Engineering transferrable microvascular meshes for subcutaneous islet transplantation

Abstract

The success of engineered cell or tissue implants is dependent on vascular regeneration to meet adequate metabolic requirements. However, development of a broadly applicable strategy for stable and functional vascularization has remained challenging. We report here highly organized and resilient microvascular meshes fabricated through a controllable anchored self-assembly method. The microvascular meshes are scalable to centimeters, almost free of defects and transferrable to diverse substrates, ready for transplantation. They promote formation of functional blood vessels, with a density as high as ~220 vessels mm-2, in the poorly vascularized subcutaneous space of SCID-Beige mice. We further demonstrate the feasibility of fabricating microvascular meshes from human induced pluripotent stem cell-derived endothelial cells, opening a way to engineer patient-specific microvasculature. As a proof-of-concept for type 1 diabetes treatment, we combine microvascular meshes and subcutaneously transplanted rat islets and achieve correction of chemically induced diabetes in SCID-Beige mice for 3 months.

Improvement of islet transplantation by the fusion of islet cells with functional blood vessels

“…Significant research efforts have been conducted to promote the revascularization and, thus, to improve nutrient and oxygen supply of grafted islets during the first post‐transplantational days (Song et al , 2019; Menger et al , 2020). A promising strategy to achieve this is the prevascularization of the transplantation site, as already described for subcutaneous tissue by means of a catheter technique (Pepper et al , 2015).…”

Biofabrication of tissue engineering vascular systems

“…4(f) ]. MVSs have been incorporated into other organ systems such as lung, 230 liver, 231–233 kidney, 234 and islets 235 to supply oxygen and nutrients or to study the interaction of parenchymal cells and endothelial cells in MVS.…”

hiPSC-derived 3D Bioprinted Skeletal Muscle Tissue Implants Regenerate Skeletal Muscle Following Volumetric Muscle Loss

“…17,18 The rapid vascularization of volumetric muscle constructs based on hiPSC-MPCs is of paramount importance for the cells' survival, myogenic differentiation, and maturation into functional myo bers, as these cells are metabolically active. [19][20][21][22] A common approach for building 3D implants has been the mold fabrication of hydrogel encapsulated isogenic 3D hiPSC-derived arti cial skeletal muscle constructs, which gives limited control over architecture. 23 Here, we propose a strategy of combining 3D bioprinting and hiPSC-MPC culture technologies to engineer pre-vascularized muscle tissue implants that emulate the intricate structural complexity and multi-dimensional hierarchy of native muscle, thus forming the basis for a new generation of VML repair strategies (Figure 1).…”