The field of substitution medicine is rapidly evolving. Substitution medicine is based on an integration of biomaterials as a scaffold, and the culturing of cells, resulting in a novel, tissue engineering approach.
Tissue engineering provides the opportunity to affect repair and regenerative processes through the delivery of molecular and cellular components that result in the rapid formation of new tissue at the site of the disease or injury. This editorial will focus on tissue engineering of bone and cartilage.
One of the major current sources for bone grafts is donor material. Because of the risk of disease transfer (cases of HIV and HCV transfer have been reported in this context), the most optimal solution would be bone from the patient self, ie autologous bone. The current procedure for harvesting autograft bone involves taking a fairly large piece from the iliac crest. The harvested bone is then reshaped and prepared to be used as bone filler. This harvesting procedure is quite painful, and can lead to serious pain symptoms, sometimes until a year after the intervention.
Tissue engineering will provide a much more elegant approach, leading to less discomfort for the patient, and a much improved clinical solution for both patient and the orthopaedic surgeon. First, a small aspirate of bone marrow is taken from the iliac crest.
The osteoprogenitor cells from the biopsy are stimulated towards differentiation into osteoblasts, which are cultured, and then seeded on a biomaterials scaffold. After a few weeks, the scaffold with the matrix formed by the autologous cells can be used as a bone graft (Fig. 1).
Extensive pre-clinical studies have shown the feasibility, reproducibility, and safety of these methods. The first clinical evaluation of the described procedures is now under preparation. It will take one to two years before the final data can be reported, but it is already clear that the tissue engineering of bone holds a major promise in the area of substitution medicine.
Another promising application of tissue engineered bone is the coating of implants, like revision hip joints, with a thin layer of calcium phosphate on which cultured autologous osteoblasts are seeded. The addition of osteoblasts to the biomimetic coating enhances the formation of matrix, promotes the in-growth of osteoblasts and results in a better and faster fixation of the revision implant. The ultimate goal is to achieve better long-term results from revision arthroplasties.
Cartilage is frequently injured, very often due to sports activities. The goal in treating articular cartilage injury is the repair or regeneration of the damaged surface, resulting in long-term improvement of clinical symptoms. With conventional treatment modalities it is not possible to achieve a complete and sustainable resolution of the complaints. The consensus is that optimal treatment of the damaged cartilage of the knee will come from replacing it by autologous articular cartilage.
One of the methods currently used for cartilage autograft is called mosaicplasty: osteochondral biopsies from one (donor) spot in the knee are transferred to the damaged spot, locally forming a mosaic (Fig. 2). Obviously this approach creates damage to the knee at the donor site. Although the material is harvested at a site which supposedly has no, or less weight bearing duties and is less subject to high pressures, the result is another weak spot, which in the long run may lead to additional complaints. A much more elegant approach is taking only a very small biopsy, and to use these cells for culturing more autologous material, which after a few weeks, having increased in volume, is implanted at the site of the defect.
An even better approach is expected to be the combination of the material properties of synthetic scaffolds with chondrocytes to form new functional tissue: tissue engineered cartilage. IsoTis is one of the companies specifically following this approach.
ENQUIRY No 69
Luc G W Sterkman, MD, MFPM, is with IsoTis, Bilthoven, The Netherlands. <a href=
"http://www.isotis.com“ target=_self>www.isotis.com</a>
