A dual-ink 3D printing strategy to engineer pre-vascularized bone scaffolds in-vitro

Twohig, Chelsea; Helsinga, Mari; Mansoorifar, Amin; Athirasala, Avathamsa; Tahayeri, Anthony; França, Cristiane Miranda; Amaya-Pajares, Silvia P.; Abdelmoniem, Reyan; Scherrer, Susanne S.; Durual, Stéphane; Ferracane, Jack L.; Bertassoni, Luiz E.

doi:10.1016/j.msec.2021.111976

Cited by 30 publications

(44 citation statements)

References 49 publications

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“…164 Methacrylic acid is added as a modifying group to the main chain of hyaluronic acid, which gives hyaluronic acid photopolymerization properties bringing great convenience for encapsulating MSCs. Methacrylamide-functionalized gelatin (GelMA) 165 and HA functionalized with norbornene groups (NorHA) 166 adopted a similar strategy in the design of culture system. Adding specific response groups to enable biomaterials to have new characteristics is the main idea for the modification of hybrid hydrogels.…”

Section: Methodsmentioning

confidence: 99%

Recent advances in 3D hydrogel culture systems for mesenchymal stem cell-based therapy and cell behavior regulation

Xia

Cai

2022

J. Mater. Chem. B

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Section: Methodsmentioning

confidence: 99%

Recent advances in 3D hydrogel culture systems for mesenchymal stem cell-based therapy and cell behavior regulation

Xia

Cai

2022

J. Mater. Chem. B

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“…Moreover, this same method was used for a dual-ink 3D printing approach where strands of vascular capillaries were printed adjacent to strands of a rigid beta tricalcium phosphate bone scaffold material, paving the way for fabrication of larger pre-vascularized bone grafts. [157] This same method was then used to manipulate fluid flow as a reconfigurable (movable) microfluidic valve in 3D-printed hydrogel channels, showing some additional versatility to this approach. [158] Many other strategies have emerged to address the issue of connectivity between cells in a tissue.…”

Section: The Complexity Of Tissue Connectivity-bioprinting the Human Vasculaturementioning

confidence: 99%

“…with extensive success, only a few papers have included the presence of perivascular cells, which are known to regulate important physiologic process of endothelial barrier function, among others. [154,157] Extensive work by our group has been conducted to characterize the specific microenvironmental and tissue fabrication conditions that enable the consistent and reproducible fabrication of vascular capillaries in vitro, [168][169][170][171][172] and many other groups have generated vascularized organoids as well. [173] It has been demonstrated that biological requirements, such as stem cell source, [169] mechanical properties, [172] hydrogel and medium composition, [157] cell ratios, [157] and a variety of different conditions, all play a significant role in ensuring adequate endothelial-perivascular cell communication.…”

Section: The Complexity Of Tissue Connectivity-bioprinting the Human Vasculaturementioning

confidence: 99%

“…[154,157] Extensive work by our group has been conducted to characterize the specific microenvironmental and tissue fabrication conditions that enable the consistent and reproducible fabrication of vascular capillaries in vitro, [168][169][170][171][172] and many other groups have generated vascularized organoids as well. [173] It has been demonstrated that biological requirements, such as stem cell source, [169] mechanical properties, [172] hydrogel and medium composition, [157] cell ratios, [157] and a variety of different conditions, all play a significant role in ensuring adequate endothelial-perivascular cell communication. These are aspects that are likely to be needed if one intends to reliably print fully vascularized and functional solid organs.…”

Section: The Complexity Of Tissue Connectivity-bioprinting the Human Vasculaturementioning

confidence: 99%

“…First and foremost, arguably the primary engineering challenge toward fabrication of meaningful organs, is the ability to recreate tissue heterogeneity with precision. To a great extent, despite the development of many multi-ink bioprinters in recent years, [46,122,179] methods that enable a system to replicate the accuracy and precision at which tissue and cell heterogeneity is displayed in the body remain limited. Extrusion methods have been particularly good at attempting to recreate tissue heterogeneity (Figure 4a), [180] owning to the relative ease at which syringe print heads can be positioned on a printing axis and used interchangeably.…”

Section: Engineering Challenges To Replicate Microscale Organ Heterogeneitymentioning

confidence: 99%

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Bioprinting of Complex Multicellular Organs with Advanced Functionality—Recent Progress and Challenges Ahead

Bertassoni

2021

Advanced Materials

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Bioprinting has emerged as one of the most promising strategies for fabrication of functional organs in the lab as an alternative to transplant organs. While progress in the field has mostly been restricted to a few miniaturized tissues with minimal biological functionality until a few years ago, recent progress has advanced the concept of building three‐dimensional multicellular organ complexity remarkably. This review discusses a series of milestones that have paved the way for bioprinting of tissue constructs that have advanced levels of biological and architectural functionality. Critical materials, engineering and biological challenges that are key to addressing the desirable function of engineered organs are presented. These are discussed in light of the many difficulties to replicate the heterotypic organization of multicellular solid organs, the nanoscale precision of the extracellular microenvironment in hierarchical tissues, as well as the advantages and limitations of existing bioprinting methods to adequately overcome these barriers. In summary, the advances of the field toward realistic manufacturing of functional organs have never been so extensive, and this manuscript serves as a road map for some of the recent progress and the challenges ahead.

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High‐Throughput Bioprinting of Geometrically‐Controlled Pre‐Vascularized Injectable Microgels for Accelerated Tissue Regeneration

Franca,

Athirasala,

Subbiah

et al. 2023

Adv Healthcare Materials

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Successful integration of cell‐laden tissue constructs with host vasculature depends on the presence of functional capillaries to provide oxygen and nutrients to the embedded cells. However, diffusion limitations of cell‐laden biomaterials challenge regeneration of large tissue defects that require bulk‐delivery of hydrogels and cells. Here, a strategy to bioprint geometrically controlled, endothelial and stem‐cell laden microgels in high‐throughput is introduced, allowing these cells to form mature and functional pericyte‐supported vascular capillaries in vitro, and then injecting these pre‐vascularized constructs minimally invasively in‐vivo. It is demonstrated that this approach offers both desired scalability for translational applications as well as unprecedented levels of control over multiple microgel parameters to design spatially‐tailored microenvironments for better scaffold functionality and vasculature formation. As a proof‐of‐concept, the regenerative capacity of the bioprinted pre‐vascularized microgels is compared with that of cell‐laden monolithic hydrogels of the same cellular and matrix composition in hard‐to‐heal defects in vivo. The results demonstrate that the bioprinted microgels have faster and higher connective tissue formation, more vessels per area, and widespread presence of functional chimeric (human and murine) vascular capillaries across regenerated sites. The proposed strategy, therefore, addresses a significant issue in regenerative medicine, demonstrating a superior potential to facilitate translational regenerative efforts.

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A dual-ink 3D printing strategy to engineer pre-vascularized bone scaffolds in-vitro

Cited by 30 publications

References 49 publications

Recent advances in 3D hydrogel culture systems for mesenchymal stem cell-based therapy and cell behavior regulation

Recent advances in 3D hydrogel culture systems for mesenchymal stem cell-based therapy and cell behavior regulation

Bioprinting of Complex Multicellular Organs with Advanced Functionality—Recent Progress and Challenges Ahead

High‐Throughput Bioprinting of Geometrically‐Controlled Pre‐Vascularized Injectable Microgels for Accelerated Tissue Regeneration

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