Functional Human Vascular Network Generated in Photocrosslinkable Gelatin Methacrylate Hydrogels

By Ying-Chieh Chen, Ruei-Zeng Lin, Hao Qi, Y. Yang, Hojae Bae, J. Melero-Martin, Ali Khademhosseini. Advanced Functional Materials, 2012

720 citations recorded by the source corpus.

The generation of functional, 3D vascular networks is a fundamental prerequisite for the development of many future tissue engineering‐based therapies. Current approaches in vascular network bioengineering are largely carried out using natural hydrogels as embedding scaffolds. However, most natural hydrogels present a poor mechanical stability and a suboptimal durability, which are critical limitations that hamper their widespread applicability. The search for improved hydrogels has become a priority in tissue engineering research. Here, the suitability of a photopolymerizable gelatin methacrylate (GelMA) hydrogel to support human progenitor cell‐based formation of vascular networks is demonstrated. Using GelMA as the embedding scaffold, it is shown that 3D constructs containing human blood‐derived endothelial colony‐forming cells (ECFCs) and bone marrow‐derived mesenchymal stem cells (MSCs) generate extensive capillary‐like networks in vitro. These vascular structures contain distinct lumens that are formed by the fusion of ECFC intracellular vacuoles in a process of vascular morphogenesis. The process of vascular network formation is dependent on the presence of MSCs, which differentiate into perivascular cells occupying abluminal positions within the network. Importantly, it is shown that implantation of cell‐laden GelMA hydrogels into immunodeficient mice results in a rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, it is shown that the degree of methacrylation of the GelMA can be used to modulate the cellular behavior and the extent of vascular network formation both in vitro and in vivo. These data suggest that GelMA hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.

Subfields: Biomaterials, Biomedical Engineering, Surgery

View Paper: https://www.semanticscholar.org/paper/ee170bd9db03c1454652b82a797ed24b4baf4b29

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biomaterials

In Biomedical Engineering

In Surgery

Citations in the corpus

Functionalization, preparation and use of cell-laden gelatin methacryloyl–based hydrogels as modular tissue culture platforms (2016, methodology): “…of the GelMA tool box, we developed different hydrogel formulations to generate hybrid hydrogels with varying chemical, biological, mechanical, and electrical properties that enable the differentiation of stem cells to desired cell types and the formation of vascular networks (Figure 5) 42 .”
Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip (2016, positive): “To the best of our knowledge, prior li terature on the construction of 3D endothelialized myocardium for both regeneration an d in the on-chip formats has been rare, with most studies focusing on single cell type cult ures [12, 26, 27] and/or simplified cocultures with limited structural similarity ”
Reinforcement of hydrogels using three-dimensionally printed microfibres (2015, positive): “GelMA is a hydrogel platform with recent use that allows for matrix deposition by embedded cells, for example, vascular networks or cartilage matrix 14,36,37 .”
Vascularization and Angiogenesis in Tissue Engineering: Beyond Creating Static Networks. (2016, background): “Depending on the culture conditions and the cell type with which the endothelial cells are combined, the morphology of the vascular networks ranges from immature cord-like networks with a limited amount of lumen [21,22], to more mature networks containing well-developed lumen [4,19] (Figure 1A).”
Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels (2015, methodology): “8 shown that the pore sizes in GelMA hydrogel can be tuned by changing the degree of methacryloyl substitution (Figure 1C) [9, 38].”
Gelatin-Methacryloyl Hydrogels: Towards Biofabrication-Based Tissue Repair (2016, methodology): “Capillary-like structures have been formed by self-organization of MSCs and endothelial colony-forming cells (ECFCs) [7,35] or human umbilical vein endothelial cells (HUVECs) [5] that were combined within a gelMA bulk hydrogel.”