Tissue defects may arise as a consequence of either congenital anomalies or acquired pathological conditions. The latter encompasses the occurrence of tissue damage resulting from various aetiologies, such as pathological processes, traumatic events, or surgical interventions (Bara et al., 2018). Numerous methodologies have been devised for the management of tissue defects, encompassing the utilization of autografts, allografts, and xenografts. While autografts have long been the preferred choice, their procurement results in the co-occurrence of comorbidity at the donor site, and the availability of autografts is also limited (Ansari et al., 2022). One of the primary concerns inherent in the utilization of grafts pertains to the post-transplant viability of cells (Grounds, 2018). The utilization of allografts was investigated, particularly in instances involving osseous and cutaneous tissues (Mamidi et al., 2022). The utilization of xenografts has been proposed as an alternative approach; however, it is imperative to note that this course of action may elicit significant immune responses and potentially entail the transmission of infectious agents (Fernandes et al., 2022). Furthermore, the utilization of animal-derived sources as potential alternatives is impeded by ethical and cultural considerations. The ongoing pursuit of alternatives has encompassed the utilization of alloplastic materials for the purpose of regenerative application as well as the exploration of cellular replacement therapy, specifically involving hormone-secreting cells. Additionally, the investigation has extended to the examination of biomolecules that hold potential for facilitating tissue regeneration, particularly within the skeletal system and the integumentary system (Margiana et al., 2022; Samandari et al., 2022).
In an alternative perspective, there have been suggestions for the utilization of tissue engineering methodologies that involve the amalgamation of biomaterials with cellular components. In recent times, the utilization of the three-dimensional (3D) bioprinting technique has been employed for the purpose of cultivating living tissue constructs in controlled laboratory environments. Additionally, a multitude of bioinks have been formulated to facilitate the construction of 3D biomimicking models, thereby encompassing the intricate characteristics of tissues in relation to their biological, physical, and mechanical properties (Ashammakhi et al., 2019a). Due to the fact that the presence of functional cells within a bone construct is crucial for tissue-engineered bone to effectively repair large bone defects, scientists evaluated the functionality of mesenchymal stem cells (MSCs) subsequent to an extended period of continuous severe hypoxia (Deschepper et al., 2011). Consequently, it is important for newly developed capillaries (a process known as angiogenesis) to be promptly established within the transplanted tissues in order to address the limitations of oxygen diffusion. Given that angiogenesis requires a certain amount of time to occur, it is vital to develop a strategic approach to address this temporal gap. This approach is necessary to maintain a continuous and uninterrupted provision of essential nutrients and oxygen to implanted constructs, thereby preventing the untimely demise of cells (Coronel et al., 2019).
The oxygen supply during graft integration is crucial to the success of engineered bone in regenerative engineering. Tissue necrosis and programmed cell death occur due to a lack of oxygen (Hirao et al., 2007). Blood is the main transport medium for oxygen and nutrients throughout the body’s vascular system. The diffusion limit of oxygen and nutrients within a tissue is considered to be 200 μm from a vessel. Therefore, all cells must be within 200 μm of a vessel in order for the engineered tissue to be sustainable and for optimal vasculature to supply sufficient nutrients. Postimplantation complete vascularization typically necessitates a gradual progression (Rouwkema and Khademhosseini, 2016). The process of achieving 83% vascularity in a transplant may take approximately 6 weeks. This period allows for the integration of the host’s capillaries and blood arteries into the designed implant (Rouwkema and Khademhosseini, 2016).
In a broad sense, oxygen can be administered through direct means, such as utilizing perfluorocarbon-based systems that release oxygen, or alternatively, it can be conveyed through the use of a carrier composed of biomaterials (Corrales-Orovio et al., 2023). Various biomaterials have been extensively investigated as scaffolds; however, the incorporation of oxygen-releasing agents remains a relatively unexplored area (Liang et al., 2021). A major issue that has arisen pertains to the rapid release of oxygen, which has the potential to exhibit cytotoxic effects on cells. The provision of sustainable oxygen release can offer support to cells existing within the implanted construct prior to the occurrence of angiogenesis, which typically takes place within a period of one to 2 weeks. Once angiogenesis occurs, new capillaries take over the responsibility of supplying oxygen to the cells (Ashammakhi et al., 2019b). This problem has been predominantly resolved through the use of hydrophobic carrier biomaterials, which possess the ability to gradually release oxygen over extended durations, lasting up to a maximum of 10 days (White et al., 2014). The in vitro experiments have established the efficacy of these biomaterials and their effect on cell viability. Moreover, apart from providing assistance to developed constructs during the crucial period immediately following implantation, materials that generate oxygen can also be beneficial in the management of injured tissues, such as persistent wounds and complications arising from the obstruction of blood vessels that supply nutrients, for example, myocardial infarction (Fan et al., 2018). In addition, materials capable of generating oxygen can be employed to provide support for cells with higher metabolic activity, including neurons, hepatocytes, and muscle cells. To date, the majority of research work has been directed towards the combining of diverse carrier biomaterials with an oxygen source. The literature has shown that there is evidence of advantageous outcomes in the fields of bone and muscular tissue engineering (Touri et al., 2018; Agarwal et al., 2021).
This review focuses on the examination of oxygen source materials, carrier scaffolds, production techniques, release mechanisms, characterization methodologies, and their impact on cellular behavior and in vivo experimentation. In addition, we emphasize the difficulties and prospects and provide a concise overview of recent advancements in this dynamic and significant field. Anticipated are further advancements and implementations of oxygen generating systems, which are projected to significantly impact the future of engineered tissue structures and their clinical applications.
https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2024.1292171/full