# Geometrically Tunable Scaffold‐Free Muscle Bioconstructs for Treating Volumetric Muscle Loss

## TL;DR

Researchers developed customizable, scaffold-free muscle tissues that improve muscle regeneration and function in mice with severe muscle injuries.

## Contribution

A mold-based method to create scaffold-free muscle bioconstructs with customizable geometry and improved therapeutic potential.

## Key findings

- Scaffold-free muscle bioconstructs in rectangular shapes improved muscle force recovery in mice.
- Pre-formed cell-cell interactions enhanced myogenic pathways related to muscle contraction and assembly.
- The method supports integration with medical imaging and AI for customized intraoperative use.

## Abstract

Traumatic muscle injuries associated with volumetric muscle loss (VML) are characterized by muscle loss beyond intrinsic regeneration capacity, leading to permanent functional impairment. Experimental therapies to augment muscle regeneration, such as cell injection, are limited by low cell transplantation capacity, whereas conventional engineered muscle tissue transplants lack geometric customization to conform to the shape of the muscle defect. Here, a facile approach to engineer scaffold‐free high‐density muscle tissues in customizable geometric shapes and sizes with high cell viability and integration potential is developed. Using a facile mold‐based approach to engineer scaffold‐free modular units, transcriptional profiling is performed to uncover the role of pre‐formed cell–cell interactions within scaffold‐free muscle bioconstructs on myogenesis, an the efficacy of muscle bioconstructs in a mouse model of VML is then evaluated. RNA sequencing revealed that pre‐formed cell–cell interactions supported myogenic pathways related to muscle contraction and myofibril assembly, unlike dissociated monodisperse cells. This work further demonstrates the therapeutic efficacy of 3D rectangular solid‐shaped scaffold‐free transplants in improving muscle function and vascular regeneration. Finally, toward clinical translation, the feasibility of this technology to integrate with medical imaging and artificial intelligence‐driven customized bioconstruct design and assembly for intraoperative use is illustrated.

Volumetric muscle loss is associated with traumatic muscle resulting in permanent functional impairment. Mold‐based, scaffold‐free, high‐density muscle tissue bioconstructs are developed in customizable geometric shapes and sizes. The transplanted rectangular solid‐shaped muscle bioconstructs improved muscle force recovery and tissue regeneration in the ablated mouse muscle.