Prevascularized grafts with spatially organized MSC spheroids to accelerate therapeutic angiogenesis in ischemic disease

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Objective Ischemic diseases, characterized by impaired blood flow and progressive tissue necrosis, remain a major challenge in regenerative medicine. Surgical revascularization remains the gold standard for restoring blood flow in major vessels, but still shows limited effects on microvascular regeneration. To address this unmet need, various strategies in therapeutic angiogenesis have been explored to induce microvascular formation, including delivery of bioactive molecules, stem cells, or pre-vascularized grafts. However, injection-based approaches often suffer from off-target effects, and conventional implantable grafts lack sufficient angiogenic secretory activity. To address these limitations, we aimed to develop a dual-function prevascularized graft that accelerates neovascularization and promotes vascular integration to restore tissue perfusion in ischemic conditions. Methods and results The graft was engineered by combining a microvascular pattern (µVP) with spatially organized mesenchymal stem cell (MSC) spheroids, fabricated via high-precision coprinting of endothelial cells and MSCs. Optimization of spheroid density and spatial arrangement enhanced VEGF secretion and increased host capillary infiltration nearly two-fold. In a murine critical limb ischemia model, implantation of these engineered grafts achieved a 60% limb salvage rate and reduced limb loss by ~ 15%, r

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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