Bioengineered skeletal muscle for defect replacement in a rodent model

Abstract

Loss of functional skeletal muscle due to congenital and acquired conditions, such as traumatic injury, tumor excision, etc., produces a physiological deficit for which there is still no effective clinical treatment. The goal of these studies is to develop clinically relevant tissue engineered skeletal muscle (TESKM) that can eventually be used for functional restoration of injured muscle in vivo. TESKM constructs developed by seeding rat muscle precursor cells on porcine bladder acellular matrix were preconditioned in a bioreactor for one week and implanted in nude mice (for 1–2 months) to repair a defect created by excising 50% of the native Latissimus Dorsi muscle (LD). Isometric tetanic specific force (ITSF) generated by the un‐repaired defect only group (49.2± 1.8 mN/mm2) was significantly lower (p<0.01) than that of native LD (161.1± 22.4 mN/mm2). ITSF of TESKM constructs increased over time from one month (20.06± 6.4 mN/mm2) to two month (86.75± 45.7 mN/mm2) which is 53% of native LD. Besides this, the TESKM constructs recorded higher tension than the unrepaired group (12.6± 4.1 g) both at 1 month (16.88± 7.1 g) and 2 month (22.34± 5.6 g, p<0.05), with the latter being 73% of native LD (30.67± 4.4g). Taken together, these initial observations indicate that TESKM can generate approximately half the ITSF of native LD after two months of implantation, illustrating the potential clinical utility of this approach. Grant Funding Source: AFIRM

Regenerative Medicine

“…Using this approach, we have observed robust functional recovery within 2 months of implantation. 95 Taken together, the initial work in the field bodes well for the use of using a tissue engineering platform for the treatment of VML and related skeletal muscle disease/dysfunction.…”

“…91–94 However, another goal is to create tissue-engineered skeletal muscle in vitro that can subsequently be implanted for restoration of muscle function in vivo. 95 Examples of each approach are briefly reviewed below.…”

“…Three general approaches are currently being pursued to restore function after VML, and they are as follows: (1) implantation of scaffold only, 97 (2) implantation of scaffold followed by injection of stem cells, 98 or (3) implantation of scaffold seeded with cells followed by bioreactor preconditioning. 95 With respect to the scaffold only approach, Merritt et al, 97 created a 1 Â 1 cm 2 full-thickness surgical defect in the rat gastrocnemius muscle to model VML. Creation of this surgical defect resulted in an initial 25% reduction in force, and implantation of a decellularized gastrocnemius muscle matrix at the site of injury did not facilitate functional recovery 42 days after injury.…”