Upgrading prevascularization in tissue engineering: A review of strategies for promoting highly organized microvascular network formation

Sharma, Dhavan; Ross, David; Wang, Guifang; Jia, Wenkai; Kirkpatrick, Sean J.; Zhao, Feng

doi:10.1016/j.actbio.2019.03.016

Cited by 94 publications

(86 citation statements)

References 168 publications

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“…Therefore, one should guide the angiogenesis within newly fabricated tissues that can be achieved via biochemical and mechanical cues provided by the microenvironment. 4 In tissue engineering, the microenvironment is mostly formed by biomaterials (scaffolds, hydrogels, etc.). Among them, brin has been shown to be an effective tool to produce capillary-like networks and can be used as a biomaterial design platform to fabricate pre-vascularized tissues.…”

Section: Introductionmentioning

confidence: 99%

Digging deeper: structural background of PEGylated fibrin gels in cell migration and lumenogenesis

et al. 2020

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Section: Introductionmentioning

confidence: 99%

Digging deeper: structural background of PEGylated fibrin gels in cell migration and lumenogenesis

et al. 2020

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“…generated inside the construct. However, this process is too slow to ensure timely vascularization to significant depths, causing cell death after transplantation and failure of tissue formation (Sharma et al, 2019). We previously investigated the potential of providing a highly vascularized tissue source around the constructs (Scheufler et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…On the contrary, in constructs of clinically relevant size (i.e., a few cubic centimeters) the distance for diffusion of oxygen and nutrients is exceeded and vessel in-growth depends on physiological VEGF upregulation by ischemic conditions generated inside the construct. However, this process is too slow to ensure timely vascularization to significant depths, causing cell death after transplantation and failure of tissue formation ( Sharma et al, 2019 ). We previously investigated the potential of providing a highly vascularized tissue source around the constructs ( Scheufler et al, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

VEGF Over-Expression by Engineered BMSC Accelerates Functional Perfusion, Improving Tissue Density and In-Growth in Clinical-Size Osteogenic Grafts

Largo

Burger

Harschnitz

et al. 2020

Front. Bioeng. Biotechnol.

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The first choice for reconstruction of clinical-size bone defects consists of autologous bone flaps, which often lack the required mechanical strength and cause significant donor-site morbidity. We have previously developed biological substitutes in a rabbit model by combining bone tissue engineering and flap pre-fabrication. However, spontaneous vascularization was insufficient to ensure progenitor survival in the core of the constructs. Here, we hypothesized that increased angiogenic stimulation within constructs by exogenous VEGF can significantly accelerate early vascularization and tissue in-growth. Bone marrow stromal cells from NZW rabbits (rBMSC) were transduced with a retroviral vector to express rabbit VEGF linked to a truncated version of rabbit CD4 as a cell-surface marker. Autologous cells were seeded in clinical-size 5.5 cm 3 HA scaffolds wrapped in a panniculus carnosus flap to provide an ample vascular supply, and implanted ectopically. Constructs seeded with VEGFexpressing rBMSC showed significantly increased progenitor survivival, depth of tissue ingrowth and amount of mineralized tissue. Contrast-enhanced MRI after 1 week in vivo showed significantly improved tissue perfusion in the inner layer of the grafts compared to controls. Interestingly, grafts containing VEGF-expressing rBMSC displayed a hierarchically organized functional vascular tree, composed of dense capillary networks in the inner layers connected to large-caliber feeding vessels entering the constructs at the periphery. These data constitute proof of principle that providing sustained VEGF signaling, independently of cells experiencing hypoxia, is effective to drive rapid vascularization and increase early perfusion in clinical-size osteogenic grafts, leading to improved tissue formation deeper in the constructs.

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“…To introduce increased complexity with network compartments, numerous studies using novel culture platforms have been reported. [14,[41][42][43][44] Because endothelial and neuron cells cannot form vascular and neural networks efficiently in conventional culture systems, their microenvironment and culture conditions have been modified by innovative approaches. Low et al fabricated a 3D printed fluidic chip composed of an ECM hydrogel and kidney organoids.…”

Section: Strategies To Scale Up Number Of Dimensions Of Engineered Timentioning

confidence: 99%

“…h) Reproduced with permission. [ 44 ] Copyright 2016, National Academy of Sciences. i) Reproduced under the terms of the CC‐BY Creative Commons Attribution 4.0 International license ( https://creativecommons.org/licenses/by/4.0/).…”

Section: Strategies To Scale Up Number Of Dimensions Of Engineered Timentioning

confidence: 99%

Organ‐Level Functional 3D Tissue Constructs with Complex Compartments and their Preclinical Applications

et al. 2020

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There is an increasing interest in organ-level 3D tissue constructs, owing to their mirroring of in vivo-like features. This has resulted in a wide range of preclinical applications to obtain cell-or tissue-specific responses. Additionally, the development and improvement of sophisticated technologies, such as organoid generation, microfluidics, hydrogel engineering, and 3D printing, have enhanced 3D tissue constructs to become more elaborate. In particular, recent studies have focused on including complex compartments, i.e., vascular and innervation structured 3D tissue constructs, which mimic the nature of the human body in that all tissues/organs are interconnected and physiological phenomena are mediated through vascular and neural systems. Here, the strategies are categorized according to the number of dimensions (0D, 1D, 2D, and 3D) of the starting materials for scaling up, and novel approaches to introduce increased complexity in 3D tissue constructs are highlighted. Recent advances in preclinical applications are also investigated to gain insight into the future direction of 3D tissue construct research. Overcoming the challenges in improving organ-level functional 3D tissue constructs both in vitro and in vivo will ultimately become a life-saving tool in the biomedical field.

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Upgrading prevascularization in tissue engineering: A review of strategies for promoting highly organized microvascular network formation

Cited by 94 publications

References 168 publications

Digging deeper: structural background of PEGylated fibrin gels in cell migration and lumenogenesis

Digging deeper: structural background of PEGylated fibrin gels in cell migration and lumenogenesis

VEGF Over-Expression by Engineered BMSC Accelerates Functional Perfusion, Improving Tissue Density and In-Growth in Clinical-Size Osteogenic Grafts

Organ‐Level Functional 3D Tissue Constructs with Complex Compartments and their Preclinical Applications

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