In-situ engineering of native extracellular matrix to improve vascularization and tissue regeneration at the ischemic injury site

Ischemic injury causes dynamic damage to the native extracellular matrix (ECM), which plays a key role in tissue homeostasis and regeneration by providing structural support, facilitating force transmission, and transducing key signals to cells. The main approach aimed at repairing injury to ischemic tissues is restoration of vascular function. Due to their potential to form capillary niches, endothelial cells (ECs) are of greatest interest for vascular regeneration. Integrin binding to ECM is crucial for cell anchorage to the surrounding matrix, spreading, migration, and further activation of intracellular signaling pathways.

The team led by Dake Hao and Aijun Wang from University of California Davis proposed to establish an in-situ engineering strategy to remodel the ECM at the ischemic site to guide EC endogenous binding and establish effective EC/ECM interactions to promote revascularization. They designed and constructed a dual-function molecule (LXW7)2-SILY, which is comprised of two functional domains: the first one (LXW7) binds to integrin αvβ3 expressed on ECs, and the second one (SILY) binds to collagen. In vitro, they confirmed (LXW7)2-SILY improved EC adhesion and survival. After in situ injection, (LXW7)2-SILY showed stable retention at the injured area and promoted revascularization, blood perfusion, and tissue regeneration in a mouse hindlimb ischemia model.

With the abundant expression of collagen across tissues and organs and the significance of vascularization in tissue repair and regeneration, (LXW7)2-SILY technology holds promise across various tissue regeneration and clinical applications. Moreover, (LXW7)2-SILY could also be used in functionalizing collagen-based biomaterials and scaffolds for improved vascularization in treating various diseases and conditions.