Short-term hypoxic preconditioning promotes prevascularization in 3D bioprinted bone constructs with stromal vascular fraction derived cells

Kuss, Mitchell; Harms, R. H.; Wu, Shaohua; Wang, Ying; Untrauer, Jason B.; Carlson, Mark A.; Duan, Bin

doi:10.1039/c7ra04372d

Cited by 64 publications

(73 citation statements)

References 58 publications

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“…Recently, we described the further development of our approach by MP of the CPC in combination with a cell‐laden bioink . This enables the integration of osteogenic and vasculogenic progenitor cells in such biphasic scaffolds that might be a more effective, future‐oriented alternative as described recently …”

Section: Discussionmentioning

confidence: 99%

3D Plotted Biphasic Bone Scaffolds for Growth Factor Delivery: Biological Characterization In Vitro and In Vivo

Ahlfeld

Schuster

Förster

et al. 2019

Adv Healthcare Materials

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Bioprinting enables the integration of biological components into scaffolds during fabrication that has the advantage of high loading efficiency and better control of release and/or spatial positioning. In this study, a biphasic scaffold fabricated by extrusion‐based 3D multichannel plotting of a calcium phosphate cement (CPC) paste and an alginate/gellan gum (AlgGG) hydrogel paste laden with the angiogenic factor VEGF (vascular endothelial growth factor) is investigated with regard to biological response in vitro and in vivo. Rat mesenchymal stromal cells are able to adhere and grow on both CPC and AlgGG strands, and differentiate toward osteoblasts. A sustained VEGF release is observed, which is able to stimulate endothelial cell proliferation as well as angiogenesis in vitro that indicates maintenance of its biological activity. After implantation into a segmental bone defect in the femur diaphysis of rats, a clear reduction of the defect size by newly formed bone tissue occurs from the distal and proximal ends of the host bone within 12 weeks. The CPC component shows excellent osteoconductivity whereas the local VEGF release from the AlgGG hydrogel gives rise to an enhanced vascularization of the defect region. This work contributes to the development of novel therapeutic concepts for improved bone regeneration which are based on 3D bioprinting.

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Section: Discussionmentioning

confidence: 99%

3D Plotted Biphasic Bone Scaffolds for Growth Factor Delivery: Biological Characterization In Vitro and In Vivo

Ahlfeld

Schuster

Förster

et al. 2019

Adv Healthcare Materials

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“…The viability and circularity of encapsulated cells was determined using a Live/Dead assay (Invitrogen) after differentiation and induction as previously described [38], and fluorescence images were obtained using a confocal laser scanning microscope (CLSM, LSM 710, Carl Zeiss). Cell viability was semi-quantitatively measured via counting live (green) and dead (red) cells based on Live/Dead images (at least six images were analyzed for each hydrogel sample), using ImageJ [39].…”

Section: Methodsmentioning

confidence: 99%

Effects of tunable, 3D-bioprinted hydrogels on human brown adipocyte behavior and metabolic function

Kuss

Kim

et al. 2018

Acta Biomaterialia

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Obesity and its related health complications cause billions of dollars in healthcare costs annually in the United States, and there are yet to be safe and long-lasting anti-obesity approaches. Using brown adipose tissue (BAT) is a promising approach, as it uses fats for energy expenditure. However, the effect of the microenvironment on human thermogenic brown adipogenesis and how to generate clinically relevant sized and functioning BAT are still unknown. In our current study, we evaluated the effects of endothelial growth medium exposure on brown adipogenesis of human brown adipose progenitors (BAP). We found that pre-exposing BAP to angiogenic factors promoted brown adipogenic differentiation and metabolic activity. We further 3D bioprinted brown and white adipose progenitors within hydrogel-based bioink with controllable physicochemical properties and evaluated the cell responses in 3D bioprinted environments. We used soft, stiff, and stiff-porous constructs to encapsulate the cells. All three types had high cell viability and allowed for varying levels of function for both white and brown adipocytes. We found that the soft hydrogel constructs promoted white adipogenesis, while the stiff-porous hydrogel constructs improved both white and brown adipogenesis and were the optimal condition for promoting brown adipogenesis. Consistently, stiff-porous hydrogel constructs showed higher metabolic activities than stiff hydrogel constructs, as assessed by 2-deoxy glucose uptake (2-DOG) and oxygen consumption rate (OCR). These findings show that the physicochemical environments affect the brown adipogenesis and metabolic function, and further tuning will be able to optimize their functions. Our results also demonstrate that 3D bioprinting of brown adipose tissues with clinically relevant size and metabolic activity has the potential to be a viable option in the treatment of obesity and type 2 diabetes.

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“…It is well known that hypoxia is important in regulating endochondral ossification and triggers the expression of osteogenic and angiogenic factors in engineered bone (Rankin et al, ). 3D bioprinted hybrids of PCL/nHA with stromal vascular fraction derived cell‐laden hydrogel bioinks, which were preconditioned in hypoxic conditions resulted in the formation of extensive microvasculature perfused in osseointegrated constructs in vivo (Kuss et al, ). Therefore, with a lot of promising techniques evolving in vascularized bone formation, efforts must be done towards synergizing vascular development with bone formation in the temporal manner.…”

Section: D Bioprintingmentioning

confidence: 99%

“…bioprinted hybrids of PCL/nHA with stromal vascular fraction derived cell-laden hydrogel bioinks, which were preconditioned in hypoxic conditions resulted in the formation of extensive microvasculature perfused in osseointegrated constructs in vivo (Kuss et al, 2017).…”

Section: Vascularized Bone Formationmentioning

confidence: 99%

Advances in three‐dimensional bioprinting of bone: Progress and challenges

Midha

Dalela

Sybil

et al. 2019

J Tissue Eng Regen Med

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Several attempts have been made to engineer a viable three‐dimensional (3D) bone tissue equivalent using conventional tissue engineering strategies, but with limited clinical success. Using 3D bioprinting technology, scientists have developed functional prototypes of clinically relevant and mechanically robust bone with a functional bone marrow. Although the field is in its infancy, it has shown immense potential in the field of bone tissue engineering by re‐establishing the 3D dynamic micro‐environment of the native bone. Inspite of their in vitro success, maintaining the viability and differentiation potential of such cell‐laden constructs overtime, and their subsequent preclinical testing in terms of stability, mechanical loading, immune responses, and osseointegrative potential still needs to be explored. Progress is slow due to several challenges such as but not limited to the choice of ink used for cell encapsulation, optimal cell source, bioprinting method suitable for replicating the heterogeneous tissues and organs, and so on. Here, we summarize the recent advancements in bioprinting of bone, their limitations, challenges, and strategies for future improvisations. The generated knowledge will provide deep insights on our current understanding of the cellular interactions with the hydrogel matrices and help to unravel new methodologies for facilitating precisely regulated stem cell behaviour.

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Short-term hypoxic preconditioning promotes prevascularization in 3D bioprinted bone constructs with stromal vascular fraction derived cells

Abstract: Short-term hypoxia promoted prevascularization in 3D bioprinted bone constructs with stromal vascular fraction derived cells.

Cited by 64 publications

References 58 publications

3D Plotted Biphasic Bone Scaffolds for Growth Factor Delivery: Biological Characterization In Vitro and In Vivo

3D Plotted Biphasic Bone Scaffolds for Growth Factor Delivery: Biological Characterization In Vitro and In Vivo

Effects of tunable, 3D-bioprinted hydrogels on human brown adipocyte behavior and metabolic function

Advances in three‐dimensional bioprinting of bone: Progress and challenges

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