A Treatment Paradigm for Femoracetabular Impingement (FAI) - Abstract: Fewer than 1 in 5 young patients suffering from activity limiting hip osteoarthritis (OA) choose to
undergo total hip replacement (THR) surgery, opting instead for symptom management. Despite being the
standard of care in hip OA, THR is not an ideal procedure for the young patient population because they will
require multiple revision surgeries in their lifetime, each iteration posing additional complications, quicker
implant failures, and overall decreased satisfaction. While the etiology of disease in this young population is
diverse, one clear target for intervention is femoroacetabular impingement (FAI), which directly leads to
osteochondral (OC) damage within the joint. Currently, there are no effective treatments for the OC lesions
caused by FAI, so these joints continue to degenerate and eventually require a THR. As such, there is a critical
need for new interventions that delay or halt the progression of FAI disease and the need for that initial joint
replacement. Our technology restores the function of the joint while only replacing the surface-level, diseased
tissue. The technological basis of our implant is a 3D woven scaffold, engineered to mimic the mechanical
properties of articular cartilage, which is then thermally bonded to a rigid printed substrate, which is engineered
for bone ingrowth. In order to function long-term in vivo, the implant must be populated with cells capable of
robust tissue synthesis. In this context, preculture with bone marrow derived mesenchymal stem cells (MSCs)
may be required for clinical use. However, a clear need exists to prove the chondrogenic potential of highly
variable MSC lots prior to their use clinically. The goals of this Direct to Phase II SBIR application are
therefore to first devise a method for rapidly screening the chondrogenic potential of allogeneic MSCs
using RNA sequencing in Aim 1, and then in Aim 2, to tissue-engineer a MSC-based joint resurfacing
implant to repair a large OC acetabular defect in an ovine model of FAI (CAM-type), at a site often
implicated in the young patient. All animals will receive an osteochondroplasty procedure to relieve
impingement and then be randomized to one of the following groups: 1) Control, debridement only; 2) acellular
‘implant only’ control; and 3) allogeneic MSC-based, tissue-engineered implant. Outcome measures are
selected to longitudinally track lameness, pain, and function during the study. As MRI is the gold standard for
clinical assessment, all animals will receive an MRI at the beginning of the study and after sacrifice, and these
scans will be correlated to histological and biomechanical properties of joint tissues. Systemic toxicity testing
will also be assessed according to ISO 10993-11. We expect that positive outcomes will enable us to move this
technology closer to clinical practice, with the ultimate goal of developing strategies to treat FAI and other
cartilage-related disease.
