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Articular cartilage repair | |
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Specialty | orthopedic |
Articular cartilage repair treatment involves the repair of the surface of the articular joint's hyaline cartilage, though these solutions do not perfectly restore the articular cartilage. These treatments have been shown to have positive results for patients who have articular cartilage damage. They can provide some measure of pain relief, while slowing down the accumulation of damage, or delaying the need for joint replacement (knee replacement) surgery.
Though the different articular cartilage repair procedures differ in the technologies and surgical techniques used, they all share the same aim to repair articular cartilage whilst keeping options open for alternative treatments in the future. Broadly taken, there are five major types of articular cartilage repair:[ citation needed ]
Arthroscopic lavage is a "cleaning up" procedure of the knee joint. This short-term solution is not considered as an articular cartilage repair procedure but rather a palliative treatment to reduce pain, mechanical restriction and inflammation. Lavage focuses on removing degenerative articular cartilage flaps and fibrous tissue. The main target groups are patients with very small defects of the articular cartilage.
Marrow stimulating techniques attempt to solve articular cartilage damage through an arthroscopic procedure. Firstly, the damaged cartilage is drilled or punched until the underlying bone is exposed. By doing this, the subchondral bone is perforated to generate a blood clot within the defect. Studies, however, have shown that marrow stimulation techniques often have insufficiently filled the chondral defect and the repair material is often fibrocartilage (which is not as good mechanically as hyaline cartilage). The blood clot takes about 8 weeks to become fibrous tissue and it takes 4 months to become fibrocartilage. This has implications for the rehabilitation.[ citation needed ]
Further on, chances are high that after only 1 or 2 years of the surgery symptoms start to return as the fibrocartilage wears away, forcing the patient to reengage in articular cartilage repair. This is not always the case and microfracture surgery is therefore considered to be an intermediate step.[ citation needed ]
An evolvement of the microfracture technique is the implantation of a collagen membrane onto the site of the microfracture to protect and stabilize the blood clot and to enhance the chondrogenic differentiation of the MSCs. This technique is known as AMIC (Autologous Matrix-Induced Chondrogenesis) and was first published in 2003. [1]
Microfracture techniques show new potential, as animal studies indicate that microfracture-activated skeletal stem-cells form articular cartilage, instead of fibrous tissue, when co-delivered with a combination of BMP2 and VEGF receptor antagonist. [2]
A hydrogel implant to help the body regrow cartilage in the knee is currently being studied in U.S. and European clinical trials. [3] Called GelrinC, the implant is made of a synthetic material called polyethylene glycol (PEG) and denatured human fibrinogen protein.[ citation needed ]
During the standard microfracture procedure, the implant is applied to the cartilage defect as a liquid. It is then exposed to UVA light for 90 seconds, turning it into a solid, soft implant that completely occupies the space of the cartilage defect. The implant is designed to support the formation of hyaline cartilage through a unique guided tissue mechanism. It protects the repair site from infiltration of undesired fibrous tissue while providing the appropriate environment for hyaline cartilage matrix formation. Over six to 12 months, the implant resorbs from its surface inward, enabling it to be gradually replaced with new cartilage. [4] [5] [6]
Preliminary clinical studies in Europe have shown the implant improves pain and function.{{Dubious [this reference is no longer available December 2023]|date=July 2023|this reference does not seem to indicate that?}} [7]
A 2011 study reports histologically confirmed hyaline cartilage regrowth in a 5 patient case-series, 2 with grade IV bipolar or kissing lesions in the knee. The successful protocol involves arthroscopic microdrilling/ microfracture surgery followed by postoperative injections of autologous peripheral blood progenitor cells (PBPC's) and hyaluronic acid (HA). [8] PBPC's are a blood product containing mesenchymal stem cells and is obtained by mobilizing the stem cells into the peripheral blood. Khay Yong Saw and his team propose that the microdrilling surgery creates a blood clot scaffold on which injected PBPC's can be recruited and enhance chondrogenesis at the site of the contained lesion. They explain that the significance of this cartilage regeneration protocol is that it is successful in patients with historically difficult-to-treat grade IV bipolar or bone-on-bone osteochondral lesions.[ citation needed ]
Saw and his team are currently conducting a larger randomized trial and working towards beginning a multicenter study. The work of the Malaysian research team is gaining international attention. [9]
This technique/repair requires transplant sections of bone and cartilage. [10] First, the damaged section of bone and cartilage is removed from the joint. Then a new healthy dowel of bone with its cartilage covering is punched out of the same joint and replanted into the hole left from removing the old damaged bone and cartilage. The healthy bone and cartilage are taken from areas of low stress in the joint so as to prevent weakening the joint. [11] Depending on the severity and overall size of the damage multiple plugs or dowels may be required to adequately repair the joint, which becomes difficult for osteochondral autografts. The clinical results may deteriorate over time. [12]
For osteochondral allografts, the plugs are taken from deceased donors. This has the advantage that more osteochondral tissue is available and larger damages can be repaired using either the plug (snowman) technique or by hand carving larger grafts. There are, however, worries on the histocompatibility, though no rejection drugs are required and infection has been shown to be lesser than that of a total knee or hip. Osteochondral allografting using donor cartilage has been used most historically in knees, but is also emerging in hips, ankles, shoulders and elbows. Patients are typically younger than 55, with BMI below 35, and have a desire to maintain a higher activity level that traditional joint replacements would not allow. Advances in tissue preservation and surgical technique are quickly growing this surgery in popularity.
This technique involves physically separating a joint for a period of time (typically 8–12 weeks) to allow for cartilage regeneration. [13]
Aiming to obtain the best possible results, scientists have striven to replace damaged articular cartilage with healthy articular cartilage. Previous repair procedures, however, always generated fibrocartilage or, at best, a combination of hyaline and fibrocartilage repair tissue. Autologous chondrocyte implantation (ACI) procedures are cell-based repairs that aim to achieve a repair consisting of healthy articular cartilage. [14]
ACI articular cartilage repair procedures take place in three stages. First, cartilage cells are extracted arthroscopically from the patient's healthy articular cartilage that is located in a non load-bearing area of either the intercondylar notch or the superior ridge of the femoral condyles. Then these extracted cells are transferred to an in vitro environment in specialised laboratories where they grow and replicate, for approximately four to six weeks, until their population has increased to a sufficient amount. Finally, the patient undergoes a second surgery where the in vitro chondrocytes are applied to the damaged area. In this procedure, chondrocytes are injected and applied to the damaged area in combination with either a membrane or a matrix structure. These transplanted cells thrive in their new environment, forming new articular cartilage.
For years, the concept of harvesting stem cells and re-implanting them into one's own body to regenerate organs and tissues has been embraced and researched in animal models. In particular, mesenchymal stem cells have been shown in animal models to regenerate cartilage. Recently, there has been a published case report of decrease in knee pain in a single individual using autologous mesenchymal stem cells. An advantage to this approach is that a person's own stem cells are used, avoiding transmission of genetic diseases. It is also minimally invasive, minimally painful and has a very short recovery period. This alternative to the current available treatments was shown not to cause cancer in patients who were followed for 3 years after the procedure. [15]
See also Stem cell transplantation for articular cartilage repair
While there are currently no drugs approved for human use, there are multiple drugs currently in development which are aimed at slowing the progression of cartilage degeneration and even potentially repairing it.[ citation needed ] These are usually referred to DMOADs.
Rehabilitation following any articular cartilage repair procedure is paramount for the success of any articular cartilage resurfacing technique. The rehabilitation is often long and demanding. The main reason is that it takes a long time for the cartilage cells to adapt and mature into repair tissue. Cartilage is a slow adapting substance. Where a muscle takes approximately 35 weeks to fully adapt itself, cartilage only undergoes 75% adaptation in 2 years. If the rehabilitation period is too short, the cartilage repair might be put under too much stress, causing the repair to fail.
New research by Robert Litchfield, September 2008, of the University of Western Ontario concluded that routinely practised knee surgery is ineffective at reducing joint pain or improving joint function in people with osteoarthritis. The researchers did however find that arthroscopic surgery did help a minority of patients with milder symptoms, large tears or other damage to the meniscus — cartilage pads that improve the congruence between femur and tibia bones. [16] Similarly, a 2013 Finnish study found surgery to be ineffective for knee surgery (arthroscopic partial meniscectomy), by comparing to sham treatment. [17]
Cartilage is a resilient and smooth type of connective tissue. It is a semi-transparent and non-porous type of tissue. It is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck and the bronchial tubes, and the intervertebral discs. In other taxa, such as chondrichthyans, but also in cyclostomes, it may constitute a much greater proportion of the skeleton. It is not as hard and rigid as bone, but it is much stiffer and much less flexible than muscle. The matrix of cartilage is made up of glycosaminoglycans, proteoglycans, collagen fibers and, sometimes, elastin. It usually grows quicker than bone.
Chondropathy refers to a disease of the cartilage. It is frequently divided into 5 grades, with 0-2 defined as normal and 3-4 defined as diseased.
Osteochondritis dissecans is a joint disorder primarily of the subchondral bone in which cracks form in the articular cartilage and the underlying subchondral bone. OCD usually causes pain during and after sports. In later stages of the disorder there will be swelling of the affected joint which catches and locks during movement. Physical examination in the early stages does only show pain as symptom, in later stages there could be an effusion, tenderness, and a crackling sound with joint movement.
A meniscus transplant or meniscal transplant is a transplant of the meniscus of the knee, which separates the thigh bone (femur) from the lower leg bone (tibia). The worn or damaged meniscus is removed and is replaced with a new one from a donor. The meniscus to be transplanted is taken from a cadaver, and, as such, is known as an allograft. Meniscal transplantation is technically difficult, as it must be sized accurately for each person, positioned properly and secured to the tibial plateau. Its success also depends on donor compatibility, stability of the transplant, and long-term health of the underlying articular cartilage.
Chondrogenesis is the process by which cartilage is developed.
Articular cartilage, most notably that which is found in the knee joint, is generally characterized by very low friction, high wear resistance, and poor regenerative qualities. It is responsible for much of the compressive resistance and load bearing qualities of the knee joint and, without it, walking is painful to impossible. Osteoarthritis is a common condition of cartilage failure that can lead to limited range of motion, bone damage and invariably, pain. Due to a combination of acute stress and chronic fatigue, osteoarthritis directly manifests itself in a wearing away of the articular surface and, in extreme cases, bone can be exposed in the joint. Some additional examples of cartilage failure mechanisms include cellular matrix linkage rupture, chondrocyte protein synthesis inhibition, and chondrocyte apoptosis. There are several different repair options available for cartilage damage or failure.
Microfracture surgery is an articular cartilage repair surgical technique that works by creating tiny fractures in the underlying bone. This causes new cartilage to develop from a so-called super-clot.
Articular cartilage damage in the knee may be found on its own but it will more often be found in conjunction with injuries to ligaments and menisci. People with previous surgical interventions face more chances of articular cartilage damage due to altered mechanics of the joint. Articular cartilage damage may also be found in the shoulder causing pain, discomfort and limited movement. Cartilage structures and functions can be damaged. Such damage can result from a variety of causes, such as a bad fall or traumatic sport-accident, previous knee injuries or wear and tear over time. Immobilization for long periods can also result in cartilage damage.
Autologous chondrocyte implantation is a biomedical treatment that repairs damages in articular cartilage. ACI provides pain relief while at the same time slowing down the progression or considerably delaying partial or total joint replacement surgery. The goal of ACI is to allow people suffering from articular cartilage damage to return to their old lifestyle; regaining mobility, going back to work and even practicing sports again.
Mesenchymal stem cells (MSCs) are multipotent cells found in multiple human adult tissues, including bone marrow, synovial tissues, and adipose tissues. Since they are derived from the mesoderm, they have been shown to differentiate into bone, cartilage, muscle, and adipose tissue. MSCs from embryonic sources have shown promise scientifically while creating significant controversy. As a result, many researchers have focused on adult stem cells, or stem cells isolated from adult humans that can be transplanted into damaged tissue.
Kevin Robert Stone is an American physician, orthopedic surgeon, clinician, researcher, and company founder of The Stone Clinic and the Stone Research Foundation in San Francisco.
Autologous matrix-induced chondrogenesis (AMIC) is a treatment for articular cartilage damage. It combines microfracture surgery with the application of a bi-layer collagen I/III membrane. There is tentative short to medium term benefits as of 2017.
Cartilage repair techniques are the current focus of large amounts of research. Many different strategies have been proposed as solutions for cartilage defects. Surgical techniques currently being studied include:
Orthopedic surgery is the branch of surgery concerned with conditions involving the musculoskeletal system. Orthopedic surgeons use both surgical and nonsurgical means to treat musculoskeletal injuries, sports injuries, degenerative diseases, infections, bone tumours, and congenital limb deformities. Trauma surgery and traumatology is a sub-specialty dealing with the operative management of fractures, major trauma and the multiply-injured patient.
The treatment of equine lameness is a complex subject. Lameness in horses has a variety of causes, and treatment must be tailored to the type and degree of injury, as well as the financial capabilities of the owner. Treatment may be applied locally, systemically, or intralesionally, and the strategy for treatment may change as healing progresses. The end goal is to reduce the pain and inflammation associated with injury, to encourage the injured tissue to heal with normal structure and function, and to ultimately return the horse to the highest level of performance possible following recovery.
Autologous cultured chondrocytes on porcine collagen membrane (Maci) is a treatment to correct cartilage defects in the knee. It is used to treat symptomatic, full-thickness cartilage defects of the knee with or without bone involvement. Autologous cultured chondrocytes on porcine collagen membrane is an autologous cellularized scaffold product. This treatment is approved by the US Food and Drug Administration (FDA). It is only administered to adults. Healthy cartilage is removed from the person's own knees and a 'scaffold' is created on which the healthy tissue growths. This is an autologous matrix-induced chondrogenesis procedure which prevents tissue rejection complications since the transplanted cartilage comes from the same person.
Nasal chondrocytes (NC) are present in the hyaline cartilage of the nasal septum and in fact are the only cell type within the tissue. Similar to chondrocytes present in articular cartilage, NC express extracellular matrix proteins such as glycosaminoglycans and collagen.
Artificial cartilage is a synthetic material made of hydrogels or polymers that aims to mimic the functional properties of natural cartilage in the human body. Tissue engineering principles are used in order to create a non-degradable and biocompatible material that can replace cartilage. While creating a useful synthetic cartilage material, certain challenges need to be overcome. First, cartilage is an avascular structure in the body and therefore does not repair itself. This creates issues in regeneration of the tissue. Synthetic cartilage also needs to be stably attached to its underlying surface i.e. the bone. Lastly, in the case of creating synthetic cartilage to be used in joint spaces, high mechanical strength under compression needs to be an intrinsic property of the material.
Craniofacial regeneration refers to the biological process by which the skull and face regrow to heal an injury. This page covers birth defects and injuries related to the craniofacial region, the mechanisms behind the regeneration, the medical application of these processes, and the scientific research conducted on this specific regeneration. This regeneration is not to be confused with tooth regeneration. Craniofacial regrowth is broadly related to the mechanisms of general bone healing.
Spheroids of human autologous matrix-associated chondrocytes, sold under the brand name Spherox, is a medication used to repair defects to the cartilage in the knee in adults who are experiencing knee pain and problems moving the knee. It is used where the affected area is no larger than 10 cm2 (1.6 sq in).