Clinical Evaluation of Autologous Micro-fragmented Adipose Tissue as a Treatment Option for Meniscus Tears
Phase: PHASE2
Conditions: Tibial Meniscus Injuries, Osteoarthritis, Knee
Sponsor: New Jersey Regenerative Institute, LLC

Protocol Number: LG-MN-201v2 
                      Renewal Date: September 27, 2017 
Approval Date: January 6, 2016 
  Continuing Review Date: September 19, 2018 
 
1 
 
Clinical Evaluation of Autologous Micro-Fragmented Adipose Tissue  
as a Treatment Option for Meniscus Tears  
  
 
 
Protocol Number:   
LG-MN-201v2 
 
 
Version date:   
 
January 6, 2016 
 
 
Principal Investigator:  Gerard Malanga, MD 
 
 
Location:   
 
New Jersey Sports Medicine, LLC 
197 Ridgedale Avenue 
Cedar Knolls, New Jersey 07927 
 
 
Co-Sponsors:  
 
New Jersey Sports Medicine, LLC 
Lipogems SPO 
  
 
 
PURPOSE 
 
The purpose of this study is to explore the potential of Lipogems micro-fragmented adipose tissue 
as a meaningful treatment option for meniscus tears.  
 
STUDY DESIGN 
 
We propose a non-randomized, single site, prospective study of 20 subjects to evaluate the effects 
of non-digested micro-fragmented adipose tissue (Lipogems) on patients with evidence of a 
meniscus tear where there may also be osteoarthritis.  
 
Patients will be treated with Lipogems by intra articular meniscal and joint injection under 
ultrasound guidance and evaluated using follow up function questionnaires, physical examination 
and MRI imaging.  
 
BACKGROUND  
IRCM-2016-090 
September 27, 2017 
 

Protocol Number: LG-MN-201v2 
                      Renewal Date: September 27, 2017 
Approval Date: January 6, 2016 
  Continuing Review Date: September 19, 2018 
 
2 
 
Osteoarthritis is a joint disease that mostly affects cartilage. Cartilage is the slippery tissue that 
covers the ends of bones in a joint. Healthy cartilage allows bones to glide over each other. It also 
helps absorb shock of movement. In osteoarthritis, the top layer of cartilage breaks down and 
wears away. This allows bones under the cartilage to rub together. The rubbing causes pain, 
swelling, and loss of motion of the joint. Also, bone spurs may grow on the edges of the joint. (1). 
 
Meniscus tears are among the most common knee injuries. Athletes, particularly those who play 
contact sports, are at risk for meniscus tears. However, anyone at any age can tear a meniscus. 
When people talk about “torn cartilage” in the knee, they are usually referring to a torn meniscus. 
 
Sudden meniscus tears often happen during sports or other activities. Older people are more likely 
to have degenerative meniscus tears. Cartilage weakens and wears thin over time. Aged, worn 
tissue is more prone to tears. Just an awkward twist when getting up from a chair may be enough 
to cause a tear, if the menisci have weakened with age (2). 
 
Standard treatment for meniscal tears include: rest, ice, anti-inflammatory and physical therapy. 
For persistent pain and swelling, patients are often given an injection of corticosteroid and/or 
hyaluronic acid. Unfortunately, many patients have persistent pain, swelling and limitations on 
activities of daily living and are then offered arthroscopic surgery which involves resecting and 
debriding the worn or torn piece of meniscus referred to as arthroscopic partial meniscetomy 
(APM). Recent well designed studied have questioned the effectiveness of this treatment which 
includes randomized studies where a “sham” procedure is performed. These studies have shown 
that  APM is no better than physical therapy nor was it superior to the sham surgery. In addition, 
APM has been shown to accelerate the degenerative process in the knees of patients who also have 
early arthritis of their knee. None-the-less, many people continue to suffer with ongoing pain and 
many will then proceed to even greater surgery which includes total knee replacement (TKR) and 
great economic costs as well as the potential for complications, long rehabilitation, etc. Therefore, 
an effective and noninvasive treatment for patients with continuous knee pain related to meniscal 
tears meniscus is greatly needed.  
 
There are a few studies that have demonstrated the potential benefit of using a patient’s own 
biologic product such as platelet-rich plasma (PRP) and their own stem cells. Several studies have 
used bone marrow and others have used adipose tissue that is harvested directly from the patient. 
 
Here, we present a study, highlighting the safety and the potential reparative and regenerative 
mechanisms in the treatment of damaged knee joints by percutaneous injection using real time 
continuous ultrasound imaging into the knee joint and menisci with Lipogems autologous micro-
fragmented, non-digested adipose tissue containing bioactive and regenerative elements (3).  
 
 
 
THE KNEE JOINT 
The knee joint joins the thigh with the leg and consists of two articulations: one between the femur 
and tibia, and one between the femur and patella. It is the largest joint in the human body and 

Protocol Number: LG-MN-201v2 
                      Renewal Date: September 27, 2017 
Approval Date: January 6, 2016 
  Continuing Review Date: September 19, 2018 
 
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perhaps the most clinically challenging. The knee joint is vulnerable to acute injury as well as the 
development of progressive degenerative changes.  
 
MENISCUS 
The menisci of the knee are two fibrocartilaginous tissue pads which serve to disperse friction in 
the knee joint between the lower leg or tibia and the upper leg or femur. Each knee joint has two 
menisci. One is in the medial knee and the other in the lateral knee.  They are semi-lunar in shape 
and are attached to small depression in the tibia and between the condyles of the tibia 
(intercondyloid fossa), and towards the center they are unattached and their shape narrows to a thin 
shelf. The blood flow of the meniscus is from the periphery (outside) to the central meniscus. 
Blood flow decreases with age and the central meniscus is avascular by adulthood leading to very 
poor healing rates (4). 
 
The menisci act to disperse the weight of the body and reduce friction during movement. Since the 
condyles of the femur and tibia meet at one point which changes during range of motion, the 
menisci spread the load of the body's weight. 
 
Meniscal damage is diagnosed by magnetic resonance imaging (MRI) scans. Clinical information 
can be gleaned by diagnostic musculoskeletal ultrasound to provide detailed imaging of the 
meniscus anteriorly, however, is not considered diagnostic of meniscal tears. 
 
CURRENT STANDARD OF CARE AND TREATMENT OPTIONS  
 
There are currently very few options for treatment of osteoarthritis with tears in the medial or 
lateral meniscus in the knee.  
1. Lifestyle Modification 
Reduced activity and weight loss to relieve stress and pressure on the affected knee. 
2. Physical Therapy 
Manual therapies and supervised exercises to strengthen, increase range of motion and bracing to 
improve functional abilities to reduce the joint pain. 
3. Exercises to Strengthen the Knee and Relieve Pain 
Exercises designed to strengthen the supporting structures of the knee to relieve strain and pain.  
4. Medications for Treatment of Knee Pain and Arthritis 
Non-steroidal anti-inflammatory drugs NSAIDS to reduce inflammation and relieve pain.  
5. Injections and Procedures for Knee Pain 
Cortisone injections are often recommended to relieve inflammation. Platelet Rich Plasma a 
treatment whereby growth factor from plasma are concentrated and injected to stimulate the repair 
mechanisms (2). 
6. Knee Surgery 

Protocol Number: LG-MN-201v2 
                      Renewal Date: September 27, 2017 
Approval Date: January 6, 2016 
  Continuing Review Date: September 19, 2018 
 
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If knee pain persists, surgery may be the option. Different knee surgeries include knee 
replacements and knee arthroscopy (5).  
 
When such conservative treatment fails, and arthroscopic procedures are administered the efficacy 
has not been well established. The major drawback of the arthroscopic procedures is accelerated 
osteoarthritis (6) (7).  
 
Recently the use of concentrated growth factors from patient blood called platelet rich plasma has 
been studied and numerous publications have been emerging with varying degrees of success (3). 
  
Arthroscopic repair of the damaged meniscus may be recommended. However, the current 
treatment with arthroscopic surgery and meniscectomy, even with partial one, is associated with 
accelerated osteoarthritis in the already afflicted knee (8).  
 
Therefore the lack of a non-invasive treatment to improve joint function and preserve joint 
structure in the damaged knee joint presents a major therapeutic challenge.  
 
The purpose of this study is to explore the potential of Lipogems micro-fragmented adipose tissue 
as a meaningful treatment option.  
 
There are many applications of biologic preparations in treating musculoskeletal conditions and 
often several are combined. With this comes the inherent inability to assess the impact of each 
biological on outcomes and the conclusions subsequently drawn. 
 
For the purpose of this study, Lipogems in its processed form will be used without combining any 
other biological or pharmacologic elements to the treatment.  
 
ANIMAL STUDIES 
 
Autologous stem cells have been demonstrated to be extraordinarily effective in treating animals 
with arthritis. Several veterinary stem cell companies are now in operation, utilizing adipose 
derived stem cells (SVF) to accelerate healing in horses as well as provide regenerative therapy for 
osteoarthritic dogs. Vet-Stem (www.Vet-Stem.com) has treated more than 10,000 animals since 
2003 (9) and published data showing efficacy in double blinded studies of canine osteoarthritis, 
showing statistically significant improvements in lameness, range of motion, and overall quality of 
life (10). 
 
RATIONALE 
We have seen evidence that is capable of exhibiting significant anti-inflammatory effects, which 
may subsequently provide some relief from the pain associated with. fat graft containing reparative 
tissue. We intend to examine whether a direct injection of Lipogems micro fractured adipose tissue 
can provide an effective treatment option and an alternative to arthroscopic surgery in the 
treatment of meniscus tears.   

Protocol Number: LG-MN-201v2 
                      Renewal Date: September 27, 2017 
Approval Date: January 6, 2016 
  Continuing Review Date: September 19, 2018 
 
5 
 
STUDY OBJECTIVES 
To evaluate the use of Lipogems, micro-fractured adipose tissue, in soft tissue defects of the 
meniscus.   
 
INCLUSION CRITERIA 
  
(1) Age 35 and older  
(2) Symptoms consistent with torn meniscus (at least one of clicking popping, giving way, pain 
with pivot or torque, pain that is episodic) 
(3) Pain that can be provoked by palpitation or compression of the joint line. 
(4) Pain located in the medial joint line that has persisted for at least 3 months. 
(5) MRI or arthroscopic evidence of meniscal tear. 
(6) Failed conservative treatment which has included: anti-inflammatory or other medications 
for pain; physical therapy; injections including corticosteroid injections and/or hyaluronic 
acid injections. This would include patients who have been told by an orthopedic surgeon 
that they would be a candidate for arthroscopic partial meniscectomy. 
 
EXCLUSION CRITERIA 
 
     (1) Chronically locked knee. 
     (2) Prior surgery performed on effected knee 
     (3) Assessment showing anything other than degenerative tears of the medial meniscus 
           requiring surgical intervention.  
     (4) Recent (within 6 weeks) treatment with PRP, cortisone oral or by injection, or Hyaluronic  
           injection. 
     (5) Any disease or condition the investigator feels would hinder treatment. 
     (6) Any contra-indication to lipoaspirate which includes: bleeding disorder, infection,    
           pregnancy; allergy to anesthetic agents. 
      (7) Malignancy within the last 5 years. 
 
 
STUDY PROCEDURES AND GUIDELINES 
The patient is restricted from taking steroids, and nonsteroidal anti-inflammatory medications for 
three days prior to Lipogems treatment and for 4 weeks after Lipogems treatment.  
 
Informed Consent: informed consent is signed by the patient prior to conducting study related 
activities.  

Protocol Number: LG-MN-201v2 
                      Renewal Date: September 27, 2017 
Approval Date: January 6, 2016 
  Continuing Review Date: September 19, 2018 
 
6 
 
 
PRE-TREATMENT ASSESSMENT   
• MRI   
• 
KL OA score  
• 
Joint specific Function Scores KOOS  
• 
VAS visual analogue pain scales  
• 
Pre-Treatment range of motion with a goniometer  
 
DEMOGRAPHICS  
Demographic information (date of birth, gender, race) will be recorded at Screening. 
 
MEDICAL HISTORY 
Relevant medical history, including history of current disease, and information regarding 
underlying diseases will be recorded at Screening. 
 
FAT HARVEST PROCEDURE 
 
1. Informed consent is obtained. 
2. Patient is placed supine on procedure table.  
3. Abdomen is marked with a surgical marker in an oval demarcating the region for fat 
harvest.  
4. Area is bordered by sterile drapes.  
5. Abdomen is swabbed with Chloroprep.  
6. 500cc of tumescent is prepared by combining 500cc sterile saline, 50cc 1% Lidocaine and 
1cc of 1:1000 Epinephrine.  
7. Using an18-gauge needle the injection site injected with anesthetic tumescent for local 
anesthesia and the needle tip used to slightly expand the entry point to make access for 
insertion of the cannula.  
8. Using a17-gauge blunt end cannula the harvest site is irrigated subcutaneously penetrating 
below Scarpa’s fascia channeling with 60cc – 120cc tumescent.  
9. After waiting10-15minutes using a 13-gauge blunt end cannula adipose tissue is aspirated. 
(Amount of decanted fat should equal approximately a 4:1 ratio to volume necessary for 
final injectate).  
10. Following fat harvest the injection site is cleaned and sterile bandages applied.  
 
PROCESSING LIPOGEMS 
 
STEP 1: The Lipogems disposable medical device is removed from sterile package and laid out on 
a sterile field. The Lipogems kit is assembled and connected to a bag of 1000cc sterile saline. The 
waste bag is connected and laid on the floor out of the way of foot traffic.  The assembly is 
prefilled with saline solution and flushed by gravity to obtain and completely closed system free of 
air.  
 

Protocol Number: LG-MN-201v2 
                      Renewal Date: September 27, 2017 
Approval Date: January 6, 2016 
  Continuing Review Date: September 19, 2018 
 
7 
STEP 2: The syringe containing the lipoaspirate is then connected to the Lipogems device. The 
first step in cluster reduction is obtained as the lipoaspirate in injected into the kit passing through 
the first reduction filter.  
 
STEP 3: The line from the saline bag and is opened allowing blood and oil residues to drain 
through the system into the waste collection bag. Then line is closed.   
 
STEP 4:The device containing stainless steel ball bearings is shaken for thirty seconds in order to 
fragment and wash the lipoaspirate.  Stop and allow adipose clusters to float to the top. 
 
STEP 5: The rinsing and shaking steps are repeated until the tissue is bright yellow and the saline 
in the chamber is clear (strands of connective tissue may be present).   
 
STEP 6: The device is turned 180 degrees, and a 10cc sterile syringe is attached to each end.  With 
only the input portal (lower) opened, 10cc saline is drawn into the lower syringe. With the palm of 
one hand, the lower syringe is pushed upwards, forcing the washed tissue through the second 
reduction filter and filling the upper syringe with Lipogems.  
 
STEP 7: The syringe is decanted, removing excess saline, and is now ready for use without any 
further washing or preparation.  
 
STEPS 2-7 may be repeated by injecting additional lipoaspirated adipose tissue into the device 
until the desired final volume of Lipogems is obtained.  
 
TREATMENT  
Following the fat harvest and preparation of the Lipogems fat graft, diagnostic ultrasound is used 
to identify the target structures in coordination with historical imaging from MRI. If a large 
effusion is detected the effusion will be aspirated prior to the injection of Lipogems.  
 
The injection will be performed using sterile technique. Lidocaine may be used topically, but will 
not be introduced into the injection site. Generally, a 22 guage needle 1.5 to 2.5 inches in length 
will be used depending on the patient’s anatomy. The injection will be performed under direct 
ultrasound guidance into the hypoechoic defects within of the medial and or lateral meniscus tears. 
Ultrasound imaging will determine the placement of the needle tip and visualizing complete 
lipofilling of the soft tissue defects. All injectate volumes and locations will be recorded. The 
patient will remain in the supine position for 10 minutes and post-injection vital signs obtained. 
Post-injection guidelines will included non-weightbearing with crutches X 1 week and the weight 
bearing for simple daily activities, refraining from running and jumping activities and repeptitive 
fleion beyond 90 degrees for 4 weeks total. The patient will then be placed on a progressive 
strengthening program over weeks 4-6. If there is no pain, swelling; significant joint line 
tenderness and near full range of motion, unrestricted activities will be allowed at the 6-8 week 
time-frame. If there are abnormal findings of pain, tenderness; swelling etc.; the patient will be 
reassessed and limited in their activities for 8 weeks from the time of the procedure and then 
monitored for their response following this. 
 
OUTCOME MEASURES 

Protocol Number: LG-MN-201v2 
                      Renewal Date: September 27, 2017 
Approval Date: January 6, 2016 
  Continuing Review Date: September 19, 2018 
 
8 
 
Follow up outcome assessment will be conducted by phone and functional questionnaires in 
addition to physical examination and functional measurements when in-office follow up visits are 
applicable.  Numeric Pain Scale (NPS) and Knee Innjury and Osteoathritis Outcome Score 
(KOOS) will be utilized. The NPS will be a subjective measure of pain using a scale of 0 = No 
pain through 10 worse pain ever. This will be preferred over a visual analogue scale (VAS) as it 
can be given over the phone and does not necessary require the patient’s presence in the clinical 
area. KOOS is widely used for research purposes in clinical trials, large-scale databases and 
registries. KOOS is also extensively used for clinical purposes. In the clinic, KOOS is used to 
monitor groups and individuals over time. Due to its comprehensiveness, when the questionnaire is 
completed prior to a consultation, it can be used to guide the consultation as to the symptoms and 
difficulties experienced by the patient. 
KOOS is intended to be used for knee injury that can result in post traumatic osteoarthritis (OA); 
i.e. ACL (anterior cruciate ligament) injury, meniscus injury, chondral injury, etc. 
KOOS is also used in knee OA. An advantage of the KOOS is the inclusion of two different 
subscales of physical function relating to daily life, and sport and recreation. This enhances the 
instrument’s validity for patients with a wide range of current and expected physical activity levels. 
KOOS is intended to be used over short- and long-term time intervals; to assess changes from 
week to week induced by treatment (medication, operation, physical therapy) or over years 
following a primary injury or OA. 
KOOS can be used in research to assess groups and to monitor individuals. 
KOOS’ content validity was based upon a literature search, a pilot study and an expert panel (from 
US and Sweden) consisting of patients, orthopedic surgeons and physical therapists. 
KOOS consists of 5 subscales; Pain, other Symptoms, Function in daily living (ADL), Function 
in sport and recreation (Sport/Rec) and knee related Quality of life (QOL). The previous week 
is the time period considered when answering the questions. Standardized answer options are 
given (5 Likert boxes) and each question is assigned a score from 0 to 4. A normalized score (100 
indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. A 
total score has not been validated and is not recommended. For the purpose of an RCT, KOOS 
subscale scores can be aggregated and averaged as the primary outcome. The five individual 
KOOS subscale scores are then given as secondary outcomes to enable clinical interpretation. 
Please see FAQ for further information on this procedure. The results of the 5 subscales can be 
plotted as an outcome profile (order of subscales from left to right: Pain, Symptoms, ADL, 
Sport/Rec and QOL), preferably in a graph with scores from 0-100 on the y-axis and the five 
subscales on the x-axis  
KOOS is patient-administered, the format is user friendly, and takes about 10 minutes to complete. 
KOOS is in the public domain and is free of charge. No licensing or permission to use KOOS or 
the other questionnaires available from www.koos.nu is required 

Protocol Number: LG-MN-201v2 
                      Renewal Date: September 27, 2017 
Approval Date: January 6, 2016 
  Continuing Review Date: September 19, 2018 
 
9 
FOLLOW UP SCHEDULE 
 
Immediately post treatment:  
NPS pain score  
 
24 Hours 
NPS pain score 
 
One week following treatment:  
NPS  
 
Five weeks following treatment:  
NPS  
Function scores (KOOS)  
Range of motion when in person assessment  
Quadriceps strength when in person assessment  
 
Three months following treatment:  
NPS  
Function scores (KOOS)  
Range of motion when in person assessment  
 
Six months following treatment:  
NPS  
Function scores (KOOS)  
Range of motion when in person assessment 
Repeat MRI  
 
One year following treatment: 
NPS 
Function Scores (KOOS) 
Repeat MR 
 
INFORMED CONSENT  
 
The risks, benefits, and alternatives discussed with patient. Patient understands all post procedure 
instructions and follow-ups. All questions answered to satisfaction.  
 
VULNERABLE SUBJECTS  
 
No vulnerable subjects will be included. Children, pregnant women, nursing home residents or 
other institutionalized persons, students, employees, prisoners, and persons with decisional 
incapacity will not be included in this study.  
 
RECRUITMENT, ENROLLMENT, AND REMUNERATION  

Protocol Number: LG-MN-201v2 
                      Renewal Date: September 27, 2017 
Approval Date: January 6, 2016 
  Continuing Review Date: September 19, 2018 
 
10 
 
Recruitment of patients into the study will be done from clinics previous patients, referrals from 
other physicians, patient advocacy groups, direct website inquiries, and public outreach 
informational events.  
1. Marketing:  
Marketing will be done primarily online via informational websites, patient outreach and 
advocacy groups.  
2. Referrals:  
Recruitment of patients into the study will also be done via referral from physicians. No 
compensation will be given to referring physicians.  
3. Patient fees:  
Patients will pay a fee for treatment that is within the normal range of comparative 
treatments worldwide. This will cover all costs including physicians and nursing staff, 
surgery center fees. Routine screening will be paid for by patient, however, no fees will be 
charged to the patient for additional images or tests directly related to the study.  
 
POSSIBLE SIDE EFFECTS  
 
Besides soreness from the fat harvest procedure, and at the site of injection, there have been very 
few adverse effects reported with autologous biologic therapies. Patients may experience 
aggravated stiffness and pain in the treated area.  
 
 
 
ADVERSE EVENT REPORTING  
 
Study sites will document all adverse reactions that occur (whether or not related to study drug or 
procedure) Significant adverse events will be reported to the IRB immediately.  
 
FOLLOW UP AND REVIEW  
 
At 24 hours, 1 week, 5 weeks, 3 month, 6 month, and 1 year intervals patients will be asked to 
participate in follow up protocols. Patients will not incur any and also be made available for the 
IRB to review.  
 
PATIENT CONFIDENTIALITY  
 
Patient names will be removed prior to submitting to any third party for review in order to 
maintain patient confidentiality.  
 
WITHDRAWALS  
 

Protocol Number: LG-MN-201v2 
                      Renewal Date: September 27, 2017 
Approval Date: January 6, 2016 
  Continuing Review Date: September 19, 2018 
 
11 
Participation in the study is voluntary and patients may withdraw at any time. Patients who 
withdraw prematurely will not be replaced, but investigators will determine if it is in the best 
interest of the study to extend the study in order to obtain the desired number of subjects. An 
inquiry will be made as to the reason for termination and an assessment of the patient’s wellbeing 
at the time. If the termination is the result of an adverse event this will be reported.  
 
DATA COLLECTION, RETENTION AND MONITORING 
 
Information from initial patient screening including demographic variables, data from follow up 
visits and self-administered questionnaires will be entered or uploaded into a comprehensive 
HIIPA compliant database. 
SUBJECT CONFIDENTIALITY  
 
In order to maintain confidentiality, only a subject number and initials will identify all study 
subjects entered into the database and on all documentation submitted to the Sponsor.    
STATISTICAL METHODS 
Patients who receive at least one follow up visit will be included in the analysis. Data for 
presentation and publication will be shared between investigator and sponsor.  
 
 
END POINT  
 
At both 6 months and 1 year assessments will be made with the patient to assess the above 
outcome measure and adverse effects from treatment. This will be evaluated along with the images 
and functional scores to evaluate clinical outcome. Patient tracking will continue for an additional 
2 years.  
INVESTIGATOR RESPONSIBILITYIES 
 
The Investigator agrees to: 
1. Conduct the study in accordance with the protocol and only make changes after notifying the 
Sponsor (or designee), except when to protect the safety, rights or welfare of subjects. 
2. Personally conduct or supervise the study (or investigation). 
3. Ensure that the requirements relating to obtaining informed consent and IRB review and 
approval meet federal guidelines, as stated in § 21 CFR, parts 50 and 56. 
4. Report to the Sponsor or designee any AEs that occur in the course of the study, in accordance 
with §21 CFR 312.64. 

Protocol Number: LG-MN-201v2 
                      Renewal Date: September 27, 2017 
Approval Date: January 6, 2016 
  Continuing Review Date: September 19, 2018 
 
12 
5. Ensure that all associates, colleagues and employees assisting in the conduct of the study are 
informed about their obligations in meeting the above commitments. 
6. Maintain adequate and accurate records in accordance with §21 CFR 312.62 and to make 
those records available for inspection with the Sponsor (or designee). 
7. Ensure that an IRB that complies with the requirements of §21 CFR part 56 will be 
responsible for initial and continuing review and approval of the clinical study. 
8. Promptly report to the IRB and the Sponsor (or designee) all changes in the research activity 
and all unanticipated problems involving risks to subjects  
9. Seek IRB approval before any changes are made in the research study, except when necessary 
to eliminate hazards to the patients/subjects. 
10. Comply with all other requirements regarding the obligations of clinical investigators and all 
other pertinent requirements listed in § 21 CFR part 312 
 
REFERENCES 
 
1. Wikipedia Anatomy of the Knee 
2. Bianchi F, Maioli M, Leonardi E, Olivi E, Pasquinelli G, Valente S, Mendez AJ, Ricordi C, 
Raffaini M, Tremolada C, Ventura C. A new nonenzymatic method and device to obtain a 
fat tissue derivative highly enriched in pericyte-like elements by mild mechanical forces 
from human lipoaspirates. Cell Transplant 2013;22(11):2063-77. 
3. Meniscectomy as a risk factor for knee osteoarthritis: a systematic review. Papalia R1, Del 
Buono A, Osti L, Denaro V, Maffulli N. 
4. National Institute of Arthritis and Musculoskeletal and Skin Diseases. 
5. Arthritis Foundation 
6. American Academy of Orthopedic Surgeons 
7. Arthroscopic surgery for degenerative knee: systematic review and meta-analysis of benefits and 
harms 
8. 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h2747 (Published 16 June 2015) Cite this as: BMJ 
2015;350:h2747 
9. Shiel WC. Osteoarthritis. http://www.medicinenet.com/osteoarthritis/article.htm 
10. Black LL, Gaynor J, Gahring D, Adams C, Aron D, Harman S, et al. Effect of adipose-derived 
mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the 
coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial. Vet Ther. 2007; 
8(4):272-84.