New Approach Enables Customized Muscle Tissue Without Biomaterial Scaffolds

Volumetric muscle loss is a traumatic loss of skeletal muscle that often leads to permanent functional impairment and limited reconstructive options. Current experimental strategies struggle to deliver sufficient regenerative cells and to match irregular, defect-specific geometries, hindering durable restoration of muscle structure and strength. Researchers have now introduced a scaffold-free, patient-tailored tissue engineering approach designed to address both delivery and fit challenges.

The approach, developed at the Stanford Department of Cardiothoracic Surgery (Stanford, CA, USA), creates dense “muscle patches” without external biomaterial scaffolds. Using a simple mold-based method, cells are grown into customizable shapes and sizes that match a defect. The constructs are designed to fit unique injuries and to maximize the volume available for therapeutic cells.

Eliminating exogenous biomaterials allows more cells to be delivered into a defined injury volume while relying on the cells’ own extracellular matrix secretion for structural support. The tissues self-organize within the mold prior to implantation, establishing pre-formed cell-to-cell interactions. In study observations, this preorganization was associated with gene and protein expression resembling a more robust muscle identity compared with conventional cell suspensions.

The study was published in Advanced Healthcare Materials on March 10, 2026, where it was featured on the front cover. The team reported that scaffold-free constructs can be geometrically tuned and integrate with injured areas upon contact, supporting a proof-of-principle in which smaller modules combine into larger, more complex shapes. The work involved collaborators from the Stanford Cardiovascular Institute and the VA Palo Alto Health Care System.

Planned next steps include integrating modular muscle constructs into more complex, multicellular tissues incorporating vascular and neural components. The investigators also envision building a library of scaffold-free shapes and pairing the method with robotic assistance, clinical imaging, and artificial intelligence to map defect geometries and enable precise placement, with surgeons overseeing the procedure.

"Our custom molding technology makes it easy to design any geometry for the tissue constructs, including shapes that form letters and words like 'Stanford'," said Ngan F. Huang, PhD, Associate Professor of Cardiothoracic Surgery (Research) at the Stanford Department of Cardiothoracic Surgery.

“We believe that the pre-formed cell-to-cell interactions afforded by these scaffold-free tissues allow the cells to communicate with one another, ultimately leading to more effective muscle cells,” said Dr. Huang.

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Stanford Department of Cardiothoracic Surgery