High oxygen preservation hydrogels to augment cell survival under hypoxic condition

Li, Chao; Guan, Yue; Dang, Yu; Li, Xiaofei; Fan, Zhongjie; Shen, Jie; Ma, Liang; Guan, Jianjun

doi:10.1016/j.actbio.2020.01.017

Cited by 44 publications

(37 citation statements)

References 64 publications

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“…It is particularly hard to maintain homogeneous O 2 distribution within cell-loaded hydrogels, and hypoxic zones may arise even in the normoxic culture conditions [ 36 ]. For example, the O 2 level in a synthetic hydrogel was measured around 1.5% after 7 days, and this low O 2 availability adversely affected the MSC viability [ 37 ]. Our readings were above 1.5%, which suggesting that the required O 2 level for MSC viability was preserved in the 3D collagen/silk fibroin scaffold.…”

Section: Discussionmentioning

confidence: 99%

Evaluating Oxygen Tensions Related to Bone Marrow and Matrix for MSC Differentiation in 2D and 3D Biomimetic Lamellar Scaffolds

Sayın

Baran²,

Elsheikh

et al. 2021

IJMS

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The physiological O2 microenvironment of mesenchymal stem cells (MSCs) and osteoblasts and the dimensionality of a substrate are known to be important in regulating cell phenotype and function. By providing the physiologically normoxic environments of bone marrow (5%) and matrix (12%), we assessed their potential to maintain stemness, induce osteogenic differentiation, and enhance the material properties in the micropatterned collagen/silk fibroin scaffolds that were produced in 2D or 3D. Expression of osterix (OSX) and vascular endothelial growth factor A (VEGFA) was significantly enhanced in the 3D scaffold in all oxygen environments. At 21% O2, OSX and VEGFA expressions in the 3D scaffold were respectively 13,200 and 270 times higher than those of the 2D scaffold. Markers for assessing stemness were significantly more pronounced on tissue culture polystyrene and 2D scaffold incubated at 5% O2. At 21% O2, we measured significant increases in ultimate tensile strength (p < 0.0001) and Young’s modulus (p = 0.003) of the 3D scaffold compared to the 2D scaffold, whilst 5% O2 hindered the positive effect of cell seeding on tensile strength. In conclusion, we demonstrated that the 3D culture of MSCs in collagen/silk fibroin scaffolds provided biomimetic cues for bone progenitor cells toward differentiation and enhanced the tensile mechanical properties.

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Section: Discussionmentioning

confidence: 99%

Evaluating Oxygen Tensions Related to Bone Marrow and Matrix for MSC Differentiation in 2D and 3D Biomimetic Lamellar Scaffolds

Sayın

Baran²,

Elsheikh

et al. 2021

IJMS

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“…While the transplanted cells, which are within a distance of ≈200 µm of the adjacent host capillary, can depend on oxygen diffusion (Lovett et al 2009), cells that are located in the center of large-sized tissue constructs, injected into ischemic regions, or residing in coronal portion of root canal may undergo cell necrosis due to the lack of oxygen supply. Therefore, one of the key objectives in various studies is accelerating blood perfusion by inducing vascular ingrowth or by other independent means to provide oxygen to the transplanted cells, ensuring their survival and angiogenesis (Silva et al 2018; Gholobova et al 2020; Montesdeoca et al 2020; Niu et al 2020).…”

Section: Discussionmentioning

confidence: 99%

“…MgO 2 , CaO 2 , and H 2 O 2 encapsulated into microspheres, polymers, or hydrogels can release oxygen from several hours to 2 wk. The released oxygen could promote cell survival in hypoxic conditions (Niu et al 2020). CaO 2 has higher purity (60% to 80%) than MgO 2 (15% to 25%) and is considered one of the safest peroxides and a leading O 2 -generating biomaterial (Lu et al 2019).…”

Section: Discussionmentioning

confidence: 99%

“…However, prevailing hypoxia within the root canal space mimics infarcted cardiac and ischemic cerebral tissues, characterized by a low oxygen content that may hinder the survival of the transplanted cells. Transplanted cells may undergo instant death when the oxygen level drops to 1%, a condition close to the ischemic tissues, but the cells may survive with a 5% oxygen level (Niu et al 2020). Moreover, when compared with the transient drop of oxygen tension, prolonged hypoxia causes more extensive cell death (Salim et al 2004; Potier et al 2007).…”

Section: Introductionmentioning

confidence: 99%

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In Situ Oxygen Generation Enhances the SCAP Survival in Hydrogel Constructs

et al. 2021

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Prolonged and severe hypoxia is the main cause of death of transplanted cells prior to the establishment of functional circulation. In situ generation of oxygen by oxygen-producing scaffolds—a unique solution that could produce and deliver oxygen to the adjacent cells independently of blood perfusion—has attracted considerable attention to enhance the survivability of the transplanted cells. However, the application of oxygen-generating scaffolds for facilitating cell survival in pulp-like tissue regeneration is yet to be explored. In this study, gelatin methacryloyl (GelMA)—a biocompatible scaffolding material that closely mimics the native extracellular matrix and is conducive to cell proliferation and differentiation—was used to fabricate oxygen-generating scaffolds by loading various concentrations of CaO2. The CaO2 distribution, topography, swelling, and pore size of CaO2-GelMA hydrogels were characterized in detail. The release of O2 by the scaffold and the viability, spreading, and proliferation of stem cells from apical papilla (SCAPs) encapsulated in the GelMA hydrogels with various concentrations of CaO2 under hypoxia were evaluated. In addition, cellular constructs were engineered into root canals, and cell viability within the apical, middle, and coronal portions was assessed. Our findings showed that 0.5% CaO2-GelMA was sufficient to supply in situ oxygen for maintaining the embedded SCAP viability for 1 wk. Furthermore, the 0.5% CaO2-GelMA hydrogels improved the survivability of SCAPs within the coronal portion of the engineered cellular constructs within the root canals. This work demonstrated that 0.5% CaO2-GelMA hydrogels offer a potential promising scaffold that enhances survival of the embedded SCAPs in endodontic regeneration.

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“…The EPR spectrum was recorded using an X-band EPR instrument (Bruker). The parameters used in this experiment were 0.1 mW for microwave power, 1.0 db for attenuation and 9.8 GHz for frequency, following our reported method (80,81). Oxygen partial pressure (pO2) was calculated from the linewidth of the spectrum, and calibration curve of linewidth vs. oxygen concentration.…”

Section: Measurement Of Intracellular Oxygen Contentmentioning

confidence: 99%

Sustained Oxygenation Accelerates Diabetic Wound Healing by Simultaneously Promoting Epithelialization and Angiogenesis, and Decreasing Tissue Inflammation

Guan¹,

Huang²,

Z³

et al. 2021

Preprint

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Non-healing diabetic wound is one of the most common complications for diabetic patients. Chronic hypoxia is among the prominent factors that delay the wound healing process. Therefore, sustained oxygenation to alleviate hypoxia is hypothesized to promote diabetic wound healing. Yet it cannot be achieved by current clinical approaches including hyperbaric oxygen therapy. Herein, we developed a sustained oxygenation system consisting of oxygen-release microspheres and a reactive oxygen species (ROS)-scavenging hydrogel. The hydrogel was used to capture the ROS that is elevated in the diabetic wounds, and that may be generated due to oxygen release. The sustainedly released oxygen augmented survival and migration of keratinocytes and dermal fibroblasts; promoted angiogenic growth factor expression, and angiogenesis in the diabetic wounds; and decreased M1 macrophage density. These effects led to a significant increase of wound closure rate. These findings reveal that sustained oxygenation alone without using drugs is capable of healing diabetic wounds.

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High oxygen preservation hydrogels to augment cell survival under hypoxic condition

Cited by 44 publications

References 64 publications

Evaluating Oxygen Tensions Related to Bone Marrow and Matrix for MSC Differentiation in 2D and 3D Biomimetic Lamellar Scaffolds

Evaluating Oxygen Tensions Related to Bone Marrow and Matrix for MSC Differentiation in 2D and 3D Biomimetic Lamellar Scaffolds

In Situ Oxygen Generation Enhances the SCAP Survival in Hydrogel Constructs

Sustained Oxygenation Accelerates Diabetic Wound Healing by Simultaneously Promoting Epithelialization and Angiogenesis, and Decreasing Tissue Inflammation

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