Oxygen-Generating Scaffolds: One Step Closer to the Clinical Translation of Tissue Engineered Products.

The lack of oxygen supply in engineered constructs has been an ongoing challenge for tissue engineering and regenerative medicine. Upon implantation of an engineered tissue, spontaneous blood vessel formation does not happen rapidly, therefore, there is typically a limited availability of oxygen in engineered biomaterials. Providing oxygen in large tissue-engineered constructs is a major challenge that hinders the development of clinically relevant engineered tissues. Similarly, maintaining adequate oxygen levels in cell-laden tissue engineered products during transportation and storage is another hurdle. There is an unmet demand for functional scaffolds that could actively produce and deliver oxygen, attainable by incorporating oxygen-generating materials. Recent approaches include encapsulation of oxygen-generating agents such as solid peroxides, liquid peroxides, and fluorinated substances in the scaffolds. Recent approaches to mitigate the adverse effects, as well as achieving a sustained and controlled release of oxygen, are discussed. Importance of oxygen-generating materials in various tissue engineering approaches such as ex vivo tissue engineering, in situ tissue engineering, and bioprinting are highlighted in detail. In addition, the existing challenges, possible solutions, and future strategies that aim to design clinically relevant multifunctional oxygen-generating biomaterials are provided in this review paper.

Hydrogel-Impregnated Self-Oxygenating Electrospun Scaffolds for Bone Tissue Engineering.

Bone defects resulting from trauma, disease, or aging present significant challenges in the clinic. Although biomaterial scaffolds for bone-tissue engineering have shown promising results, challenges remain, including the need for adequate mechanical strength and suitable bioactive agents within scaffolds to promote bone formation. Oxygen is a critical factor for successful bone formation, and low oxygen tension inhibits it. In this study, we developed gelatin methacryloyl (GelMA) hydrogel-impregnated electrospun polycaprolactone (PCL) scaffolds that can release oxygen over 3 weeks. We investigated the potential of composite scaffolds for cell survival in bone-tissue engineering. Our results showed that the addition of an increased amount of CaO2 nanoparticles to the PCL scaffolds significantly increased oxygen generation, which was modulated by GelMA impregnation. Moreover, the resulting scaffolds showed improved cytocompatibility, pre-osteoblast adhesion, and proliferation under hypoxic conditions. This finding is particularly relevant since hypoxia is a prevalent feature in various bone diseases. In addition to providing oxygen, CaO2 nanoparticles also act as reinforcing agents improving the mechanical property of the scaffolds, while the incorporation of GelMA enhances cell adhesion and proliferation properties. Overall, our newly developed self-oxygenating composite biomaterials are promising scaffolds for bone-tissue engineering applications.

Oxygen-generating microparticles in chondrocytes-laden hydrogels by facile and versatile click chemistry strategy.

Currently, oxygen supply for in vitro cell culture is one of the major challenges in tissue engineering, especially in three-dimensional (3D) structures, such as polymeric hydrogels, because oxygen is an essential element for cells survival. In this context, oxygen levels must be maintained in articular cartilage to promote the differentiation, viability, and proliferation of chondrocytes due to the low level of oxygen presence in this region. Although some technologies employ oxygen-generating materials to add sufficient oxygen levels, the limitations and challenges of current technologies include the lack of controlled, sustained, and prolonged release of the oxygen. Moreover, the fabrication methods may leave some impurities or residues resulting in toxicity to the cells. "Click" chemistry is a facile, versatile, and compatible chemical strategy to engineer hydrogels for tissue engineering applications. Herein, we disclose the engineering of oxygen-generating microparticles in chondrocytes-laden hydrogels through a versatile catalyst-free tetrazine and norbornene inverse electron demand Diels‒Alder (iEDDA) click reaction. The hydrogels combine chondroitin sulfate (CS) and poly(ethylene glycol) (PEG) crosslinked in situ, displaying tunable rheological and mechanical properties, for sustained and prolonged oxygen-release. Gene expression analysis of the chondrocytes by real-time reverse transcription polymerase chain reaction (RT-PCR) demonstrated promising cell response within the engineered hydrogel.