# Aligned and Conductive 3D Collagen Scaffolds for Skeletal Muscle Tissue Engineering

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2020 · $195,544

## Abstract

ABSTRACT
Skeletal muscle injuries and diseases are pervasively common in patients of many backgrounds ranging from
elite athletes and soldiers to the elderly. Despite the ability of skeletal muscle to remodel and repair following
injury, there are still a variety of traumatic injuries (as well as congenital and acquired disorders) that result in
an irrecoverable loss of muscle mass and function, termed volumetric muscle loss (VML). Moreover, the
majority of muscle injuries occur at the fibers near the interface with the tendon, known as the
musculotendinous junction (MTJ). Despite these facts, clinical and tissue engineering approaches to VML and
MTJ regeneration are lacking. The objective of this proposal is to assess the ability of a biomaterial scaffold
mimicking the collagenous composition and continuous, graded nature of native orthopedic interfaces to
promote MTJ regeneration. We will take an innovative biomaterials approach using two enabling technologies:
1) we will leverage our experience with collagen-GAG (CG) scaffolds to develop a fully three-dimensional (3D)
scaffold with aligned macropores mimicking the structural anisotropy of skeletal muscle and the MTJ, and 2)
we will incorporate dispersed polypyrrole (PPy) microparticles throughout the scaffold to simulate the
endogenous conductivity of skeletal muscle. We hypothesize that a 3D conductive scaffold with highly aligned,
anisotropic pores will present an instructive microenvironment to facilitate the repair of VML injuries. We will
test this hypothesis through two aims. In Aim 1 we will interrogate the combined roles of scaffold conductivity
and 3D alignment on in vitro muscle-derived cell (MDC) phenotype. Bioelectrical stimuli are known to be
important in organ regeneration and are integral to normal skeletal muscle function, including the cell-cell
signaling that coordinates synchronous contraction. In addition to characterization of scaffold microstructural,
mechanical, and conductive properties, we will assess rat MDC viability, migration, proliferation, cytoskeletal
organization, and myotube formation. In Aim 2 we will assess the combined roles of scaffold conductivity and
3D alignment on in vivo repair of a rat MTJ VML defect. We will combine the directional solidification approach
described above with a layering technique to fabricate graded anisotropic scaffolds with spatially-defined
conductivity and mechanics toward the repair of a VML defect in a rat model of tibialis anterior MTJ injury.
Repair will be evaluated using a suite of histological and functional assays. The key innovation of this work is
the design of an anisotropic conductive biomaterial that incorporates spatially-stratified compositional and
architectural cues, namely the inclusion of a 3D conductive milieu with an open pore, aligned microstructure
that should facilitate cell infiltration and organization. This approach is likely to establish an innovative
paradigm for regenerating multi-tissue interfaces....

## Key facts

- **NIH application ID:** 9983595
- **Project number:** 5R21AR075181-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Steven Caliari
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $195,544
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983595

## Citation

> US National Institutes of Health, RePORTER application 9983595, Aligned and Conductive 3D Collagen Scaffolds for Skeletal Muscle Tissue Engineering (5R21AR075181-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9983595. Licensed CC0.

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