University of Pittsburgh scientists have discovered soluble components of anterior and posterior cruciate ligament (ACL/PCL) extracellular matrix (ECM) extracts can promote proliferation and differentiation of stem cells. Ligament damage impacts quality of life, causing debilitating pain and potentially irreversible damage to joints. In professional athletes, these injuries can prematurely end careers. ECMs that can promote tenogenic differentiation could present a novel treatment for various ligament injuries, improving patient outcomes and long-term quality of life.

Description

In the US, between 100 000 and 200 000 people per year injure the ACL, one of four major ligaments in the knee. These injuries often require costly surgery and long recovery times. Another frequent ligament injury, damage to the periodontal ligament due to traumatic avulsion of teeth, can result in patients requiring dental implants and surgery to restore facial appearance and function. Currently, healthcare costs in the US associated with this dental emergency exceed $500 million annually. Novel treatments to promote ligament regeneration and repair could save patients from surgery costs, recovery time, and lifelong impacts related to permanent damage associated with ligament injuries.

Applications

• Orthopaedics
• Sports injuries
• Dentistry

Advantages

The current treatment for ligament injuries like ACL tears is often surgery, where a healthy tendon is sacrificed from the patient for an autograft procedure. This procedure can be costly and carries risks for the patient. Traumatic facial injuries, common in children and young adults playing sports, can result in tooth avulsion where the periodontal ligament anchoring the tooth to the alveolar socket is completely torn. Tooth reinsertion 30 minutes after the avulsion has limited success.
These novel ECM extracts promote cell proliferation, and differentiation in stem cells to a tenogenic phenotype. These extracts could allow for novel regenerative therapies to be developed for ligament injuries. Additionally, these extracts are cell-free and DNA/RNA-free and, therefore, likely to reduce adverse events, including immune rejection.

Invention Readiness

In vitro testing using isolated bovine adipose-derived stem cells (bASC) over one week found that treatment with ACL or PCL ECM extracts promoted cell proliferation, viability, and tenogenic differentiation. Of note, PCL ECM extract was more effective than ACL ECM extract in the proliferation and differentiation of stem cells. Further work is now required to investigate the use of these extracts in vivo to optimize their use as therapeutics.

IP Status

https://patents.google.com/patent/US20240374650A1

Regenerative Ligament Repair Therapy