An innovative project is looking to tackle a major hurdle in orthopedic medicine: the irreversible muscle degeneration that occurs after a tendon rips.
The study will pioneer a new nanotherapeutic solution that could turn harmful fat into healthy tissue after a rotator cuff tear.
“When patients undergo surgical intervention, often the muscle doesn’t regenerate. It stays atrophied and with irreversible fatty infiltration,” explained Hugo Giambini, PhD, assistant professor in the Department of Biomedical Engineering at the Margie and Bill Klesse College of Engineering and Integrated Design. “There is no optimum treatment yet. Our focus is engineering tools to modulate that environment.”
Giambini will co-lead the effort with Maria Gonzalez Porras, PhD, assistant professor in the Klesse College, with support from a highly competitive $2.9 million R01 grant from the National Institutes of Health (NIH).
The team will combine cutting-edge orthopedics and biomechanics with advanced nanotechnology to address the problem.
The challenge of shoulder repair
Rotator cuff tears are incredibly common, especially as people age or experience physical trauma. While surgeons can reattach the torn tendon to the bone, the attached muscle often remains weak, atrophied and heavily infiltrated by fat tissue. This phenomenon, known as fatty infiltration, permanently reduces shoulder function and increases the likelihood that the tendon will tear again.
The new study aims to improve muscle regeneration by altering that fat. Instead of allowing harmful, energy-storing white fat to accumulate and suffocate the muscle, the researchers are using custom nanoparticles to transform it into beige fat, also called brown-like fat. Often referred to as “good fat,” beige fat is highly metabolically active, generating heat and releasing biochemical signals that can promote tissue repair and regeneration.
Giambini specializes in rotator cuff injury and treatment, while Gonzalez Porras’ research focuses on nanotherapy that tackles fat.
“We saw potential to collaborate when we realized the applicability of our technology targeting fat within the injured muscles in the shoulder,” Gonzalez Porras said. “We want to use this nanotherapy to convert that bad fat into good fat, which will stimulate muscle regeneration and reduce inflammation.”
Advancing nanotherapy and its potential applications
The delivery system uses nanoparticles as vehicles to deliver molecules that stimulate fat browning. Once injected directly into the muscle, these nanoparticles release the therapeutic compound slowly over time, minimizing the need for frequent injections and preventing systemic side effects.
While this specific NIH grant focuses on rotator cuff repairs, the underlying nanoparticle platform has significant potential to treat a range of medical conditions. Because the technology can simultaneously target fat tissue and promote muscle growth, it could eventually be used to treat any chronic injury or medical condition where muscle atrophy and fibrosis limit a patient’s recovery.
Beyond orthopedic trauma, the core technology is highly adaptable. Gonzalez Porras was recently awarded a separate grant of nearly $250,000 from the Cancer Prevention and Research Institute of Texas (CPRIT) to use this precision nanoparticle platform to treat obesity-linked endometrial cancer. In that oncology application, her lab is modifying the particles to target different molecular pathways, stopping fat-derived cells from migrating to the endometrium and accelerating tumor growth.
A collaborative approach to healing
To successfully bridge the gap between nanotechnology and clinical practice, the five-year project relies heavily on interdisciplinary collaboration across institutions. Gonzalez Porras’ GP Fat Lab will provide the expertise needed to develop and finetune the nanoparticles to target fat cells and modulate their metabolism within muscle.
Giambini’s laboratory brings a deep understanding of rotator cuff injury mechanisms to the project. By applying biomechanical models, Giambini will evaluate whether the nanotherapy restores muscle strength and function.
“We are tracking how the muscles heal,” Giambini said. “Our goal is to see a true recovery of function so that the patient doesn’t just have a repaired tendon, but a shoulder that can bear normal function again.”
The team is collaborating closely with Blake Rasmussen, PhD, professor and chair of the Department of Cellular and Integrative Physiology in the Joe R. and Teresa Lozano Long School of Medicine. Rasmussen’s expertise in muscle biology and cellular metabolism will help the team evaluate the tissue at the molecular level, ensuring the nanotherapy effectively promotes muscle regeneration.
The federal award marks a significant milestone, representing one of the first major collaborative R01 grants since the university’s recent integration. Over the next five years, graduate students from both laboratories will work side-by-side to transition the nanoparticle platform into preclinical models, moving closer to a therapy that could redefine standard care for millions of patients.
