Abstract

Volumetric muscle loss (VML), a severe injury involving irreversible loss of both muscle tissue and vasculature, poses a major barrier to the development of clinically viable muscle grafts. Functional restoration requires engineered constructs capable of reconstructing both contractile and vascular components that can functionally integrate with the host vasculature. Here, we introduce SPARC (spatio-chimeric, plasma-based, anisotropic, and shear-responsive construct), a mechanically bimodal fibrin hydrogel engineered via shear-guided assembly of plasma fibrin to recreate the structural and mechanical heterogeneity of native muscle. Controlled microfluidic shear generates aligned fibrillar bundles and a spatially graded bimodal stiffness architecture, establishing stiff, bundle-dense regions that favor myogenic differentiation and compliant regions that promote endothelial morphogenesis. When co-cultured with myoblasts and endothelial cells, the resulting anisotropic matrix directs spatially organized myogenic maturation and endothelial morphogenesis. In vivo evaluation in a murine VML model shows that vascularized muscle SPARC grafts restore muscle architecture and function, promoting neovascularization, myofiber regeneration, and enhanced motor recovery. Through its spatially mechano-programmed design, SPARC enables coordinated myogenic and endothelial organization within a single construct, establishing a scalable biofabrication strategy for functional repair of extensive muscle defects.

A research team, affiliated with UNIST has reported a new tissue engineering approach that regenerates muscle and blood vessels at the same time, using only the patient's blood. This technology offers a promising solution for treating extensive muscle loss caused by trauma or surgery.

Led by Professor Joo H. Kang of the Department of Biomedical Engineering at UNIST, the team collaborated with Professor Yoonhee Jin from Yonsei University to create a platform called SPARC (spatio-chimeric, plasma-based, shear-responsive construct). Using microfluidics, they assemble fibrin—an essential protein involved in blood clotting—into a structured scaffold. By applying controlled shear stress within tiny channels, they align fibrin fibers in specific patterns. Dense, stiff regions support muscle cell growth, while softer areas promote blood vessel formation. The result is a single, integrated scaffold that guides both tissues to develop side by side.

In tests on mice with large muscle wounds, the grafts successfully connected with the host's blood supply, encouraging the formation of new vasculature and muscle tissue. The animals regained strength and mobility, demonstrating the therapy's potential to restore function.

This approach is notable because it uses fibrin derived solely from the patient's blood, reducing the risk of immune rejection. It also simplifies scaffold fabrication by leveraging physical forces to create distinct microenvironments within one material.

“We harness fibrin's natural ability to organize under mechanical shear, creating a multifunctional scaffold from a single, biocompatible material,” said Professor Kang. “This technology could revolutionize treatments for severe muscle injuries and tissue defects.”

The findings of this research were published in the online edition of  Advanced Materials on April 22, 2026. The study was supported by the Ministry of Science and ICT (MSIT) and the National Research Foundation of Korea (NRF).

Journal Reference

Su Hyun Jung, Minjun Kim, Da-Yoon Kim, et al., “Mechanically Spatio-Chimeric Fibrin Assembly Enables Vascular-Integrated Muscle Reconstruction for Volumetric Muscle Loss Repair,”   Adv. Mater., (2026).