Synthetic extracellular matrices with tailored adhesiveness and degradability support lumen formation during angiogenic sprouting

Abstract

A major deficit in tissue engineering strategies is the lack of materials that promote angiogenesis, wherein endothelial cells from the host vasculature invade the implanted matrix to form new blood vessels. To determine the material properties that regulate angiogenesis, we have developed a microfluidic in vitro model in which chemokine-guided endothelial cell sprouting into a tunable hydrogel is followed by the formation of perfusable lumens. We show that long, perfusable tubes only develop if hydrogel adhesiveness and degradability are fine-tuned to support the initial collective invasion of endothelial cells and, at the same time, allow for matrix remodeling to permit the opening of lumens. These studies provide a better understanding of how cell-matrix interactions regulate angiogenesis and, therefore, constitute an important step towards optimal design criteria for tissue-engineered materials that require vascularization.

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

“…In detail, hydrogels could help ECs recall evolutionary memory and enable them to assemble into micro-capillary networks within 3D hydrogel, which was beneficial for the integration of engineered tissues after implantation. 52 , 374 Campbell et al developed an alginate-based hydrogel incorporating lyase for EC delivery. The EC-loaded hydrogels could promote new blood vessels generation on an in vivo evolving chicken egg via the interaction between ECs and chick chorioallantoic membrane (CAM) after implantation.…”

Endothelial inflammation and neutrophil transmigration are modulated by extracellular matrix composition in an inflammation-on-a-chip model

“…Alternatively, it could be that the HUVEC alter the underlying ECM, either by remodelling or by depositing their own ECM during culture. The ability of endothelial cells to degrade the ECM during angiogenesis is well established 95 – 97 , but whether remodelling of the ECM occurs in mature vessels is more uncertain.…”

The ECM: To Scaffold, or Not to Scaffold, That Is the Question

“…In an ECM-mimetic hydrogel, RGD sequences on PEGMA (-monoacrylate) can be copolymerized with PEGDA (-diacrylate) molecules to achieve an adherable hydrogel surface for cells [ 113 ]. By blending, copolymerizing, or post-polymerizing hydrogels with RGD peptides, hydrogel adhesiveness has shown to promote cell survival [ 114 ], differentiation [ 115 ], and angiogenesis [ 116 ]. Another synthetic polymer that shows potency is polyamidoamine (PAMAM).…”

“…Previous research by Patterson et al illustrated that PEG hydrogels functionalized with GPQGIWG or VPMSMRGG peptides, respectively, led to slower or faster cleavage rates by proteolytic enzymes MMP1 and MMP2, promoting cell migration [ 128 ]. In a recent report, dextran methacrylate (DexMA) and vinyl sulfone (DexVS) functionalized with an array of adhesive peptides and crosslinked with MMP-sensitive dicysteine peptides has a robust effect in angiogenic sprouting, leading to lumen formation [ 116 ]. Aside from these, several biomaterials show capability for controlled release of various substances, including growth factors and morphogens [ 129 ], oxygen [ 130 ], and drugs [ 131 ] among others.…”