Abstract
Different strategies have been employed to provide adequate nutrients for engineered living tissues. These have mainly revolved around providing oxygen to alleviate the effects of chronic hypoxia or anoxia that result in necrosis or weak neovascularization, leading to failure of artificial tissue implants and hence poor clinical outcome. While different biomaterials have been used as oxygen generators for in vitro as well as in vivo applications, certain problems have hampered their wide application. Among these are the generation and the rate at which oxygen is produced together with the production of the reaction intermediates in the form of reactive oxygen species (ROS). Both these factors can be detrimental for cell survival and can severely affect the outcome of such studies. Here we present calcium peroxide (CPO) encapsulated in polycaprolactone as oxygen releasing microparticles (OMPs). While CPO releases oxygen upon hydrolysis, PCL encapsulation ensures that hydrolysis takes place slowly, thereby sustaining prolonged release of oxygen without the stress the bulk release can endow on the encapsulated cells. We used gelatin methacryloyl (GelMA) hydrogels containing these OMPs to stimulate survival and proliferation of encapsulated skeletal myoblasts and optimized the OMP concentration for sustained oxygen delivery over more than a week. The oxygen releasing and delivery platform described in this study opens up opportunities for cell-based therapeutic approaches to treat diseases resulting from ischemic conditions and enhance survival of implants under severe hypoxic conditions for successful clinical translation.
Highlights
Higher-level organisms have evolved advanced circulatory systems that provide tissues with nutrients, e.g., glucose and oxygen via blood
It seems that the stabilizing molecules in the form of surfactants that act as capping layer for these oxygen releasing microparticles (OMPs) play a pivotal role in defining the degree of diffusion of the medium, facilitating the exchange of nutrients and oxygen for the cells
We developed an oxygenating platform which acts as a good oxygen source to maintain healthy cellular function, including under ischemic conditions
Summary
Higher-level organisms have evolved advanced circulatory systems that provide tissues with nutrients, e.g., glucose and oxygen via blood. Oxygen releasing materials aim to sustain or restore a tissue’s aerobic respiration, which drives carbohydrate metabolism and all the downstream physiologic functions These biomaterials have been shown to improve cell survival under hypoxic conditions where oxygen supply is limited [4]. We present an engineered system consisting of oxygen releasing microparticles (OMPs) and explore these to sustain aerobic respiration of artificial tissues over a period of approximately 2 weeks Chemical species such as calcium peroxide (CPO)-based oxygen generation have been exploited sustaining the cells’ metabolic needs under anoxic conditions; the unrestrained oxygen generation and release detrimentally affected the consequent oxygen tensions’ stability [5,9]. Polycaprolactone (PCL) encapsulation results in controlling hydrolysis of CPO by limiting water access and leads to sustained oxygen release (Figure 1). OMPs obtained directly from the desiccator were used for imaging
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