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. 2022 Apr 13;8(4):239. doi: 10.3390/gels8040239

Table 5.

Comparison analysis of the engineered strategies to improve oxygen delivery.

Categories Perfusion Channels [40] Perfluorocarbons (PFCs) [41] Peroxides [42]
General
Description
Uses microfluidics to construct perfusable networks within printed constructs. PFCs are non-toxic, chemically inert, immiscible fluids with high oxygen and carbon dioxide transportability. Peroxides are oxygen generators upon ready decomposition.
Mechanism of oxygenation The perfusable channels are made of sacrificial materials to allow for mass O2 and nutrient exchange and later for guided development of blood vessels. PFCs are hydrocarbon structures having fluorine or halogen substitutes in place of hydrogen within the polymer backbone. Being an electron-acceptor, fluorine can dissolve gases (e.g., O2) through diffusion. Peroxides can interact with water to undergo hydrolytic decomposition and produce oxygen.
Requirements Co-axial printing to allow simultaneous deposition of the structural bioink and the sacrificial template. Being extremely hydrophobic with certain lipophilic characteristics, PFCs require surfactants such as lecithin to form suitable emulsions that can be incorporated within the bioink. Peroxide decomposition into water and oxygen is related to the formation of hydrogen peroxide that is detrimental to cells. The incorporation of catalase enzyme within the printed bioink, along with the oxygen-generating peroxides.
Need Inducement of angiogenesis through growth factors requires long intervals to establish functional vasculature during which mass transport may be compromised due to diffusion limitation in the thicker structures [12]. Pre-vascularization offers immediate oxygen and nutrient perfusion, by-passing the time lag associated with vasculature formation. In view of the high molecular ratios of dissolved O2 in PFC (5O2:1PFC), 1000-times higher than water, the incorporation of PFCs within bioinks can help attract and direct oxygen from the growth medium to the cells encapsulated within the printed construct to better oxygenate the cells. Incorporation of peroxides within bioinks can assist in timely decomposition of hydrogen peroxide decomposition and maintain cell viability within the printed construct (as seen in the pictorial representation below) [134].
Examples Sacrificial channels can be made from temperature-sensitive biomaterials such as gelatin, GelMA, or Pluronic. Perfluoro-octyl bromide (PFOB) and perfluoro-decalin (PFD) can be used. Calcium, magnesium, or sodium peroxides can be used.
Efficiency Co-fabrication of perfusable vascular channels has seen improved cell survival (maintained 80% viability over a 14-day period) and function within the printed structures [40]. Molecular ratios of dissolved O2 are 1O2:200water in water, but 5O2:1PFD in PFD, resulting in a 1000-times increased molecular solubility of O2 for PFD compared to water (as seen in pictorial representation below). Cell viability analysis on day 7 after incorporating 1% calcium peroxide is 80% [134].
Pictorial
Representation
graphic file with name gels-08-00239-i001.jpg Inline graphic graphic file with name gels-08-00239-i003.jpg