dependent activation of the NLRP3 inflammasome and IL-1β secretion; while needle-shaped and smaller HA particles significantly enhanced cytokine secretion, larger particles did not. Moreover, HA particle characteristics profoundly influenced patterns of innate immune cell recruitment and cytokine production following injection. While small, needle-shaped particles induced a strong inflammatory response, this was not observed with smooth, spherical particles of comparable size or with larger particles. These findings indicate that hydroxyapatite particle characteristics dictate immune cell recruitment and the ensuing inflammatory response, providing an opportunity to tailor HA particle characteristics to regulate immune responses induced after biomaterial implantation.
Highlights
Due to an increasingly ageing population and an exponential growth in lifestyle-related diseases, the use of biomaterials to replace or regenerate damaged tissue is steadily rising[1]
S0.1 particles are approximately 157 nm in size and have a spherical and smooth morphology; N5 particles are needle-shaped with a mean size of 5 μm; S20 and R20 have a mean size around 20 μm and differ in surface topography with S20 exhibiting a smooth surface and R20 a rough porous surface; the S100 particles have a mean size around 100 μm and have a smooth surface (Table 1)
We sought to evaluate the immunostimulatory potential of HA particles in bone marrow derived dendritic cells (BMDC) and bone-marrow derived macrophages (BMDMs), established models for assessing in vitro responses to biomaterials
Summary
Due to an increasingly ageing population and an exponential growth in lifestyle-related diseases, the use of biomaterials to replace or regenerate damaged tissue is steadily rising[1]. Tissue repair approaches have grown in sophistication, with the advent of several natural and synthetic materials that interact with host cells to enhance tissue repair and regeneration. In this context, while the composition of materials has been explored extensively, it is only recently that biophysical and biochemical cues have been implicated in driving tissue regeneration. In situ tissue engineering approaches can influence the microenvironment surrounding tissue engineered constructs to improve the outcome of implantation In this context, the presence of specific immune cell populations (including neutrophils, mast cells, monocytes and macrophages) following implantation may be predictive of implant efficacy[8]. Small-needle shaped hydroxyapatite particles induced the greatest inflammatory response, while limited responses were triggered by similar sized spherical particles or larger particles, in macrophages
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