Traumatic and non-traumatic musculoskeletal disorders are responsible for substantial morbidity, pain and disability, affecting athletes, soldiers, active working people and elder population. This implies major social and economic hurdles, as musculoskeletal injuries represent a cost of $30 billion in U.S. each year. After injury, different therapeutic approaches are currently used in the clinics, including surgical application of autologous or allogeneic grafts. Nevertheless, complications are often associated to surgical repair including nerve injury, infection, scarring, limitations of tissue graft supply, concerns with immunological response and poor healing capacity of injured tissue. Indeed, natural healing and surgical procedures are inefficient in restoring functionality of injured muscles, resulting in a poor quality of life. Thus, a new paradigm for the treatment of musculoskeletal tissue damage is needed that can provide an effective, and long-term therapy for most patients. Here, we plan to engineer nanofibrous scaffolds with biomimetic mechanical properties that control- releases angiogenic and myogenic factors eluted through patient specific platelet-rich plasma (PRP). The nanofibrous scaffolds will be coated with a layer of hydrogel containing culture of induced pluripotent stem cells derived myogenic precursor cells (iPS-MPCs), which are expected to differentiate into highly organized myotubes. The accomplishment of the aims of this proposal will be a paradigm shift in engineering muscle tissues towards their use in treating muscular disorders and provides an effective and long-term therapy for most patients.

Public Health Relevance

Traumatic and non-traumatic musculoskeletal disorders are responsible for substantial morbidity, pain and disability, affecting athletes, soldiers, active working people and elder population. Indeed, natural healing and surgical procedures are inefficient in restoring functionality of injured muscles, resulting in a poor quality of life. Here, we plan to engineer nanofibrous scaffolds coated by biomimetic hydrogels containing patient-specific growth factors and cells for engineering implantable muscle tissues.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR073822-04
Application #
10023160
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Wang, Fei
Project Start
2019-11-01
Project End
2023-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Biomedical Engineering
Type
Schools of Dentistry/Oral Hygn
DUNS #
022254226
City
Farmington
State
CT
Country
United States
Zip Code
06030