Biological Hip Resurfacing for Osteoarthritis Treatment in a Canine Model

Presented by: Masataka Enomoto

 

Authors: Masataka Enomoto (1), Bradley T Estes (2), Franklin T Moutos (2), Megan A Gallagher (1), Dianne Little (3), Jonathan Stallings (4), Farshid Guilak (5), B Duncan X Lascelles (1)

Affiliations: (1) North Carolina State University College of Veterinary Medicine (2) Cytex Therapeutics, Inc. (3) Purdue University College of Veterinary Medicine (4) North Carolina State University (5) Washington University and Shriners Hospital for Children

Introduction: Osteoarthritis (OA) is a major source of persistent pain and disability. Given the limited capacity for intrinsic repair of articular cartilage, there have been numerous attempts to develop repair techniques for focal cartilage defects. Unfortunately, to date, these techniques have had limited success in halting the progression of OA. Several issues have limited the broader application of current cartilage repair approaches for the treatment of OA, namely the inability to repair large defects due to the lack of functional mechanical properties or maintenance of geometry of engineered grafts.

Hypothesis / Objectives: Our objective was to evaluate the ability of a textile-based, anatomically shaped biphasic poly(caprolactone) implant seeded with autologous bone marrow derived mesenchymal stem cells to repair large osteochondral hip lesions and to prevent development of OA in a canine model.

Materials and Methods: Twelve castrated-male purpose-bred hounds (approximately 3 year-old) were randomized to either the implant group or control group. During surgery, a large osteochondral lesion was created on the femoral head. The defect was repaired with the tissue-engineered implant in the implant group, and was left empty in the control group. Pre- and post- outcome measures were collected through a 6-month recovery period, followed by histological and mechanical evaluation of the repaired tissue. All statistical analyses were performed using PROC MIXED, implementing the Kenward-Roger denominator degrees-of-freedom method. Tukey adjustments were used to account for multiple comparison (alpha=0.05).

Results: The dogs that received the tissue-engineered implant returned to normal activity levels as measured by a collar-mounted accelerometer, and a significant effect of treatment was observed. Kinetic gait analysis also revealed normal limb function (peak vertical force; vertical impulse) on the operated limb postoperatively after 3 months in the implant group, with significant higher values than the control group. Pain assessments and limb circumference data also showed recovery to normal values postoperatively in the implant group relative to the control group (p<0.05). Additionally, histological and mechanical analyses supported our clinical findings, demonstrating improvement over the non-treated OA joints.

Conclusions: By all outcome metrics, the dogs receiving the tissue-engineered implant returned to normal preoperative values by 6-months postop. Additionally, functional changes in this canine model of OA appear comparable to those previously identified in dogs with naturally occurring hip OA, making this an appropriate model for studying regenerative therapies. Our data, in total, indicate that our resorbable biomimetic tissue-engineered construct restored the contour of the femoral head to its native condition and was functioning as intended from a structural, biological, and anatomical viewpoint to restore joint function and relieve pain in a model of hip OA.

Acknowledgements, Funding, and Conflicts of Interest: Acknowledgements: The authors acknowledge Dr. Sarah Compton for her work culturing the MSCs in this study.

Funding: Supported in part by NIH grant AR055042, the AO Foundation, and the Arthritis Foundation.

Conflicts of Interest: Masataka Enomoto, Megan A Gallagher, Sarah J Wall, Jonathan Stallings, and B Duncan X Lascelles, have no conflicts of interests. Dianne Little is a paid consultant for Cytex Therapeutics Inc. Farshid Guilak, Franklin T Moutos and Bradley T Estes are employees and shareholders of Cytex Therapeutics Inc.