ADIPOSE TISSUE IN regenerative orthopedics

Regenerative Medicine encompasses many medical fields – Orthopedics and Spine Surgery, Sports Medicine, Gynecology, Urology, Oncology, Dermatology, Plastic surgery, Vascular Surgery, Cardiac surgery, etc.

Regenerative Medicine is the branch of medicine that develops methods to regrow, repair or replace damaged or diseased cells, organs or tissues. Regenerative medicine includes the generation and use of therapeutic stem cells, tissue engineering and the production of artificial organs. It uses autologous blood, bone marrow or adipose components to stimulate the body’s own repair processes. A common source for regenerative cells and growth factors are bone marrow aspirate concentrate (BMAC), platelet rich plasma (obtained from one’s own blood) and adipose derived stem cells.

PATHOLOGY

CHRONIC ACHILLES TENDON INJURY

The Achilles tendon is the strongest tendon in the body, linking the heel bone to the calf muscle. Problems with the Achilles are some of the most common conditions seen by sports medicine doctors. Chronic, long-lasting Achilles tendon disorders can range from overuse injuries to tearing of the tendon. Pain in the heel is often caused by a combination of both acute and chronic problems, including inflammation (paratenonitis, insertional tendonitis and retrocalcaneal bursitis) and tendinosis.

Achilles tendon inflammation injuries

What is paratenonitis?

Paratenonitis is an acute Achilles injury caused by overuse. It involves inflammation of the covering of the Achilles tendon. “In really acute cases, the tendon can appear sausage-like, because it is so severely swollen,” says Russell Warren, MD, a sports medicine orthopedic surgeon at Hospital for Special Surgery in New York. Marathon runners often experience this type of swelling after long runs. Runners may complain of stiffness and discomfort at the beginning of the run, but push through the discomfort. Symptoms are typically aggravated by running and relieved by rest. If left untreated, paratenonitis may progress to the point that any running becomes difficult.

What is insertional tendonitis?

Insertional tendonitis involves inflammation at the point where the Achilles tendon inserts into the heel bone. People with this condition often have tenderness directly over the insertion of the Achilles tendon, which is commonly associated with calcium formation or a bone spur forming just above the insertion point. This condition can occur along with retrocalcaneal bursitis (see below) and a bony enlargement of the heel bone, known as Haglund’s deformity (someimtes is referred to as a “pump bump”). “Most cases of Haglund’s deformity occur in women who wear high-heeled shoes or men and women hockey players because of the skate rubbing on the back of the heel,” says Scott Rodeo, MD, a sports medicine orthopedic surgeon at Hospital for Special Surgery.

What is retrocalcaneal bursitis?

Retrocalcaneal bursitis is caused by movement-related irritation of the retrocalcaneal bursa, the fluid-filled cushioning sac between the heel bone and the Achilles tendon. This condition involves pain in front of the Achilles tendon, in the area between the tendon and the heel bone. The bursa can become inflamed or thickened and stick to the tendon, as a result of overuse or repetitive loading. Pain may result from squeezing the tendon itself or the space just in front of the tendon. “Although retrocalcaneal bursitis can be associated with rheumatoid arthritis in 10 percent of people, most occurrences in athletes only involve one side and are not associated with a systemic disease,” says Dr. Warren.

GONARTHROSIS

Gonarthrosis is most frequently defined as changes involving articular cartilage damage, abnormal bone formation, reactive changes in synovial membrane and pathologic synovial fluid. The site of initial damage remains unknown. It is known presently that in the development of the process, reparative reaction of chondrocytes expressed by increase of synthesis of the main collagen types (type II, in lower degree types IX, VI, XI) and also of proteoglycans, is the primary event, at cell level. The final result of the pathological process in gonarthrosis is imbalance between synthesis of articular cartilage and damage leading to its loss. Each cause or process inducing cartilage degradation exerts effects on the occurrence and progression of gonarthrosis.

Gonarthrosis is diagnosed on the basis of clinical and radiological examinations. Magnetic resonance, bone scintigraphy and arthroscopy are also of importance. However, in the future, the markers of articular cartilage destruction products in body fluids would be the key to determination of the time of the onset of the disease, its progression and advances of treatment. Great hopes in the treatment of gonarthrosis could be connected with BMAC therapy.

FRACTURE NON-UNIONS

Nonunion is permanent failure of healing following a broken bone unless intervention (such as surgery) is performed. A fracture with nonunion generally forms a structural resemblance to a fibrous joint, and is therefore often called a “false joint” or pseudoarthrosis (the Greek stem “pseudo-” means false and “arthrosis” means joint). The diagnosis is generally made when there is no healing between two sets of medical imaging such as X-ray or CT scan. This is generally after 6–8 months.

Nonunion is a serious complication of a fracture and may occur when the fracture moves too much, has a poor blood supply or gets infected. Patients who smoke have a higher incidence of nonunion. The normal process of bone healing is interrupted or stalled.

Since the process of bone healing is quite variable, a nonunion may go on to heal without intervention in a very few cases. In general, if a nonunion is still evident at 6 months post injury it will remain unhealed without specific treatment, usually orthopedic surgery. A non-union which does go on to heal is called a delayed union.

BIMALLEOLAR FRACTURES

A bimalleolar fracture is a fracture of the ankle that involves the lateral malleolus and the medial malleolus. Studies have shown that bimalleolar fractures are more common in women, people over 60 years of age, and patients with existing comorbidities.

Bimalleolar fractures can cause severe pain, swelling, and bruising in the injured ankle. They also can be tender to the touch and make walking or putting any weight on the affected foot very difficult and painful.

ROTATOR CUFF TENDINITIS

Rotator cuff tendinitis, or tendonitis, affects the tendons and muscles that help move your shoulder joint. If you have tendinitis, it means that your tendons are inflamed or irritated. Rotator cuff tendinitis is also called impingement syndrome.

This condition usually occurs over time. It can be the result of keeping your shoulder in one position for a while, sleeping on your shoulder every night, or participating in activities that require lifting your arm over your head.

Athletes playing sports that require lifting their arm over their head commonly develop rotator cuff tendinitis. This is why the condition may also be referred to as:

swimmer’s shoulder
pitcher’s shoulder
tennis shoulder

Sometimes rotator cuff tendinitis can occur without any known cause. Most people with rotator cuff tendinitis are able to regain full function of the shoulder without any pain.

The symptoms of rotator cuff tendinitis tend to get worse over time. Initial symptoms may be relieved with rest, but the symptoms can later become constant. Symptoms that go past the elbow usually indicate another problem.

Symptoms of rotator cuff tendinitis include:

pain and swelling in the front of your shoulder and side of your arm
pain triggered by raising or lowering your arm
a clicking sound when raising your arm
stiffness
pain that causes you to wake from sleep
pain when reaching behind your back
a loss of mobility and strength in the affected arm

ACL INJURY

An ACL injury is a tear or sprain of the anterior cruciate (KROO-she-ate) ligament (ACL) — one of the major ligaments in your knee. ACL injuries most commonly occur during sports that involve sudden stops or changes in direction, jumping and landing — such as soccer, basketball, football and downhill skiing.

Many people hear or feel a “pop” in the knee when an ACL injury occurs. Your knee may swell, feel unstable and become too painful to bear weight.

Depending on the severity of your ACL injury, treatment may include rest and rehabilitation exercises to help you regain strength and stability or surgery to replace the torn ligament followed by rehabilitation. A proper training program may help reduce the risk of an ACL injury.

Symptoms

Signs and symptoms of an ACL injury usually include:

A loud “pop” or a “popping” sensation in the knee
Severe pain and inability to continue activity
Rapid swelling
Loss of range of motion
A feeling of instability or “giving way” with weight bearing

When to see a doctor

Seek immediate care if any injury to your knee causes signs or symptoms of an ACL injury. The knee joint is a complex structure of bones, ligaments, tendons and other tissues that work together. It’s important to get a prompt and accurate diagnosis to determine the severity of the injury and get proper treatment.

COXARTHROSIS

The hip is the joint between the pelvis and the femur, and hip osteoarthritis is the wear and tear of the cartilage rubbing between these two bones. This wear causes joint inflammation resulting in pain and discomfort, which worsen as the disease progresses: the bone under the damaged cartilage grows forming bone spurs (osteophytes) around the joint.

Pain is generally one of the first signs in the diagnosis of hip osteoarthritis, or coxarthrosis. This pain can be felt in the groin, and sometimes the buttock or the back of the thigh. Knee pain can also point to this diagnosis, which will of course be confirmed by an x-ray. Joint pain, functional impairment and limping will progressively worsen, except in rare cases of “rapidly destructive” coxarthrosis for which the progression is very fast. Hip osteoarthritis is a serious disease that becomes rapidly incapacitating as it affects a weight-bearing joint.

Medical treatment of hip osteoarthritis

At the first symptoms of hip osteoarthritis, a healthy lifestyle (healthy weight, appropriate, low-impact physical activities) is necessary to limit the pain and stop the disease worsening. Sports such as swimming are therefore highly recommended. During flare-ups, paracetamol or any non-steroidal anti-inflammatories can be used to help relieve the pain.

When these treatments are no longer effective, corticosteroid injections, hyaluronic acid viscosupplementation, or platelet rich plasma therapy (PRP) can be envisaged. Stem cell injections can also be discussed.

OSTEOCHONDRAL LESIONS

Osteochondral lesions or osteochondritis dessicans can occur in any joint, but are most common in the knee and ankle. Such lesions are a tear or fracture in the cartilage covering one of the bones in a joint. The cartilage can be torn, crushed or damaged and, in rare cases, a cyst can form in the cartilage.

In the knee, such cartilage damage can occur between the femur (thigh bone) and the tibia (shin bone). In the ankle, osteochondral lesions usually occur on the talus, which is the bone that connects the leg to the foot.

After the initial pain and discomfort of a strain or sprain subsides, individuals usually resume or even increase their activity level. If an osteochondral lesion has occurred, however, everyday activities that put pressure on the joint, may lead to pain and swelling, although the joint usually is fine when at rest. A patient with an osteochondral lesion will often feel a dull ache in the joint and may also experience a mild locking or clicking of their knee or ankle joint. The affected joint may also seem to be loose.

It can be challenging to diagnose an osteochondral lesion at the time of injury. Many scans may miss the damage caused by the lesion, which is also masked by the sprain or trauma that caused the injury.

A physician will examine the joint for instability and range of motion. An X-ray may be ordered, but a cartilage tear is difficult to see on an X-ray, so a magnetic resonance imaging (MRI) or computed tomography (CT) scan may be required. In some cases, both an MRI and CT are needed to diagnose an osteochondral lesion.

SUPPORTING EVIDENCE

ORTHO & SPORT MEDICINE APPLICATIONS

Adipose-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage: A Systematic Review on Preclinical and Clinical Evidence

Francesco Perdisa, Natalia GostyNska, Alice Roffi,2 Giuseppe Filardo, Maurilio Marcacci and Elizaveta Kon – Hindawi Publishing

Corporation Stem Cells International Volume 2015, Article ID 597652, 13 pages http://dx.doi.org/10.1155/2015/597652

Adipose-derived stem cells in orthopaedic pathologies

Federico Giuseppe Usuelli, Riccardo D’Ambrosi, Camilla Maccario, Cristian Indino, Luigi Manzi and Nicola Maffulli – British Medical

Bulletin, 2017, 1–24 doi: 10.1093/bmb/ldx030

Mesenchymal Stem Cells injection in hip osteoarthritis: preliminary results

Carlo Dall’Oca, Stefano Breda, Nicholas Elena, Roberto Valentini, Elena Manuela Samaila, Bruno Magnan – Acta Biomed 2019; Vol.

90, Supplement 1: 75-80 DOI: 10.23750/abm.v90i1-S.8084

Intra-Articular Administration of Autologous Micro-Fragmented Adipose Tissue in Dogs with Spontaneous Osteoarthritis: Safety, Feasibility and Clinical Outcomes

Offer Zeira, Simone Scaccia, Letizia Pettinari, Erica Ghezzi, Nimrod Asiag, Laura Martinelli, Daniele Zahirpour, Maria P. Dumas, Martin Konar, Davide M. Lupi, Laurence Fiette, Luisa Pascucci, Leonardo Leonardi, Alistair Cliff, Giulio Alessandri, Augusto Pessina,

Daniele Spaziante, Marina Aralla – Stem Cells Translational Medicine 2018;00:1–10

Micro-fragmented adipose tissue injection associated with arthroscopic procedures in patients with symptomatic knee osteoarthritis

G. Cattaneo, A. De Caro, F. Napoli, D. Chiapale, P. Trada and A. Camera – Cattaneo et al. BMC Musculoskeletal Disorders (2018)

19:176 https://doi.org/10.1186/s12891-018-2105-8

The Effect of Intra-articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis

Damir Hudetz, Igor Borić, Eduard Rod, Željko Jeleč , Andrej Radić, Trpimir Vrdoljak, Andrea Skelin, Gordan Lauc, Irena Trbojević-

Akmačić, Mihovil Plečko, Ozren Polašek and Dragan Primorac – Genes 2017, 8, 270; doi: 10.3390/genes8100270

Autologous and micro-fragmented adipose tissue for the treatment of diffuse degenerative knee osteoarthritis

A. Russo, V. Condello, V. Madonna, M. Guerriero and C. Zorzi – Russo et al. Journal of Experimental Orthopaedics (2017) 4:33

DOI 10.1186/s40634-017-0108-2

Non-Responsive Knee Pain with Osteoarthritis and Concurrent Meniscal Disease Treated With Autologous Micro-Fragmented Adipose Tissue Under Continuous Ultrasound Guidance

R.D. Striano, H. Chen, N. Bilbool, K. Azatullah, J. Hilado, K. Horan – CellR4 2015; 3 (5): e1690

Non-Responding Knee Pain with Osteoarthritis, Meniscus and Ligament Tears Treated with Ultrasound Guided Autologous, Micro-Fragmented and Minimally Manipulated Adipose Tissue

Richard David Striano, Valeria Battista, Norma Bilboo – Open Journal of Regenerative Medicine, 2017, 6, 17-26

http://www.scirp.org/journal/ojrm

Safety and Efficacy of Percutaneous Injection of Lipogems Micro-Fractured Adipose Tissue for Osteoarthritic Knees

Jay Panchal, MD Gerard Malanga, MD Mitchell Sheinkop, MD – Am J Orthop. 2018;47(11)

Microfragmented adipose injections in the treatment of knee osteoarthritis

Gerard A. Malanga, Sean Bemanian – Journal of Clinical Orthopaedics and Trauma, https://doi.org/10.1016/j.jcot.2018.10.021

Autologous micro-fragmented adipose tissue for the treatment of diffuse degenerative knee osteoarthritis: an update at 3 year follow-up

Russo, D. Screpis, S. L. Di Donato, S. Bonetti, G. Piovan and C. Zorzi – Russo et al. Journal of Experimental Orthopaedics (2018) 5:52

https://doi.org/10.1186/s40634-018-0169-x

Preliminary results of autologous adipose-derived stem cells in early knee osteoarthritis: identification of a subpopulation with greater response

Alfredo Schiavone Panni & Michele Vasso & Adriano Braile & Giuseppe Toro & Annalisa De Cicco & Davide Viggiano & Federica

Lepore – International Orthopaedics (SICOT) (2019) 43:7–13

Refractory Shoulder Pain with Osteoarthritis and Rotator Cuff Tear Treated With Micro-Fragmented Adipose Tissue

Richard D Striano, Gerard A Malanga, Norma Bilbool, Khatira Azatullah – BIBLIOTICS JOURNALS Orthop Spine Sports Med (2018) 2:1 014

Injection of autologous micro-fragmented adipose tissue for the treatment of post-traumatic degenerative lesion of knee cartilage: a case report

M. Franceschini, C. Castellaneta, G. Mineo – CellR4 2016; 4 (1): e1768

Video Article Autologous Microfractured and Purified Adipose Tissue for Arthroscopic Management of Osteochondral Lesions of the Talus

Riccardo D’Ambrosi, Cristian Indino1, Camilla Maccario, Luigi Manzi, Federico Giuseppe Usuelli –

BPB MEDICA®