Tissue Engineering: Making a Meniscus
Abstract & Commentary
Synopsis: An animal model using a collagen scaffold derived from porcine small intestine produced gross and histologic meniscal regeneration in the rabbit model.
Source: Gastel JA, et al. Meniscal tissue regeneration using a collagenous biomaterial derived from porcine small intestine submucosa. Arthroscopy. 2001;17(2):151-159.
This pilot study evaluated the meniscal regeneration potential of a collagen scaffold derived from porcine small intestine submucosa (SIS). Twelve animals had a 3 mm wedge defect from the central third of the lateral meniscus treated with a patch of SIS. The opposite limb served as the control with an identical empty defect created in the lateral meniscus. Four animals were euthanized at 4, 12, and 24 weeks. At each time period, 2 animals were studied with microscopic histology and the remainder evaluated only grossly.
Based on gross evaluation, the control group had less densely opaque tissue compared with the SIS side. Both groups showed significant signs of healing on histological evaluation at 6 months. At this late time period, remnants of the graft were no longer identifiable in the healing tissue. Furthermore, the experimental specimens showed more organized tissue resembling that of the native meniscus.
Comment by Robert C. Schenck, Jr., MD
Tissue engineering in orthopaedic surgery is taking the specialty beyond the days of repair to that of tissue regeneration, and the orthopaedic surgeon must become familiar with these concepts. Regeneration involves the creation of identical tissue to that lost or injured and can be contrasted to repair, which restores the damaged area with a functional but different tissue. It is in regeneration that tissue engineering is directed and involves the manipulation of connective tissues through the use of 3 components: cells, scaffolds, and growth factors. The term "cell" in most tissue engineering recipes is usually the mesenchymal stem cell (MSC). Despite differing names (connective tissue progenitor cells, colony forming units, etc), MSCs involve a true progenitor cell that has limitless self renewal and can differentiate down multiple pathways (ie, to become bone, cartilage, tendon, meniscus, or ligament).1 The greatest source for MSCs is from bone marrow. Scaffolds or matrices (matrix) provide a specialized template or pathway, which is conductive for tissue growth (thus the term osteoconductive implies a scaffold for bone growth). Morphogens or growth factors, through a chemical or physical factor, stimulate cell activity and differentiation to produce bone, cartilage, meniscus, etc. Finally, genetic engineering, a slightly different twist, uses some vector (usually a virus), which transfects a cell with the intent to insert a segment of DNA such that the cell produces a protein or morphogen from the specific inserted genetic code. In summary, these mechanisms create new tissue and are described with the suffix "genesis."1,2
For tissue regeneration to occur successfully, at least 2 of the 3 mechanisms are required. Nonetheless, regenerate can occur with 1 of the 3 but is less reliable and requires a completely normal host bed as is seen in this study by Gastel et al. However, as recently noted at an AAOS symposium on tissue engineering, the most reliable technique of tissue regeneration was to have all 3 components present.2 Of the 3, cells for regrowth are the key ingredient and have been the most difficult to create as a straightforward preparation, especially in cartilage, tendon, and meniscus.2 The process of creating stem cells for connective tissue regeneration was pioneered with advances in skin replacements, and these techniques and concepts are being applied to the musculoskeletal system.2 These applications have evolved at different rates and appear in the following order of current clinical applications: bone, hyaline cartilage, tendon/ligament, and as noted in the reviewed animal study, the meniscus.
In the study by Gastel et al, primarily the scaffold ingredient for the tissue engineering recipe for meniscal regeneration is used, as in another study performed by Stone et al.3 Regeneration in such a strategy is dependent upon cell ingrowth and local growth factors. The SIS material is known to contain numerous growth factors as well and may offer an advantage in tissue regeneration. The SIS graft was resorbed, did not produce degenerative or synovial changes about the knee, and did appear to heal better than control. The potential availability and clinical application of this porcine-derived collagen scaffold is exciting. Interestingly, Arnoczky used a fibrin clot which also produced significant meniscal regeneration.4 The fibrin clot contains both growth factors and a scaffold, and although cellular, not of the stem cell type. Reliable success with the collagen scaffold may likely involve addition of the 2 remaining ingredients, cells and growth factors, with the latter probably more readily available.
In summary, the orthopaedist must learn the concepts of tissue engineering to evaluate potential devices or implants based on the major 3 components: cells, scaffolds, and growth factors. Successful tissue regeneration of the meniscus is nearing a reality and studies such as this one make it 1 step closer.
References
1. Schenck RC. Strategic strategies: Contemporary tissue engineering. Medscape. 2001.
2. Goldberg VM, et al. Tissue engineering: A contemporary treatment strategy for musculoskeletal tissue loss. Presented at: Annual Meeting of American Academy of Orthopaedic Surgeons, Symposium; March 2, 2001;San Francisco, Calif.
3. Stone KR, et al. Regeneration of meniscal cartilage with use of a collagen scaffold: Analysis of preliminary data. J Bone Joint Surg. 1997;79:1770-1777.
4. Arnoczky SP, et al. Meniscal repair using an exogenous fibrin clot: An experimental study in dogs. J Bone Joint Surg. 1988;70:1209-1217.
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