Comparison of BioCartilage Versus Marrow Stimulating Procedure for Cartilage Defects of the Knee
Conditions: Defect of Articular Cartilage
Sponsor: University of Missouri-Columbia

University of Missouri Health Care 
Missouri Orthopaedic Institute 
RUNNING HEAD: BioCartilage® 
 
1 
 
 
 
 
 
 
Comparison of BioCartilage® versus Marrow Stimulating  
Procedure for Cartilage Defects of the Knee 
 
 
 
 
 
IRB Project #: 1211220 
 
PROTOCOL NUMBER: MOI_2015_09_23_1.5 
PROTOCOL VERSION NUMBER: 1.5 
DATE: 23 September 2015  
 
 
 
 
 
 
 
 
 
Principal Investigator:  
James P. Stannard, MD 
Study Site: 
Missouri Orthopaedic Institute  
1100 Virginia Avenue 
Columbia, MO 65212 
 
Sponsor Contact Information: 
Josh Karnes 
Manager, Research Development 
Arthrex Inc 
1370 Creekside Boulevard 
Naples, FL 34108 
800-933-7001 
 

University of Missouri Health Care 
Missouri Orthopaedic Institute 
RUNNING HEAD: BioCartilage® 
 
2 
 
TABLE OF CONTENTS 
1. Background and Significance 
2. Trial Objectives and Purpose 
3. Selection of Subjects 
4. Study Procedure 
5. Safety Assessment 
6. Tentative Timeline 
7. Confidentiality of Data 
8. References 
 
 
1. Background and Significance 
 
Recent developments in the treatment of articular cartilage defects have resulted in several 
techniques that involve the stimulation of native cellular components for the purpose of 
differentiation and proliferation in the cartilage defect. Techniques of interest for this study are 
the use of microfracture combined with platelet rich plasma (PRP), and a recently developed 
augmentation of the microfracture procedure—BioCartilage®.  
 
The microfracture procedure is performed with PowerPick™. During the procedure, a patient 
with focal cartilage defect undergoes arthroscopic debridement of the defect before microfracture 
is used to create holes in the subchondral plate in order to provide access to mesenchymal stem 
cells (MSCs). The procedure is complete at this point for patients undergoing a MSP without 
BioCartilage®.Other patients, who are undergoing a marrow stimulating procedure (MSP) with 
the BioCartilage® adjunct, will then have the microfractured region filled with PRP harvested 
intraoperatively from the patient, and a fibrin glue is then used to cover the defect and hold the 
PRP repair in place.  
 
This basic MSP has been shown to regenerate cartilage tissue and improve joint function. 
Microfracture treatments using PRP are “shown to have good to excellent short-term outcomes 
in appropriately indicated patients” (Abrams, Mall, Fortier, Roller, & Cole, 2013), however 
successful long-term outcomes have not been demonstrated in the literature.  
 
BioCartilage®, a novel therapy developed by Arthrex Inc, is implemented as an augmentation of 
the basic approach of using microfracture and PRP. All aspects of the procedure, as well as 
indications for the procedure, are the same as the basic MSP described above, except the PRP is 
combined with BioCartilage® powder, which acts as a scaffolding for cellular growth. 
BioCartilage® is an FDA approved augmentation of microfracture treatment with PRP, and the 
powder itself contains no living cells.  
 
Animal models using BioCartilage® have provided data that supports the assertion that the 
BioCartilage® augmentation may improve outcomes for patients who receive it; however there 
is currently no published human clinical outcomes data available for using BioCartilage® 
(Abrams et al., 2013).  
 

University of Missouri Health Care 
Missouri Orthopaedic Institute 
RUNNING HEAD: BioCartilage® 
 
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During the course of this study, we will gather and compare clinical outcomes data for patients 
who are receiving basic MSP for focal defects of the knee (trochlea or femoral condyle) to 
outcomes data for patients receiving the same MSP augmented with BioCartilage®.  
 
There are no known benefits available exclusively to the subjects participating in this study. The 
only known risk for the subjects participating in this study include a slightly increased risk of 
injury associated with an MRI performed post-operatively.  
 
 
2. Trial Objectives and Purpose 
 
The rationale for conducting this study is to obtain clinical outcomes data on human subjects 
using BioCartilage® treatment for focal cartilage defects of the trochlea and the femoral condyle. 
The null hypothesis: There is no significant difference between BioCartilage® and MSP in 
lesion tissue fill amount or quality based on MRI assessments.  
The primary endpoint is to determine whether subjects receiving MSP augmented with 
BioCartilage® have improved outcomes (measured using quality of life indicators, functional 
outcomes, and MRI) compared to subjects who receive MSP without the use of BioCartilage®.  
 
3. Selection of Subjects 
 
The population to be studied will include individuals who are undergoing MSP with or without 
BioCartilage® treatment for focal defects of the knee (trochlea or femoral condyle). Up to 60 
subjects will be enrolled in this study.  
 
Sample size selection is based on pre-study statistical power analysis using data from an equine 
study in progress with arthroscopic scoring and histology grading of defect tissue amount and 
quality.  
 
Subjects will be 18-years of age or greater, and be candidates for a procedure involving a MSP 
with microfracture and PRP, with or without BioCartilage® (or have already undergone such a 
procedure), for treatment of a focal defect of the knee (trochlea or femoral condyle). Subjects 
will be identified among the Missouri Orthopaedic Institute’s clinical and surgical patient 
population by the investigators and study staff. Recruitment will be attempted after the subject is 
identified as a study candidate according to inclusion/exclusion criteria. Informed consent will 
either be obtained at a pre-operative visit, or it will be obtained post-operatively; in both 
instances informed consent will be obtained prior to obtaining baseline data.   
 
Inclusion and Exclusion Criteria:  
I. 
Inclusion in the study will be considered when all of the following conditions are met:  
a. The subject is a candidate for the use of a MSP with microfracture and PRP, with 
or without augmentation with BioCartilage® (or has already undergone such a 

University of Missouri Health Care 
Missouri Orthopaedic Institute 
RUNNING HEAD: BioCartilage® 
 
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procedure), for treatment of a focal defect of the knee (trochlea or femoral 
condyle).  
b. The subject is 18-years of age or greater 
c. The subject is able and willing to consent to participate in the study 
d. The subject is expected to be able to safely undergo MRI at the 1-year follow-up 
visit (no contraindications present, such as metal implants) 
e. Infection or inflammatory arthropathy (such as rheumatoid arthritis) is absent in 
the operative knee  
 
II. 
Exclusion from the study will be determined by any one of the following conditions 
being met: 
a. The subject is undergoing bilateral knee surgery 
b. The subject is unwilling, or unable to consent due to psychiatric condition or legal 
incompetence 
c. The subject is either pregnant, or a prisoner 
Subjects with concomitant pathology of the knee (e.g., meniscal tear, or anterior cruciate 
ligament damage) will not be excluded, but the investigator will note concomitant pathology in 
the intraoperative data collection instrument.  
 
4. Study Procedure 
 
Patients who undergo the standard of care (SOC) treatment MSP using microfracture and PRP, 
with or without augmentation with BioCartilage®, for focal defect of the knee (trochlea or 
femoral condyle) normally meet with their physician pre-operatively, return for the operative 
procedure, and then follow-up at approximately 6 weeks, 26 weeks, 52 weeks, and 104 weeks.   
 
In the course of this study, investigators will enroll the patient either before or after they perform 
the SOC procedure (MSP with or without BioCartilage®), then they will schedule SOC follow-
up visits, and data will be captured at each visit. At the 52 week follow-up visit, the patient will 
receive a MRI that is not SOC. The MRI procedure and interpretation will be paid for by the 
sponsor of this study, Arthrex Inc. All other care will be billed to the patient as part of SOC.  
 
Patients who are enrolled (consented) after the SOC procedure has already been performed will 
be approached to discuss enrollment just prior to departure on the Operative Visit, after they 
have recovered from anesthesia. Study staff will approach the patient in their room, determine 
that the patient is alert and oriented, and then present the informed consent form for their review 
and consideration. Patients will be given as much time as they would like to consider enrollment 
in the study. Completion of study activities (surveys) normally performed during the Pre-
Operative Visit will be attempted at that time, but may be collected by phone or in person at any 
SOC clinic visit prior to the 6-Week Follow-Up Visit.  
 
 
 

University of Missouri Health Care 
Missouri Orthopaedic Institute 
RUNNING HEAD: BioCartilage® 
 
5 
 
The timeline of study activities is shown in Figure 1, below:  
 
 
Figure 1: Timeline of Study Activities* 
*Note: Study activities from the Pre-Operative Visit may be performed post-operatively during the Operative Visit 
 
In addition to the study activities listed above, if a subject enrolled in this study is having future 
knee surgery (same side or contralateral to the MSP with or without BioCartilage®), which is 
unrelated to the index procedure, the knee that had the index procedure may be arthroscopically 
viewed. The investigator may also perform knee joint aspirations if the patient is having 
complications with the knee related to the index procedure or if they are having surgery on either 
knee that is unrelated to the index procedure.  
 
 
 

University of Missouri Health Care 
Missouri Orthopaedic Institute 
RUNNING HEAD: BioCartilage® 
 
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Enrollment of a total of 60 patients will occur across two arms of the study (trochlea and femoral 
condyle), each with two cohorts (MSP with and without BioCartilage®), shown in Figure 2, 
below: 
 
Figure 2: Cohorts and Arms 
 
Assignment to a particular arm of the study will be determined by a subject’s diagnosis (i.e., 
whether the defect is located at the trochlea or femoral condyle). Assignment to a particular 
cohort (MSP with or without BioCartilage®) will be based on the treatment decision that has 
been made by the investigator who is providing care to the patient in conjunction with the 
patient's wishes based on explanation of the study and treatment options.  
 
The Informed Consent Form and HIPAA Authorization Form are modified standard forms 
provided by University of Missouri Health Sciences Institutional Review Board (IRB). The data 
collection instruments are as follows: 
1. The SF-12® Health Survey   
a. Measures quality of life indicators 
2. Marx Activity Rating Scale 
a. Measures activity type and level  
3. The Knee Injury and Osteoarthritis Outcome Score (KOOS) 
a. Measures knee pain in relation to activity type in addition to qualitative 
description of knee pain 
4. International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form 
a. Measures knee pain in relation to activity type 
5. Return to work & sport/recreation (designed to assess whether subject has returned to 
their pre-injury level of work & sport/recreation.) 
6. International Cartilage Repair Society Knee Scoring System  

University of Missouri Health Care 
Missouri Orthopaedic Institute 
RUNNING HEAD: BioCartilage® 
 
7 
 
a. Intraoperative data for cartilage repair procedures, such as lesion size, definitive 
location of lesion, concomitant pathology, etc. 
 
The Informed Consent Form and HIPAA Authorization Form will be printed on paper and all 
data collection instruments will be collected electronically using the OBERD system. In the 
event that the OBERD system is unavailable, comparable paper forms may be used in lieu of the 
OBERD data capture.  
 
After data capture is complete, data will undergo statistical analysis.  
 
 
5. Safety Assessment 
 
Patients will be monitored post-operatively until discharge from inpatient care for signs and 
symptoms indicating that an adverse event has occurred. Signs and symptoms will be monitored 
and recorded by nursing staff according to institutional protocol. The investigator who is 
assigned to provide care for the subject will be responsible for review of nursing assessment 
information and to perform an interview and physical assessment before the patient is discharged 
to home.  
 
After discharge from the operative visit, the investigator assigned to provide care to the patient 
will assess the patient at scheduled SOC follow-up visits. Any signs and symptoms indicating 
that an adverse event may have occurred will be communicated in writing via intra-
organizational, secured email to the primary investigator (PI). The PI will determine whether an 
adverse event has occurred, and if so, this will be reported to the University of Missouri Health 
Sciences IRB in accordance with institution policy.  
 
Adverse events and serious adverse events are defined below.  
Adverse events: 
I. 
Bleeding 
II. 
Infection 
III. 
Pain that is uncontrolled with standard post-operative analgesia protocol  
Serious adverse events: 
I. 
Bleeding that is significant enough to require extended hospitalization or unplanned 
critical care interventions  
II. 
Infection that is significant enough to require extended hospitalization or unplanned 
critical care interventions  
III. 
Pain that is significant enough to require extended hospitalization or unplanned critical 
care interventions 
 
 
 
 

University of Missouri Health Care 
Missouri Orthopaedic Institute 
RUNNING HEAD: BioCartilage® 
 
8 
 
6. Tentative Timeline 
 
We expect to fulfill the enrollment goal of this study (n=60) in two years or less, subject 
participation will last up to 110 weeks from the time of consent to last data capture, and data 
analysis is expected to be complete within 26 weeks of final data capture. Therefore, the study is 
expected to be completed in less than four years and 32 weeks.  
 
 
7. Confidentiality of Data 
 
Patient confidentiality during the course of this study will be protected in compliance with 
HIPAA requirements as well as the requirements of the University of Missouri Health-Sciences 
IRB.  
 
After consent is obtained, all subjects will be assigned a study identification number that requires 
the use of a key in order to decipher a subject’s personal identification information. The key will 
be kept in the Cerner Power Trials database, which is password protected. The study 
identification number will be used to label all paper data collection instruments.  
 
All subject information in electronic format will be kept in password-protected storage. All 
subject information in paper format will be kept in locked cabinets in a secured suite at the 
Missouri Orthopedic Institute, and otherwise will be archived in a secure storage facility, or 
destroyed.  
 
8. References 
 
Abrams, G.D., Mall, N.A., Fortier, L.A., Roller, B. L., & Cole, B. J. (2013). BioCartilage: 
Background and Operative Technique. Operative Techniques in Sports Medicine, (21), 
pp. 116-24. http://dx.doi.org/10.1053/j.otsm..2013.03.008