Nematic Fibrin Fibers Enabling Vascularized Thrombus Implants Facilitate Scarless Cutaneous Wound Healing

Abstract

Autologous implantable scaffolds that induce vasculogenesis have shown great potential in tissue regeneration; however, previous attempts mainly relied on cell-laden hydrogel patches using fat tissues or platelet-rich plasma, which are insufficient for generating a uniform vasculature in a scalable manner. Here, implantable vascularized engineered thrombi (IVETs) are presented using autologous whole blood, which potentiate effective skin wound healing by constructing robust microcapillary vessel networks at the wound site. Microfluidic shear stresses enable the alignment of bundled fibrin fibers along the direction of the blood flow streamlines and the activation of platelets, both of which offer moderate stiffness of the microenvironment optimal for facilitating endothelial cell maturation and vascularization. Rodent dorsal skin wounds patched with IVET present superior wound closure rates (96.08 +/- 1.58%), epidermis thickness, collagen deposition, hair follicle numbers, and neutrophil infiltration, which are permitted by enhanced microvascular circulation. Moreover, IVET treatment accelerates wound healing by recruiting M2 phenotype macrophages.