Redox regulation in regenerative medicine and tissue engineering: The paradox of oxygen

Abstract

One of the biggest challenges in tissue engineering and regenerative medicine is to incorporate a functioning vasculature to overcome the consequences of a lack of oxygen and nutrients in the tissue construct. Otherwise, decreased oxygen tension leads to incomplete metabolism and the formation of the so‐called reactive oxygen species (ROS). Cells have many endogenous antioxidant systems to ensure a balance between ROS and antioxidants, but if this balance is disrupted by factors such as high levels of ROS due to long‐term hypoxia, there will be tissue damage and dysfunction. Current attempts to solve the oxygen problem in the field rarely take into account the importance of the redox balance and are instead centred on releasing or generating oxygen. The first problem with this approach is that although oxygen is necessary for life, it is paradoxically also a highly toxic molecule. Furthermore, although some oxygen‐generating biomaterials produce oxygen, they also generate hydrogen peroxide, a ROS, as an intermediate product. In this review, we discuss why it would be a superior strategy to supplement oxygen delivery with molecules to safeguard the important redox balance. Redox sensor proteins that can stimulate the anaerobic metabolism, angiogenesis, and enhancement of endogenous antioxidant systems are discussed as promising targets. We propose that redox regulating biomaterials have the potential to tackle some of the challenges related to angiogenesis and that the knowledge in this review will help scientists in tissue engineering and regenerative medicine realize this aim.

Oxidative stress in alpha and beta cells as a selection criterion for biocompatible biomaterials

“…Importantly, it did not induce oxidative stress or affect insulin secretion. In the future, it would be interesting to investigate PEOT/PBT300 as an implantation device in in vivo studies, or to add an antioxidant inducer to an oxidative stress-inducing biomaterial [61,62] to improve the outcomes of CIT. was measured in αTC1 cells exposed to H2O2 or cultured on biomaterials on day 7 (D).…”

Oxygen and nutrient delivery in tissue engineering: Approaches to graft vascularization

“…Importantly, hyperoxic conditions are not only detrimental in vivo , but may also interfere with cell growth in cultures, slowing proliferation and eventually leading to apoptosis (Cacciuttolo, Trinh, Lumpkin, & Rao, ). The importance of oxygen in tissue engineering and its paradoxical behaviour herein have recently been reviewed (Sthijns, van Blitterswijk, & LaPointe, ), and thus lie beyond the scope of this review. Yet achieving a balanced oxygen supply is crucial for successful tissue engineering approaches and should be considered carefully when developing new tissue engineering constructs.…”

Hypoxia Inducible Factor-1α in Osteochondral Tissue Engineering

“…Alternatively, oxygen scavengers can mediate the opposite effect and lower local levels of oxygen. Indeed, it is possible to locally decrease the oxygen pressure within a biomaterial either by incorporating various molecules 52 or simply by limiting oxygen diffusion, which has been shown to stimulate the chondrogenesis of progenitor cells. 53 However, regulating oxygen itself may not be ideal as hypoxia is also known to cause oxidative stress, prompt potentially undesirable effects on cell metabolism, and negatively impact cell growth and viability, 54 all of which may be detrimental to forming tissue.…”