The characterization of decellularized human skeletal muscle as a blueprint for mimetic scaffolds

Abstract

The use of decellularized skeletal muscle (DSM) as a cell substrate and scaffold for the repair of volumetric muscle loss injuries has shown therapeutic promise. The performance of DSM materials motivated our interest in exploring the chemical and physical properties of this promising material. We suggest that these properties could serve as a blueprint for the development of next generation engineered materials with DSM mimetic properties. In this study, whole human lower limb rectus femoris (n=10) and upper limb supraspinatus muscle samples (n=10) were collected from both male and female tissue donors. Skeletal muscle samples were decellularized and nine property values, capturing key compositional, architectural, and mechanical properties, were measured and statistically analyzed. Mean values for each property were determined across muscle types and genders. Additionally, the influence of muscle type (upper versus lower limb) and donor gender (male versus female) on each of the DSM material properties was examined. The data suggests that DSM materials prepared from lower limb rectus femoris samples have an increased modulus and contain a higher collagen content then upper limb supraspinatus muscles. Specifically, lower limb rectus femoris DSM material modulus and collagen content was approximately twice that of lower limb supraspinatus DSM samples. While muscle type did show some influence on material properties, we did not find significant trends related to gender. The material properties reported herein may be used as a blueprint for the data-driven design of next generation engineered scaffolds with muscle mimetic properties, as well as inputs for computational and physical models of skeletal muscle.

Tissue-Specific Decellularization Methods: Rationale and Strategies to Achieve Regenerative Compounds

“…At present, and aiming to preserve the matrix content and tissue structure, some less aggressive detergents, salt solutions, and nucleus-specific enzymes are the preferred decellularization methods. Most of the protocols use weak acids or detergents, such as sodium deoxycholate or Triton X-100 and SDS, respectively, followed by DNase treatment-all of them at low concentrations and exposition times and with multiple repeated cycles [100,101]. In some cases, trypsin is used in low concentrations and for short times, ensuring it does not damage in excess the protein structure.…”

Tissue-Engineered Grafts from Human Decellularized Extracellular Matrices: A Systematic Review and Future Perspectives

“…Later, Wilson et al [86] described the decellularization of human rectus femoris and supraspinatus muscles. The tissues were freezed-thawed, soaked in 1% SDS with 1% EDTA in Tris–HCl buffer and then incubated in 1 kU/ml DNase/RNase buffer.…”

Codelivery of Infusion Decellularized Skeletal Muscle with Minced Muscle Autografts Improved Recovery from Volumetric Muscle Loss Injury in a Rat Model

“…Toward this end, several groups, including ours, are exploring the development of engineered extracellular matrix (ECM) scaffolds targeting VML repair. [5][6][7][8][9] ECM scaffolds prepared from a variety of tissue sources have been utilized to repair a wide range of damaged tissues in animal models [10][11][12][13] and recently in humans. 14,15 Within this class of tissue-derived ECM scaffolds, the application of decellularized skeletal muscle (DSM) as a repair strategy for VML injury has shown some promise.…”