We are currently developing noninvasive imaging tools to assess key features of skeletal muscle related to architectural, biologic, inflammatory, and volumetric changes in pathologic and normal muscle. A key focus of this project series is to carefully validate quantitative imaging biomarkers through novel simulation approaches, 3D printing precision engineered phantoms, and careful histologic validation. In conjunction with validation, we are actively using these tools to assess how factors such as aging, pain, exercise, and pathology influence biomarkers of muscle health related to muscle volume, microstructure, architecture, fatty infiltration, and fibrosis for various muscle groups in the body
Compared with acute injuries, in chronic rotator cuff disorders, back pain, osteoarthritis, and other widespread orthopedic conditions, tissue-resident cells appear to be unable to regenerate the affected tissue. Transplantation of exogenous cell sources has been a promising approach to overcome this biological hurdle and induce regeneration in pre-clinical models.
Complementary to this, our focus is to investigate regenerative approaches directly in clinical practice. Using single cell omics and other unbiased high-resolution quantitative tools, we are evaluating the regenerative potential as well as bottlenecks of current biologics used in orthopedic patients. Using this information, we develop novel therapeutics as well as (surgical) methods to obtain regenerative tissues minimally invasively.
Shoulder Injury and Repair
This project series seeks to describe time-specific morphological changes after rotator cuff tear and repair in a translational rabbit model. Muscle atrophy, degeneration, fat accumulation, and fibrosis are quantified via histology and biochemical assays. After studying the effects of tenotomy with and without delayed repair, adjuvant therapies such as systemic losartan or BaCl2 injection were trialed. Furthermore, an induced-hypercholesterolemia model is currently underway, to examine the tissue effects of this setting alone and in combination with statin drug use.
Lower Back Pain Associated Muscle Degeneration
Muscle tissue degeneration is prevalent in individuals with low back pain (LBP) and is often observed in conjunction with infiltration of fat and scar tissue (fibrosis) into the spine muscles. Importantly, the severity of muscle degeneration tracks with severity of disease, and preliminary data suggests that increased levels of muscle degeneration are a poor prognostic indicator for LBP related disability up to 1-year after lumbar spine surgery. Balancing muscle degeneration and recovery after injury is thought to involve several types of cells, including a number of tissue-resident progenitor cell populations (i.e. pericytes and fibro-adipogenic progenitor cells), along with inflammatory cells. This line of research is aimed at characterizing the cell populations and their role in muscle disease progression in patients with lumbar spine pathology. These investigations integrate histology, immunohistochemistry, cytokine panels, and gene expression to identify cellular processes involved in spinal muscle degeneration.
Cell type proportions (left) and immunofluorescent staining of the fibro-adipogenic progenitor cells (right) in muscle biopsies from patients with acute and chronic low back pain
Although skeletal muscle has an innate ability to regenerate after injury, this regenerative response fails for volumetric muscle loss injuries. We are currently developing 3D bioprinting approaches to fabricate scaffolds with precision engineered geometry, biology, and material properties to promote skeletal muscle regeneration. These scaffolds can be rapidly 3D bioprinted in a matter of seconds with any arbitrarily geometry and with user control over 3D material properties. Furthermore, various biologic adjuvants such as decellularize extracellular matrix or growth factors can be incorporated to further tune muscle regeneration biology.
Image Analysis of Spine Biomechanics
Using upright MRI, we have developed an approach to assess how external factors such as load magnitude, load distribution, ergonomics, functional positions, and training influence spinal posture. Using this technique, we can assess 3D spinal posture using a validated semi-automated algorithm as well as changes in the biomechanics of the soft tissue of the spine (i.e. intervertebral disc, spinal cord, paravertebral muscles).