Functional Tissue Engineering for Cartilage Repair

Abstract It is estimated that only aboutof young patients suffering from!activity limiting hip osteoarthritisOAchoose to undergo traditional hip replacement surgeryThis low percentage is attributed to the shortened projected lifetime of hip implants for active patients and the subsequent need for revision surgeries that are plagued with higher complication rates and overall decreased effectivenessTo address the needs of this young arthritic patient population with debilitating diseasewe have developed a functional bi layered implant that is comprised of a three dimensionallyDwoven scaffold on its surface that is microscopically bonded to a rigid printed substrateThe top layer of the implant is engineered from a high performanceD woven bioresorbablepoly e caprolactoneor PCLtextile to mimic many of the constitutive properties of native articular cartilageand the bioprinted base layer is engineeredalso from PCLto facilitate integration with host bony tissuesIn totalthe implant is designed to resurface pathologic areas of the articular surfaces afflicted with arthritic disease andconsequentlyprovides abiosyntheticsolution to this young patient in a manner less invasive than is required for a traditional joint prosthesisThe implant can be easily manufactured in a variety of anatomical shapes or even custom shaped to fit the exact contour of the patient s anatomyIn the present studyour goal is to perform in vivo studies in a canine OA model that we have recently developed to examine the potential of repairing the load bearing cartilage of the hip femoral heada site often implicated in the initiation of OA in the young patientThe following three groups will be testedamm diameter xmm deep empty defect on the cranio dorsal aspect of the femoral headOA control groupthe samemm xmm defect filled with our biomimetic implantacellular experimental treatment groupandthe same defect seeded with MSCsand pre cultured ex vivo to create an anatomically shaped layer of living cartilagetissueengineered treatment groupAll groups will be tested in vivo formonthsthis duration is consistent with FDA recommendations for cartilage repair models and will therefore facilitate engagement with FDA to define preclinical testing strategies and plans for our implantOutcome measureslimb girthradiographykinetic gait analysisand spontaneous activity measurementwill be obtained at baseline and every month formonths following surgerySequential radiographs of the hipbaseline and every monthwill also be taken to monitor any joint morphological changesAt sacrificethe histological and biomechanical properties of the joint tissues will be compared to radiograph based measurementsSerumsynovial fluidsynoviumand lymph nodes will be analyzed for biomarkers of osteoarthritisas well as for adverse inflammatory reactionsWe expect that positive outcomes from this study will enable us to move this technology closer to clinical practicewith the ultimate goal of developing tissue engineered strategies to treat OA and other cartilage related diseaseWe further expect to use these data to attract investors as we seek capital to advance this technology to market!Project Narrative The purpose of this project is to further the development of a treatment for osteoarthritis in the young patient population that currently has no good treatment optionsOur approach comprises a unique bilayered scaffold that is engineered to withstand joint loading while supporting the regeneration of diseased joint tissuesthereby offering distinct advantages over invasive prosthetic devicesA successful outcome will help move this technology closer to the clinicpotentially becoming a viable treatment for osteoarthritis and other joint diseases