Orthopedic Stemcell

Osteoarthritis (OA)

Osteoarthritis (OA) is an inflammatory condition still lacking effective treatments which are the most common chronic health problems in the world that causes disability and chronic pain with reduced mobility and is a progressive degenerative disease in weight-bearing joints such as the knee. The pathology of the joint resulting from OA includes loss of cartilage volume and cartilage lesions leading to inflammation of the articular joint structures; its incidence and progression are associated with a variety of risk factors. Most of the current treatments focus on symptom management such as physical and occupational therapies, pharmacological intervention for pain management, and surgical intervention with limited success and do not address nor halt the progression of the disease. In this review, we will describe the current treatment options for OA and the exciting new translational medical research currently underway utilising mesenchymal stem cells for OA therapy.
Mesenchymal stem/stromal cells (MSCs) have been successfully employed in pre-clinical models aiming to resurface the degenerated cartilage. In early-phase clinical trials, intra-articular (IA) administration of MSCs leads to pain reduction and cartilage protection or healing. However, the consistent lack of engraftment indicates that the observed effect is delivered through a “hit-and-run” mechanism, by a temporal release of paracrine molecules. MSCs express a variety of chemokines and cytokines that aid in repair of degraded tissue, restoration of normal tissue metabolism and, most importantly, counteracting inflammation. Secretion of therapeutic factors is increased upon licensing by inflammatory signals or apoptosis, induced by the host immune system. Trophic effectors are released as soluble molecules or carried by extracellular vesicles (ECVs). This review provides an overview of the functions and mechanisms of MSC-secreted molecules found to be upregulated in models of OA, whether using in vitro or in vivo models.



Chondral Defect

The knee is one of the most complex and largest joints within the body. It joins the shinbone (tibia) and the thighbone (femur). The smaller bone running along the tibia is called the fibula, and the knee cap (patella) is the other bones making up the knee joint. Tendons keep the knee bones connected with the leg muscles that are responsible for moving the knee joint. Ligaments keep the knee bones joined together and deliver stability to the knee.

The lateral and medial menisci are two c-shaped cartilage pieces that serve as shock absorbers between the tibia and the femur. Countless fluid-filled sacs help the knee to move freely.

The development of osteoarthritis depends on several factors:

- The patient's age when the degeneration starts. - The patient's activity level and weight. - The presence of ligament damage.

Articular cartilage problems can be particularly difficult to treat because the onset, while occasionally sudden, often occurs gradually and thus is not immediately detected.

What is articular cartilage and what does it do?


There are two types of cartilage in the human knee:

Meniscus cartilage - This is the cartilage most commonly referred to when the term "torn cartilage" is used. These two rubbery shock absorbers sit between the upper bone of the thigh (femur) and the large bone in the lower leg (tibia). Articular cartilage - This cartilage is the shiny, white surface that covers the ends of most bones. Articular cartilage protects the ends of bones and allows the joints to glide smoothly with less friction. It also helps to spread the loads applied to a joint. This covering is only a few millimeters thick and it has no blood supply to facilitate the healing process. Therefore, if it gets damaged, there is very little capacity for healing.

Chondral damage is graded from mild to severe, and all grades can have characteristics of osteoarthritis. Grade I - The cartilage "blisters" and becomes soft in the earliest form of damage. Grade II and III - As the condition worsens, the cartilage may become fibrillated (it has a shredded appearance). The grade of injury depends on the size of the involved area and how much of the cartilage thickness is worn down. Noise as the knee bends, called crepitus, may be present. Grade IV - The cartilage may wear away completely, leaving the underlying bone exposed in small or widespread areas. When the involved areas are large, pain usually becomes more severe, causing a limitation in activity.

How to Treat a Chondral Defect:

Stop aggravating the problem

Arthroscopy
If a partial thickness injury to the cartilage and the mechanical symptoms for intermittent and catching pain are present, arthroscopy might be necessary to smooth the surface of the joint and remove any loose cartilage. Also the defect can be drilled slightly which can fill the area with blood and stimulate healing (see microfracture below).

Fixation
In certain instances, the damaged cartilage area and the underlying bone will stay attached partially or they can be loose but still in one piece in the joint. Depending on the situation, fragment fixation back to the defect is desirable. This is a rare form of treatment.

Microfracture
If a full thickness of cartilage is detected, the aim is to restore the cartilage that covers the bone underneath. Articular cartilage doesn’t have a blood supply, so it doesn’t possess the ability to heal when damaged. A microfracture operation is completed along with keyhole surgery where they make multiple small holes within the bony base of the defect that allows the blood to enter into the cavity and start the healing process. Post-operative treatment is imperative to the success of the procedure.





HTO

First introduced by Jackson and Waugh in 1961, high tibial osteotomy (HTO) has become popular by Conventry since 1965 as a treatment modality for medial compartment osteoarthritis of the knee with varus deformity. The goals of HTO are two fold: 1) To reduce knee pain by transferring weight-bearing loads to the relatively unaffected lateral compartment in varus knees; and 2) To delay the need for a knee replacement by slowing or stopping destruction of the medial joint compartment.

Although the employment of HTO has declined recently due to the improvement of knee arthroplasty, it is indisputable that appropriate patient selection, precise surgical planning, and various operative techniques can provide favorable treatment outcomes of HTO. The remaining areas of controversy regarding HTO include the choice of opening vs. closing wedge HTO, graft selection in opening wedge HTO, type of fixation, comparative advantages over uni-compartmental knee arthroplasty and the influence of HTO on subsequent knee arthroplasty.

Preoperative Planning


Patient assessment
Patient's age, career, level of activity, previous history of surgery on the knee, and expectation should be taken into consideration before deciding upon surgery. Closing wedge HTO may be more beneficial in reducing the risk of nonunion than opening wedge HTO for heavy-smoking patient.

The good range of motion (ROM), degree of deformity, ligamentous instability, and leg length discrepancy should be assessed through physical examination. Valgus HTO can be performed for minor or moderate medial instability that can be caused by bone loss in medial compartment osteoarthritis. The status of the hip joint can have an influence on the medial osteoarthritis of the ipsilateral knee. Abduction of the hip that occurs during the stance period increases stress on the lateral compartment of the knee, which gives rise to the involvement of the stabilizers (gluteus maximus, tensor fascia latae, and biceps femoris) that results in higher forces on the lateral knee. Therefore, hip abductor muscle weakness or restriction or ankylosis of the hip joint should be treated prior to HTO.

Radiographic assessment


Multiple views should be obtained for preoperative radiographic assessment: bilateral weight-bearing anterior-posterior views in full extension, tunnel views with the knee in 30° of flexion, Rosenberg views with the knee in 45° of flexion, lateral views, and skyline views. The severity of medial osteoarthritis and bone loss can be evaluated from the anterior-posterior views and patellar height can be measured from the lateral views using Insall-Salvati, Blackburne-Peel, or Caton-Deschamps index. A severe patella alta may necessitate the combined use of tibial tubercle osteotomy and closing/opening HTO. Lower limb alignment can be assessed from the full length radiographs of the lower extremity that visualizes the alignment of the hip, knee, and ankle joints. Magnetic resonance imaging can be helpful in detecting intraosseous lesions, meniscal tears, ligamentous lesions, osteochondral defects, osteonecrosis, or subchondral edema.

Rehabilitation


Once adequate fixation is achieved after medial opening wedge osteotomy, early joint exercises should be initiated. Partial weight bearing exercises should be performed with the knee protected in a hinged brace allowing 0°-90° of motion for 6 weeks. Weight bearing should be increased progressively between 6 to 12 weeks with the knee brace removed. Maintenance of correction and bone union should be assessed through radiography on a regular basis and the lower limb alignment on full length radiographs of the lower extremity at 6 months postoperatively. After lateral closing wedge osteotomy, partial weight bearing exercises are allowed immediately after surgery. A hinged knee brace should be worn for 6 postoperative weeks and weight bearing can be increased progressively depending on the state of bone union.

Complications


Fracture of the medial or lateral tibial cortical hinge and intra-articular fracture are commonly encountered after HTO, which can disrupt stability and healing at the osteotomy site and congruence of the articular surface. In these cases, the use of locking metal plates or extra screws and metal plates can provide stale fixation for reduction of the risk of loss of correction and nonunion. The incidence of nonunion after HTO has been reported to be 0.7-4.4%. The risk factors for nonunion include large degree of correction in HTO, smoking, and insufficient fixation.

Due to the recent advancement in internal fixation techniques, early joint exercises are allowed after HTO. In the past, long-term cast immobilization was unavoidable after closing HTO, during immobilization patellar infera secondary to patellar tendon contracture could occur with a prevalence of 7.6-8.8%. In addition, severe patella infera has a negative influence on the prognosis of HTO and renders conversion to TKA difficult.

The incidence of common peroneal nerve palsy caused by nerve damage during HTO is 2-16% and fibular shaft osteotomy (at 15 cm distal to the fibular head) can be useful for reduction of such damage. The reported rate of infection following external fixation is 2.3-54.5%, whereas that of infection following internal fixation is ≤4%. Other possible complications include fixation failure, loss of correction, pseudoarthrosis, deep venous thrombosis, pulmonary embolism, and compartment syndrome.