Del-1 overexpression in endothelial cells increases vascular density in tissue-engineered implants containing endothelial cells and adipose-derived mesenchymal stromal cells.

We used a combination of strategies to stimulate the vascularization of tissue-engineered constructs in vivo including a modular approach to build larger tissues from individual building blocks ("modules") mixed together. Each building block included vascular cells by design; modules were submillimeter-sized collagen gels with an outer layer of endothelial cells (ECs), and with embedded adipose-derived mesenchymal stromal cells (adMSCs) to support EC survival and blood vessel maturation in vivo. We transduced the ECs that coat the modules with a lentiviral construct to overexpress the angiogenic extracellular matrix (ECM) protein Developmental endothelial locus-1 (Del-1).

Using Del-1 to tip the angiogenic balance in endothelial cells in modular constructs.

Modular tissue engineering is a method of building vascularized tissue-engineered constructs. Submillimeter-sized collagen pieces (modules) coated with a layer of endothelial cells (EC; vascular component), and with embedded functional cells, are self-assembled into a larger, three-dimensional tissue. In this study, we examined the use of developmental endothelial locus-1 (Del-1), an extracellular matrix protein with proangiogenic properties, as a means of tipping the angiogenic balance in human umbilical vein endothelial cells incorporated in modular tissue-engineered constructs.

Fabrication of micro-tissues using modules of collagen gel containing cells.

This protocol describes the fabrication of a type of micro-tissues called modules. The module approach generates uniform, scalable and vascularized tissues. The modules can be made of collagen as well as other gelable or crosslinkable materials.

A poloxamine-polylysine acrylate scaffold for modular tissue engineering.

A new polymer, poloxamine-polylysine acrylate (PPA), was synthesized for tissue-engineering applications. Polylysine was used to confer endothelial cell attachment properties to the poloxamine-based polymer, while the acrylate groups made it photo-cross-linkable. The PPA polymer was synthesized in three reaction steps.