Endothelial sprouting and network formation in collagen- and fibrin-based modular microbeads

Rioja, Ana Y.; Annamalai, Ramkumar T.; Paris, Spencer; Putnam, Andrew J.; Stegemann, Jan P.

doi:10.1016/j.actbio.2015.10.022

Cited by 40 publications

(53 citation statements)

References 70 publications

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“…80 Fibrin is used as a bioink for cell-loaded applications to support vascularization, but its bioactivity to support endothelial cell growth and proliferation may suggest its use for cell-free bioink formulations. 31, 39, 98 Because cell-free bioink depends on separate delivery of materials and cells, the use of this cell-free bioink may provide fabrication of “off-the-shelf” channeled scaffolds for later in vitro cell seeding or host tissue cellular integration.…”

Section: Cell-free Bioinkmentioning

confidence: 99%

3D Bioprinting for Vascularized Tissue Fabrication

et al. 2016

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3D bioprinting holds remarkable promise for rapid fabrication of 3D tissue engineering constructs. Given its scalability, reproducibility, and precise multi-dimensional control that traditional fabrication methods do not provide, 3D bioprinting provides a powerful means to address one of the major challenges in tissue engineering: vascularization. Moderate success of current tissue engineering strategies have been attributed to the current inability to fabricate thick tissue engineering constructs that contain endogenous, engineered vasculature or nutrient channels that can integrate with the host tissue. Successful fabrication of a vascularized tissue construct requires synergy between high throughput, high-resolution bioprinting of larger perfusable channels and instructive bioink that promotes angiogenic sprouting and neovascularization. This review aims to cover the recent progress in the field of 3D bioprinting of vascularized tissues. It will cover the methods of bioprinting vascularized constructs, bioink for vascularization, and perspectives on recent innovations in 3D printing and biomaterials for the next generation of 3D bioprinting for vascularized tissue fabrication.

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Section: Cell-free Bioinkmentioning

confidence: 99%

3D Bioprinting for Vascularized Tissue Fabrication

et al. 2016

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“…Fibrin hydrogels can be seeded with cells and/or other molecular payloads – such as proteins, genes, or drugs - that aid in tissue regeneration [7]. In a conventional fibrin matrix, passive diffusion of the entrapped payload yields a burst release [8].…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo assessment of controlled release and degradation of acoustically responsive scaffolds

et al. 2016

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Spatiotemporally controlled release of growth factors (GFs) is critical for regenerative processes such as angiogenesis. A common strategy is to encapsulate the GF within hydrogels, with release being controlled via diffusion and/or gel degradation (i.e., hydrolysis and/or proteolysis). However, simple encapsulation strategies do not provide spatial or temporal control of GF delivery, especially non-invasive, on-demand controlled release post implantation. We previously demonstrated that fibrin hydrogels, which are widely used in tissue engineering and GF delivery applications, can be doped with perfluorocarbon emulsion, thus yielding an acoustically responsive scaffold (ARS) that can be modulated with focused ultrasound, specifically via a mechanism termed acoustic droplet vaporization. This study investigates the impact of ARS and ultrasound properties on controlled release of a surrogate payload (i.e., fluorescently-labeled dextran) and fibrin degradation in vitro and in vivo. Ultrasound exposure (2.5 MHz, peak rarefactional pressure: 8 MPa, spatial peak time average intensity: 86.4 mW/cm2), generated up to 7.7 and 21.7-fold increases in dextran release from the ARSs in vitro and in vivo, respectively. Ultrasound also induced morphological changes in the ARS. Surprisingly, up to 2.9-fold greater blood vessel density was observed in ARSs compared to fibrin when implanted subcutaneously, even without delivery of pro-angiogenic GFs. The results demonstrate the potential utility of ARSs in generating controlled release for tissue regeneration.

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“…A variety of materials and cell populations can be employed to engineer microtissues, depending on the application [14–21]. For revascularization strategies, pure fibrin and composites made from fibrin, agarose, collagen, and gelatin have been used to develop engineered tissues capable of supporting endothelial vessel formation [22–25]. …”

Section: Introductionmentioning

confidence: 99%

“…Past work by our group has shown that cell-encapsulating fibrin and collagen-fibrin microtissues can foster endothelial sprout formation and inosculation in a three-dimensional (3D) in vitro model [25, 26]. In particular, we have used co-cultures of endothelial cells and stromal cells to promote vessel formation in engineered tissues.…”

Section: Introductionmentioning

confidence: 99%

Distributed vasculogenesis from modular agarose-hydroxyapatite-fibrinogen microbeads

et al. 2017

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Critical limb ischemia impairs circulation to the extremities, causing pain, disrupted wound healing, and potential tissue necrosis. Therapeutic angiogenesis seeks to repair the damaged microvasculature directly to restore blood flow. In this study, we developed modular, micro-scale constructs designed to possess robust handling qualities, allow in vitro pre-culture, and promote microvasculature formation. The microbead matrix consisted of an agarose (AG) base to prevent aggregation, combined with cell-adhesive components of fibrinogen (FGN) and/or hydroxyapatite (HA). Microbeads encapsulating a co-culture of human umbilical vein endothelial cells (HUVEC) and fibroblasts were prepared and characterized. Microbeads were generally 80–100 microns in diameter, and the size increased with the addition of FGN and HA. Addition of HA increased the yield of microbeads, as well as the homogeneity of distribution of FGN within the matrix. Cell viability was high in all microbead types. When cell-seeded microbeads were embedded in fibrin hydrogels, HUVEC sprouting and inosculation between neighboring microbeads were observed over seven days. Pre-culture of microbeads for an additional seven days prior to embedding in fibrin resulted in significantly greater HUVEC network length in AG+HA+FGN microbeads, as compared to AG, AG+HA or AG+FGN microbeads. Importantly, composite microbeads resulted in more even and widespread endothelial network formation, relative to control microbeads consisting of pure fibrin. These results demonstrate that AG+HA+FGN microbeads support HUVEC sprouting both within and between adjacent microbeads, and can promote distributed vascularization of an external matrix. Such modular microtissues may have utility in treating ischemic tissue by rapidly re-establishing a microvascular network.

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Endothelial sprouting and network formation in collagen- and fibrin-based modular microbeads

Cited by 40 publications

References 70 publications

3D Bioprinting for Vascularized Tissue Fabrication

3D Bioprinting for Vascularized Tissue Fabrication

In vitro and in vivo assessment of controlled release and degradation of acoustically responsive scaffolds

Distributed vasculogenesis from modular agarose-hydroxyapatite-fibrinogen microbeads

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