Biomimetic sponges improve muscle structure and function following volumetric muscle loss

Haas, Gabriel; Dunn, Andrew; Madsen, Josh; Genovese, Peter; Chauvin, Hannah; Au, Jeffrey; Ziemkiewicz, Natalia; Johnson, David Y.; Paoli, Allison; Lin, Andrew; Pullen, Nicholas; Garg, Koyal

doi:10.1002/jbm.a.37212

Cited by 12 publications

(7 citation statements)

References 83 publications

(105 reference statements)

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“…The TA muscle was cut axially at the defect site, and the top portion was frozen in 2‐methyl butane, which was super‐cooled in a liquid nitrogen bath. Muscle cross‐sections (15 µm) were used for histological analysis as described previously 33–35 . The bottom half of the TA was snap‐frozen in liquid nitrogen for RNA isolation and quantitative RT‐PCR, as described previously.…”

Section: Methodsmentioning

confidence: 99%

“…Muscle cross-sections (15 µm) were used for histological analysis as described previously. [33][34][35] The bottom half of the TA was snap-frozen in liquid nitrogen for RNA isolation and quantitative RT-PCR, as described previously. Additional details regarding histological and gene expression analysis can be found in the Supporting Information files.…”

Section: Rodent Model Of Vmlmentioning

confidence: 99%

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Electrically stimulated eccentric contraction training enhances muscle mass, function, and size following volumetric muscle loss

Ziemkiewicz

Chauvin

et al. 2023

Journal Orthopaedic Research

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Volumetric muscle loss (VML) overwhelms muscle's innate capacity for repair and can lead to permanent disability. The standard of care for VML injuries includes physical therapy, which can improve muscle function. The objective of this study was to develop and evaluate a rehabilitative therapy using electrically stimulated eccentric contraction training (EST) and determine the structural, biomolecular, and functional response of the VML‐injured muscle. This study implemented EST using three different frequencies (50, 100, and 150 Hz) in VML‐injured rats starting at 2 weeks postinjury. Four weeks of EST at 150 Hz showed a progressive increase in eccentric torque with an improvement in muscle mass (~39%), myofiber cross‐sectional area, and peak isometric torque (~37.5%) relative to the untrained VML‐injured sham group. EST at 150 Hz group also increased the number of large type 2B fibers (>5000 µm2). Elevated gene expression of markers associated with angiogenesis, myogenesis, neurogenesis, and an anti‐inflammatory response was also observed. These results suggest that VML‐injured muscles can respond and adapt to eccentric loading. The results of this study may aid in developing physical therapy regimens for traumatized muscles.

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Section: Methodsmentioning

confidence: 99%

Section: Rodent Model Of Vmlmentioning

confidence: 99%

Electrically stimulated eccentric contraction training enhances muscle mass, function, and size following volumetric muscle loss

Ziemkiewicz

Chauvin

et al. 2023

Journal Orthopaedic Research

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“…Garg et al utilize a 20% VML animal model to determine the effect of biomimetic approaches in muscle regeneration. They used enhanced immunomodulatory properties by incorporation of tacrolimus in biomimetic sponges [63]. Tacrolimus is an immunosuppressant that is approved by the FDA [64].…”

Section: Biological Scaffolds In Vmlmentioning

confidence: 99%

Immunomodulation and Biomaterials: Key Players to Repair Volumetric Muscle Loss

Kiran

Dwivedi

Kumar

et al. 2021

Cells

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Volumetric muscle loss (VML) is defined as a condition in which a large volume of skeletal muscle is lost due to physical insult. VML often results in a heightened immune response, resulting in significant long-term functional impairment. Estimates indicate that ~250,000 fractures occur in the US alone that involve VML. Currently, there is no active treatment to fully recover or repair muscle loss in VML patients. The health economics burden due to VML is rapidly increasing around the world. Immunologists, developmental biologists, and muscle pathophysiologists are exploring both immune responses and biomaterials to meet this challenging situation. The inflammatory response in muscle injury involves a non-specific inflammatory response at the injured site that is coordination between the immune system, especially macrophages and muscle. The potential role of biomaterials in the regenerative process of skeletal muscle injury is currently an important topic. To this end, cell therapy holds great promise for the regeneration of damaged muscle following VML. However, the delivery of cells into the injured muscle site poses a major challenge as it might cause an adverse immune response or inflammation. To overcome this obstacle, in recent years various biomaterials with diverse physical and chemical nature have been developed and verified for the treatment of various muscle injuries. These biomaterials, with desired tunable physicochemical properties, can be used in combination with stem cells and growth factors to repair VML. In the current review, we focus on how various immune cells, in conjunction with biomaterials, can be used to promote muscle regeneration and, most importantly, suppress VML pathology.

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“…There are varying tissue-engineered approaches that can incorporate growth factors and/or cells within a biomaterial scaffold. Cell-based approaches, namely the addition of cells into an extracellular matrix (ECM)-based scaffold, are advantageous because they enhance muscle regeneration in part by supplying additional myoblasts or satellite cells, the local progenitor cells of skeletal muscle, that can integrate into the host tissue [6]. These treatments are limited, however, due to the high cost of treatment, risks associated with the collection, isolation, and/or expansion of autologous cells, and regulatory hurdles that must be overcome to use these cell therapies in clinical settings [5].…”

Section: Introductionmentioning

confidence: 99%

Aligned Collagen Sponges with Tunable Pore Size for Skeletal Muscle Tissue Regeneration

Kozan,

Caswell,

Patel

et al. 2023

JFB

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Volumetric muscle loss (VML) is a traumatic injury where at least 20% of the mass of a skeletal muscle has been destroyed and functionality is lost. The standard treatment for VML, autologous tissue transfer, is limited as approximately 1 in 10 grafts fail because of necrosis or infection. Tissue engineering strategies seek to develop scaffolds that can regenerate injured muscles and restore functionality. Many of these scaffolds, however, are limited in their ability to restore muscle functionality because of an inability to promote the alignment of regenerating myofibers. For aligned myofibers to form on a scaffold, myoblasts infiltrate the scaffold and receive topographical cues to direct targeted myofiber growth. We seek to determine the optimal pore size for myoblast infiltration and differentiation. We developed a method of tuning the pore size within collagen scaffolds while inducing longitudinal alignment of these pores. Significantly different pore sizes were generated by adjusting the freezing rate of the scaffolds. Scaffolds frozen at −20 °C contained the largest pores. These scaffolds promoted the greatest level of cell infiltration and orientation in the direction of pore alignment. Further research will be conducted to induce higher levels of myofiber formation, to ultimately create an off-the-shelf treatment for VML injuries.

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Biomimetic sponges improve muscle structure and function following volumetric muscle loss

Cited by 12 publications

References 83 publications

Electrically stimulated eccentric contraction training enhances muscle mass, function, and size following volumetric muscle loss

Electrically stimulated eccentric contraction training enhances muscle mass, function, and size following volumetric muscle loss

Immunomodulation and Biomaterials: Key Players to Repair Volumetric Muscle Loss

Aligned Collagen Sponges with Tunable Pore Size for Skeletal Muscle Tissue Regeneration

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