A Biologic Joint Replacement Strategy to Treat Patients With Severe Knee Trauma and Post-Traumatic Knee Osteoarthritis
Conditions: Post-traumatic Osteoarthritis
Sponsor: James Stannard

University of Missouri Health Care 
Missouri Orthopaedic Institute 
 
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A Biologic Joint Replacement Strategy to Treat Patients with Severe Knee                         
Trauma and Post-Traumatic Knee Osteoarthritis 
 
 
 
IRB Project #: 2002751 
 
 
PROTOCOL VERSION NUMBER: 1.2 
DATE: 23 JUN 2017 
 
 
 
 
 
 
Principal Investigator:  
James P. Stannard, MD 
Co-Investigators:  
James L. Cook, DVM, PhD; Aaron M. Stoker, MS, PhD; Ferris M. Pfeiffer, PhD 
Study Site: 
University of Missouri Health System  
Missouri Orthopaedic Institute  
1100 Virginia Avenue 
Columbia, MO 65212 
 
 
Sponsor Contact Information: 
Department of Defense 
U.S. Army Medical Research and Materiel Command 
Congressionally Directed Medical Research Programs 
2014 Peer Reviewed Orthopaedic Research Program 
Translational Research Award 
 

University of Missouri Health Care 
Missouri Orthopaedic Institute 
 
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TABLE OF CONTENTS 
1. Background and Significance 
2. Trial Objectives and Purpose 
3. Selection of Subjects 
4. Study Procedure 
5. Safety Assessment 
6. Confidentiality of Data 
7. References 
 
 
1. Background and Significance 
 
Significant damage to the knee from athletic activities, military training, blunt trauma, or 
penetrating trauma inevitably leads to dysfunction, pain, and post-traumatic osteoarthritis (PTOA), 
and is the most common unfitting condition in medically retired military personnel [1-3].  As 
identified in the most recent Extremity War Injuries (EWI) symposium, PTOA accounts for more 
than $3 billion in aggregate financial costs [3]. Additionally, this symposium identified that 
“94.4% of the OA can be attributed to combat injury” [3], but fell short of identifying effective 
treatments other than joint replacement once OA develops. Cross et al. ranked degenerative 
arthritis with the third highest impact factor and the “most common unfitting condition” in their 
2011 study of long-term disabilities in military personnel [1]. Damaged knees rarely demonstrate 
substantive functional healing. Current practices in orthopaedic surgery attempt to limit the 
incidence and severity of joint deterioration, but despite recent advances and state-of-the-art 
treatment protocols, trauma to the joints can be associated with as high as a 65% incidence of 
debilitating osteoarthritis (OA) [4].  
 
The fundamental problem driving this high rate of OA is the relative inability of articular cartilage 
to functionally heal [5-8]. Risk factors that significantly influence the incidence and severity of 
OA after joint injury include the patient’s age, extent of injury, and type and timing of treatments 
[7, 9]. Ideally, biologic “regenerative” treatments performed prior to the onset of debilitating OA 
would be used in these patients to prevent, or at least minimize, joint deterioration and dysfunction.  
However, regenerative strategies in orthopaedic trauma are not well-developed, and therefore, 
salvage procedures such as total joint replacements are often necessary. While joint replacement 
with metallic and plastic implants generally succeeds in decreasing joint pain and improving limb 
function, the limited lifespan of implants, associated morbidity and complications are significant 
concerns.   
 
Perhaps more importantly, patients with total knee replacements cannot return to athletic activities, 
high-demand physical labor, or active military duty.  Buckwalter and Lohmander have stated that 
“no currently available synthetic material or combination of materials duplicates the ability of 
articular cartilage to provide a painless, low-friction gliding surface and to distribute loads across 
a synovial joint [9].”  Therefore, our solution is to use novel articular tissue transplantation 
strategies to functionally rebuild damaged knees, thus avoiding the limitations of plastic and 
metallic implants while restoring full use of the limb for patients. Specifically, we have developed 
three allografting techniques that allow us to replace damaged cartilage, meniscus and bone with 
viable tissues that can integrate and function at high levels. Our approach allows us to preserve 

University of Missouri Health Care 
Missouri Orthopaedic Institute 
 
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organ donor tissues at the highest level of quality for more than twice as long as current technology, 
replace entire joint surfaces with “young” cartilage, and replace the entire meniscus with a viable, 
healthy meniscus.  Importantly, all of these techniques have been validated in our translational 
canine model and used to treat clinical canine patients at our veterinary medical teaching hospital. 
This biologic joint replacement strategy has proven successful in restoring native joint structure 
and function such that working and performance dogs have returned to full athletic function while 
further degradation of the joint has been avoided for up to 6 years after surgery.  
 
This proposal stems from the critical clinical need for more optimal treatment options for the 
millions of young to middle-aged, active patients with damaged knees, including active duty and 
veteran populations who have demonstrated a risk of injury at a level 10 times that of the civilian 
population [10-12].  Our team, comprised of clinicians and basic scientists, has developed methods 
to address the current limitations in restoring these patients to high-level function.  We subscribe 
to the “joint as an organ” philosophy and have used this philosophy to develop biologic solutions 
to articular disorders through a collaborative and comparative translational approach.  The 
proposed research will allow us to move these solutions further forward in successfully treating 
traumatic joint injury in soldiers and civilians, while also benefitting their four-legged companions. 
 
Preliminary Studies: 
We recognize that successful completion of the specific aims for this proposal requires proven 
proficiency in cartilage harvest, preservation, and transplantation.  These techniques have 
composed the core of our interdisciplinary research efforts for more than a decade.  As such, we 
have produced a body of work covering the foundational basic science, translational, and 
veterinary and human clinical research that provides the inspiration and road map for achieving 
similar success in the proposed research.  The following data from three of our previous studies 
summarize our capabilities and progress in the area of regenerative orthopaedics. 
 
1. Improved Preservation of Osteochondral Allografts[13, 14] 
Background: While osteochondral allografts (OCAs) provide a current method for regenerative 
treatment of focal cartilage defects in the knee, they presently have limited clinical use. Current 
storage protocols require that time from harvest of cadaveric tissue to implantation should be 28 
days or less. Due to required disease testing and donor matching protocols, as many as 80% of 
potential OCAs go unused. In order to make biologic knee replacement a reality, it is necessary 
to improve preservation of OCAs such that they can be made more widely available.  Therefore, 
we have developed The Missouri OCA Preservation System (MOPS), a novel patented 
preservation method, which has been shown in vitro to significantly prolong the period of time 
for which the grafts can be stored with sufficient viability prior to surgical implantation. In the 
following study, we optimized and validated this system in vivo with respect to functional 
outcomes of OCAs preserved using the MOPS compared to OCAs preserved using the current 
standard of care method for tissue banks. 
 
Materials and Methods: All procedures were approved by the University of Missouri Animal 
Care and Use Committee (#7332).  The stifles (knees) of skeletally mature adult male mongrel 
dogs were aseptically harvested after humane euthanasia was performed for reasons unrelated to 
this study.  The knees were randomly assigned to one of four groups:  

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Missouri Orthopaedic Institute 
 
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• Standard of care (SOC) 30 - 30-day storage at 4o C (4C) in standard tissue bank media 
(n=12) 
• Missouri OCA Preservation System (MOPS) 30 - 30-day storage at 25o C (25C) in 
MOPS media (n=12) 
• SOC 60 - 60-day storage at 4o C (4C) in standard tissue bank media (n=12) 
• MOPS 60 - 60-day storage at 25o C (25C) in MOPS media (n=12) 
All soft tissues were removed in the operating room and the knees were fully inspected to ensure 
no pathology was present.  For samples assigned to the SOC groups, the distal femurs were 
placed in standard storage media and stored in a dedicated refrigerator at 4o C for 30 days or 60 
days.  For samples assigned to the MOPS group, the distal femurs were placed in defined media 
(proprietary) and stored in a dedicated clean room at 25o C for 30 or 60 days.  Samples of media 
were collected weekly for both groups for microbial testing and metabolic assay for MOPS 
OCAs.  
 
Sixteen adult mongrel female dogs (2-5 years old, 25-35 kg body weight judged free of OA in all 
joints based on complete examination and radiographs of the hips, elbows, and knees, were 
enrolled in the study.  At 30 or 60 days after graft procurement, surgically created defects were 
filled with site-matched 8 mm OCAs obtained from the adult male cadaveric distal femurs 
preserved by either SOC or MOPS and implanted using the press-fit methodology of the OATS 
allograft system.  At each time point (30 days or 60 days after graft procurement), each knee 
received one SOC graft and one MOPS OCA, which were alternated between medial and lateral 
femoral condyles.  At the time of implantation, samples of the bone and cartilage from each 
distal femur and from the preservation media were obtained and processed for microbial testing. 
 
Radiographic and arthroscopic evaluations were made at 12 weeks and 6 months post-surgery.  
The dogs were humanely sacrificed 6 months after surgery.  Both knees of each dog were 
carefully disarticulated, and examined for gross appearance, cell viability, cell source 
determination, histologic assessment, biomechanical and biochemical characteristics. 
 
Results: Viability during storage: Day 30 viability ranged from 22.9-99% with a mean of 60.2% 
for SOC grafts and a mean of 82.9% for MOPS grafts.  Day 60 viability ranged from 24.7-99% 
with a mean of 52.7% for SOC grafts and a mean of 89.8% for MOPS grafts.  Day 60 viability 
was significantly (p=0.002) higher for MOPS grafts than for SOC grafts. 
Clinical assessments: All dogs were successfully implanted with OCAs and recovered well 
without complications for the intended study duration.   
Radiographically: Immediate postoperative radiographs showed appropriate implantation of all 
grafts with no evidence for malpositioning or technical errors.  Radiographic assessments 
performed at 3 and 6 months after implantation showed evidence for progressive osseous 
integration of both SOC and MOPS grafts with variable degrees of associated sclerosis. 

University of Missouri Health Care 
Missouri Orthopaedic Institute 
 
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For 30-day preservation, 
MOPS and SOC grafts were 
similar in appearance based 
on arthroscopic, gross and 
histologic appearance 
performed 6 months after 
implantation,  For 60-day 
preservation, MOPS grafts 
were subjectively superior 
to SOC grafts with respect 
to arthroscopic, gross and histologic appearance when 
assessed 6 months after implantation.  For both 
preservation periods, chondrocyte viability at the time of 
implantation appeared to correspond well to subjective 
arthroscopic, gross and histologic assessments. 
Biochemical Assessments: GAG content was significantly (p<0.009) higher in native articular 
cartilage compared to cartilage from SOC and MOPS 30-day grafts and SOC 60-day grafts when 
assessed 6 months after implantation.  GAG content was not significantly different in native 
articular cartilage compared to cartilage from MOPS 60-day grafts when assessed 6 months after 
implantation. There were no statistically significant differences in collagen (HP) content in 
native cartilage compared to cartilage from SOC and MOPS 30-day or 60-day grafts when 
assessed 6 months after implantation.   
Biomechanics: Young’s modulus was significantly (p<0.041) higher in native articular cartilage 
and cartilage from MOPS 60-day grafts compared to SOC 60-day grafts when assessed 6 months 
after implantation.  Young’s modulus was not significantly different in native articular cartilage 
compared to cartilage from MOPS 60-day grafts when assessed 6 months after implantation. 
 
Discussion and Conclusion: The Missouri OCA Preservation System allows for preservation of 
chondrocyte viability for up to 60 days at sufficient levels to result in functional outcomes in a 
canine model of articular defects in the knee.  Functional outcomes associated with MOPS-stored 
OCAs were superior to those using the current standard of care system used by tissue banks 
suggesting that the MOPS system could be employed clinically at this time. 
 
2. Mitigating Mechanical Damage to Osteochondral Allografts During 
Implantation[15] 
Background: In order to treat large post-traumatic cartilage defects, more effective implantation 
techniques are needed in order to preserve a maximum amount of available viable tissue.  
Current techniques for osteochondral allograft (OCA) transplantation require insertion of the 
graft into a cylindrical cavity with a press-fit interface. Mechanical impaction to overcome 
frictional resistance has a negative effect on chondrocyte viability and long term clinical 
outcomes. Our goal was to develop and test a novel tapered OCA system that could maintain 
graft stability while mitigating detrimental insertion forces, thereby preserving chondrocyte 
viability in comparison to standard cylindrical systems. 
 
Materials and Methods: Fresh femoral condyles were obtained from dogs euthanatized for 
reasons unrelated to this study. Cylindrical plugs (8mm diameter, 6mm depth) were harvested 
Fig 1. Arthroscopic (top) and 
histologic (middle) appearance 
of OCAs implanted into the 
femoral condyles of dogs in 
this study with corresponding 
cell viability images (bottom) 
demonstrating the consistently 
superior appearance of MOPS 
osteochondral allografts. 
60-day SOC     60-day MOPS 

University of Missouri Health Care 
Missouri Orthopaedic Institute 
 
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and implanted in the same specimen using a commercially available system. In a similar manner, 
tapered plugs (8mm diameter top surface, 6mm depth) were harvested and implanted using our 
novel tapered system.  Superficial cell death and total cell viability were assessed on Day 0 and 
Day 3, and compared statistically. Insertion force and extraction strength for cylindrical and 
tapered OCAs were tested using an Instron 8821S servo-hydraulic machine, and compared 
statistically. 
 
Results: The total cell viability did not differ significantly between tapered and cylindrical OCA 
at Day 0 or Day 3 (p=0.535, p=0.147), however, tapered OCAs had significantly less superficial 
cell death compared to cylindrical grafts (p=0.003) (Figs 2 and 3).  
 
Tapered OCAs required significantly less insertion force and energy for proper implantation 
compared to cylindrical OCAs (p=0.012, p=0.008). Importantly, there was no significant 
difference in extraction strength between tapered and cylindrical systems (p=0.881) (Figs 4-6). 
 
Discussion and Conclusion: In this ex vivo model, our novel tapered OCA system required 
lower insertion force to properly seat the grafts without compromising extraction strength when 
compared to cylindrical OCAs. Importantly, plugs inserted using the tapered system had 
significantly higher chondrocyte viability in the superficial zone, which suggests that clinical 
outcomes associated with the tapered system would be improved based on current best evidence.   
 
3. Unicompartmental Tibial Allografting with Native Meniscus 
Background: Frozen meniscal allograft transplantation (MAT) can be an effective strategy for 
treatment of meniscal-deficient knees.  However, graft extrusion and shrinkage, degeneration of 
the horns, and failure of fixation are frequent complications.  These issues may be associated 
with the use of non-viable tissue and/or lack of anatomical placement and fixation of the graft to 
the tibia. Another factor affecting the clinical success of MAT is the state of the underlying tibial 
cartilage of the patient.  Replacing the meniscus does not address cartilage pathology of the tibial 
plateau, which is a common and limiting component in most patients being evaluated as 
candidates for MAT.  Therefore, use of a viable MAT that allows for anatomical placement of 
the graft on the tibial plateau could significantly reduce complications and improve long-term 
success of the procedure and increase the number of patients that MAT can be considered for 
clinically. After determining that the viability and structural properties of meniscal-tibial plateau 
Cylinder 
Taper 
Figure 3. Area of Superficial Cell 
Superficial Cell Death: The superficial area of cell 
death was found by taking the area of superficial 
death over the total area of the cartilage as seen in 
Figure 2. The area of superficial cell death was 
significantly lower (p=0.003) in tapered OCA 
plugs compared to cylindrical plugs (Figure 3). 
This signifies that there is less trauma received by 
the 
tapered 
plugs 
during 
impaction 
then 
compared to what cylindrical plugs experience. 
Figure 2 

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Missouri Orthopaedic Institute 
 
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allografts (MTPAs) could be maintained for a clinically relevant period of time when stored at 
25°C, we designed the present study to determine the feasibility of performing medial tibial 
plateau and meniscus replacement in research dogs using viable, stored MTPAs.  We 
hypothesized that viable meniscal-tibial plateau allografts implanted into the medial 
compartment of the knee of dogs would effectively integrate with recipient tissues and maintain 
viability and function for at least 3 months after implantation. 
 
Materials and Methods: Graft creation and assessment of viability were first determined by 
aseptically harvesting the entire tibial plateau (TP) from the hind limbs of 58 dogs euthanatized 
for reasons unrelated to this study.  This initial research provided evidence for our ability to 
maintain cell viability, tissue composition and material properties at appropriate levels through 
56 days of storage at room temperature using our preservation system. Based on the success of 
the in vitro study, in vivo implantation of MTPAs was undertaken with IACUC approval.  
MTPAs from the right knee of two purpose-bred research dogs were aseptically harvested and 
stored for 30 days using our tissue preservation system.  After disease testing and assessment for 
viability during storage, the grafts were implanted into the knees of two size-matched purpose-
bred research dogs.  Using a medial mini-arthrotomy, the medial meniscus and medial tibial 
condyle were resected en bloc from each dog with preservation of the medial collateral ligament, 
cranial and caudal cruciate ligaments.  The MTPA was then inserted and stabilized to the 
proximal tibia using divergent Kirschner wires. The dogs were recovered and allowed to use the 
limbs in their runs immediately after surgery.  The dogs were assessed at weeks 5, 8, and 12 after 
surgery using measures of knee function, second look arthroscopy and radiographs.  Three 
months after implantation, the dogs were humanely euthanatized and assessed grossly and 
histologically for evidence of graft location and stability, graft incorporation, tissue architecture, 
and articular cartilage health. 
 
Surgical implantation of the MTPAs was accomplished in dogs without intraoperative or 
postoperative complications.  Dogs ambulated on the operated limbs immediately after surgery 
and were using the limbs with no apparent lameness and normal knee range of motion (105o and 
107o) 3 months after surgery.  Five and twelve weeks after implantation, arthroscopic assessment 
revealed maintenance of meniscal positioning with evidence for synovial attachment to the 
periphery of the transplanted meniscus in both dogs.  Femoral and tibial articular cartilage in the 
medial compartment showed no evidence of softening, fibrillation, or erosions.  All other intra-
articular tissues were normal in appearance with no evidence for untoward immune or 
inflammatory responses.  Radiographic assessments at 8 and 12 weeks after surgery showed mild 
joint effusion and evidence for progressive healing of donor to recipient bone with maintenance 
of graft and implant positioning.  Gross and histologic assessments at the time of sacrifice were 
consistent with all clinical findings.  Meniscal positioning was maintained such that subluxation 
or extrusion was not noted.  All articular surfaces were normal in appearance with no evidence of 
pathology.  Evidence for bone union between donor bone and recipient bone was noted. 
 

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Figure 4. Representative images from clinical canine case of MTPA including a) resected 
meniscus and graft, b) scope at 3 mo post op, c) radiograph at 3 mo post op, and d) 
histologic section at 3 mo post op. 
 
Discussion and Conclusions: These data provide initial evidence for the feasibility of 
performing complete replacement of the medial tibial plateau and meniscus using viable 
meniscal-osteochondral grafts stored using our preservation system for at least 30 days.  Clinical, 
arthroscopic, radiographic, gross and histologic assessments all provided evidence for graft 
integration and healing, maintenance of function, and lack of associated morbidity. 
 
Military Benefit: Combat and combat-related joint injuries account for more than $3 billion in 
aggregate financial costs. Outcomes for surgical interventions to repair articular fractures and 
ligament ruptures are quite good in short term follow-up studies. However, there is currently 
little that can be done to prevent/mitigate the development of PTOA following articular fracture 
and/or ligament injury long term. Thus, often the only option is joint replacement in a relatively 
young patient population. Our proposed interventions provide a vital surgical option for injured 
joints of military personnel, which addresses the risk of PTOA while still maintaining future 
surgical options if necessary. 
 
 
2. Trial Objectives and Purpose 
 
Evaluate safety and efficacy of unicompartmental biologic arthroplasty of the knee in a 
limited clinical trial. 
 
With IRB approval, a limited pilot study will be performed to assess safety and efficacy of biologic 
unicompartmental arthroplasty.  Ten patients who require tibial plateau and meniscus arthroplasty 
plus a femoral condyle arthroplasty, based on physical examination, radiographs, and knee 
arthroscopy, will be enrolled. Range of motion, VAS pain score, SF-12, Tegner score, International 
Knee Documentation Committee (IKDC) subjective and objective scores, PROMIS Bank v1.2 – 
Physical Function-Mobility, PROMIS v1.1 – Global Health, PROMIS Bank v1.1- Pain 
Interference, PROMIS Bank v1.2 – Physical Function, and Marx score as well as complete 
radiographs of the affected knee will be obtained prior to surgery and at 6 weeks, 3 months, 6 
months, and 12 months after surgery to evaluate healing, function and evidence for arthrosis.  We 
will document all complications, including joint or incision infection, graft failure, hardware 
failure, and arthrofibrosis.  Patients with a VAS pain score >5 beyond 3 months postoperatively or 
clinical or radiographic evidence for nonunion or graft collapse will undergo MRI of the knee to 
determine the appropriate clinical course of action. 
a) 
b) 
c) 
d) 

University of Missouri Health Care 
Missouri Orthopaedic Institute 
 
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This proposal stems from the critical clinical need for more optimal treatment options for the 
millions of young to middle-aged, active patients with damaged knees. Our team, comprised of 
clinicians and basic scientists, has developed methods to address the current limitations in 
restoring these patients to high level function. We subscribe to the “joint as an organ” philosophy 
and have used this philosophy to develop biologic solutions to articular disorders through a 
collaborative and comparative translational approach. The proposed research will allow us to 
move these solutions further forward in successfully treating traumatic joint injury in soldiers, 
civilians, and their four-legged companions. 
 
Rationale: Prior to widespread clinical use, the safety and efficacy of our unicompartmental 
biologic arthroplasty must be confirmed in a controlled clinical trial.  Clinical patients (n=10) 
with unicompartmental post-traumatic knee OA will be treated with unicompartmental biologic 
knee arthroplasty and evaluated for functional outcomes. 
 
 
Based on our preliminary studies and long-term outcomes in clinical veterinary patients, we are 
optimistic that the final technique for unicompartmental biologic knee arthroplasty that is 
optimized in specific aim 1 will prove to be vastly superior to non-surgical management of knee 
OA in the translational model described in specific aim 2.  We are confident that clinical use of 
this technique in specific aim 3 will be safe based on our previous work in conjunction with current 
evidence regarding clinical use of allografts.  If efficacy is as high as expected in the first 10 
patients, we will initiate a multi-center clinical trial to include military bases while we continue to 
follow all patients long term.   
 
 
 
3. Selection of Subjects 
 
With IRB approval and informed consent, patients (n=10) (18-50 years old) with post-traumatic 
knee OA and requiring a tibial plateau and meniscus arthroplasty plus a femoral condyle 
arthroplasty will be enrolled in the study.  Primary criteria for inclusion will be Grade IV changes 
in the articular cartilage of the femoral condyle and tibial plateau and meniscal pathology in the 
medial or lateral femorotibial joint as determined by physical examination, diagnostic imaging and 
knee arthroscopy by the PI. Exclusion criteria include Grade III or IV changes in any other 
compartment of the knee, acute injury to any other part of the affected lower extremity, or inability 
to comply with the protocol. 
 
 
Inclusion Criteria: 
 
1. Patient requiring repair via tibial plateau and meniscus arthroplasty plus a femoral 
condyle arthroplasty 
2. The subject is able and willing to consent to participate in the study 
 
 

University of Missouri Health Care 
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Exclusion Criteria: 
 
1. Acute injury to any other part of the affected lower extremity 
2. The subject is unwilling, or unable to consent due to psychiatric condition or legal 
incompetence 
3. BMI > 40 
4. Age > 50 at the time of enrollment  
5. The subject is either pregnant, or a prisoner 
6. Currently involved in a workers’ compensation case at the time of enrollment  
 
 
4. Study Procedure 
 
After enrollment, patients will undergo standardized knee radiography, and complete assessments 
(described below). Size-matched (standard clinical methodology) proximal tibia with meniscus 
and distal femur allografts from the same donor will be obtained from a tissue bank 
(Musculoskeletal Transplant Foundation, Edison, NJ) who has licensed the MOPS technology. 
The medial or lateral femoral condyle will be replaced using our novel instrumentation and 
technique described above.  Tibial plateau-meniscus grafts will be trimmed and used to replace the 
entire medial or lateral tibial condyle while sparing the attachments of ACL, PCL and respective 
collateral ligament. The tibial plateau graft will be fixated using commercial available implants 
used for bone fixation. In the event that the meniscus has been detached from the tibial plateau 
during graft harvest, the periphery of the meniscus will be sutured to the capsule following standard 
meniscus transplant procedure. 
 
Patients will undergo controlled post-operative rehabilitation according to standard protocols for 
osteochondral with concurrent meniscus allografts. . 
 
Range of motion, VAS pain score, SF-12, Tegner score, International Knee Documentation 
Committee (IKDC) subjective and objective scores, PROMIS Bank v1.2 – Physical Function-
Mobility, PROMIS v1.1 – Global Health, PROMIS Bank v1.1- Pain Interference, PROMIS Bank 
v1.2 – Physical Function and Marx score as well as complete radiographs of the affected knee will 
be obtained prior to surgery and at 6 weeks, 3 months, 6 months, and 12 months after surgery to 
evaluate healing, function and evidence for arthrosis[21].  
 
We will document all complications, including joint or incision infection, graft failure, hardware 
failure, and arthrofibrosis.   
 
Patients with a VAS pain score >5 beyond 3 months postoperatively or clinical or radiographic 
evidence for nonunion or graft collapse will undergo MRI of the knee to determine the appropriate 
clinical course of action. 
 
For all specific aims, data will be compiled and analyzed using descriptive statistics as well as 
appropriate tests (t-Test, ANOVA, rank sum, repeated measures) for significant (p<0.05) 
differences using SigmaStat.  The investigators on the research team have extensive experience in 

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data analysis and biostatistics and have the full resources of the university’s medical informatics 
and department of statistics available if questions arise. 
 
 
5. Safety Assessment 
 
Patients will be monitored post-operatively for signs and symptoms indicating that an adverse 
event has occurred. The investigator will assess the patient for adverse events at scheduled SOC 
follow-up visits. Any signs and symptoms indicating that an adverse event may have occurred 
will be treated by the investigator, and the details will be collected for study purposes. The PI 
will determine whether an adverse has occurred, and if so, will determine if the event meets the 
submission requirements of the University of Missouri Health Sciences IRB.  
 
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 
 
 
6. 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 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 either the 
Missouri Orthopedic Institute, and otherwise will be archived in a secure storage facility, or 
destroyed.  
 
7. References 
 
 

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1. 
Cross, J., et al., Battlefield Orthopaedic Injuries Cause the Majority of Long-term 
Disabilities. J Am Acad Orthop Surg, 2001. 19(suppl 1): p. S1-S7. 
2. 
Langworthy, M., F. Nelson, and B. Owens, Viscosupplementation for treating 
Osteoarthritis in the Military Population. Military Medicine, 2014. 179(8): p. 815-20. 
3. 
Jaquet, G., EWI VIII: Sequelae of Combat Injuries, in AAOS 2013. July 2013. 
4. 
Vallier, H.A., et al., Surgical Treatment of Talar Body Fractures. J Bone Joint Surg Am 
2003. 85-A: p. 1716-24. 
5. 
Buckwalter, J., Articular cartilage. Part I and Part II:Tissue design and chondrocytes-
matrix interaction. J Bone Joint Surg Am, 1997. 79A: p. 600-11. 
6. 
Buckwalter, J. Articular cartilage: injury and repair. in AAOS. 1998. Park Ridge, Ill. 
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Marsh, J.L., et al., Articular Fractures: does an anatomic reduction really change the 
result? . J Bone Joint Surg Am, 2002. 84-A: p. 1259-71. 
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Newman, A.P., Articular Cartilage Repair. Am J Sports Med, 1998. 26: p. 309-24. 
9. 
Buckwalter, J., Articular Cartilage Injuries. Clin Orthop Relat Res, 2002: p. 21-37. 
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Cameron, K., et al., Incidence of Physician-diagnosed Osteoarthritis Among Active Duty 
United States Military Service Members. Arthritis Rheum, 2011. 63: p. 2974-82. 
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Jones, J., et al., Incidence and Risk Factors Associated with Meniscal Injuries Among 
Active-Duty US Military Service Members. J Athl Train, 2012. 47: p. 67-73. 
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Rivera, J., et al., Post-traumatic Osteoarthritis Caused by Battlefield Injuries: The Primary 
Source of Disability in Warriors. J Am Acad Orthop Surg, 2012. 20(suppl 1): p. S64-9. 
13. 
Garrity, J.T., et al., Improved Osteochondral Allograft Preservation Using Serum-Free 
Media at Body Temperature. Am J Sports Med, 2012. 40(11): p. 2542-48. 
14. 
Stannard, J.P., et al., Evaluation of Cell Viability, Repopulation, and Clinical Function of 
Osteochondral Allografts in a Canine Model. 2013, Comparative Orthopaedic Lab, 
University of Missouri: Columbia. 
15. 
Pfeiffer, F.M., et al. Mitigating Mechanical Damage to Osteochondral Allografts During 
Implantation. in Orthopaedic Research Society. 2013. San Antonio, TX. 
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Araki, D., et al., An analysis of surface profile for cylindrical osteochondral grafts of the 
knee quantitative evaluation using a three-dimensional laser scanner. Knee Surg Sports 
Traumatol Arthrosc, 2012. Epub. 
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Choate, C.J., et al., Effect of lateral meniscectomy and osteochondral grafting of a lateral 
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List of Abbreviations 
 
ACL – Anterior Cruciate Ligament 
EWI – Extremity War Injuries 
GAG – Glycosaminoglycans 

University of Missouri Health Care 
Missouri Orthopaedic Institute 
 
13 
 
HP – Hydroxyproline 
IACUC – International Animal Care and Use Committee 
IKDC – International Knee Documentation Committee 
IRB – Institutional Review Board 
MAT – Meniscal Allograft Transplantation 
MOPS – Missouri Osteochondral Allograft Preservation System 
MTPAs – Meniscal-Tibial Plateau Allografts 
MR – Meniscal Release 
OA – Osteoarthritis 
OCAs – Osteochondral Allografts 
PCL – Posterior Cruciate Ligament 
PTOA – Post-traumatic Osteoarthritis 
SOC – Standard of Care 
TP – Tibial Plateau 
VAS – Visual Acuity Scale 
 
 
 
STUDY ACTIVITY Pre-Op/Baseline
Surgery 
6 weeks (+/- 2 
weeks)
3 Months (+/- 
2 weeks)
6 Months (+/- 2 
weeks)
12 Months (+/- 1 
month)
If Applicable Per Protocol 
Consent/HIPAA
X
Inclusion/Exclusion 
Evaluation
X
Demographics
X
ROM
X
X
X
X
X
X
VAS pain score
X
X
X
X
X
X
SF-12
X
X
X
X
X
X
Tegner Score
X
X
X
X
X
X
IKDC Subjective 
X
X
X
X
X
X
IKDC Objective 
X
X
PROMIS - Mobility
X
X
X
X
X
X
PROMIS - Global 
Health
X
X
X
X
X
X
PROMIS Pain 
Interference
X
X
X
X
X
X
PROMIS Physical 
Function
X
X
X
X
X
X
Radiology 
X
X
X
X
X
X
MRI (knee)
X
A Biologic Joint Replacement Strategy to Treat Patients with Severe Knee Trauma and Post-Traumatic Knee Osteoarthritis