Table 1.

Advantages and Drawbacks of Various Oxygen-Releasing Biomaterials

Method	Mechanism	Advantages	Drawbacks	Refs
Oxygen-carrying biomaterial
HBOC	Binding of oxygen with haem groups	Use of natural human protein (i.e., Hb) Enhanced stability of encapsulated Hb Encapsulation of higher amounts of Hb compared with RBCs Long shelf life	Short half-life (and oxygen release) in blood circulation Binding of Hb to nitric oxide (can result in vasoconstriction) Oxidative damage by increase of free radicals, causing adverse effects	[23,24,111]
PFC	Dissolving oxygen in oil via Van der Waals forces	Does not require blood-type matching May be used as contrast agents with MRI Low cost Long shelf life	Rapid plasma clearance Low oxygen-carrying ability at physiological oxygen levels Induces flu-like symptoms Can bind to nitric oxide (which may result in vasoconstriction) Causes severe adverse effects	[105–107,112]
NSP	Binding of oxygen to cyclodextrins	Oxygen release can be enhanced externally (offers more control) Biocompatible, biodegradable, and nontoxic	Short release times of oxygen limits applicability Needs external stimulus for enhanced oxygen generation	[31,32]
LOM	Encapsulation of gaseous oxygen in microbubbles	Can be used as contrast agents for ultrasound imaging Lipid bubble increases oxygen-loading capacity Able to release high amounts of oxygen in short time	Short release times of oxygen Often have relatively large sizes (> 10μm) Limited shelf life Can cause adverse haemodynamic effects	[33,35,110]
Oxygen-generating biomaterials
Liquid peroxides	Decomposition of H2O2	Faster oxygen release due to higher solubility in water Can be bound to high-molecular-weight polymers to tailor oxygen generation Catalysts can be used to catalyse reaction	Catalyst needed to lower cytotoxic effect of H2O2 and ROS Hard to control release rate and burst release	[36]
SP	Generation and decomposition of H2O2	Ease of use High payload CPO: high purity for sustained release SPC: biocompatible products MPO: slowest oxygen formation	Hard to control release rate and burst release Catalyst needed to lower cytotoxic effects of by-products By-products (e.g., calcium hydroxide) increase local pH CPO: lowest solubility SPC: less purity MPO: less purity	[39,43]
HOG	Generation and decomposition of H2O2 in microparticles	Ease of use Better control over oxygen release Extended release duration High payload	Catalyst needed to lower cytotoxic effects of by-products	[38,44,45,47]
EP	Decomposition of aromatic molecules in endoperoxides to generate 1O2	No cytotoxic by-products Can be linked to polymer or scaffold to control oxygen release	Toxic main product (1O2) Requires energy (e.g., heat) to generate 1O2 Long treatment times needed for effective therapeutic treatment Short half-life	[51–54]
Algae-based biomaterials	Oxygenic photosynthesis	Theoretically infinite oxygen production Can be genetically engineered to secrete growth factors	Limited applications due to required light exposure Not extensively tested in vivo for safety Likely not immunocompatible	[55–58]
Mn-based materials	Catalysed decomposition of H2O2	Lower ROS-related cytotoxicity Enhanced MRI performance due to reduction of MnO2 into Mn2+	Oxygen release dependent on H2O2-rich environments More extensive (human) in vivo studies needed to determine safety Excessive Mn2+ can lead to oxidative damage in liver	[60,62,65]