MuscleInk: A multifunctional colloidal scaffold for the treatment of muscle loss

PROJECT SUMMARY/ABSTRACT
Volumetric muscle loss (VML), which refers to an en bloc deficit of skeletal muscle mass, commonly occurs
following traumatic injury or tumor extirpation and results in substantial morbidity, pain, and disability. When
VML occurs in the lower extremities, as is most common, it particularly limits mobility and autonomy. Recovery
from VML is uniformly poor, with muscle strength and motion never returning to normal. Although free muscle
transfer and rehabilitation may improve outcomes, most limbs remain severely deficient functionally. Free
muscle transfer itself is also associated with risks, including donor site deficits and muscle atrophy following
transfer. Thus, a new paradigm for the treatment of VML injury is needed to provide an effective, long-term
restoration of function in patients. Tissue engineering approaches, including placement of 3D printed scaffolds
and growth factor delivery, promote muscle recovery following VML in pre-clinical models, but are hindered by
poor incorporation. In addition, translation to patient treatment remains difficult as the printing process takes
significant time, is prohibitively expensive, and requires specialized facilities. To address these issues, Inprint
Bio has developed MuscleInk, a multiscale porous gelatin-methacryloyl (GelMA)-based scaffolds that is
crosslinked in situ. MuscleInk is impregnated with long arginine 3- insulin-like growth factor 1 (IGF1-LR3) to
generate MuscleInk+ to improve remnant skeletal muscle hypertrophy following VML and promote
myogenesis. The porous materials are delivered using a specialized applicator and photocrosslinked in situ,
leading to excellent adhesion to surrounding tissue without the use of sutures. In Aim 1, the physical and
mechanical properties of MuscleInk will be characterized before and after sterilization and the optimal condition
will be determined. In Aim 2, the effectiveness of stable IGF1-LR3 will be verified and the benefit of MuscleInk+
for inducing myogenesis will be verified in vitro and in vivo using murine models of VML injuries. The
completion of this work will demonstrate the feasibility of the technology, lead to testing in a translational pig
model of VML, prepare us to identify the regulatory pathway for the target product de novo for MuscleInk vs
PMA for MuscleInk+, and initiate the regulatory process. MuscleInk or MuscleInk+ will address an unmet
clinical need for treatment of patients with VML injury. The final product will be sold as a one-time filler/scaffold
to plastic surgery and surgery departments of large hospitals.

Grant Number: 1R43AR083322-01A1
NIH Institute/Center: NIH
Principal Investigator: Lindsay Barnum