Cartilage regeneration an area of growing orthopedic interest

Cartilage regeneration an area of growing orthopedic interest

Duane Feldman

As seen during the annual meeting of the American Academy of Orthopaedic Surgeons (AAOS; Rosemont, Illinois) in San Francisco, California, earlier this year, areas with growth expectations include cell-based tissues and genetic therapies which will grow the cell ex vivo. Mesenchymal stem-cell technology also is promising, since these cells have demonstrated the ability to distinguish viable chondrocytes which can then be turned into hyaline-like cartilage. Another growing area of interest seen at AAOS was viscoelastics, for use in treating arthritis, preventing adhesions after surgery, and other uses.

Swedish, American procedures vie

Two methods being studied as alternatives to total knee replacement or reconstruction are autologous chondrocyte transplantation (ACT), also known as the “Swedish procedure,” and articular cartilage autografting (ACA), known as the “American procedure.” Both are procedures for implanting cartilage.

The ACT procedure removes a small amount of chondrocyte cells from a non-weightbearing location in a healthy knee. These cells then are cultured for several weeks, after which the cultured cells are re-implant-ed into the problem area. Developed at the University of Goteborg (Goteborg, Sweden) in 1994, ACT is the most-used process at present. However, test results for ACT have not been definitive and the technique does require two surgeries. The method provides an effective way of minimizing the number of chondrocytes removed from a healthy location and the ability to build up the quantity for implantation.

An interesting new development associated with ACT is magnetic-tagging, developed by the Michigan State University School of Medicine at its Kalamazoo, Michigan, campus in conjunction with Cornell University’s North Shore University Hospital (Manhasett, New York). In this procedure, a very small magnet is introduced at the site in need of repair, with the intention of holding the transplanted chondrocytes in place. The tagging is accomplished with ferromagnetic nanoparticles to avoid these cells drifting away from the desired position. Results of studies with rabbits showed new tissue morphology equivalent to the original hyaline articular cartilage, and additional animal studies using growth factors to speed cartilage development are being planned.

A process vying with ACT is ACA, with trial results from the Stone Foundation for Sports Medicine and Arthritis Research. This procedure is accomplished by directly transplanting cartilage cells from a healthy, non-weight-bearing area of the knee to the damaged site. The ACA procedure is performed in a single arthroscopic outpatient operation. This treatment has demonstrated the ability to stimulate growth of predominantly type II hyaline cartilage. One advantage of this course would be that only one surgery is required.

Genzyme Tissue Repair (Cambridge, Massachusetts) has developed the Carticel cartilage repair service, using the ACT process. Studies have indicated a significant improvement of knee condition in those treated. Genzyme is directing Carticel toward experienced physicians and younger patients without arthritis.

ReGen Biologics has developed a synthetic bovine cartilage/collagen template with applications in disc and carpal/metacarpal repair. The studies of their meniscal implant have shown patient improvement in trials. Sulzer Orthopedics (Austin, Texas) provided capital for this research and subsequently has been given the distribution rights to collagen-based meniscal implants in countries outside of the U.S. Sulzer also bought the proprietary rights for other uses for this product.

Smith & Nephew (Memphis, Tennessee) and Advanced Tissue Sciences (ATS; La Jolla, California) have formed a joint venture to create tissue-engineered cartilage with the goal of meniscal healing in the knee cartilage. They have also worked together on spinal discs and joints with testing coming up on implants of specific cartilage into a damaged disc.

Osiris Therapeutics’ technology is based on mesenchymal stem cell for external tissue growth. Osiris reportedly intends to implant those tissues as a meniscal replacement.

OsteoBiologics (San Antonio, Texas), Wright Medical Technology (Arlington, Tennessee) and Biomaterials Corp. have two joint ventures. OsteoBiologics developed the Osteochondral implant for repairing cartilage in vivo. It has entered into a distribution agreement with Wright Medical for this implant. OsteoBiologics also has entered into a separate agreement with Biomaterials Corp. to develop bioactive materials used in bone and cartilage repair. OsteoBiologics manufactures other goods such as biodegradable devices for bone or cartilage repair, scaffolds for chronic bone repair, and grafts to repair articular defects.

Viscoelastics eyed for arthritis, adhesions

For those with an eye to conservative treatments and/or preventive medicine, viscoelastics is an area to watch. Viscoelastics are being studied for their possible applications in treating arthritis, the prevention of post-surgical adhesions, for replacing synovial joint fluid, and for failed back surgery syndrome. One of the main ingredients in this area of research is hyaluronic acid. This is a viscoelastic binding and protective fluid used in lubricating joints, the preservation of tissue structure, and sustaining hyaline cartilage. Eventually, with the aid of a surgical procedure, it is believed this product will dry up. This will allow the patient more productive use of the joint.

At this time, Biomatrix (Ridgefield, New Jersey) is leading developers with its treatments for osteoarthritis. Synvisc hyaluronic acid treatment provides pain relief via lubrication to joints. This product is applied by injecting it right into the joint. A new product under study is Arletan, a viscoelastic product with uses in arthroscopic surgery.

Replasyn hyaluronic-based products are Bioniche’s entry in the osteoarthritis market, as a non-steroidal anti-inflammatory medication.

Another company showing success with osteoarthritis products, Fidia, is marketing Hyalgen intra-articular sodium hyaluronate. This has shown to be effective as a non-steroidal anti-inflammatory drug.

The emphasis of Focal (Lexington, Massachusetts) has been postsurgical adhesion prevention through the use of a biodegradable, polymer-based gel.

Gliatech (Cleveland, Ohio) has created adhesion control gels. Adcon-T/N and Adcon-L are bioresorbable, carbohydrate-based and currently available in 15 countries. Adcon-L is designed to restrict drastic scarring after lumbar spine surgery. Adcon-T/N, having received FDA approval in 1995, has applications in inhibiting postsurgical adhesions after tendon and peripheral nerve surgeries.

DePuy’s (Warsaw, Indiana) Canadian division is distributing a hyaluronic acid-based product, Orthovisc, which was developed by Anika Research (Woburn, Massachusetts).

Other companies or joint ventures currently active in this market include: Biomet (Warsaw, Indiana)/LifeCore (Chaska, Minnesota), Chesapeake Bay Labs/Linvatec (Largo, Florida), Johnson & Johnson Professional (Raynham, Massachusetts)/MedChem (Woburn, Massachusetts), Zimmer (Warsaw, Indiana)/Pharmacia & Upjohn (Kalamazoo, Michigan).

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